Activation of methane by homogeneous catalyst in weakly acidic solvents

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Content ACTIVATION OF METHANE BY HOMOGENEOUS CATALYSTS IN WEAKLY ACIDIC SOLVENTS by Vadim Rinatovich Ziatdinov A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFONIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CHEMISTRY) May 2007 Copyright 2007 Vadim Rinatovich Ziatdinov ii DEDICATION to the synthetic chemists iii ACKNOWLEDGEMENTS First of all, I would like to extend my deep and sincere gratitude to my research advisor, Professor Roy A. Periana, for the unique opportunity to learn and do cutting-edge science and experience the excitement of a real scientific discovery. This would not have been possible without your tremendous erudition, endless support, inspiration, and patience. I would also like to thank Professor Robert Bau, Professor Karl O. Christe, Professor George A. Olah, Professor John A. Petruska, and Professor G. K. Surya Prakash for their excellent support and encouragement. Their profound knowledge in both chemistry and philosophy has truly inspired me. I would like to acknowledge all the past and present members of the Periana group. I personally acknowledge Dr. Oleg A. Mironov, Cj Jones, Dr. Xiang Yang Liu, Dr. Antek G. Wong-Foy, and Dr. Gaurav Bhalla, whose work on laboratory setup was indispensable, who established the group, and really helped to boost my experimental chemistry. My thanks to Dr. K. J. H. Young, William Tenn, who joined the group simalteneously with me and provoked a healthy competition. I thank each of the later group members and visiting scholars including Satoshi, Somesh, Steven, and Brian for scientific discussions and fine time. I am grateful to our collaborators Professor W. A. Goddard, III, Dr. Jonas Oxgaard, Dr Robert Smith Nielsen, and Dr. Jason Gonzales at iv Beckmann Institute, California Institute of Technology, for their wize advices amd recommendations in theoretical chemistry. I would also like to thank Professor William C. Kaska at UCSB for his valuable suggestions and insights. I thank Professor Flood for his insight on reaction mechanisms. I recognize Dr Olah, Dr Periana for his valuable time as Ph.D. committee member. I’d like to thank Dr. Muhammed Yousufuddin, and Tim athy Stewart for their help in X-Ray crystallography. I also thank Dr. Thomas Mathew and Dr. Mihirbaran Mandal for their help with high-pressure experiments. I thank Alex Alexander for the wide help regarding synthesis, purification as well as for moral support. Especially I thanks my high-school and graduate school roammate, Nikolay Markovskiy, for his wise advices, life-saving support, and endless patience. I would also like to thank many other friends and colleagues including Konstantin, Sergey Malyk, Anton Zadorozhnyi, Misha, Nadja, Roman, Yegor, Daniil, Sergey Levchenko, Jinbo, Ryan, Kevin, Sean, Anton, Doug, Eugene, Elena, Frederico, Thomas, and many others. I thank the staff members of the chemistry department, especially Michele, Heather, David, Carole, and Jessy for their kind support. I thank Allan, Jaime, Frank, Bruno, Ross, and Jim for their technical help. I thaks Stella and Harry who show me California and let me enjoy family environment far away from homeland and my family. I thank my country, Russia, and especially my city, Saint-Petersburg, for providing the opportunity to obtain great fundamental education and for v protecting my family and me at this difficult time of Russian history. I thank to Los Angeles, California and USA people and government for creating friendly environment for deep scientific studies by scientists from all over the world. I thank all my large family and especially I am forever grateful to my parents, Rinat Nagimovich Ziatdinov and Tatiana Borisovna Ziatdinova, for their selfless support and enormous confidence in me, and endless source of wisdom without which this would not have been possible. Despite of my effort I will never be able to pay it back. vi TABLE OF CONTENTS DEDICATION............................................................................... ii ACKNOWLEDGEMENTS .......................................................... iii LIST OF TABLES....................................................................... vii LIST OF FIGURES ........................................................................x LIST OF SCHEMES....................................................................xiv ABSTRACT ................................................................................xvi 1 Chapter One: Introduction........................................................1 1.1 Background........................................................................1 1.2 C-H activation Reaction .....................................................4 1.3 C-H activation in Strongly Acidic Solvents ........................9 1.3.1 Acid Enhanced Selectivity ..........................................9 1.3.2 Acid Enhanced Catalyst Activity ..............................10 1.3.3 High Yield Conversion of Methane to Methyl Bisulfate Catalyzed by Iodine Cations ......................14 1.3.4 C-H Activation by Electrophilic Mechanism in Acidic Solvents: Hg(II) System............................................18 1.4 Research strategies towards novel catalytic systems in weakly acidic media. ........................................................23 1.5 References........................................................................27 2 Chapter Two: High Yield Conversion of Methane to Methyl Bisulfate Catalyzed by Gold ..................................................31 2.1 Introduction......................................................................31 2.2 Results and Discussion. ....................................................31 2.3 Conclusion. ......................................................................42 2.4 Experimental ....................................................................42 2.5 References........................................................................46 vii 3 Chapter Three: Mechanism of the High-yield, Methane to Methanol Pt(bpym)Cl 2 /H 2 SO 4 Conversion System. ...............48 3.1 Introduction......................................................................48 3.2 Results..............................................................................51 3.3 Discussion. .......................................................................75 3.3 Conclusion. ......................................................................87 3.4 Experimental. ...................................................................88 3.5 References......................................................................111 4 Chapter Four: C 6 H 6 Activation in Weakly Acidic Media via 6-Membered Cyclic Transition State. ............................115 4.1 Introduction....................................................................115 4.2 Results and Discussion ...................................................118 4.3 Conclusion .....................................................................124 4.4 Experimental Section......................................................125 4.5 References......................................................................141 5 Chapter Five: Fast C 6 H 6 Activation in Weakly Acidic Media via Resting State Destabilization. ........................................142 5.1 Introduction....................................................................142 5.2 Results and Discussion ...................................................143 5.3 Conclusion. ....................................................................149 5.4 Experimental. .................................................................149 5.5 References......................................................................165 6 Chapter Six: CH 4 Activation in Weakly Acidic Media via Transition State Stabilization. ........................................166 6.1 Introduction....................................................................166 6.2 Results and Discussion. ..................................................168 6.3 Conclusion. ....................................................................175 6.4 Experimental. .................................................................175 6.5 References......................................................................192 viii 7 Chapter Seven: CH Activation Perspective in a Weakly Acidic Media. .................................................................................192 7.1 Introduction....................................................................192 7.2 Discussion. .....................................................................193 7.3 Conclusion .....................................................................198 7.4 References......................................................................199 BIBLIOGRAPHY.......................................................................200 ix LIST OF TABLES Table 2.1. Methanol yield under different reaction conditions. 35 Table 3.1. Ratio of deuteromethanes (d 1 :d 2 :d 3 :d 4 ) from direct catalytic reaction with CH 4 and from reverse reaction of Pt II -CH 3 deuterolysis. 60 Table 3.2. Product yield table, Pt II /Pt IV -CH 3 + D 2 SO 4 reaction. 70 Table 3.3. Crystal data and structure refinement for Pt(bpym)Cl 4 ⋅0.5DMF. 99 Table 3.4. Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)Cl 4 ⋅0.5DMF. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. 100 Table 3.5. Bond lengths [Å] and angles [°] for Pt(bpym)Cl 4 ⋅0.5DMF. 101 Table 3.6. Anisotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)Cl 4 ⋅0.5DMF. The anisotropic displacement factor exponent takes the form: -2π 2 [ h 2 a* 2 U 11 + ... + 2 h k a* b* U 12 ] 103 Table 3.7. Hydrogen coordinates ( x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)Cl 4 ⋅0.5DMF. 104 Table 3.8. Crystal data and structure refinement for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . 104 Table 3.9. Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. 105 Table 3.10 Bond lengths [Å] and angles [°] for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . 106 x Table 3.11. Anisotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . The anisotropic displacement factor exponent takes the form: -2π 2 [ h 2 a* 2 U 11 + ... + 2 h k a* b* U 12 ] 108 Table 3.12. Hydrogen coordinates ( x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . 109 Table 4.1. Deuterium insertion study by (bpym)Pt in C 6 H 6 /DTFA reaction. 130 Table 4.2. Deuterium insertion study in C 6 H 6 /DTFA reaction without any catalyst. 131 Table 4.3. Kinetic of deuterium insertion by (bpym)Pt in C 6 H 6 /DTFA reaction. 132 Table 4.4. DFT estimation of thermodynamic data of (bpym)Pt(TFA) 2 . 134 Table 4.5. DFT estimation of thermodynamic data of (bpym)Pt(TFA)(C 6 H 6 ) intermediate. 136 Table 4.6. DFT estimation of thermodynamic data of 6- membered cyclic CH cleavage transition state (bpym)Pt(TFA-H-C 6 H 5 ) with TFA- ion around. 137 Table 4.7. DFT estimation of thermodynamic data of (bpym)Pt(Ph)(HTFA) intermediate 139 Table 5.1. Deuterium insertion study by (pic)Pt in C 6 H 6 /DTFA reaction. 155 Table 5.2. Kinetic of deuterium insertion by (pic)Pt in C 6 H 6 /DTFA reaction. 156 Table 5.3. DFT estimation of thermodynamic data of (pic)Pt(TFA) 2 - . 158 Table 5.4. DFT estimation of thermodynamic data of (pic)Pt(TFA)(C 6 H 6 ) intermediate. 159 xi Table 5.5. DFT estimation of thermodynamic data of 6- membered cyclic CH cleavage transition state (pic)Pt(TFA-H-C 6 H 5 ) with TFA- ion around. 161 Table 5.6. DFT estimation of thermodynamic data of (pic)Pt(Ph)(HTFA) intermediate 162 Table 6.1. Deuterium insertion study by (nap)Pt(TFA) 2 in C 6 H 6 /DTFA reaction at 85 o C. 178 Table 6.2. Deuterium insertion study by (nap)Pt(TFA) 2 in C 6 H 6 /DTFA reaction at 100 o C. 178 Table 6.3. Deuterium insertion study by (nap)Pt(TFA) 2 in C 6 H 6 /DTFA reaction at 115 o C. 179 Table 6.4. Deuterium insertion study by (nap)Pt(TFA) 2 in C 6 H 6 /DTFA reaction at 130 o C. 179 Table 6.5. DFT estimation of thermodynamic data of (nap)Pt(TFA)(TFA) intermediate. 180 Table 6.6. DFT estimation of thermodynamic data of (nap)Pt(TFA)(HTFA) + intermediate. 181 Table 6.7. DFT estimation of thermodynamic data of (nap)Pt(TFA)(C 6 H 6 ) + intermediate. 183 Table 6.8. DFT estimation of thermodynamic data of (nap-H- Ph)Pt(TFA)+ transition state. 185 Table 6.9. DFT estimation of thermodynamic data of (nap)Pt(TFA)(Ph) intermediate. 187 Table 6.10. DFT estimation of thermodynamic data of (nap-H- CH 3 )Pt(TFA) transition state. 189 xii LIST OF FIGURES Figure 1.1. Comparison of the Likely Active Catalyst in the Pt(bpym)Cl 2 /H 2 SO 4 system with the Weakly Coordinating BARF anion. 12 Figure 1.2. Proposed Electrophilic CH Activation Mechanism for the Iodine Catalyzed Oxidation of Methane in Oleum. 16 Figure 2.1. 13 C NMR spectrum of the reaction mixture with 13 CH 4 . 36 Figure 2.2. Calculated enthalpies (kcal mol -1 ) relative to 1, including solvation by sulfuric acid (e = 50). Spectator sulfuric acid molecules have been omitted from some structures for clarity. 39 Figure 2.3. Calculated enthalpies (kcal mol -1 ) at 175 o C relative to 7, including solvation by sulfuric acid (e = 50). For clarity, spectator H 2 SO 4 groups have been omitted from some structures. The top curve illustrates electrophilic substitution, while the bottom curve illustrates oxidative addition. 40 Figure 2.4. Stepwise mass-spectrum deconvoution method for a mixture of methane isotopomers. 44 Figure 2.5. Least squares fit mass-spectrum deconvoution method for a mixture of methane isotopomers: Experimental (¦ ) vs. Fitted (¦ ) (a*CH 4 + b*CH 3 D + .. + e*CD 4 ) mass-spectrum. 45 Figure 3.1. Kinetics of CH 4 deuteration by Pt(bpym)Cl 2 /D 2 SO 4 . [Pt(bpym)Cl 2 ] = 2.5 mM, temperature 150 °C. 52 Figure 3.2. Plot of observed H/D exchange rate vs. agitation speed. [Pt(bpym)Cl 2 ] = 2.5 mM, temperature 165 °C, reaction time 40 min. 53 Figure 3.3. Plot of turnover number for methane H/D exchange vs. methane pressure, [Pt(bpym)Cl 2 ] = 5 mM, temperature 165 °C, reaction time 40 min. 54 xiii Figure 3.4. Plot of observed reaction rate for H/D exchange (?) and oxidation to methanol (•) vs. catalyst concentration. Temperature 165 °C, p methane = 25 psi. 55 Figure 3.5. Eyring plot for the Pt(bpym)Cl 2 catalyzed H-D exchange of CH 4 with D 2 SO 4 . [Pt(bpym)Cl 2 ] = 35 mM, temperature range 169 - 190 °C. 56 Figure 3.6. Eyring plot for the Pt(bpym)Cl 2 catalyzed oxidation of CH 4 to CH 3 OH. [Pt(bpym)Cl 2 ] = 35 mM, temperature range 169 - 190 °C. 57 Figure 3.7. Correlation of CH activation rate (measured as CH 4 /D 2 SO 4 H-D exchange turnover frequency at 150 °C) with solvent acidity. 58 Figure 3.8. 1 H NMR of Pt-CH 3 Region on Protonation of Pt(bpym)(CH 3 )TFA with FSO 3 H/SbF 5 in Liquid SO 2 at –50 o C. 62 Figure 3.9. No Pt-H resonances are observed during protonolysis of Pt(bpym)(CH 3 )TFA. 64 Figure 3.10. Protonation of Pt(bpym)(CH 3 ) 2 in SO 2 with magic acid at -65 °C. 66 Figure 3.11. A set of 1 H NMR spectra of deuterolysis reaction of Pt(bpym)(CH 3 )TFA in CD 3 COOD (see text). 67 Figure 3.12. Methane isotopomers arising from protonolysis of Pt(bpym)(CH 3 )TFA complex in acetic acid-d. 68 Figure 3.13. Pt(bpym)(CH 3 )TFA oxidation yields based on the starting material and on added Pt(bpym)Cl 4 complex. 74 Figure 3.14. Solution-phase potential energy diagram for the C– H activation of the Catalytica Pt catalyst with one added proton. Energy values are ΔH 0K , kcal/mol. 32 78 Figure 3.15. Explanation for the observed multiple H-D exchange in C-H activation step. 79 Figure 3.16. Ground state stabilization by products. 83 xiv Figure 3.17. Rate of CH 3 X product formation for fast, intermediate, and synchronous parallel oxidation reaction. 87 Figure 3.18. ORTEP drawing of Pt(bpym)Cl 4 . 91 Figure 3.19. ORTEP drawing of Pt(bpym)(CH 3 )(TFA). 96 Figure 4.1. Hydrocarbone reactivity through CH activation mechanism . 115 Figure 4.2. Water/methanol inhibition as result of sulfuric acid dilution during reaction course. 116 Figure 4.3. Two approaches to reactivity: resting state destabilization or transition state stabilization. 117 Figure 4.4. CH activation by internal electrophilic substitution through 6-membered cyclic transition state versus external electrophilic substitution ORTE. 118 Figure 4.5. 6-membered cyclic and less favorable electrophilic substitution transition states. 119 Figure 4.6. Preparation of active catalyst, (bpym)Pt(TFA) 2 . 120 Figure 4.7. Study of isotopologes appearance in H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by (bpym)Pt(TFA) 2 /AgOAc at 150 o C. Black – C 6 H 6 ; Dark blue – C 6 H 5 D; Blue – C 6 H 4 D 2 ; Light blue – C 6 H 3 D 3 ; Green -– C 6 H 2 D 4 ; Orange – C 6 HD 5 ; Red – C 6 D 6 . 121 Figure 4.8. Thermodynamics of Calculated Mechanism for the Benzene C-H Activation by Pt(bpym). 122 Figure 4.9. C-H cleavage transition state TS1. 123 Figure 4.10. (Bpym)Pt(Ph) 2 complex. 126 Figure 4.11. (Bpym)Pt(Ph)(TFA) complex. 128 Figure 4.12. (Bpym)Pt(TFA) 2 complex. 129 xv Figure 4.13. Turn over number versus time(hours) of H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by (bpym)PtCl 2 /AgOAc at 150 o C. 132 Figure 5.1. Effect of anionic ligand on resting state of catalyst. 143 Figure 5.2. Picolinic acid. 144 Figure 5.3. Preparation of active catalyst. 145 Figure 5.4. Thermodynamics of Calculated Mechanism for the Benzene C-H Activation: Pt(pic) – solid line; Pt(bpym) – dashed line. 146 Figure 5.5. C-H cleavage transition state TS1. Bond lengths in Å. 148 Figure 5.6. (Pic)Pt(Me)(Et 2 S) complex. 151 Figure 5.7. (Pic) 2 Pt complex. 152 Figure 5.8. K(Pic)Pt(OAc) 2 complex. 153 Figure 5.9. 1 H NMR of Platinum picolinate in trifluoroacetic acid after one day at 100 o C. 154 Figure 5.10. Study of isotopologes appearance in H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by K(pic)PtCl 2 /AgOAc at 100 o C. 157 Figure 5.11. Turn over number versus time(hours) of H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by K(pic)PtCl 2 /AgOAc at 100 o C. 157 Figure 6.1. Strong 6-membered cyclic interaction present in intermediates as well as in transition states. 167 Figure 6.2. Energy shift of 6-membered cyclic interactions compare to the resting state by controlling of acid- base properties of proton acceptor. 168 Figure 6.3. Synthesis of active catalyst - “(nap)Pt(TFA) 2 ”. 170 Figure 6.4. Study of isotopologes appearance in H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by xvi (nap)PtCl 2 /AgOAc at 115 o C. Dark blue – C 6 H 5 D; Blue – C 6 H 4 D 2 ; Dark green – C 6 H 3 D 3 ; Green -– C 6 H 2 D 4 ; Orange – C 6 HD 5 ; Red – C 6 D 6 . 171 Figure 6.5. Methane C-H cleavage transition state. Bond lengths in Å. 172 Figure 6.6. Thermodynamics of postulated mechanism for the benzene C-H activation: Pt(nap) – solid line; Pt(bpym) – dashed line. 173 Figure 6.7. (nap)Pt(Cl) 2 complex. 177 xvii LIST OF SCHEMES Scheme 1.1. Low cost process via MeOH intermediate. 2 Scheme 1.2. Syngas methane-to-methanol conversion method. 3 Scheme 1.3. Definition of C-H activation. 4 Scheme 1.4. Conventional catalytic scheme for alkane oxidation based on the C-H activation reaction. 5 Scheme 1.5. Alternative mechanisms for alkane C-H bond cleavage. 8 Scheme 1.6. Electrophilic Hg(II) catalyst activated by acid solvents. 13 Scheme 1.7. Conversion of methane to methyl bisulfate catalyzed by iodine cations. 14 Scheme 1.8. Proposed electrophilic CH activation mechanism for the oxidation of methane to methanol by the Hg(II)/H 2 SO 4 system. 19 Scheme 1.9. Methane activation by HgSO 4 . 20 Scheme 1.10. Possible Transition States for Generation of Methanol from CH 3 HgX. 22 Scheme 1.11. Two approaches to reactivity: resting state destabilization or transition state stabilization. 25 Scheme 2.1. Proposed mechanism for the oxidation of methane to methanol though CH activation with Au(I) and Au(III) in H 2 SO 4 . 33 Scheme 2.2. Stoichiometric methane to methanol oxidation by Au(III) in H 2 SO 4 , X = OSO 3 H. 33 Scheme 2.3. Stoichiometry of catalytic oxidation of methane to methanol by H 2 SeO 4 catalysed by gold in H 2 SO 4 . 34 Scheme 3.1. Pt(bpym)Cl 2 /H 2 SO 4 system for selective methane oxidation. 49 xviii Scheme 3.2. Proposed overall mechanism for the oxidation of methane to methanol catalyzed by Pt(bpym)Cl 2 in H 2 SO 4 . 50 Scheme 3.3. CH 4 /D 2 SO 4 proton/deuterium exchange catalyzed by Pt(bpym)Cl 2 at 150 °C. 51 Scheme 3.4. Protonation of bipyrimidine ring system and anion exchange, leading to four new Pt-CH 3 resonances upon protonation of Pt(bpym)(CH 3 )TFA with magic acid. 63 Scheme 3.5. Tandem mechanism of the Catalytica system. 84 Scheme 3.6. General tandem M n /M n+m C-H activation/oxidation mechanism. 86 xix ABSTRACT This dissertation describes the latest development in engaging simple hydrocarbons in reaction by CH activation. From initially fuming oleum condition and catalysis like halogens, the trend g oes to gold catalyst in 96% sulfuric acid, and later to variety platinum complexes in weak organic acids. The story concentrates on discovery of basic physical phenomenons to enhance reactivity versus specific synthetic applications. Chapter One introduces the C-H activation and functionalization of alkanes via the electrophilic mechanism, and discusses the role of non- coordinating solvents and the related problem of inhibition of electophilic catalysts by products such as methanol and water. The simplest iodine and mercury in sulfuric acid catalysts described. Chapter Two shows another simple catalytic system reported to date for converting methane to a methyl product below 200 °C. Gold dissolved in 2% oleum catalyzes the selective, high yield oxidation of methane to methyl bisulfate using selenic acid as stoichiometric oxidant. Chapter Three discusses in details the mechanism of the most efficient and selective low-temperature catalytic system for the conversion of methane to methanol, comprised of a solution of the complex Pt(bpym)Cl 2 (bpym=η 2 - {2,2'-bipyrimidyl}) in concentrated sulfuric acid, investigated in direct reactions as well as in microscopic reverse reactions of model intermediates. xx Chapter Four describe the discovety of highly effective 6-membered transition state for activation benzene in weak acids such as trifluoroacetic acid and other organic acids by Pt(bpym) TFA 2 . Chapter Five describes the discovery of new fast CH activation of benzene via conceptually proposed resting state destabilization phenomenon and experimentally supported by Pt(pic)TFA 2 (pic - picolinate). Chapter Six discribes the discovery of CH 4 CH activation at conditions unprecedented before. Conceptual model for transition state stabilization is discussed and experimentally supported by Pt(nap)TFA 2 (nap - 2-(2- Pyridinyl)-1,8-naphthyridine). Chapter Seven summarizes the above results and makes attemptes to show future directions in CH activation. 1 1 Chapter One: Introduction 1.1 Background Natural gas is gradually becoming an increasingly important raw material for the chemical industry, as worldwide natural gas reserves continue to increase while oil reserves are diminishing. Current global reserves of natural gas are estimated at some 170 trillion cubic meters, more than half of which can be classified as stranded gas (i.e. gas without direct access to market). 1 However, because such gas deposits are located in remote areas, direct use of these resources is hampered by high costs of transportation of natural gas, either in compressed or liquefied form. Indeed, because of these associated high costs more than 40 billion cubic meters of natural gas are vented or flared annually, causing losses of valuable feedstock and serious ecological consiquences. 2 These costs could be considerably lowered if natural gas is converted into useful liquid products at normal conditions like methanol, acetic acid, high alkanes. They can easily be shipped from remote area to consumers with further used either directly, or as a chemical feedstock for subsequent transformations, Figure 1.1. Current methods to convert methane into other useful chemicals require an initial formation of synthesis gases (H 2 +CO+CO 2 ) at high temperatures (800–1400 °C) via highly energy- and cost-intensive processes, Scheme 1.2. The development of new, selective, energy efficient chemistry for the direct, oxidative conversion of 2 natural gas (which is the primary methane) at temperatures below 250 °C, is commercially valuble. Potentically, it can lead to a new paradigm in energy and petrochemical technologies. It will be environmentally and economically superior and allow the vast reserves of natural gas to be employed directly as feedstocks for fuels and chemicals. This area is one of the most important problems in current catalytic science. 3, 4g At the same time, it is extremmly challenging scientifically. MeOH Gasoline Olefins Liquid Fuel Fuel Cells Other Chemicals Fischer-Tropsch Products Polymers DMM Natural Gas Air Direct Methane to Methanol Unit Scheme 1.1. Low cost process via MeOH intermediate. Our group applies a new approach to replace the current capital-intensive methane-to-methanol technology based on syngas (Scheme 1.2). It is suggested more efficient, low temperature direct oxidation process, which is less capital intensive. At the same time, the most economically valuable alternative to the syngas technology would be a hypothetical process for the direct, high-yield, one- step oxidation of methane to methanol. Economic evaluations indicate that even for such an idealized process, single-pass conversions in excess of 30% at greater 3 than 80% selectivity 5 are required for an economical process. 6 However, the direct, catalytic, oxidative conversion of alkanes at lower temperatures to products, such as versatile alcohols, presents many challenges. CH 4 + H 2 O —(>800 °C, 10-20 atm)? CO + 3 H 2 CO + H 2 O ? CO 2 + H 2 CO + 2 H 2 —(250 °C, 50-100 atm)? CH 3 OH CO 2 + 3 H 2 ? CH 3 OH + H 2 O Scheme 1.2. Syngas methane-to-methanol conversion method. A primary reason that technologies for direct, selective hydroxylation of alkanes to alcohols remain a challenge is that the current commercial catalysts for alkane oxidation (typically solid metal oxides) are not sufficiently active for the functionalization of alkane C-H bonds and high temperatures and harsh conditions must be employed with low reaction selectivity. 3 The key issue with selective oxidation of methane to methanol is that methane is relatively non-polar, inert molecule versus the polar and reactive methanol. As a result, existing oxidation catalysts require high temperatures for methane conversion and selectivity to methanol is typically much less than 1%. The key feature of catalyst should be unique selectivity to methane versus methanol or its derivatives. By using super acid as solvent George Olah showed activation of methane and its convertion to methanol in 1972. 3 The selectivity for mathanol of this 4 process is close to 100% and fast rate does not require special abnormal pressure or temperature conditions. The reaction product dilutes super acid and stops reaction. In 1967 Shylov show the catalytic and selective methane oxidation based on the C-H activation reaction. The development of valuable catalyst will require addressing multiple challenges of catalyst design: thermal and protic catalyst stability, rates of the multistep process, product separation, oxidant and mathane consumption. 1.2 C-H activation Reaction C-H activation can be defined as a facile CH cleavage reaction with an “MX” species that proceeds by coordination of an alkane to the inner-sphere of “M” (either via an intermediate “alkane complex” or a transition state) leading to a M-C intermediate, Scheme 1.3. Important to this definition is the requirement that during the CH cleavage the hydrocarbyl species remains in the inner-sphere and under the influence of “M”. C H + MX XM C H XM C Scheme 1.3. Definition of C-H activation. 5 Suitably designed homogenous complexes have been identified that can coordinate to and cleave the C -H bond of alkanes at low temperatures and with extraordinary selectivity via the C-H Activation reaction. 4 This reaction is of particular interest from a scientific as well as an economic viewpoint as it could be utilized to design the next generation of low temperature, selective, recyclable, Wacker-type, methane oxidation catalysts based on a generalized catalytic sequence shown in Scheme 1.4. However, despite the large body of work on the CH activation reaction that has been generated over the last three decades, to date relatively few catalytic systems that are based on this approach have been reported that allow the direct conversion of alkanes to useful products such as alcohols or other oxygenated products. This is likely due to the challenges associated with designing complexes that a) react by the CH activation reaction, b) generate functionalized products in a catalytic sequence, c) stable to the oxidizing conditions required for the oxidative functionalization reaction, d) product separation from reaction media. CH Activation 1/2 O 2 CH 3 -M CH 4 M Ox H 2 OX CH 3 OH H 2 O + + H 2 O Oxidation Functionalization Scheme 1.4. Conventional catalytic scheme for methane oxidation based on the C-H activation reaction. 6 Some of the notable systems that catalyze the oxidative conversion of alkanes to products containing C-O bonds and that may operate via the CH activation reaction shown in Figure 1.1. 7, 8,9,10,11,12,13,14,15 Periana N N N N Pt Cl Cl Hg(II) Pt Cl H 2 O H 2 O Cl Shilov Au(III) N N N N Pd Br Br R R Herrmann RhCl 3 /Cl - /l - /CO Pd/CO/CuCl 2 Sen I 2 + Pd(II) Fijuwara (H 5 PV 2 Mo 10 O 40 ) V O V Figure 1.1. Examples of systems that oxidatively convert alkanes to C-O functionalized products. Most of organic chemistry, characterized by relatively mild reaction conditions and high reaction selectivity, can be classified as inner-sphere coordination chemistry at carbon centers; i.e. chemistry that occurs within the first- coordination sphere of three, four and five coordinate carbon species. While the coordination chemistry of carbon in functionalized organic molecules is well- developed, the coordination chemistry of alkanes is much less so and is characterized by reactions with superacids, superbases, free-radicals or carbenes. 7 These very reactive species are generated either under high-energy conditions, or with high-energy precursors and are generally not amenable to efficient syntheses with alkanes as starting materials. The CH activation reaction can also be classified as a coordination reaction of alkanes with some reactive species, “M”, that takes place within the inner-sphere of the carbon to generate a M-C intermediate without the involvement of high energy species such as free-radicals, carbocations or carbanions. An important consequence of the coordination characteristics of the C-H activation reaction are low activation barriers and remarkable selectivities. Thus, the C -H activation reaction of alkanes has been reported at temperatures below 0 o C and with greater selectivity for primary over tertiary C -H bonds, arene C -H over alkane C -H bonds, and reactions of alkanes over alcohols. 4 The high rate of the C-H activation reaction results partly from formation of strong M-C bonds that compensate for the cleavage of the strong C -H bonds (thermodynamics) and availability of appropriate orbitals on the central atom, M, that ensure good overlap in the transition states (kinetics). Coupled with the possibility for oxidative conversion of the M-C intermediate to functionalized products with regeneration of “M”, as outlined in Scheme 1.4, the C-H activation reaction can provide a basis for the development of the next generation catalysts for the atom and energy efficient conversion of alkanes directly to useful products. 8 Scheme 1.5. Alternative mechanisms for alkane C-H bond cleavage. Various mechanisms of C -H cleavage are shown in Scheme 1.5. All of them require preliminary methane complex formation by coordination. The coordination step can be associative or dissociative in nature. Direct presence of methane complex is unique for inner sphere chemistry. M C H X + C H M X Alkane Complex M C H X + H X M C Sigma Bond Metathesis M C H X + H X M C Electrophilic Substitution M C H X M C H X Oxidative Addition XMC + HMX M C H X 1,2 Addition M C XH Metalloradical C H MX XM M C H X + C H C H M X M X Alkane Complex M C H X + H X M C + H X H X M C M C Sigma Bond Metathesis M C H X + H X M C Electrophilic Substitution M C H X + H X M C + H X H X M C M C Electrophilic Substitution M C H X M C H X Oxidative Addition XMC + HMX M C H X 1,2 Addition M C XH M C H X 1,2 Addition M C XH Metalloradical C H MX XM M C H X + C H M X Alkane Complex M C H X + H X M C Sigma Bond Metathesis M C H X + H X M C Electrophilic Substitution M C H X M C H X Oxidative Addition XMC + HMX M C H X 1,2 Addition M C XH Metalloradical C H MX XM M C H X + C H C H M X M X Alkane Complex M C H X + H X M C + H X H X M C M C Sigma Bond Metathesis M C H X + H X M C Electrophilic Substitution M C H X + H X M C + H X H X M C M C Electrophilic Substitution M C H X M C H X Oxidative Addition XMC + HMX M C H X 1,2 Addition M C XH M C H X 1,2 Addition M C XH Metalloradical C H MX XM 9 1.3 C-H activation in Strongly Acidic Solvents 1.3.1 Acid Enhanced Selectivity It is clear that designing a catalyst that exhibit preference for methane in presence of methanol product, and at the same time efficiently activate and functionalize C-H bonds is an enormous task. Such processes are complicated by the increasing reactivity of its oxidation products. Most oxidants capable of reacting with methane (BDE(C-H) = 104 kcal/mol) follow a hydrogen atom abstraction route and hence react more readily with the weaker C -H bonds of methanol (BDE(C-H) = 93 kcal/mol), placing an inherent limit on the yield. 16 An efficient approach to circumvent this problem is to “protect” the methanol from the catalyst by chemical modification. 6 The concept of protection is well-established in organic chemistry. For example, the nitro group slows or “protects” nitrobenzene from further electrophilic nitration relative to benzene. Thus, several highly efficient methane oxidation systems based on Hg(II), I 2 + , Pd(II), Au(III) and Pt(II), and concentrated H 2 SO 4 or oleum as solvent, have been reported by us. 8,9,10,11,12 Under these conditions, it was estimated that methane can be as much as 100 times more reactive than me thyl bisulphate, its oxidation product. 16c This is the highest selectivity observed at present for any methane to methanol conversion and should be sufficient for commercially valuable process. 10 1.3.2 Acid Enhanced Catalyst Activity It is a well-known phenomenon at present that both Lewis and Bronsted acids on mixing increase their acid properties. It allows more affectivily cleave CH bond by more electrophilic metal center. At the same time, it facilitates coordination of reactants. 17 Indeed, some of the most active systems reported for the stoichiometric CH activation can be seen as complexes that have been activated by addition of a Lewis acid. Thus, one of the most active complexes know for catalytic CH activation developed by Bergman, 18 [Cp * Ir(PMe) 3 Me(CH 2 Cl 2 )] + [MeB(C 6 F 5 ) 3 ] - , is generated by reaction of the Lewis acid, B(C 6 F 5 ) 3 , with Cp * Ir(PMe) 3 Me 2 in the poorly coordinating solvent, CH 2 Cl 2 . One reason that this complex is quite reactive with methane (at -10 o C) is that all the possible competing ligands in the reaction system [MeB(C 6 F 5 ) 3 ] - and CH 2 Cl 2 , are poorly coordinating species that minimize ground state stabilization and allow methane to effectively compete for coordination to the metal center. While this strategy of stoichiometric use of weakly coordinated complex can lead to very active catalysts in reactions where no strongly coordinating reactants, solvents, or products are present, such catalysts could not be expected to remain active in the presence of stoichiometric or greater amounts of coordinating species such as water or methanol. In the presence of these materials the weakly coordinated groups will be readily displaced, resulting in severe ground state inhibition of the catalyst. Consequently, this approach of 11 stoichiometric use of weakly coordinating groups would not be suitable for catalytic systems where the desired product is methanol and many catalyst turnovers are required. One approach that could be considered is to run the reaction in liquid B(C 6 F 5 ) 3 as solvent because under these conditions any methanol produced would form a strong acid-base adduct with the excess B(C 6 F 5 ) 3 . Under these conditions the methanol would be unavailable for coordination to the metal thereby preventing product coordination by methanol and subsequent ground state inhibition. The key issue with this strategy is that B(C 6 F 5 ) 3 is expensive and most likely it would not be cost effective to attempt to separate the MeOH:B(C 6 F 5 ) 3 complex and recycle the B(C 6 F 5 ) 3 . However, if the Lewis acid utilized is inexpensive and thermally robust, this could be potentially useful strategy. This is the essential idea behind the use of inexpensive sulfuric acid solvent for facilitating the selective oxidation of methane. 6,8-12 Liquid sulfuric acid, at concentrations > ~85%, is a polar, strongly Bronsted acidic, poorly nucleophilic liquid in which the strongest nucleophile (or ligand) that can exist, HSO 4 - , is substantially less coordinating that water or methanol. Above this concentration of acid solvent, any water or methanol generated (or any other species more basic than HSO 4 - ) is essentially fully protonated and not available for coordination to the metal center, minimizing catalyst inhibition by ground state inhibition. Below this acid concentration the solvent acidity drops rapidly 19 and water or methanol can 12 become available for coordination to the metal center leading to inhibition of the CH activation reaction. The key challenge to utilizing this strategy is the identification of catalysts, reactants and products that are thermally stable in such a medium. Both methane and methanol are thermally stable in sulfuric acid at temperature below 250 o C and several catalyst systems have been identified that are stable in this media for the selective oxidation of methane to methanol. Both the Hg(II) and Pt(bpym)Cl 2 system have been found to be an efficient catalyst for methane oxidation to methanol at ~200 o C in this solvent as both are very stable in this media. BARF anion Weak coordinating Ligands that can be displaced by methane Likely active Pt(II) Catalyst N N HN N S O O OH OH H S O O O O H S O O O OH H S O OH O O Pt Cl + F F F F F B F F F F F F F F F F F F F F F - Figure 1.1. Comparison of the Likely Active Catalyst in the Pt(bpym)Cl 2 /H 2 SO 4 system with the Weakly Coordinating BARF anion. Consistent with the concept of basicity leveling, theoretical studies show that, at sulfuric acid concentrations > 90%, the ground state of these catalysts, [(Hbpym)PtCl(HSO 4 )] + and Hg(HSO 4 ) 2 , are coordinated to weakly binding HSO 4 - that is most likely extensively hydrogen bonded to solvent H 2 SO 4 molecules as 13 shown in Figure 1.1 for the Pt(bpym)Cl 2 /H 2 SO 4 system. As can be seen, this weakly coordination of HSO 4 - in sulfuric acid leads to a highly dispersed anion that is similar to the weakly coordinating anion, B(C 6 F 5 ) 3 Me] - and that can be expected to be displaced by methane more readily than water. Protonation of ligand increases electrophilicity of metal center Protonation of X facilitates loss of X. This opens coordination site (empty orbital) and increases electrophilicity of metal center CH bond is electrophilically activated to CH cleavage X -H g-X + 2HX + C H 4 H X H X-H g- 2 [H X 2 ] - 2 + CH 3 H 2 + H X-H g HX -H g-C H 3 C H 4 H X H X H X 2 [H X 2 ] - H X 2 + H X 2 [HX 2 ] - HX Good metal bond strength lowers activation energy Protonation of ligand increases electrophilicity of metal center Protonation of X facilitates loss of X. This opens coordination site (empty orbital) and increases electrophilicity of metal center CH bond is electrophilically activated to CH cleavage X -H g-X + 2HX + C H 4 H X H X-H g- 2 [H X 2 ] - 2 + CH 3 H 2 + H X-H g HX -H g-C H 3 C H 4 H X H X H X 2 [H X 2 ] - H X 2 + H X 2 [HX 2 ] - HX Good metal bond strength lowers activation energy Scheme 1.6. Electrophilic Hg(II) catalyst activated by acid solvents. Thus, acid solvent has several beneficial properties: a) it increases reactivity of electrophilic catalysts; b) it prevents inhibition of catalyst by products of oxidation; and c) it protects product the product (methanol) from overoxidation, as shown on an example of Hg(II) system in Scheme 1.6. 14 1.3.3 High Yield Conversion of Methane to Methyl Bisulfate Catalyzed by Iodine Cations in Oleum. It was reported by our group that 1–10 mM elemental iodine dissolved in sulfuric acid containing 2-3% SO 3 (oleum) generates a stable, active species that at 165 - 220 o C catalyzes the functionalization of methane (500 psig) to methyl bisulfate, Scheme 1.7). Concentrations of methyl bisulfate of up to 1M, 50% yields (based on methane) at >90% selectivity, volumetric productivities of ~10 -7 mol/cc.sec, turn-over numbers of 300 and turn-over-frequencies of 3⋅10 -2 s -1 have been observed. Carbon mass-balances of >95% based on unreacted methane and methyl bisulfate confirmed the high reaction selectivity and yield. Only SO 2 and very low levels (<1% based on added CH 4 ) of CO 2 were observed in the gas phase. The reaction rates and selectivities are reproducible and first order dependence on both methane and iodine were observed. The reaction rate is also strongly dependent on the concentration of SO 3 in the sulfuric acid solvent and does not proceed in <98% H 2 SO 4 where free SO 3 is not present. 20 Evidently, the increased rates of proton catalyzed side reactions with these higher alkanes make them unsuitable substrates in oleum. CH 4 + 2 SO 3 CH 3 OSO 3 H + SO 2 I 2 + HS 2 O 7 - H 2 SO 4 /SO 3 Scheme 1.7. Conversion of methane to methyl bisulfate catalyzed by iodine cations. 15 Other researchers have reported on the use of sulfuric acid and other strong acid solvents for conversion of methane but in these cases, the product yields, selectivities and volumetric productivities were significantly lower and relatively expensive oxidants, such as persulfate were utilized. 3,21 Gillespie has shown that the characteristic bright blue color formed on dissolution of iodine in oleum is due to the formation of I 2 + . 22 The reported disproportionation of I 2 + in oleum with decreasing SO 3 7 to form the more stable, poly-iodo cations, I 3 + or I 4 + , coupled with our observations of the strong dependence of the methane oxidation reaction on SO 3 concentration is consistent with either I 2 + or possibly I + (which could be formed at the elevated reaction temperatures although it has never been synthesized) being the reactive species. Other possible reactive species are iodyl sulfate (IO 2 + HSO 4 - ), 23 iodosyl sulfate (IO + HSO 4 - ) 8 and I(HSO 4 ) 3 24 as these are also reported to be formed on oxidation of iodine in sulfuric acid. These observations are consistent with I 2 + (or I + ) species as the active catalyst but do not indicate whether free radicals are involved. While the free radical reaction of atomic iodine with methane can be discounted, 25 free radical reactions are plausible with the stronger oxidants I 2 + , IOHSO 4 , IO 2 HSO 4 or I(HSO 4 ) 3 . However, given the high reaction yield and selectivity as well as reproducible, first order kinetics with respect to both methane and iodine, we are biased toward a non-free radical pathway. 16 CH ACTIVATION H 2 S 2 O 7 + I SO 3 SO 2 + H 2 O CH 3 OSO 3 H CH 3 -I CH 4 I 2 + HS 2 O 7 - H 2 SO 4 H 2 S 2 O 7 + 1/2 I 2 FUNCTIONALIZATION OXIDATION HI I 2 + 2 SO 3 + 0.5 H 2 SO 4 - 0.5 SO 2 . Figure 1.2. Proposed Electrophilic CH Activation Mechanism for the Iodine Catalyzed Oxidation of Methane in Oleum. The proposed electrophilic substitution by I 2 + shown in Figure 1.2, is not without precedent. Similar electrophilic substitutions of CH bonds have been proposed for the reaction of alkanes with H + , O 3 + , NO 2 + , and other electrophiles. 5,26 The electrophilic substitution of arenes by aryl iodo cations is also known. 27 Consistent with the proposed Functionalization step in Figure 1.2 and the observations that no free methyl iodide is observed, we find that addition of methyl iodide to 2.5% oleum at room temperature leads to the immediate and quantitative formation of methyl bisulfate and blue colored species due to I 2 + . Consistent with the observation that I 2 does not catalyze H/D exchange between D 2 SO 4 /SO 3 and CH 4 , no methane is produced in this reaction. The proposed 17 Oxidation step in Figure 1.2 has been reported. 7,9 Elemental sulfur, selenium and tellurium are also reported to generated cationic species on dissolution in oleum and we have found that these species also catalyze reaction between methane and oleum, but at much lower efficiencies as compared to iodine. Elemental bromine and chlorine as methane oxidation catalysts in 2 – 3% oleum were investigated. In both of these cases, both the reaction rates and selectivities to methyl bisulfate were significantly lower, than with iodine. Instead, extensive poly-halogenated methanes, that are typical for free-radical reactions, were observed. This marked difference in reactivity between chlorine, bromine and iodine is consistent with the proposal for the involvement of iodo cations such as I 2 + as it has been reported that the related cations of bromine and chlorine are not stable in oleum. 7 The unusually high reaction efficiency and product selectivity for methane conversion, along with the strong dependence on solvent acidity is very similar to the reported, high yield oxidation of methane in sulfuric acid solvent to methyl bisulfate catalyzed by the soft, stable, redox-active electrophile, Hg(II). 2 Based on the proposal that Hg(II) catalyzes methane oxidation via CH activation by electrophilic substitution, 2 it is possible that the poorly coordinated I 2 + H 2 S 2 O 7 - ¸ in spite of its known radical character, 7 is sufficiently electrophilic, soft and stable to also react with methane by a predominantly electrophilic substitution pathway as shown in Figure 1.2, that does not involve the formation of free radicals. 18 The properties of iodine that lead to this efficient reaction with methane in strongly acidic media can be described as “soft”, “redox active” and “electrophilic”. These properties are also shared by the late third and second row elements of the periodic table due to their high Z eff , high principal quantum number and large size. Consistently, it has been found that the cations Hg(II), (bpym)PtCl 2 , Au(III), Au(I), Tl(III) and Pd(II) all react readily with methane in strongly acid media to generate methanol presumably via an ES C -H activation reaction mechanism. Consistent with the important electrophilic properties, all of these systems are inhibited by good ligands such as water or methanol or anions such as HSO 4 - or Cl. 1.3.4 C-H Activation by Electrophilic Mechanism in Acidic Solvents: Mercury System Alkane C -H activation can be compared to Wacker reaction which is an inner-sphere process. 4 As identified in the Wacker reaction (activation, functionalization and reoxidation), following steps can also be seen in catalytic, alkane C-H activation and functionalization systems that operate with electrophilic catalysts. Thus, the coordination of the double bond of the olefin to electrophilic Pd(II) followed by cleavage of the coordinated double bond by nucleophilic attack of water can be compared to C-H Activation of CH 4 by an Electrophilic Substitution (ES) pathway, as shown in Scheme 1.8 for the Hg(II)/H 2 SO 4 system. 19 H 2 X + X - C-H Cleavage Functionalization Oxidation XHg Sol + Sol H CH 3 + HX X - Methane Coordination X - CH 4 + 3HX CH 3 OH HX XHg XHg CH 3 Hg 2 X 2 2 H 2 O + SO 2 + HgX 2 HgX 2 + H 2 O + HX CH 4 X = HSO 4 Electrophilic CH Activation Scheme 1.8. Proposed electrophilic CH activation mechanism for the oxidation of methane to methanol by the Hg(II)/H 2 SO 4 system. C-H bond activation has been demonstrated with the “soft,” powerful electrophilic species, [XHg] + , generated by dissolving HgX 2 salts in strongly acidic solvent such as sulfuric acid or triflic acid. These stable, active oxidation catalysts that operate via the alkane C-H activation reaction utilize metals that can be readily dissolved with suitable oxidants to generate “soft”, electrophilic, oxidizing metal cations in poorly coordinating solvents. Reasoning that “soft”, electrophilic, oxidizing, third or second row metal cations, MX, could form relatively stable covalent bonds to methyl groups and M-CH 3 intermediates that 20 can subsequently be oxidized, use of soluble Hg(II) cations in sulfuric acid as an effective catalyst for the selective oxidation of methane to methanol. 9 Thus, reaction of methane (500 psig) with 96% sulfuric acid at ~180°C containing 20mM concentration of Hg(HSO 4 ) 2 efficiently generates methanol at concentrations of ~1 M with selectivities >90% and yields of ~40% based on added methane, Scheme 1.9. The reaction can be carried out in triflic acid to generate methyl triflate, but in this case the reaction is stoichiometric in Hg(II) which serves as both the catalyst and stoichiometric oxidant. CH 4 + H 2 SO 4 CH 3 OH + SO 2 + H 2 O H 2 SO 4 HgSO 4 Scheme 1.9. Methane activation by HgSO 4 . As shown in Scheme 1.8, the proposed mechanism of the Hg system is characterized by the same three steps: C-H activation of methane, functionalization of the CH 3 -Hg to generate methanol and the reoxidation of the resulting Hg(I) species. 9 This system seems to be the simplest case of C-H activation of methane by an ES pathway. It is proposed that the soft and powerful electrophilic species, [XHg] + , is generated upon dissolution of HgX 2 salts in hot sulfuric acid and readily reacts with methane. It seems likely that the high solvation energy of the proton in sulfuric acid and the formation of the strong Hg-CH 3 bond are the driving force of this step. 21 The intermediacy of the CH 3 HgX species in this step is confirmed by the direct observation of this species in the reaction media. 28 It is also found that approximately the same catalytic activity (TOF) is obtained with the use of CH 3 HgX directly in place of HgSO 4 . Additionally, under the reaction conditions, independently synthesized CH 3 HgX is readily converted to both methane, methanol and the reduced Hg 2 (II) species (Hg 2 X 2 ). It is interesting to speculate on how the m ethanol is formed in this reaction. Kinetic studies show that the rate of formation of CH 3 OH is independent of the concentration of added Hg(II). This rules out a free Hg(II)-assisted bimolecular electrophilic substitution pathway as shown in Scheme 1.10. It is also well known that Hg(II) with strong field ligands such as CH 3 - adopts a linear, two coordinate geometry. This would suggest that a concerted reductive elimination is unlikely. On the basis of preliminary theoretical and experimental studies, it is proposed that the reaction occurs by solvent assisted heterolysis of the [CH 3 -Hg] + species with simultaneous capture of the departing incipient fragment, CH 3 + , by H 2 SO 4 (or by either HSO 4 - or H 2 O) to generate CH 3 OSO 3 H, or CH 3 OH and Hg(0). The Hg(0) is not observed because Hg(II) is known to react rapidly with Hg(0) to generate Hg 2 (II), which is observed. Kinetic studies on [CH 3 HgX] in sulfuric acid show that the activation energy of the functionalization step is higher than that for the C-H activation step. The Hg 2 (II) species generated in the functionalization step has been shown to reoxidize to Hg(II) in hot sulfuric acid. Experiments suggest that Hg 2 (II) is the resting state of the catalyst and suggests that the oxidation step is rate-determining in the overall 22 catalytic cycle. It should be noted that the possibility of a free-radical pathway operating concurrently has been suggested by other researchers. 29 However, based on the observation of high yields and selectivities and that added oxygen does not change the reaction rates or selectivities, it is not believed that free-radical pathways play a significant role in this system. 30 HX XHg CH 3 XHg HX XHg CH 3 HX α+ α+ Unimolecular solvent Assisted Heterolysis Bimolecular Electrophilic Substitution Scheme 1.10. Possible transition states for generation of m ethanol from CH 3 HgX. The basis for the high selectivity in this system, confirmed by both theoretical and experimental results, is that the active catalyst [XHg] + reacts at least 1000 times faster with the C-H bonds of methane compared to the those of CH 3 OH, which exists primarily as the protonated, or sulfated forms, [CH 3 OH 2 ] + or CH 3 OSO 3 H respectively, in sulfuric acid. This greater reactivity of the methane C- H bonds compared to those of methanol can be traced to substantially lower reactivity of the electrophilic [XHg] + catalyst towards the C-H bonds of methanol, which due to the electron withdrawing effect of protonation or sulfonation are substantially less electron rich than those of methane. 23 The properties of Hg(II) that lead to this efficient reaction with methane in strongly acidic media can be described as “soft”, “redox active” and “electrophilic”. These properties are also shared by the late third and second row elements of the periodic table due to their high Z eff , high principal quantum number and large size. Consistently, it has been found that the cations (bpym)PtCl 2 , Au(III), Au(I), Tl(III) and Pd(II) all react readily with methane in strongly acid media to generate methanol presumably via an ES C -H activation reaction mechanism. Consistent with the important electrophilic properties, all of these systems are inhibited by good ligands such as water or methanol or anions such as HSO 4 - or Cl. However, the tendency can be observed, if iodine need oleum, Hg(II) can react at more dilute H 2 SO 4 conditions. 1.4 Research strategies towards novel catalytic systems active in weakly acidic media. Previous and current mechanistic studies on the electrophilic catalyst in sulfuric acid which are the most efficient catalyst system known to date, showed that the fundamental issue with this catalyst system was that it was inhibited at practical concentrations of methanol. This inhibition of the most active catalyst by methanol (which is generally considered to be a poor ligand), illustrates one of the fundamental challenges that must be met to developing the next generation of low temperature methane to methanol catalysts; methane is a much weaker ligand than 24 most typical weak-acidic solvents (such as water, acetic acid, trifluoroacetic acid etc.) and coordination of methane to the catalyst (which is required for reaction) in the presence of the higher concentration of such coordinating solvents can be anticipated to be a major issue. The key to developing this next generation of catalysts is the recognition that catalysts such as Pt(bpym)Cl 2 operated primarily as soft, redox active, Lewis acids or electrophiles and as such would be expected to preferentially bind tighter to water or methanol rather than methane as these materials are much stronger Lewis bases than methane. Critically, this knowledge suggests that the next generation of catalysts, to be tolerant to weak acidic solvents must be less Lewis acidic (or less electrophilic) than the Pt(bpym)Cl 2 in H 2 SO 4 system. Preliminary study suggests that the major inhibition by water and methanol come from CH activation step versus oxidation. It is significant to concentrate initial effort on the most difficult step to avoid stratigical failure, despite of the fact that rate determining step in Hg(II), Pt(bpym)Cl 2 is oxidation step and CH activation is relatively fast. The deeper understanding suggests that CH activation cannot be rate-determining step in effective catalytic system due to overoxidation issue. Therefore, the oxidation step is limited by slow CH activation in favour of the overall catalytic rate. All this considerations and understanding allow to concentrate major attention on CH activation step with attempts to develop oxidation chemistry for milestones CH activation systems. 25 The development of highly active catalyst for CH activation in less acidic media is crucial. Based on our understanding of the mechanism of the Pt(bpym)Cl 2 /H 2 SO 4 system, 31 we identified two key steps that contribute to the overall CH activation barrier: A) coordination of the hydrocarbon (RH) and B) cleavage of the coordinated CH bond. To achieve improved reactivity two approaches can be applied: a) stabilization of transition state; b) destabilization of ground state. Figure 1.11. Two approaches to reactivity: resting state destabilization or transition state stabilization. In designing improved catalysts it is important that both steps be explicitly considered to ensure that catalyst modifications that decrease the energy M-X M-(Hydrocarbon) Hydrocarbon Coordination TS C-H Bond Cleavage TS M-R Ground State Destabilization Transition State Stabilization 26 requirements for one step does not proportionately increase the other. This should be possible since the bonding in the ground state and cleavage transition state should be different. Therefore, deeper understanding of the C-H activation and the exploiting the nature of C -H bonds could lead to the development of the next generation of hydrocarbon conversion catalysts and a new paradigm in energy and petrochemical technologies. 27 1.5 Chapter One References 1 a) Chen, J. Q.; Vora, B. V.; Pujado, P. R.; Grønvold, Å ; Fuglerud, T.; Kvisle, S. Natural Gas Conversion VII. Studies Surf. Sci. 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Ed., 2004, 43, 4626. 13 Muehlhofer, M.; Strassner, T; Herrmann, W. A. Angew. Chem. Int. Ed. 2002, 41, 1745. 14 a) Lin, M.; Hogan, T. E., Sen, A. J. Am. Chem. Soc., 1996, 118, 4574; b) Lin, M.; Hogan, T.; Sen, A. J. Am. Chem. Soc. 1997, 6048.c) Sen, A. Acc. Chem. Res. 1998, 31, 550. 15 a) Piao, D.-G.; Inoue, K.; Shibasaki, H.; Taniguchi, Y.; Kitamura, T.; Fujiwara, Y. J. Organomet. Chem. 1999, 574, 116; b) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 31, 550. 16 a) Labinger, J. A. Catal. Lett. 1988, 1, 371; b) Crabtree, R. H. Chem. Rev. 1995, 95, 987; c) Labinger, J. A.; Bercaw, J. E.; Luinstra, G. A.; Lyon, D. K.; Herring, A. M. In: Natural Gas Conversion II: Proceedings of the Third International Gas Conversion Symposium, Sydney, Australia, July 4-9, 1993; Howe, R. F., Curry-Hyde, E., Eds.; Elsevier: Amsterdam, 1994; pp 515-520. 17 Mechanisms of Inorganic Reactions, 2 nd Ed. Basolo, F. and Pearson, R. G. Wiley, John and Sons, New York, USA, 1967. 29 18 a) Klei, S. R.; Golden, J. T.; Burger, P.; Bergman, R. G. J. Mol. Cat. A: Chem. 2002, 189, 79; b) Tellers, D. M.; Yung, C. M.; Arndtsen, B. A.; Adamson, D. R.; Bergman, R. G. J. Am. Chem. Soc. 2002, 124, 1400; c) Burger, P.; Bergman, R. G. J. Am. Chem. Soc. 1993, 115, 10462. 19 Superacids Olah, G. A.; Prakash, G. K. S. and Sommer, J. Wiley, New York, USA, 1985. 20 We did not examine oleum concentrations >5 wt% SO 3 as many species are catalysts for the methane oxidation under those conditions. A patent (Bjerrum, N. J; Radhusvej, C.; Xiao, G.; Bauneporten, L.; Hjuler, H. A.; Dreyervej, R. K. WO 99/24383) claiming the use of many materials including iodine as catalysts for conversion of methane to methyl bisufate in 65 wt% oleum was reported after we carried out our initial work. The observations in this work generally agree with ours with respect to iodine catalysis. No mechanistic work was reported in this patent. 21 Sen, A. Acc. Chem. Res. 1998, 31, 550 and references therein. 22 Gillespie, R. J.; Morton, M. J. Quart. Rev. 1971, 25, 553. O’Donnel, T. A. Super Acid and Acidic Melts as Inorganic Chemical Reaction Media, VCH Publishers Inc: New York, 1992, Chapter 4 and references therein. 23 R. J. Gillespi and J. B. Senio, Inorg. Chem. 1964, 3, 972. 24 F. Aubke, H. A. Carter, H; S. P. Jones, Inorg. Chem., 1970, 9, 2485. A. Bali, K. C. Malhotra, J. Inorg. Nucl. Chem., 1976, 38, 411. 25 The reaction of iodine radicals with methane is highly endothermic and not a viable pathway for catalytic methane oxidation (Golden, D. M and Benson, S. W., Chem. Rev. 1969, 69, 125). 26 Such reaction may involve inner-sphere proton-coupled electron transfer: Fokin, A. A.; Shubina, T. E.; Gunchenko, P. A.; Isaev, S. D.; Yurchenko, A. G.; Schreiner, P. R. J. Am. Chem. Soc., 2002, 124, 10718. 27 P. J. Stang and V. V. Zhdankin, Chem. Rev. 1996, 96, 1123; V. A. Grushin, Chem. Soc. Rev. 2000, 29, 315 30 28 CH 3 HgX species is also an intermediate of sulfonation of methane in oleum. See; Sen, A.; Benvenuto, M. A.; Lin, M.; Huston, A. C.; Basickes, N. J. Am. Chem. Soc. 1994, 116, 998-1003. 29 Basickes, N.; Hogan, T. E.; Sen, A. J. Am. Chem. Soc. 1996, 118, 13111. 30 Bhalla, G.; Mironov, O.; Jones, C.; Tenn, W. J., III; Nakamura, S.; Periana, R. A.; In: Handbook of CH Transformations: Applications in Organic Synthesis; Dyker, G., Ed.; Wiley-VCH: 2005, p. 529. 31 (a) Xu, X.; Kua, J.; Periana, R. A.; Goddard, W. A. Organometallics 2003, 22, 2057 (b) Kua, J.; Xu, X.; Periana, R. A.; Goddard, W. A Organometallics 2002, 21, 511. 31 2 Chapter Two: High Yield Conversion of Methane to Methyl Bisulfate Catalyzed by Gold Cations 2.1 Introduction. Recently, several reports of alkane CH activation by homogeneous, cationic metal complexes with poorly coordinating anions in poorly coordinating solvents have been reported. 1 The success of this strategy relies on the ease of substitution of the weakly coordinating anion or solvent by the poorly coordinating alkanes. A related strategy that lends itself well to net CH functionalization via the CH activation reaction is to generate such poorly coordinated cationic species by use of strongly acidic, oxidizing solvents. We have been examining the use of stable, “soft”, redox-active, cationic species capable of CH activation as catalysts for the selective oxidation of methane by sulfuric acid as this solvent is both a strong acid and an oxidant that can be readily recycled with air. Advantageously, by using a strong acid as solvent any potentially coordinating anions or products from catalytic alkane oxidation, such as alcohols, that could coordinate to the cationic catalyst would be protonated by the large excess of acid solvent thereby minimizing catalyst inhibition. Attesting to the utility of this strategy, to date, the highest reported yields and selectivities for the low temperature oxidation of methane to methanol are with cationic 32 catalysts in sulfuric acid solvent. 2 A key requirement for working in such strongly acidic, oxidizing media is that the catalysts be stable. 2.2 Results and Discussion. Gold cations are uniquely efficient electrophilic catalysts for methane conversion because, as shown in the conceptual catalytic cycle, Scheme 1.10, both Au(I) and Au(III) oxidation states could be active for heterolytic C-H activation as well as oxidative functionalization; this is likely because Au(I) (d 10 , two- coordinate) and Au(III) ions (d 8 , square planar) are both “soft” electrophiles that are isoelectronic and isostructural with the neighboring cations (Hg(II) and Pt(II), respectively) that have been shown to be active for electrophilic C-H activation of methane. 3, 4 This situation is not common, and in most catalytic systems based on “soft”, redox-active electrophiles only one oxidation state of the redox couple is active for C -H activation. Thus, we sought to explore the catalytic chemistry of gold cations for the oxidation of methane. To our knowledge, while gold complexes have been reported to facilitate free-radical reactions of alkanes with peroxides in low yields, 5 no homogeneous gold catalysts that operate by heterolytic C-H activation and oxidative functionalization have been reported for the selective functionalization of alkanes. This is possibly because of the strong propensity for irreversible formation of gold metal, and any attempts to develop redox catalysis based on homogeneous Au cations must address this issue. 33 Scheme 2.1. Proposed mechanism for the oxidation of methane to methanol though CH activation with Au(I) and Au(III) in H 2 SO 4 . In strong acid solvents such as triflic or sulfuric acid, Au(III) cations (generated by dissolution 6 of Au 2 O 3 ) react with methane at 180 o C to selectively generate methanol (as a mixture of the ester and methanol) in high yield (Table 2.1, entries 1 and 2). As expected, the irreversible formation of metallic gold is very evident after these reactions and, unlike reactions with Hg(II), 2 Pt(II), 4d and Pd(II) 3a that are catalytic in 96% H 2 SO 4 , only stoichiometric reactions (turnover numbers (TON < 1) are observed with Au(III), Scheme 2.2. 3CH 4 + 2AuX 3 + 3H 2 O 3CH 3 OH + 6HX + 2Au 0 HX 180 o C, 2h Scheme 2.2. Stoichiometric methane to methanol oxidation by Au(III) in H 2 SO 4 , X = OSO 3 H. 34 Soluble cationic gold is essential for these reactions as no methanol is observed under identical conditions without added Au(III) ions (Table 2.1, entry 3), or in the presence of metallic gold (Table 2.1, entry 4) which is not dissolved in hot H 2 SO 4 . Consistent with the known nobility of gold metal, no methanol formed when SO 3 or persulfate (K 2 S 2 O 8 ) were added as possible oxidants of metallic gold (Table 2.1, entries 5 and 6). We considered the use of Se(VI) ions as a more suitable oxidant. Se(VI) ions are a more powerful oxidizing agent than S(VI) ions (E o =1.5 V SeO 4 2- /H 2 SeO 3 , E o =0.17 V SO4 2- /H 2 SO 3 , respectively) and, critically, the hydrated form, selenic acid (H 2 SeO 4 ), is known to oxidize gold metal. 7 Equally important, selenic acid is also almost as acidic as sulfuric acid, 7, 8 and it was anticipated that neither the acid nor the conjugate base (HSeO 4 - ) would inhibit catalysis with electrophilic, cationic gold by blocking the required coordination of methane to the metal center. 4a The 3M solution of H 2 SeO 4 in 96% sulfuric acid solvent containing 27 mg metallic gold (added as a 20 mesh powder) leads to catalytic oxidation of methane (27 bar) to methanol at 180 o C, Scheme 2.3. 9 CH 4 + H 2 SeO 4 CH 3 OH + H 2 SeO 3 + CO 2 AuX 3 180 o C, 10h 96% H 2 SO 4 TOF = 10 -3 s -1 27bar 3M 0.35M >90% Sel. 3% Scheme 2.3. Stoichiometry of catalytic oxidation of methane to methanol by H 2 SeO 4 catalysed by gold in H 2 SO 4 . 35 Table 2.1. Methanol yield under different reaction conditions. Entry Au[nM] Additives t [h] TON TOF MeOH % sel MeOH [mM] CH 4 % conv CO 2 [mol %] 1 Au 2 O 3 [50] - 1 0.8 10 -3 > 90 60 < 2 < 1 2 Au 2 O 3 [50] 100% CF 3 SO 3 H 1 0.9 10 -3 > 90 70 < 2 < 1 3 - - 6 0 0 0 0 < 1 < 1 4 Au 0 [27] - 1 0 0 0 0 < 1 < 1 5 Au 0 [27] 2 wt % SO 3 3 0 0 0 0 < 1 < 1 6 Au 0 [27] 0.1 M K 2 S 2 O 8 2 0 0 0 <5 < 1 < 2 7 Au 0 [27] 3M H 2 SeO 4 2 9 10 -3 81 240 11 3 8 Au 0 [5] 3M H 2 SeO 4 9 32 10 -3 77 178 8 2 9 Au 2 O 3 [81] 3M H 2 SeO 4 10 4 10 -3 74 350 15 6 10 Au 0 [27] 3M SeO 3 + 6 bar O 2 2 8 10 -3 86 215 10 2 11 Au 0 [81] 3M SeO 3 + 2% SO 3 3 15 10 -3 94 627 28 2 12 - 3M H 2 SeO 4 6 0 - 68 69 3 < 2 Turnover number of up to 30 and turnover frequencies of about 10 -3 s -1 have been observed in methanol concentrations of up to 0.6M in sulfuric acid with >90% selectivity, (Table 2.1, entries 7–11). Both gold and selenic acid are required for the reaction; no methanol is observed in the absence of Se(VI) ions with or without Au(0) (Table 2.1, entries 3 and 4) and only small amounts of methanol are formed in the presence of selenic acid without Au(0) (Table 2.1, entry 12). Use of 100% enriched [ 13 C] methane as well as 1 H, 13 C NMR spectroscopic, and HPLC analyses of the crude reaction mixtures confirmed that methanol is the predominant liquid-phase product generated from methane. 36 Figure 2.1. 13 C NMR spectrum of the reaction mixture with 13 CH 4 . 10 As can be seen from an NMR spectrum of the crude reaction mixture, Figure 1.3, only a small amount of methane selenoic acid (CH 3 SeO 3 H) is observed in the liquid phase. Very low levels (<5% based on added CH 4 ) of CO 2 is observed in the gas phase along with recovered CH 4 . The observation that addition of O 2 to the reaction mixture (Table 2.1, entry 10) has no significant effect on the reaction (compare Table 2.1, entry 7) and the high reaction selectivity and reproducibility suggests that free radicals are not involved. Carrying out the stoichiometric reaction with Au 2 O 3 at several temperatures between 100 o C and 200 o C leads to an estimated activation barrierof about 30 kcal mol -1 . Control experiments confirm that selenic acid can dissolve gold metal. Thus, addition of metallic gold powder or 37 gold metal (separately obtained from stoichiometric reactions between Au 2 O 3 and methane) to a 3M solution of selenic acid in 96% sulfuric acid leads to rapid dissolution of the gold metal upon warming to 100 o C to generate a clear yellow solution of cationic gold. While we have not obtained kinetic data on the various reaction steps proposed in Figure 2.1, this visual observation of rapid dissolution at low temperature suggests that the rate-determining step for methane oxidation catalyzed by cationic gold is not Au(0) reoxidation. Even the exact oxidation state of the dissolved gold has not been determined, but on the basis of known redox potentials we expect that Au(III) ions are the major species. However, it is possible that Au(I) ions (potentially stabilized to disproportionation by Se anions) could be present. The possibility that both Au(III) and Au(I) ions may be present in solution leads to the challenging question of whether one or both oxidation states (Au(I) and Au(III)) are active for the C-H activation of methane. This is an important point because, as discussed above, both Au(I) and Au(III) ions are potential catalysts. The observation that reactions starting from Au(III) ions (with Au 2 O 3 as the source) lead to stoichiometric conversion of methane into methanol, Scheme 2.1, does not require that Au(III) ions are the active species. The C-H activation reaction could occur with catalytic amounts of Au(I) ions, formed by reduction of Au(III) ions with adventitious reductants, and in both cases the stoichiometry shown in Scheme 2.2 would be expected. As observed with the related Hg(II),[2] Pt(II),[4] and Pd(II) [2] systems, some evidence for the formation of an Au-CH 3 intermediate is the observation that 38 low levels of CH 3 D (< 2%, which is not produced in the absence of added Au(III)) are produced when the reactions are carried out in D 2 SO 4 . The DFT calculations were used to determine the feasibility of the steps proposed in Scheme 1. B3LYP/LACVP**++, 11 as implemented by the Jaguar 5.5 package, 12 was applied with the basis set for sulfur augmented with an extra, compact d-like polarization shell to better describe high oxidation states. 13,14 A dielectric continuum surrounding the models at a probe radius of 2.205 L represented the sulfuric acid solvent with e=50. 15 Enthalpies describe solutes in ideal solution at 175 o C. Entropy changes, which are not accounted for, must be kept in mind as species enter and exit the models. A survey of complexes of gold ions with H n SO 4 (n = 0, 1, 2) showed that the square planar Au(III)(SO 4 ) 2- ion (1) and linear Au(I)(HSO 4 ) 2- ion (7) are the most stable Au(III) and Au(I) species in solution. However, bidentate sulfate ions, bisulfate ions, and water made similarly strong bonds to gold, so other complexes are most likely present in equilibrium quantities. Figure 2.2 illustrates the Au(III) pathway, by which 1 reacts with methane to produce the [Au(III)(CH 3 )(HSO 4 ) 3 ] - complex 5. Calculations show that a key role of the acid solvent is the generation of various protonated states of the gold complexes, such as 2, that are sufficiently labile to allow methane to substitute into the coordination sphere of the metal. C-H activation can proceed through a number of transition states, the most accessible of which is an electrophilic substitution pathway 3 ‡ , which features an intramolecular abstraction of a proton from methane by the neighboring bisulfate, with an activation energy of 28.1 kcal mol -1 . 39 Figure 2.2. Calculated enthalpies (kcal mol -1 ) relative to 1, including solvation by sulfuric acid (e = 50). Spectator sulfuric acid molecules have been omitted from some structures for clarity. Alternative mechanisms with slightly higher enthalpies include intermolecular reactions with bisulfate ions in solution. The resulting Au(III)-CH 3 complex 4 most likely converts into the lowest energy Au(III)-CH3 complex 5 before functionalization. Oxidative functionalization of 5 proceeds with a low energy barrier (? H = 10.8 kcal mol -1 ) through an S N 2 type attack on the methyl group by a free bisulfate ion 6 ‡ . This process is facilitated by the dissociation of the ligand trans to the CH 3 group. A reductive elimination mechanism was a lso found, but with a ?H ‡ value of 32.9 kcalmol -1 . Au(I) species can follow a similar electrophilic substitution C-H activation mechanism (Figure 2.3) to produce [Au(I)(CH 3 )(H 2 SO 4 )] (10) with an activation energy of 26.2 kcalmol -1 from 7. Interestingly, an oxidative addition mechanism was also found with an activation energy of 21.1 kcal mol -1 , somewhat lower than the electrophilic substitution. The resulting Au(III) species 12 is a stable intermediate, but the compound is acidic 40 enough that deprotonation would rapidly lead to the same Au(I)-CH 3 complex 10 for the electrophilic substitution pathway. Figure 2.3. Calculated enthalpies (kcal mol -1 ) at 175 o C relative to 7, including solvation by sulfuric acid (e = 50). For clarity, spectator H 2 SO 4 groups have been omitted from some structures. The top curve illustrates electrophilic substitution, while the bottom curve illustrates oxidative addition. While C-H activation with Au(I) ions is feasible, direct functionalization from this species is not. Both reductive elimination and nucleophilic substitution yields an Au(I)·2H 2 SO 4 ion that is calculated to be 37.6 kcalmol -1 higher in energy than 10. However, 10 can most likely be oxidized to the Au(III) species 5, either 41 through selenic acid, sulfuric acid, or 1. Indeed, the calculations show that the redox exchange 10+1 ? 5+7 is exothermic by about 32 kcal mol -1 , and would thus be feasible even for the stoichiometric process. Based on these results, it appears that oxidative addition to Au(I) ions is the favored pathway, which is 7.0 kcalmol -1 lower in energy than the electrophilic substitution pathway for Au(III) ions. However, these energies do not take the relative concentrations of the Au(III) and Au(I) cations into account, and the concentration of Au(I) ions should be significantly lower than Au(III) ions in the presence of excess oxidant Se(VI). A difference of 7.0 kcalmol -1 corresponds to a ratio of approximately 2500:1 at 175 o C, and thus if the ratio of Au(I) to Au(III) ions is less than 1:2500, the Au(III) pathway would be favored. Since this is a feasible ratio, both Au(I) and Au(III) remain possible active species, which is in contrast to findings for Pt(II) 4a and Hg(II) ions. 2 2.3 Conclusion. In summary, we showed that cationic gold catalyzes the selective, low- temperature, oxidation of methane to methanol in strong acid solvent using Se(VI) ions as the stoichiometric oxidant. The reaction does not appear to proceed through free radicals and DFT calculations indicate that Au(I) or Au(III) species are both viable catalysts that operate by mechanisms involving overall electrophilic C -H activation and oxidative functionalization. 42 2.4 Experimental General considerations. CH 4 (UHP grade with 3% Ne internal standard for mass balancing) was obtained from Specialty Air Technologies, Inc (Long Beach, CA). Deuteromethanes, concentrated H 2 SO 4 , SO 3 , SeO 3 , H 2 SeO 4 and H 2 S 2 O 8 were obtained from Aldrich. Au(0) and Au 2 O 3 obtained from Strem. 0.5- 2.5 wt. % regular and deuterated oleum solutions was prepared by dissolving a calculated amount of SO 3 in concentrated H 2 SO 4 or 98 wt. % D 2 SO 4 (99.8% d, Cambridge Isotope) and further titrated to confirm the actual concentration. 1 H and 13 C-NMR spectra were collected on a Bruker AMX-500, AM-360 or AC-250 spectrometers. GC-MS analysis was performed on a Shimadzu GC-MS QP5000 instrument equipped with a GasPro bonded PLOT capillary column. HPLC analysis was performed on a Varian ProStar 210 system fitted with an Aminex HPX-87H ion exclusion column, with 0.05% aqueous H 2 SO 4 as the eluent. Reactions with CH 4 . In a typical reaction, a 50 ml glass-lined, stirred, high-pressure reactor containing 50 mM iodine and 2.5 wt % sulfur trioxide dissolved in 20 ml of concentrated sulfuric acid was pressurized with methane to a final pressure of 500 psig. This reaction mixture was stirred and maintained at 195 o C for 2 hr. After cooling the gas phase was vented into a Hoke sample bottle and analyzed by GC-MS. In a typical reaction, a 50-mL glass-lined, stirred, high- pressure reactor containing 27 mm of 20 mesh, gold powder and 3M H 2 SeO 4 (3 43 mL) in 96% D 2 SO 4 was pressurized with methane to a final pressure of 27 bar. This reaction mixture was vigorously stirred and maintained at 180 o C for 2 h. After cooling the mixture, the reaction gas phase was vented into an evacuated cylinder (to obtained both dissolved and undissolved gases) and analyzed by GC- MS. The liquid phase was analyzed by 1 H and 13 C NMR spectroscopy and HPLC. Quantification of H/D exchange. In experiments with CH 4 and D 2 SO 4 reaction gas phase was analyzed for deuteration of methane. Mass-spectrum of methane peak in the experimental chromatogam was compared against mass- spectra of pure CH 4 , CH 3 D, CH 2 D 2 , CHD 3 , and CD 4 . Ratio of each methane isotopomer was determined as an average of the following two methods. In the stepwise deconvolution method, the intensity of the peak with m/z = 20 was assigned to CD 4 , subspectrum of this isotopomer was calculated, using experimentally obtained data for pure CD 4 , and subtracted from the total spectrum. Next, the peak with m/z = 19 was assigned to CHD 3 , and the subtraction process repeated, and similarly for CH 2 D 2 , CH 3 D, and the remaing subspectrum was assigned to CH 4 . Ratios of isotopomers were defined as the ratios of total ionic current for each isotopomer, Figure 2.4. In the least squares method, was approximated as a combination of known spectra for each isotopomer, a*CH 4 + b*CH 3 D + .. + e*CD 4 , where a, b,.., e = isotopomer ratios, and this combination was fitted to the experimental spectrum by least squares method, Figure 2.5. 44 Figure 2.5. Stepwise mass-spectrum deconvoution method for a mixture of methane isotopomers. CH 4 +CH 3 D+CH 2 D 2 +CHD 3 +CD 4 0.0 0.2 0.4 0.6 0.8 1.0 1.2 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 +CH 3 D+CH 2 D 2 +CHD 3 0.0 0.2 0.4 0.6 0.8 1.0 1.2 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 +CH 3 D+CH 2 D 2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 +CH 3 D 0.0 0.2 0.4 0.6 0.8 1.0 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 0.00 0.01 0.02 0.03 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 +CH 3 D+CH 2 D 2 +CHD 3 +CD 4 0.0 0.2 0.4 0.6 0.8 1.0 1.2 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 +CH 3 D+CH 2 D 2 +CHD 3 0.0 0.2 0.4 0.6 0.8 1.0 1.2 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 +CH 3 D+CH 2 D 2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 +CH 3 D 0.0 0.2 0.4 0.6 0.8 1.0 12 13 14 15 16 17 18 19 20 21 m/z Intensity CH 4 0.00 0.01 0.02 0.03 12 13 14 15 16 17 18 19 20 21 m/z Intensity 45 Figure 2.5. Least squares fit mass-spectrum deconvoution method for a mixture of methane isotopomers: Experimental (¦ ) vs. Fitted (¦ ) (a*CH 4 + b*CH 3 D + .. + e*CD 4 ) mass-spectrum. 0 0.1 0.2 0.3 0.4 12 13 14 15 16 17 18 19 20 21 m/z Intensity 0 0.1 0.2 0.3 0.4 12 13 14 15 16 17 18 19 20 21 m/z Intensity 46 2.5 Chapter Two References 1 a) Arndtsen, B.A.; Bergman, R.G.; Mobley, T.A.; Peterson, T.H.; Acc. Chem. Res. 1995, 28, 154; b) Shilov, A.E.; Shul’pin, G.B.; Chem. Rev. 1997, 97, 2879; c) Crabtree, R.H.; J. Chem. Soc. Dalton Trans. 2001, 17, 2437; d) Jones, W.D.; Science 2000, 287, 1942; e) Burger, P.; Bergman, R. G. J. Am. Chem. Soc. 1993, 115, 10462; Holtcamp, M. W.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 1997, 119, 848; Johansson, L.; Wick, D. D.; Goldberg, K. I. J. Am. Chem. Soc. 1997, 119, 10235; Ryan, O. B.; Tilset, M.; J. Am. Chem. Soc. 1999, 121, 1974; Golden, J. T.; Andersenand R. A.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123, 5837. 2 Periana, R. A.; Taube, D. J.; Gamble, S.; Taube, H.; Satoh, T.; Fuji, H. Science 1998, 280, 560; Periana, R. A.; Taube, D. J.; Evitt, E. R.; Loffler, D. G.; Wentrcek, P. R.; Voss, G.; Masuda, T. Science, 1993, 259, 340. 3 a) Periana, R.A.; Mironov, O.; Taube, D.; Bhalla, G.; Jones, C.J.; Science 2003, 301, 814; b) Sen, A.; Acc. Chem. Res. 1998, 31, 550. 4 a) Xu, K.X.J.; Periana, R.A.; Goddard III, W. A.; Organometallics 2003, 22, 2057; b) Labinger, J.A.; Bercaw, J.E.; Nature 2002, 507-514, 507; c) Lin, M.; Shen, C.; Garcia-Zayas, E. A.; Sen, A.; J. Am. Chem. Soc. 2001, 123, 1000; d) Periana, R.A.; Taube, D.J.; Gamble, S.; Taube, H.; Satoh, T.; Fuji, H.; Science 1998, 280, 560; e) Stahl, S.; Labinger, J.A.; Bercaw, J.E.; Angew. Chem. 1998, 110, 2298; Angew. Chem. Int. Ed. 1998, 37, 2180; f) Shilov, A.E.; Shul’pin, G.B.; Chem. Rev. 1997, 97, 2879. 5 Shul’pin, G. B.; Shilov, A.E.; Süss-Fink, G.; Tetrahedron Lett. 2001, 42, 7253; b) Shul’pin, G.B.; J. Mol. Catal. A 2002, 189, 39. 6 a) Wickleder, M.S.; Esser, K.; J. Anorg. Allg. Chem. 2002, 628, 911; b) Wickleder, M.S.; Buchner, O.; Z. Naturforsch. B 2001, 56, 1340. 7 Greenwood, N.N.; Earnshaw, A.; Chemistry of the Elements, 2nd ed., Butterworth-Heinemann, Oxford, 1997, p.782. 8 a) McDaniel, D.H.; Steinert, L.H.; J. Am. Chem. Soc. 1966, 88, 4826; b) Wasif, S.; J. Chem. Soc. A 1967, 1, 142; c) Hussein, M.A.; Iskander, G.M.; Nour, M.M.; Wasif, S.; Zeidan, H.M.; J. Chem. Soc. Dalton Trans 1982, 9, 1645. 47 9 In a typical reaction, a 50-mL glass-lined, stirred, high-pressure reactor containing 27 mm of 20 mesh, gold powder and 3M H 2 SeO 4 (3 mL) in 96% D 2 SO 4 was pressurized with methane to a final pressure of 27 bar. This reaction mixture was vigorously stirred and maintained at 180 o C for 2 h. After cooling the mixture, the reaction gas phase was vented into an evacuated cylinder (to obtained both dissolved and undissolved gases) and analyzed by GC-MS. The liquid phase was analyzed by 1 H and 13 C NMR spectroscopy and HPLC. 4d 10 This NMR spectrum cannot be used to obtain quantitative information nor is it representative of the 13 CH 4 dissolved under reaction conditions. See reference 9. 11 Relativistic effects are incorporated into the Los Alamos Core-Valence Pseudopotential (LACVP) used for Au (P.J. Hay, W.R. Wadt, J. Chem. Phys. 1985, 82, 299). The 6-31G**++ basis was employed for other atoms (M.M. Francl, W.J. Pietro, W.J. Hehre, J.S. Binkley, M.S. Gordon, D.J. DeFrees, J.A. Pople, J. Chem. Phys. 1982, 77, 3654). In our experience, approximations implied by this finite basis cause average errors of 4 kcal mol -1 , which the implicit solvent model will increase. 12 L.L.C . Schrödinger, Jaguar 5.5, Portland, OR, 1991–2003. 13 Martin, J.M.L.; J. Chem. Phys. 1998, 108, 2791. 14 The d-like polarization shell with exponent a=0.65 was replaced with two shells: a single Gaussian with exponent a=0.55 and a two-Gaussian contraction with exponents a 1 =7.5 and a 2 =1.8 with contraction coefficients c 1 =0.2 and c 2 =1.0. 15 A high-temperature (175 o C) value was projected assuming the dielectric constant of sulfuric acid decays with temperature at a rate similar to that of water; -(1/e) de/dT=0.0045. 48 3 Chapter Three: Mechanism of the high-yield, methane to methanol Pt(bpym)Cl 2 /H 2 SO 4 Conversion system 3.1 Introduction. Saturated hydrocarbons have been quite rightfully called the “noble gases of organic chemistry”, and methane in particular, as the lightest representative of this family, has been compared with extremely inert helium. 1 Inertnes of alkanes come from low polarity of H-C as well as C -C bonds. Efficient and selective processes to convert these raw materials readily available from relatively inexpensive petrochemical and natural gas feedstock, to useful products under mild conditions, have been long sought after, but economically useful ones are still lacking. Focused efforts are directed towards the development of new methods for selective low-temperature activation and functionalization of alkanes based on C- H activation reaction. A number of excellent reviews covering achievements in this area have appeared recently. 2 Despite a large amount of work done in this area, there are very few systems reported that able directly converst alkanes to useful products such as alcohols or other oxygenated products. The first example of such system, consisting of an aqueous solution of platinum salts was reported by Shilov and coworkers. 3 Typical reaction yields, based on added methane are less than 3% with >75% selectivities to methanol and methyl chloride. Low rates, 49 short catalyst life, and the use of Pt(IV) as a stoichiometric oxidant were major disadvantages of this system. Some other systems for methane conversion to methanol and other useful products include Sen’s RhCl 3 /CO/O 2 /PFBA/H 2 O system (products: methanol, acetic acid), 4 Fujiwara’s V-POM/K 2 S 2 O 8 /TFA system (products: methyl esters), 5 Herrmann’s Pd(bis-carbene)X 2 /TFA/K 2 S 2 O 8 system (products: methyl esters), 6 and others. While these systems unarguably demonstrate unique ability to oxidize methane to useful products in mild conditions, the rates are low, and the yields based on methane are minimal (<<10%), therefore these systems still remain far from being considered for industrial applications. A major step up to economically viable new processes has been achieved by Periana et al., with the systems that use concentrated H 2 SO 4 as the solvent, SO 3 (H 2 SO 4 ) or H 2 SeO 4 as the oxidant, and Hg II , 7 I 2 , 8 Pt II , 9 Pd II , 10 or Au I /Au III 11 as catalysts, to convert methane to methanol (and acetic acid, in case of Pd II ) under relatively mild conditions. Pt II system, which uses Pt(bpym)Cl 2 as the catalyst, is shown on Scheme 3.1. CH 4 + H 2 SO 4 CH 3 OSO 3 H + SO 2 + H 2 O Pt(bpym)Cl 2 , 200 o C Scheme 3.1. Pt(bpym)Cl 2 /H 2 SO 4 system for selective methane oxidation. To our knowledge, the Pt(bpym)Cl 2 /H 2 SO 4 system, reported in 1998, remains the highest yield system for the selective conversion of methane to 50 methanol that operates below 250 0 C. This catalytic system generates an ester on methanol at 220°C in >70% one-pass yield and >80% selectivity based on methane. Methane C-H bond is activated and oxidized in this system at temperatures as low as 100°C, and the product, methyl bisulfate, is chemically protected from overoxidation to combustion products; while the Pt(bpym)Cl 2 catalyst remains stable towards precipitation of Pt 0 or (PtCl 2 ) n even at 20% oleum at 200°C for more than 50 hours. CH 4 CH Activation Functionalization Oxidation SO 2 + 2 H 2 O 3 H2SO 4 N N N N Pt Cl Cl - HCl 1 CH 3 OSO 3 H 2 H 2 SO 4 N N HN N Pt Cl CH 3 HSO 4 - + C 2+ [CH 4 ] 2 HSO 4 - N N HN N Pt Cl B H 2 SO 4 + HSO 4 - N N HN N Pt Cl OSO 3 H A + D N N HN N Pt Cl CH 3 OSO 3 H OSO 3 H HSO 4 - Scheme 3.2. Proposed overall mechanism for the oxidation of methane to methanol catalyzed by Pt(bpym)Cl 2 in H 2 SO 4 . 51 Initial experimental and theoretical studies suggested that C-H activation of methane in this system proceeds through via an electrophilic substitution, 12 and on the basis of these studies assumed overall mechanism for the operation of Pt(bpym)Cl 2 in sulfuric acid could be formulated as shown on Scheme 3.2. In this chapter the further experimental evidences are represented and discussed in detail pertaining to this mechanism. 3.2 Results. CH 4 /D 2 SO 4 proton/deuterium exchange catalyzed by Pt(bpym)Cl 2 . It was observed in catalytic runs in 98% wt. D 2 SO 4 at 220 °C that both methane and methyl bisulphate product are multiply deuterated at the end of reaction. If this experiment is done at lower temperature, for example 150 °C, deuteromethanes are still formed, but no significant oxidation to methanol is observed, Scheme 3.3. CH 4 + D 2 SO 4 CH 3 D + CH 2 D 2 + CHD 3 + CD 4 Pt(bpym)Cl 2 , 150 o C Scheme 3.3. CH 4 /D 2 SO 4 proton/deuterium exchange catalyzed by Pt(bpym)Cl 2 at 150 °C. This implies that C -H activation step could be faster than the following oxidation and functionalization steps. Consistent with this, if an external oxidant such as H 2 Pt(OH) 6 is added to this reaction mixture, methyl bisulfate is formed 52 quantitatively relative to added Pt(IV). This suggests that the functionalization step is faster than the oxidation step. Another important observation is that all deuteromethanes are formed simultaneously, i.e., reaction does not follow typical Schulz-Flory type distribution when isotopomers form sequentially, Figure 3.1. This means that several deuterium atoms are inserted during one contact of an alkane molecule with the Pt(bpym)Cl 2 complex, which in turn could suggest formation of an intermediate methane-Pt complex. Linear dependence of total amount of deuteromethanes vs. time suggests that there is no decomposition of catalyst during the reaction. y = 0.0494x R 2 = 0.9974 0.0 1.0 2.0 3.0 0 20 40 60 80 time (min) CH 4-n D n , % CH 3 D CH 2 D 2 CHD 3 CD 4 total y = 0.0494x R 2 = 0.9974 0.0 1.0 2.0 3.0 0 20 40 60 80 time (min) CH 4-n D n , % CH 3 D CH 2 D 2 CHD 3 CD 4 total Figure 3.1. Kinetics of CH 4 deuteration by Pt(bpym)Cl 2 /D 2 SO 4 . [Pt(bpym)Cl 2 ] = 2.5 mM, temperature 150 °C. 53 Reaction of methane with Pt(bpym)Cl 2 /D 2 SO 4 was studied in greater detail. Since reaction of gaseous methane with a liquid solution of catalyst involves phase transfer, it was imperative to determine the extent of mass-transfer limitations for any further experiments, for an accurate quantitative treatment of data. Figure 3.2 shows the plot of the observed reaction rate versus stirrer rotation speed. 0.0 0.5 1.0 1.5 0 500 1000 Rotation speed, rpm k H/D x10 4 , s -1 0.0 0.5 1.0 1.5 0 500 1000 Rotation speed, rpm k H/D x10 4 , s -1 Figure 3.2. Plot of observed H/D exchange rate vs. agitation speed. [Pt(bpym)Cl 2 ] = 2.5 mM, temperature 165 °C, reaction time 40 min. It can be seen from Figure 3.2 that the curve has two areas: at low values the observed rate is proportional to rotation speed, and once rotation speed reaches ~220 rpm, there is no further increase in rate even though the rotation speed increases further. Apparently at this rotational speed maximum contact surface area between gas and liquid is reached, as it was observed in similar experiments. 13 54 The initial part of the curve does not go through origin indicating that there is a certain reaction rate even without stirring. All further experiments were done at rotational speed well above the breakpoint value of 220 rpm to avoid data distortion due to inconsistent mass transfer. y = 0.0074x R 2 = 0.9684 0.0 0.5 1.0 0 50 100 150 CH 4 pressure, psi TON x10 4 y = 0.0074x R 2 = 0.9684 0.0 0.5 1.0 0 50 100 150 CH 4 pressure, psi TON x10 4 Figure 3.3. Plot of turnover number for methane H/D exchange vs. methane pressure, [Pt(bpym)Cl 2 ] = 5 mM, temperature 165 °C, reaction time 40 min. Concentration effects on H/D exchange were also studied. H/D exchange reaction rate dependence on methane pressure (in terms of turnover number, TON, for identical time periods) is a straight line with a slope of 7.4⋅10 6 psi -1 (Figure 55 3.3), which is consistent with a first order dependence of rate on methane concentration for the limiting step of the H-D exchange reaction. 14 0.0 2.5 5.0 7.5 10.0 0 5 10 15 20 25 Pt(bpym)Cl 2 , mM V obs x10 9 , mole/s 0.0 2.5 5.0 7.5 10.0 0 5 10 15 20 25 Pt(bpym)Cl 2 , mM V obs x10 9 , mole/s Figure 3.4. Plot of observed reaction rate for H/D exchange (?) and oxidation to methanol (•) vs. catalyst concentration. Temperature 165 °C, p methane = 25 psi. Figure 3.4 shows the plot of observed rates for H/D exchange and oxidation to methanol vs. catalyst concentration. For a first-order dependence of rate on catalyst concentration, as postulated by the mechanism on Scheme 3.2, a 56 linear plot would be expected. However, noticeable deviation from linearity at higher catalyst concentrations is observed experimentally for both the H/D exchange and oxidation curves (closer inspection reveals that V obs ~ [Pt(bpym)Cl 2 ] n , where 0.5<n<1). This can possibly be due to side reactions of the catalyst at higher concentrations such as dimerization into inactive species. y = -14082x + 18.234 R 2 = 0.9913 -15.0 -14.0 -13.0 -12.0 0.00212 0.00216 0.00220 0.00224 0.00228 1/T ln (k H/D /T) y = -14082x + 18.234 R 2 = 0.9913 -15.0 -14.0 -13.0 -12.0 0.00212 0.00216 0.00220 0.00224 0.00228 1/T ln (k H/D /T) Figure 3.5. Eyring plot for the Pt(bpym)Cl 2 catalyzed H -D exchange of CH 4 with D 2 SO 4 . [Pt(bpym)Cl 2 ] = 35 mM, temperature range 169 - 190 °C. As it can be seen from concentration effects studies, the rate of heterogeneous reaction of methane with solution of Pt(bpym)Cl 2 catalyst in sulfuric acid is characterized by linear dependence on methane pressure and non- linear dependence on catalyst concentration. To avoid non-linear data distortion, experiments to determine activation parameters were done in identical reactors, at 57 the same methane pressure (25±0.5 psi) and catalyst concentration (35±0.4 mM). The temperature dependence of rate of reaction of methane with Pt(bpym)Cl 2 /D 2 SO 4 solution allowed determination of activation parameters for H-D exchange: ΔH ≠ = 28.0 ± 2.4 kcal/mol, ΔS ≠ = -11.0 ± 3.3 eu, Figure 3.5, and for oxidation to methanol: ΔH ≠ = 34.3 ± 2.1 kcal/mol, ΔS ≠ = -3.8 ± 0.8 eu, Figure 3.6. y = -17251x + 21.83 R 2 = 0.9967 -19.0 -17.0 -15.0 0.00212 0.00216 0.0022 0.00224 0.00228 1/T ln (k ox /T) y = -17251x + 21.83 R 2 = 0.9967 -19.0 -17.0 -15.0 0.00212 0.00216 0.0022 0.00224 0.00228 1/T ln (k ox /T) Figure 3.6. Eyring plot for the Pt(bpym)Cl 2 catalyzed oxidation of CH 4 to CH 3 OH. [Pt(bpym)Cl 2 ] = 35 mM, temperature range 169 - 190 °C. Catalyst inhibition. Concentrated sulfuric acid is required for the catalytic system to remain effective: H-D exchange rates between CH 4 and D 2 SO 4 measured 58 at 150 °C decrease sharply with acid dilution and exchange effectively ceases in 85% wt. (~1:1 molar D 2 SO 4 :D 2 O) or less concentrated acid (Figure 3.7). 0.0 0.5 1.0 1.5 2.0 6 7 8 9 10 11 D 2 SO 4 acidity, –H 0 k H/D x10 4 , s -1 0.0 0.5 1.0 1.5 2.0 6 7 8 9 10 11 D 2 SO 4 acidity, –H 0 k H/D x10 4 , s -1 Figure 3.7. Correlation of CH activation rate (measured as CH 4 /D 2 SO 4 H-D exchange turnover frequency at 150 °C) with solvent acidity. Intermediate of the C-H activation reaction. A key intermediate in the proposed reaction mechanism, Pt-Me species, was not detected in crude reaction mixtures. Following the reaction in situ by nmr was hampered by the high reaction temperature. Therefore, to begin to elucidate the reaction pathway for the C -H activation reaction, we attempted to synthesize the proposed reaction intermediate B and study the microscopic reverse of the C-H activation reaction, at lower temperatures. Other studies have been carried out to elucidate the mechanism of the Shilov system on the basis of the principle of microscopic reversibility. 15 Significantly, to employ the principle of microscopic reversibility by study of a 59 model reaction in order to infer the mechanism of the actual system, the model system must meet minimum two requirements; a) the system must be shown to be capable of the reverse reaction by indirect means or the thermodynamics of the model reaction must be known and b) the model and actual system must be known or shown to operate by the same reaction mechanism. It should be noted that NMR studies can be used to rule out mechanisms if these two requirements cannot be met but cannot be used to support specific mechanisms. The relevance of a model system is largely determined by how close the ligands, solvent dielectric constant, acidity, and other characteristics of the model resemble the actual catalytic system. Pt(bpym)(CH 3 )Cl could be synthesized by protonolysis of the dimethyl complex, Pt(bpym)(CH 3 ) 2 . Attempts to synthesize Pt(bpym)(CH 3 )(OSO 3 H) or the related triflate were unsuccessful due to instability of these complexes, however a trifluoroacetate analog Pt(bpym)(CH 3 )(TFA) could be prepared by similar procedure. It was determined that the solubility of Pt(bpym)(CH 3 )Cl was poor in most solvents, hence, it was only used for experiments with sulfuric acid, and trifluoroacetate analog was used for all other studies. Addition of Pt(bpym)(CH 3 )Cl to concentrated D 2 SO 4 at room temperature lead to instant evolution of methane. High rate of this decomposition and high melting point of sulfuric acid prevented the nmr study of the reverse process of the C -H activation reaction in this fashion. However, an important observation was made regarding deuterium incorporation into evolving methane. Analysis of the gas phase of the Pt(bpym)(CH 3 )X + D 2 SO 4 (X = Cl, TFA) experiments at 180 °C show 60 that evolved methane is multiply deutated. The isotopomer distribution (ratio of CH 4 to CH 3 D… etc.) in this experiment was very close to that obtained from an actual catalytic cycle when D 2 SO 4 is used, Table 3.1. Table 3.1. Ratio of deuteromethanes (d 1 :d 2 :d 3 :d 4 ) from direct catalytic reaction with CH 4 and from reverse reaction of Pt II -CH 3 deuterolysis. CH 3 D CH 2 D 2 CHD 3 CD 4 Actual catalytic runs 48 38 10 4 Pt II -CH 3 deuterolysis 46 33 14 5 Hence, if these ratios are the same for the experiments done in the same solvent in similar conditions, this will be an indication that methane isotopomers are produced from the same source, that is, from alkyl platinum complexes formed as intermediates. Such a uniformity between the ratio of methane isotopomers formed in Pt II -CH 3 protonolysis and in direct H-D exchange reaction is definitive evidence that methyl platinum complexes are formed in the actual catalytic reaction, and it was also observed for other Pt catalytic systems. 16 Low-temperature protonolysis in SO 2 . Solvent of choice for a model system, which would allow observation of the transient species, must mimic well the experimental conditions of the actual atalytic reaction and therefore should be non-nucleophilic and polar, dissolve the reactants and not cause their decomposition due to reaction with the solvent. It should also maintain low 61 viscosity at low temperatures and allow control over proton concentration. Sulfur dioxide is a good non-coordinating solvent with relatively high dielectric constant, and owing to its low melting point it is perfectly suitable for low-temperature studies. It also dissolves super-acids such as CF 3 SO 3 H or FSO 3 H/SbF 5 and the resulting very strong acid solutions can be considered to be a good solvent model for the polar, strongly acidic conditions of sulfuric acid solvent that, unlike sulfuric acid, can examined at low temperatures by nmr methods. Since SO 2 insertion into Pt-C bond is known, 17 stability Pt(bpym)(CH 3 )TFA in liquid SO 2 was checked by comparing its 1 H-NMR spectra in CD 2 Cl 2 before and after dissolution in SO 2 , and it was determined that at low temperatures (-65…0 °C) within several hours, no measurable SO 2 insertion into Pt-CH 3 bond occurs. It should also be noted that no SO 2 insertion products are observed during direct catalytic experiments as well. Preliminary protonolysis experiments with triflic, sulfuric, and fluorosulfuric acids had shown that reactions with these acids as protonating agents either did not proceeded cleanly, or led to formation of several new Pt-CH 3 species that were too complicated to analyze. Addition of HCl caused precipitation of insoluble Pt(bpym)(CH 3 )Cl. Use of stronger superacid FSO 3 H/SbF 5 gave much cleaner spectra. In a typical experiment, addition of excess (10-20 equivalents) of magic acid to a solution of Pt(bpym)(CH 3 )TFA in SO 2 at -50 °C leads to slow (t ½ >1hr) disappearance of the signal due to the methyl group of the starting complex as four new well-defined Pt-CH 3 resonances appear (Figure 3.8). Methane evolution is also observed. 62 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 PPM 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 PPM Figure 3.8. 1 H NMR of Pt-CH 3 Region on Protonation of Pt(bpym)(CH 3 )TFA with FSO 3 H/SbF 5 in Liquid SO 2 at –50 o C. As can be seen there appears to be two pairs of Pt-CH 3 species (based on Pt-H satellites) whose ratios are observed to change with time. One pair of Pt-Me signals consists of two peaks at 2.3 and 2.8 ppm, and another pair at 2.6 and 3.2 ppm. The intensity of former pair of signals increases with time, while the intensity of the latter pair decreases. On the basis of the theoretical work we assign these pairs to protonation at one or the other nitrogens of the bpym ring system. 12 The change in the relative intensities of the pairs of peaks with time is proposed to result from slower anion exchange, as shown on Scheme 3.4. 63 N N N N Pt CH 3 OCOCF 3 H N N N N Pt CH 3 OCOCF 3 H N N N N Pt CH 3 OSO 2 F H N N N N Pt CH 3 OSO 2 F H + + Scheme 3.4. Protonation of bipyrimidine ring system and anion exchange, leading to four new Pt-CH 3 resonances upon protonation of Pt(bpym)(CH 3 )TFA with magic acid. At these low temperatures, the rate of methane loss from Pt(bpym)(CH 3 )(O 2 CCF 3 ) upon protonation is slow and both free methane and Pt- CH 3 species can be simultaneously observed. Importantly, however, no platinum hydride peaks (expected in the 0 to -30 ppm range) 18 are observed, even though both methane and the Pt-CH 3 species are present, Figure 3.9. This indicates that the loss of methane from intermediate B is most likely not occurring via protonation of the platinum center followed by methane loss (as that would have led to the formation of Pt-H species). Instead, these observations are more 64 consistent with loss of methane occurring by direct protonation of the Pt-CH 3 bond. It should be noted however, that this is not unequivocal as the putative Pt-H species could decompose rapidly are could not be observed. However, as related protonation studies of Pt-CH 3 by Bercaw lead to quantitative formation of the Pt-H species, 19 the complete absence in these reactions is still significant. 10 0 -10 -20 -30 -40 PPM 10 0 -10 -20 -30 -40 PPM Figure 3.9. No Pt-H resonances are observed during protonolysis of Pt(bpym)(CH 3 )(TFA). With deuterated magic acid, the evolving methane is multiply deuterated. The ratio of deuteromethanes determined by GC-MS analysis was 87:12:2:0.2 (d 1 : d 2 : d 3 : d 4 ). Deuteration at Pt-CH 3 could not be resolved by nmr, however. A blank test with DOSO 2 F/SbF 5 only (no Pt complex) and CH 4 was performed to evaluate possible activation of methane by magic acid itself (methane activation by 65 superacids including magic acid at low temperatures has been reported 20 ). No deuterium exchange was observed in the same conditions as the deuterolysis of Pt- CH 3 complex, hence any H-D exchange in the latter case is due to activation by Pt center. Protonolysis of Pt(bpym)(CH 3 ) 2 in SO 2 . In order to gain further evidence regarding the protonation of bipyrimidine ligand under the conditions of a model system, the symmetrical dimethyl complex was studied. Since Pt(bpym)(CH 3 ) 2 appears a lot more susceptible to SO 2 attack than the monomethyl complex, the following procedure was adopted: to solid Pt(bpym)(CH 3 ) 2 at the bottom of nmr tube liquid SO 2 was condensed carefully without mixing, then magic acid was added and the whole reaction was quickly mixed. Addition of excess of magic acid-d to Pt(bpym)(CH 3 ) 2 in SO 2 at -65 °C leads to disappearance of the Pt-CH 3 signal of the starting material at 0.9 ppm and appearance of two new Pt-CH 3 resonances of equal intensity at 1.8 and 2.2 ppm. Region corresponding to bipyrimidine ligand now has six different signals instead of three of the starting material (Figure 3.10). This is in agreement with the observations from the experiment with monomethyl species, and with theoretical calculations suggesting mono-protonation. No methane evolution, no Pt-CH 3 deuteration, and no hydride (Pt-H) signals (when HOSO 2 F/SbF 5 is used) are observed in these conditions. 66 10 8 6 4 2 PPM 10 8 6 4 2 PPM Figure 3.10. Protonation of Pt(bpym)(CH 3 ) 2 in SO 2 with magic acid at -65 °C. Protonolysis of Pt(bpym)(CH 3 )(TFA) complex in acetic acid. Investigating protonolysis of the Pt(bpym)(CH 3 )(TFA) complex in SO 2 /superacid system provided evidence for mono-protonation of the bipyrimidine ligand and lack of Pt-H formation, consistent with theoretical calculations. However, no evidence for deuterium incorporation into Pt-CH 3 group was obtained due to poor resolutiuon by NMR. In a search for another relatively polar, protic solvent for a model system, we turned to acetic acid solvent. Pt(bpym)(CH 3 )TFA complex is stable towards Pt-C bond protonolysis in acetic acid solution at room temperature, the only reaction taking place is the displacement of the trifluoroacetic group by acetic group. 67 1.20 1.10 1.00 PPM 1.20 1.10 1.00 PPM a b c Figure 3.11. A set of 1 H NMR spectra of deuterolysis reaction of Pt(bpym)(CH 3 )TFA in CD 3 COOD (see text). However, heating the solution up to 70-80 °C leads to slow evolution of methane. Monitoring this reaction by 1 H-NMR revealed deuterium incorporation into Pt-CH 3 group (Figure 3.11). A new peak appears upfield of the original Pt- CH 3 resonances from Pt(bpym)(CH 3 )TFA complex in acetic acid-d, along with overall decrease in the peak integration. This new peak is assigned as mono- deuterated Pt-bound methyl group: a = Pt-CH 2 D. Peaks b and c correspond to new acetato- and original trifluoroacetato- complexes, respectively (identity of the peak b established by an independent synthesis of that complex). After major part of initial Pt(bpym)(CH 3 )TFA complex reacts to liberate methane, full range of methane isotopomers can be observed, Figure 3.12, Presence of CD 4 was 68 confirmed by GC-MS analysis. (Presence of fully protonated methane likely arises from H/D exchange with protic sites on the glass surfaces of the NMR tube.) CH 4 CH 3 D CH 2 D 2 CHD 3 0.25 0.20 0.15 0.10 PPM 0.25 0.20 0.15 0.10 PPM Figure 3.12. Methane isotopomers arising from protonolysis of Pt(bpym)(CH 3 )TFA complex in acetic acid-d. From the rates of methane evolution at various temperatures (50 °C and 75 °C), activation energy for methane loss from Pt(bpym)(CH 3 )OCOCX 3 in acetic acid is estimated to be around 22 kcal/mol in this temperature range. In neat CH 3 COOH, no hydride resonances were observed from Pt(bpym)(CH 3 )TFA, which is in agreement with experiments with SO 2 /magic acid. C-H activation of methane: Pt(II) vs. Pt(IV). When methane activation takes place in such a highly oxidizing media as the concentrated H 2 SO 4 , the oxidation state of the platinum species that is responsible for C-H bond activation 69 may be unobvious. Is it Pt(II) or Pt(IV)? In Shilov’s system excess Pt IV apparently inhibits oxidation, which would not be consistent with Pt IV being the active catalyst. Protonolysis of synthesized PtMeCl 5 2- in H 2 O leads to no methane; only CH 3 OH and CH 3 Cl are formed. 21 Thus, normally accepted point of view is that Pt II inhibits C-H activation 22 , and it is the coordinatively unsaturated derivatives of Pt(II) that react with alkanes, 1 but we cannot exclude the possibility of Pt IV doing C-H activation in highly oxidizing hot concentrated H 2 SO 4 . Although examples of C-H bond activation by Pt(IV) are rare, it does occur with aromatic compounds, where presumably due to available π-system on the substrate coordination to the metal center is favorable: metalation of arenes by PtCl 4 , 23 and by PtCl 6 2- has been reported. 24 (However there are no apparent examples of alkane activation by Pt IV . Reported intramolecular H/D scrambling at sp 3 carbon atoms in a Pt IV (nacnac)(CH 3 ) 3 complex, 25 apparently goes via Pt II intermediate). We looked for an ultimate evidence that C-H activation is effected by Pt II in our case. To begin to investigate this problem, we attempted side-to-side experiments with Pt(bpym)Cl 2 and Pt(bpym)Cl 4 at 150 °C in D 2 SO 4 , evaluating deuterium incorporation into CH 4 . Somewhat unexpectedly H-D exchange was observed in both cases, however nmr analysis of the reaction mixture of the Pt(bpym)Cl 4 experiment showed decomposition of the starting complex to yield Pt(bpym)Cl 2 which effected C-H activation. It was also observed that Pt(bpym)Cl 4 in DMF or DMSO solution would spontaneously decompose within several hours at room temperature to yield Pt(bpym)Cl 2 , pointing to instability of this Pt IV 70 complex. Therefore, we looked at reverse experiment: protonation of a Pt IV -CH 3 complex in actual reaction conditions. Pt(bpym)(CH 3 )(TFA)Cl 2 complex was chosen as a good model intermediate. A small volume of a concentrated DMSO solution of this complex was rapidly added to hot (180 °C) D 2 SO 4 and the product gas and liquid phases were analyzed by GC-MS and HNMR, respectively. To verify that DMSO does not react to produce methane or methanol under these conditions, blank experiment and experiment with H 2 Pt(OH) 6 were also run in parallel. Quantification was done in reference to an internal standard ethane (for GC-MS) or acetic acid (for nmr). The results are summarized in Table 3.2. Table 3.2. Product yield table, Pt II /Pt IV -CH 3 + D 2 SO 4 reaction. Complex Methane, % yield Methanol, % yield none - - H 2 Pt(OH) 6 - - Pt II (bpym)(CH 3 )(TFA) 95% 5% Pt IV (bpym)(CH 3 )(TFA)Cl 2 <1% >99% With Pt(bpym)(CH 3 )(TFA)Cl 2 , no methane evolution is observed at all, which suggests that the kinetic barrier between Pt IV -CH 3 and free methane is high, and consequently C-H activation by Pt IV (bpym)X 4 is much less favorable than by corresponding Pt II complex. Some deuterium incorporation into the methyl group of the product methanol in case of Pt(bpym)(CH 3 )(TFA)Cl 2 was observed (<30%), 71 indicating that the barrier between free methane and the methane σ-complex is significantly higher than the barrier between the methane σ-complex and Pt IV -CH 3 . Therefore, it appears that Pt IV is not the species responsible for C -H activation, even in hot concentrated sulfuric acid; and experimental data points to very high activation energy of methane coordination to yield a s-complex as a cause of Pt IV complex inactivity. Once in the coordination sphere of Pt IV however, it is possible for CH 4 to undergo H-D exchange with the acid, as evidenced by deuterium incorporation into methanol produced from Pt(bpym)(CH 3 )(TFA)Cl 2 . Oxidative vs. Functionalization rates in solvents of different polarity and nucleophilicity. As it was mentioned earlier, if an external oxidant such as H 2 Pt(OH) 6 or Pt(bpym)Cl 4 is added CH 4 + H 2 SO 4 + Pt(bpym)Cl 2 reaction mixtures at low temperatures (where oxidation rate is negligible), methanol forms instantly. However, if Pt II -CH 3 is reacted with an oxidant in a solvent less polar and/or more coordinating than concentrated sulfuric acid, methanol or related ester is not eliminated readily. Pt(bpym)(CH 3 )(TFA) or Pt(bpym)(CH 3 )Cl react at room temperature in DMSO, dichloromethane, or acetic acid with a variety of oxidants such as Pt IV salts, free halogens, H 2 O 2 , iodosobenzene, KIO 4 to form corresponding Pt IV -CH 3 complexes. These complexes are quite stable in these solvents in presence of excess of oxidant, and elimination of CH 3 X product occurs only upon heating. Elimination occurs most easily in dichloromethane (ε = 9), and much slower in acetic acid (ε = 4) and DMSO (ε = 48, however it is a very 72 strongly coordinating solvent). It appears that the rate of product elimination from Pt IV -CH 3 is in direct relation with solvent coordinating ability rather than polarity, indicating that a pathway involving 5-coordinate Pt IV species is viable. Highly coordinating solvent may intercept the 5-coordinate species and prevent facile product elimination, as it is observed in DMSO and acetic acid cases. In addition, it was observed that Pt IV complexes decompose spontaneously in the solid phase where no solvent stabilization is possible. Oxidative Functionalization of Pt(bpym)(CH 3 )TFA complex in weak acid media. Our implicit assumption in designing more active catalysts that operate in weak acid solvents is that these catalysts will follow the CH Activation, Oxidation and Functionalization steps of the Pt(bpym)Cl 2 system, Scheme 3.2. While this is reasonable, there is no requirement that other systems follow these steps and other oxidation functionalization pathways (for example O atom insertion) may be possible. Extensive work is being carried out on the CH activation step but relatively less is known about the oxidative functionalization steps. Consequently, we have decided to explicitly study this step with the objective of A) identifying efficient oxidants and B) determining other reaction pathways other that shown in Scheme 3.2, for oxidative functionalization. We have investigated the reaction of Pt(bpym)(CH 3 )TFA complex with Cu(II), as we are particularly interested in the use of Wacker type oxidant. Cu(OCOCH 3 ) 2 does not react with Pt(bpym)(CH 3 )(TFA) in acetic acid at room temperature, however 73 heating at 80 °C for 1 hr results in complete disappearance of any Pt-CH 3 signals and formation of methyl esters, as shown by HNMR analysis of the distilled reaction mixture (to remove paramagnetic Cu II ) and GC-MS analysis. This is an important result as this shows clear viability for using Cu(OAc) 2 as an oxidant for the CH 4 conversion in acetic acid. Interestingly, partial deuteration of the methyl group in CH 3 TFA and CH 3 OCOCH 3 formed, as well as presence of CH 3 D and CH 2 D 2 is observed by HNMR. Recently an extension of original Shilov’s improvement of the Pt II /Pt IV system using polyoxometalates instead of Pt IV as the stoichiometric oxidant was reported, in which a modified Pt(bpym)Cl 2 catalyst was used in aqueous solution, and Pt IV was substituted with a polyoxometalate complex, which allowed methane functionalization in very mild conditions. 26 Autocatalytic oxidation of Pt II -CH 3 in sulfuric acid with Pt IV . Oxidation of Pt(bpym)(CH 3 )TFA in hot (180 °C) sulfuric acid containing Pt(bpym)Cl 4 at various Pt IV /Pt II ratios leads to an interesting observation. The yield of oxidation products (methanol and at high Pt IV concentration also CO 2 ) is more than 100% based on added Pt IV when Pt IV /Pt II molar ratio is small (<<1) (Figure 3.13). 74 Pt VI / Pt II molar ratio 0 1 2 3 4 0 0.5 1 CH 3 OH to Pt ratio Yield by Pt II Yield by Pt IV Pt VI / Pt II molar ratio 0 1 2 3 4 0 0.5 1 CH 3 OH to Pt ratio Yield by Pt II Yield by Pt IV Figure 3.13. Pt(bpym)(CH 3 )TFA oxidation yields based on the starting material and on added Pt(bpym)Cl 4 complex. It is plausible that added Pt(bpym)Cl 4 oxidizes certain part of Pt II -CH 3 present in solution, and afterwards is recycled by SO 3 back to Pt IV species (probably Pt(bpym)Cl 2 (HSO 4 ) 2 ), which again further oxidize the remaining Pt II - CH 3 . This implies that oxidation of Pt II -CH 3 species by SO 3 may be less favorable than of CH 3 -free Pt II . It is notable that oxidation at low Pt IV concentrations displays “saturation” behavior: that is, even with the smallest amount of external alkyl-free Pt added (12.5% mol.), the yield jumps from 5% (with no external oxidant) to ~50% and gradually increases up to 100% up to maximum concentration of external Pt IV oxidant used. However it is also possible that oxidation rate is simply enhanced by Cl - -catalyzed charge transfer. 75 3.3 Discussion. Correlation between DFT calculations and experimental studies. Original Shilov’s reaction was proposed to proceed via a CH activation reaction to generate alkyl platinum intermediates in reactions with alkanes and later experimental studies by others are consistent with this proposal. 15,27 The chemistry of many other platinum complexes related to C-H activation was studied experimentally. 28 A large body of theoretical work by various research groups was dedicated to activation and functionalization of C-H bonds by platinum complexes. Calculations by Siegbahn and Crabtree on the Shilov’s reaction mechanism in water suggested that s-bond metathesis is a likely pathway for methane C-H activation by Pt II , although oxidative addition/reductive elimination sequence involving Pt IV could not be completely excluded. 29 Hush and co-workers studied the related Pt(NH 3 ) 2 Cl 2 system in H 2 SO 4 and in water, and found that in the case of H 2 SO 4 as a solvent electrophilic substitution pathway (ES) was favored over oxidative addition pathway (OA); and C-H activation by Pt IV appeared possible on the basis of thermodynamics. In the case of water as a solvent, for the cis- isomer both ES and OA activation barriers were simlar, while for the trans- isomer oxidative addition pathway appeared to be more favorable. 30 Ziegler and co- workers studied C-H activation by Pt(bpym)Cl 2 in H 2 SO 4 and found that depending on the actual catalyst species, the process can be either s-bond 76 metathesis (for Pt(bpym)(OSO 3 H) + ), or OA (for Pt(bpym)Cl + ). 31 In a different study, Goddard and co-workers analyzed Pt(NH 3 ) 2 Cl 2 and Pt(bpym)Cl 2 catalysts in H 2 SO 4 , and found results opposite to previously reported by other researchers. OA path was found to be preferred for the ammine catalyst, while the bipyrimidine catalyst was found to react with methane preferably via electrophilic substitution pathway with the highest barrier of 40.7 kcal/mol. 12 The primary reason for the discrepancy in the results appears to arise from difference in the set of conditions, e.g., whether the counterion of Pt(N^N)(CH 3 )X+ species is included or omitted. Kinetics of C-H activation by Pt(bpym)(OSO 3 H)Cl which is likely to form in bulk H 2 SO 4 was also studied by the same group and similar conclusions were reached – C-H activation favorably proceeds via ES pathway with a barrier of 31-33 kcal/mol depending whether the bpym ligand is mono- or di-protonated. 32 In a later study, Pt(N^N)Cl 2 in H 2 SO 4 systems (N^N = (NH 3 ) 2 , bpym) were revisited, and preference for dissociative pathway for CH 4 coordination was found computationally for the ammine catalyst, and for associative pathway in case of bpym catalyst; in addition, C-H activation by Pt IV was found to be thermoneutral in case of Pt(NH 3 ) 2 Cl 2 , and -1.6…-9.1 kcal/mol downhill for Pt(bpym)Cl 2 , hence there is a possibility that oxidation step precedes C-H activation step. 33 However earlier DFT study by Ziegler et al. on SO 3 as the oxidant in Catalytica system dismisses that possibility based on the thermodynamics and kinetic calculations as well: they found that the oxidation of Pt(bpym)(CH 3 )Cl is exothermic by 22.2 kcal/mol, while the oxidation of the catalyst itself is endothermic by 8.3 kcal/mol. 77 The overall barrier for the oxidation process is 35.1 kcal/mol for the catalyst (the dichloro complex) and 15.6 kcal/mol for the methyl complex. 34 As it can be seen, no uniform conclusion could be reached from theoretical calculations regarding whether C-H activation step in the Catalytica system proceeds via ES or OA mode; whether C-H activation in such a strongly oxidizing medium as concentrated sulfuric acid is effected by Pt II or Pt IV ; and what is the nature of the oxidation step. Thus we embarked on a detailed mechanistic study of this system to find experimental evidence for theoretically considered reaction pathways. Some of the results of extensive DFT studies on the C -H activation step with the Pt bipyrimidine catalyst reported in Ref. 32 include the following: the direct activation of Pt(bpym)Cl 2 by CH 4 is unfavorable, but when H 2 O is not present, it is favorable to convert Pt(H-bpym)Cl 2 + to Pt(H-bpym)(HSO 4 )Cl + . The calculations show the mono-protonated species, Pt(H-bpym)(HSO 4 )Cl + , is the most likely resting state of the catalyst. As discussed below this conclusion is consistent with all current experiments. This result from the quantum mechanics calcuations that the working catalyst is Pt(H-bpym)(HSO 4 )Cl + and not Pt(bpym)Cl 2 is important since it allows us to understand exactly why Pt(bpym)Cl 2 is so effective and provides a rational basis on which to improve the catalyst. 78 Methane complex is an intermediate in C-H activation step. As can be seen from Figure 3.14, the quantum mechanical studies (QM) show that the C-H Activation step also involves the rate determining formation, via transition state T1, of a methane complex intermediate B, before the actual C-H cleavage step, via transition state T2, to generate intermediate C. This is an important QM result as it explains the extensive, non-Schultz-Floury, H/D exchanges between deuterated acids and methane that is observed experimentally. N N N N Pt Cl OSO 3 H CH 4 N N N N Pt Cl CH 2 H H N N N N Pt Cl CH 2 H H N N N N Pt Cl H 2 SO 4 CH 3 +33.1 +27.4 +32.4 +10.2 +35.4 A C B T1 T2 T2b OSO 3 H HO 3 SO N N N N 0.0 Pt Cl CH 3 HO 3 SO H N N N N Pt Cl CH 3 HO 3 SO H H H H H H H Figure 3.14. Solution-phase potential energy diagram for the C–H activation of the Catalytica Pt catalyst with one added proton. Energy values are ΔH 0K , kcal/mol. 32 79 The result from the QM studies that shows that the barrier T1, for methane loss from B is higher than the barrier for CH cleavage, T2, to form C is consistent with extensive H/D exchange as this allows the B and C to equilibrate with D 2 SO 4 , resulting in extensive deuterium incorporation, before loss of methane can occur. Thus, after formation of the CH 4 complex B, it is more favorable to lose the H to solvent (B à C) than for CH 4 to leave. Thus there may be many exchanges between B and B leading to incorporation of several D before the B à A releases the deuterated CH 4 back in solution (Figure 3.15). Pt-CH 4 σ-complex TS ≠ oxidative addition TS ≠ electrophilic substitution Pt(bpym)Cl 2 + CH 4 Pt-CH 3 alkyl complex ΔH Observe multiple H-D exchange! 1 2 Figure 3.15. Explanation for the observed multiple H-D exchange in C-H activation step. Similar experimental evidence was obtained from deuterolysis of, where multiple deuteration of evolving methane was observed. As discussed above for the H/D exchange between methane and D 2 SO 4 , this result of multiple deuterium incorporation on deuterolysis can also be explained by the rate determining formation of a methane complex (analogous to B with a Cl or CF 3 CO 2 counter 80 anion) on treatment of Pt(bpym)(CH 3 )(CF 3 CO 2 ) with D 2 SO 4 that can lose a proton to regenerate the Pt-CH n D n-3 starting material more rapidly than the complexed, deuterated methane can be lost. Furthermore, linear dependence of C-H activation rates observed in H -D exchange experiments, is consistent with coordination of methane being the rate limiting step, as no dependence on [CH 4 ] would be expected if C -H bond cleavage of pre-coordinated methane in a s-complex was the limiting step. Experimentally we find that the activation barrier for C-H activation step is around 32 kcal/mol, and for the reverse step – protonolysis of the model Pt(bpym)(CH 3 )TFA complex, activation energy is ~22 kcal/mol (both barriers at 60 °C), which is in good agreement with the computed values. C-H activation proceeds via Electrophilic Substitution pathway. Figure 3.14 indicates that the more favorable pathway for CH activation in Pt(H- bpym)(HSO 4 )Cl + is via electrophilic substitution rather than oxidative addition as expected on the basis of studies of C-H activation by related Pt II (tmeda) complexes. 19 Thus, the lowest energy pathway for loss of the H from the bound CH 4 in the methane complex B occurs directly to solvent molecules via transition state T2 (electrophilic substitution of the CH bond by Pt II ). This result contrasts with the common assumption that such CH cleavage processes must proceed via oxidative addition in which an intermediate or transition state is formed that has a bond between Pt and the leaving H (leading in this case to Pt IV ). Indeed a second transition state T2b for C-H activation that does involve such an oxidative addition 81 pathway could be found, however for Pt(H-bpym)(HSO 4 )Cl + , this step has a barrier of 8 kcal/mol rather than 5, making it significantly less favorable. Experimentally we could not find any evidence for the platinum hydride complex which is an assumed intermediate in the OA pathway. As discussed above, slow methane loss is observed and both free methane and Pt-CH 3 species can be simultaneously observed at –50 o C, upon protonation of Pt(bpym)(CH 3 )TFA in SO 2 with FSO 3 H/SbF 5 . Importantly, however, as the loss of methane is observed, no platinum hydride peaks (expected in the 0 to -20 ppm range) were observed. This indicates that the loss of methane from B is most likely not occurring via protonation of the platinum center followed by methane loss (as that would have led to the formation of Pt-H species). Instead, these observations are more consistent with loss of methane occurring by direct protonation of the Pt-CH 3 bond. If FSO 3 D/SbF 5 is used instead of a regular proteated magic acid, multiple deuterium incorporation into evolving methane is observed. While deuteration at Pt-CH 3 group could not be observed with deuterated magic acid in SO 2 , and only a small peak assignable to Pt-CH 2 D could be observed during deuterolysis of Pt(bpym)(CH 3 )TFA in CD 3 COOD, deuterium incorporation into the product methanol (to yield CH 2 DOH and CHD 2 OH observable by nmr) of a direct conversion of CH 4 in D 2 SO 4 is a clear evidence that Pt-CH n D 3-n intermediate species are formed. When these conclusions are considered in light of the principles of microscopic reversibility, this suggests that the C-H activation via the methane complex most likely occurs via an electrophilic substitution process 82 rather than an oxidative addition step. As discussed above, from Figure 3.14, these conclusions are consistent with the QM results showing the C -H Activation step occurs via rate determining methane complex formation, followed by more rapid CH cleavage that occurs via electrophilic substitution transitions state, T2, that is 3 kcal lower in energy rather than the transition state for oxidation addition, T2b. Bipyrimidine ligand in Pt(bpym)(HSO 4 )Cl is monoprotonated. It was shown by DFT calculations that in H 2 SO 4 mono-protonation of free bipyrimidine is almost thermoneutral, while mono-protonated form of the Pt(bpym)Cl 2 catalyst is ~8 kcal more thermodynamically stable than non-protonated form. Now we have experimental data consistent with these calculations. It was mentioned above that in protonolysis experiments with Pt(bpym)(CH 3 )TFA and Pt(bpym)(CH 3 ) 2 pairs of peaks were present in the nmr spectra, pointing to mono-protonation of the bpym ligand. Another direct evidence for mono-protonation follows from the high- temperature (100-120 °C) nmr spectra of the catalyst, Pt(bpym)Cl 2 , in solution – resonances corresponding to bpym protons are broad, lacking the fine structure which is observed for free bpym in the same solution. This can be explained by fluxionality of the protonated complex: proton can rapidly switch between the two N-atom protonation sites, leading to broad resonances. Corresponding nmr spectra in room-temperature D 2 SO 4 or DMSO solution reveals finely resolved signals. Inhibition by H 2 O and methanol. During the catalytic run water is produced as a byproduct along with methanol and decrease in overall catalytic 83 activity is observed. 9 This water lowers SO 3 concentration causing oxidation step to slow down. It seems, however, that the primary reason for catalyst inhibition is ground state stabilization ( Figure 3.16). Water and methanol have much higher affinity to the electophilic Pt(II) center than methane, and once their concentration becomes dominant compared to dissolved methane, they effectively block methane coordination. E n+ (Sol) + CH 4 E-CH 3 + HX Figure 3.16. Ground state stabilization by products. The importance of the formation of the methane complex, B, coupled with the instability of the methane complex with respect to A (~27 kcal/mol), Figure 3.14, provides a basis for understanding the severe inhibition by water and methanol. This large difference in stabilization between the ground state and the methane complex is consistent with the catalyst having a higher binding constant for good sigma-donors relative to the poorly sigma-donating methane. The QM calculations indicate that formation of the active catalyst, [Pt(H-bpym)(HSO 4 )Cl] + , 84 from [Pt(H-bpym)Cl 2 ]+ , is uphill by 6.1 kcal/mol, but favored by the large concentration of H 2 SO 4 . However, the reaction of the active catalyst with water, to yield [Pt(H-bpym)(H 2 O)Cl] 2+ , is downhill by 6.8 kcal/mol. Thus H 2 O destroys the active catalyst. Consequently the increasing amounts of water in the catalytic system (that is produced as the reaction proceeds, Scheme 3.1) leads to a new catalyst resting state that is ~35 kcal below that of the methane complex, B. This effectively leads to an increase in the activation barrier from 33 kcal/mol to 40 kcal/mol as the reaction proceeds. N N N N Pt Cl Cl SO 2 + H 2 O SO 3 + 2 H 2 SO 4 CH 4 H 2 SO 4 HSO 4 - HSO 4 - + + CH 3 OSO 3 H + HSO 4 - Pt Cl OSO 3 H N N HN N - HCl H 2 SO 4 SO 2 + H 2 O SO 3 + 2 H 2 SO 4 HSO 4 - + Pt Cl N N CH 3 OSO 3 H Pt Cl CH 3 OSO 3 H N N Pt Cl OSO 3 H OSO 3 H N N OSO 3 H Scheme 3.5. Tandem mechanism of the Catalytica system. This is sufficient to account for the observation of essentially complete inhibition of the methane oxidation reaction after ~10% by wt water builds up in the reaction system. Other nucleophiles, such as Cl - , also can cause ground state 85 stabilization of the catalyst. Inhibition of catalytic activity of platinum sulfate by addition of chloride to sulfuric acid solutions has been previously noted. 35 Oxidation step. SO 3 vs. Pt IV . As it was observed for H-D experiments at low temperature (150 °C), addition of Pt IV source to the reaction mixture leads to immediate and quantitative formation of methanol. Experimentally obtained ΔG ≠ 453K values for C-H activation step (measured by H-D exchange of CH 4 with D 2 SO 4 ) and for oxidation to methanol, 33.0 kcal/mol and 36.1 kcal/mol, respectively, are consistent with oxidation being a slower step than C-H activation. While SO 3 is thermodynamically a very powerful oxidant, apparently kinetic barriers are high enough to make oxidation a slow part of the catalytic cycle. We propose that oxidation of the intermediate Pt II -CH 3 by SO 3 occurs indirectly, via formation of a non-methyl Pt IV species first followed by an electron transfer to Pt II - CH 3 to form a Pt IV -CH 3 intermediate (Scheme 3.5). Kinetic model demonstration for methanol rate. It appears that such a mechanism can be quite general (Scheme 3.6). In any catalytic system, where only the lower oxidation state of the catalyst is active towards C-H activation, the requirement for an efficient overall reaction is that the rate at which oxidation of M n -CH 3 by M n+2 (rate k 5 ) must occur faster than the rate at which “C-H inactive” M n+2 species is accumulated (rate k 4 ). 86 CH 4 CH 3 X Ox. Red. M n M n+2 M n -CH 3 M n+2 -CH 3 k 1 Ox. Red. k 2 k 3 k 4 k 5 Scheme 3.6. General tandem M n /M n+m C-H activation/oxidation mechanism. Figure 3.17. Rate of CH 3 X product formation for fast, intermediate, and synchronous parallel oxidation reaction. 87 There may be several typical situations depending on the relative ratio of individual reaction rates in this cycle. Figure 3.17 represents characteristic cases calculated using a simple kinetic model. 3.4 Conclusion. In summary, we have determined the mechanism for the C-H and oxidation steps of the Catalytica system, and identified how water inhibition can be a difficulty. In contrast with classical Shilov’s Pt II system, where C-H activation is the limiting step of the cycle, 27a in Catalytica’s system reoxidation of Pt II to Pt IV , is the apparent limiting step. Consistent with oxidation being very fast step, very little D incorporation into CH 3 X products is observed in Shilov’s system, 36 as any alkyl group on Pt would be immediately oxidized by Pt IV present without equilibrating back to alkane s-complex; and inversely, in case of Catalytica system extensive deuteration of the methyl group of the methanol product is observed, indicating that C-H activation is faster than oxidation. Contrary to theory-based conclusions that methane C-H activation by Pt IV is possible, 33 and a two-step oxidation mechanism involving Pt IV dichloro complex is ruled out, 34 we did in fact find experimental evidence consistent with Pt IV not being involved in C- H activation, and a two-step oxidation mechanism may indeed be operating in the Catalytica system. 88 3.5 Experimental. General Information. Unless otherwise noted, all reactions were carried out under inert atmosphere of nitrogen or argon, utilizing standard Schlenk glassware and Vacuum Atmospheres drybox. Elemental analyses were carried out by Desert Analytics Laboratory, Tucson, AZ. 1 H, 13 C and 19 F NMR spectra were collected using Bruker AC-250 ( 1 H at 250.134 MHz and 13 C at 62.902 MHz), AM-360 ( 1 H at 360.138 MHz and 13 C at 90.566 MHz), and Varian Mercury 400 spectrometers ( 1 H at 400.151 MHz and 13 C at 100.631 MHz). The spectra were referenced to residual solvent protons or a known chemical shift standard and chemical shifts are reported in parts per million downfield of tetramethylsilane. All coupling constants are reported in Hertz. NMR experiments requiring air-free manipulations were carried out in Wilmad NMR tubes fitted with J.Young Teflon vacuum/pressure valves. Liquid and gas phases of reaction products were analyzed on Shimadzu QP-5000 GCMS instrument. Gas phase was analyzed using a J&W Scientific GasPro capillary column (30 m × 0.32 mm ID), liquid phase on J&W Scientific DS-5ms capillary column (30 m × 0.32 mm ID). The relative amount of each methane isotopomer (for deuteration experiments) was determined via custom deconvolution table, which was set up as an Excel spreadsheet using the mass- spectral data for standard isotopomer samples. 89 X-ray diffraction data were collected on a Bruker SMART APEX CCD diffractometer with graphite monochromated Mo K α radiation (l = 0.71073 Å). The cell parameters were obtained from the leastsquares refinement of the spots using the program SMART. A hemisphere of data was collected up to a resolution of 0.75 Å. The intensity data were processed using the program Saint-Plus. All calculations for the structure determination were carried out using the SHELXTL package (version 5.1) 37 . Initial atomic coordinates of the Pt atoms were located by direct methods, and structures were refined by least-squares methods. Empirical absorption corrections were applied using the program SADABS 38 . Calculated hydrogen positions were input and refined in a riding manner along with their attached carbons. A summary of the refinement details and the resulting parameters are given in the Supporting Information. Ortep-3 for Windows 39 was used for plotting the structures for publication. Unless otherwise noted, reagent grade chemicals were purchased from commercial suppliers and used without further purification. Hydrocarbon solvents, ether and tetrahydrofurane were distilled from sodium benzophenone ketyl under argon; inhibitor-free dry dichloromethane was obtained via standard procedures and finally purified by careful distillation from CaH 2 immediately prior to use. Deuterated solvents for NMR experiments were purified by identical procedures. SO 2 was distilled from P 2 O 5 directly into an NMR tube immediately prior to use. Pt(bpym)Cl 2 . Synthesis of this compound was reported earlier, 40 however it was found that the following simple method works best: 0.085 g of 2,2’- 90 bipyrimidine was combined with 0.222 g K 2 PtCl 4 in 15 mL H 2 O at room temperature in air. After overnight stirring, orange precipitate formed, which was filtered off and washed with acetone and dried in vacuo. Yield 99%, 1 H NMR (500.1 MHz, DMSO-d 6 ): d 8.00 (dd, 2 H, bpym H 5/5’ ), d 9.35 (dd, 2 H, bpym H 4/4’ ), d 9.68 (dd, 2 H, bpym H 6/6’ ); 13 C NMR (125.8 MHz, DMSO-d 6 ): d 124.4 (s, bpym C 5/5’ ), d 154.6 (s, bpym C 4/4’ ), d 159.7 (s, bpym C 6/6’ ), d 162.0 (s, bpym C 2/2’ ). Anal. Calcd for C 8 H 6 Cl 2 N 4 Pt (M r = 424.15): C, 22.65; H, 1.43; N 13.21; Cl, 16.72. Found: C, 23.13; H, 1.19; N 13.33; Cl, 16.74. Pt(bpym)Cl 4 . 0.9 g K 2 PtCl 6 was combined with 0.3 g 2,2’-bipyrimidine in 35 mL H 2 O and heated to 95 °C to achieve complete dissolution of the components. Solution was stirred for 1 hr, during which time orange precipitate formed (which was determined to be the desired product contaminated with Pt(bpym)Cl 2 ). After that, Cl 2 gas was bubbled through the resulting suspension for 10 min, turning the color of the precipitate to bright-lemon. The mixture was cooled to 0 °C, and the precipitate was filtered off, washed twice with chilled H 2 O and dried in vacuo. Yield 85%. 1 H NMR (500.1 MHz, DMSO-d 6 ): d 8.36 (dd, 2 H, bpym H 5/5’ ), d 9.57 (dd, 2 H, bpym H 4/4’ ), d 9.79 (dd+dd, 2 H, 3 J Pt-H = 25.7 Hz, bpym H 6/6’ ); 13 C NMR (90.6 MHz, DMSO-d 6 ): d 127.4 (s+d, 3 J Pt-C = 21.4 Hz, bpym C 5/5’ ), d 154.9 (s+d, 4 J Pt-C = 11.1 Hz, bpym C 6/6’ ), d 158.3 (s+d, 2 J Pt-C = 16.7 Hz, bpym C 2/2’ ), d 163.9 (s, bpym C 4/4’ ). Anal. Calcd for C 8 H 6 Cl 4 N 4 Pt (M r = 495.05): C, 19.41; H, 1.22; N 11.32; Cl, 28.65. Found: C, 19.44; H, 1.29; N 11.01; 91 Cl 28.76. X-ray quality yellow needles of 2×0.5DMF were grown by vapor diffusion of diethyl ether into dimethylformamide solution of 2. The crystal structure of this complex is shown on Figure 3.18 (hydrogens and DMF molecule have been omitted for clarity). Figure 3.18. ORTEP drawing of Pt(bpym)Cl 4 . Pt 2 (CH 3 ) 4 (m-S(C 2 H 5 ) 2 ) 2 . An ether solution of CH 3 Li (2.3 mL of 1.4 M solution) was added dropwise to a chilled (0 °C) suspension of 0.58 g of PtCl 2 (S(C 2 H 5 ) 2 ) 2 (mixture of cis- and trans-) in 25 mL of ether. After stirring at 0 °C for 15 min (or until reaction mixture turns from yellow to white), reaction mixture was allowed to warm up slowly to room temperature, and hydrolyzed with 5 mL of saturated NH 4 Cl solution. The ether layer was separated, dried and carefully evaporated in vacuo to give the desired product. Yield 97%, 1 H NMR 92 (500.1 MHz, CDCl 3 ): d 0.47 (s+d, w/Pt satellites, 12 H, 2 J Pt-H = 85.5 Hz, -CH 3 ), d 1.58 (t, 12 H, -CH 2 CH 3 ), d 3.02 (q, 8 H, -CH 2 CH 3 ); 13 C NMR (125.8 MHz, CDCl 3 ): d -6.4 (s+d, 1 J Pt-C = 780.2 Hz, -CH 3 ), d 12.3 ((s+d, 3 J Pt-C = 15.5 Hz, - CH 3 CH 3 ), d 29.6 (s+d, 2 J Pt-C = 38.2 Hz, -CH 3 CH 3 ). Anal. Calcd for C 12 H 32 Pt 2 S 2 (M r = 630.67): C, 22.85; H, 5.11. Found: C, 22.85; H, 4.93. Pt(bpym)(CH 3 ) 2 . A variation of the previously reported method for preparation of 1 was used. 41 Solution of 0.33 g of 3 in 18 mL CH 2 Cl 2 was quickly added to a solution of 0.828 g 2,2’-bipyrimidine (5-equiv. per Pt) in 12 mL CH 2 Cl 2 . After stirring for 1 hr at room temperature the solution turned dark-red. Small amount of black-red precipitate (bimetallic bpym complex) was formed, which was filtered off, and the obtained clear dark-red filtrate was evaporated to dryness. Recrystallization of this residue from methanol afforded pure product as bright-red microcrystalline powder, with 75% yield. 1 H NMR (500.1 MHz, CD 2 Cl 2 ): d 1.04 (s+d, 6 H, 2 J Pt-H = 87.3 Hz, -CH 3 ), d 7.64 (dd, 2 H, bpym H 5/5’ ), d 9.28 (dd, 2 H, bpym H 4/4’ ), d 9.40 (dd+dd, 2 H, 3 J Pt-H = 23.0 Hz, bpym H 6/6’ ). 13 C NMR (125.8 MHz, CD 2 Cl 2 ): d -16.9 (s+d, 1 J Pt-C = 827.3 Hz, -CH 3 ), d 124.6 (s+d, 3 J Pt-C = 15.5 Hz, bpym C 5/5’ ), d 153.6 (s+d, 2 J Pt-C = 29.4 Hz, bpym C 6/6’ ), d 157.0 (s, bpym C 4/4’ ), d 163.2 (s, bpym C 2/2’ ). Anal. Calcd for C 10 H 12 N 4 Pt (M r = 383.31): C, 31.33; H, 3.16; N, 14.62. Found: C, 31.52; H, 3.10; N, 14.53. Pt(bpym)(CH 3 )Cl. To a solution of a complex 4 in dichloromethane (38.3 mg in 4 mL), 100 mL of 1 M HCl solution in diethyl ether was added at -78 °C. On 93 addition solution color immediately changed from red to orange. After 5 min at - 78 °C followed by warm -up to room temperature the color of the solution changed to yellow and after 30 min an orange precipitate started to form. After 1 hr stirring, 20 mL pentane was added to the reaction mixture to fully precipitate the product. The orange precipitate was filtered off and dried in vacuo. Yield 93%. 1 H NMR (500.1 MHz, CD 2 Cl 2 ): d 1.16 (s+d, 3 H, 2 J Pt-H = 79.7 Hz, -CH 3 ), d 7.62 (dd, 1 H, bpym H x ), d 7.96 (dd, 1 H, bpym H x ), d 9.25 (dd, 1 H, bpym H x ), d 9.29 (dd, 1 H, bpym H x ), d 9.40 (dd+dd, 1 H, x J Pt-H = 57.5 Hz, bpym H x ) d 9.74 (dd, 1 H, bpym H x ). 13 C NMR (125.8 MHz, CD 2 Cl 2 ): d -16.0 (s, -CH 3 ), d 124.7 (s, bpym), d 124.9 (s, bpym), d 154.6 (s, bpym), d 155.0 (s, bpym), d 157.4 (s, bpym), d 159.2 (s, bpym) (tertiary carbon signals and 195 Pt- 13 C couplings were not observed due to very low solubility). Anal. Calcd for C 9 H 9 ClN 4 Pt⋅CH 2 Cl 2 (M r = 403.73): C, 24.58; H, 2.27. Found: C, 24.79; H, 1.96. Pt(bpym)(CH 3 )OAc. To 170 mg (0.443 mmol) of the dimethyl complex 3 mL of glacial acetic acid was added at room temperature. An immediate gas evolution is observed and the solution turns yellowish brown. The reaction mixture is stirred at room temperature for 5 min, followed by removal of solvent in vacuo. The brownish residue was redissolved in 2 mL CH 2 Cl 2 , and after addition of 6 mL of hexanes yellow precipitate is formed. Second reprecipitation afforded a yellow solid after solvent removal and drying in vacuo. Yield 85%. 1 H NMR (500.1 MHz, CD 2 Cl 2 ): d 0.94 (s+d, 3 H, 2 J Pt-H = 79.5 Hz, Pt-CH 3 ), d 1.97 (s, 3 H, -O 2 C-CH 3 ), d 94 7.47 (dd, 1 H, bpym H 5 ), d 7.69 (dd, 1 H, bpym H 5’ ), d 8.95 (dd, 1 H, bpym H 4’ ), d 9.13 (dd, 1 H, bpym H 4 ), d 9.15 (dd, 1 H, bpym H 6’ ) d 9.22 (dd, 1 H, bpym H 6 ). 13 C NMR (90.6 MHz, CD 2 Cl 2 ): d -13.7 (s+d, 1 J Pt-C = 807.1 Hz, -CH 3 ), d 23.8 (s, - O 2 CCH 3 ), d 124.4 (s+d, 3 J Pt-C = 44.1 Hz, bpym), d 125.1 (s, bpym), d 155.1 (s, bpym), d 156.8 (s+d, 4 J Pt-C = 42.4 Hz, bpym), d 157.3 (s, bpym), d 159.1 (s, bpym), d 161.0 (s, bpym), d 164.3 (s, bpym), d 178.2 (s, O 2 CCH 3 ). Final compound is a mixture of monomethyl-acetato- with ~10% diacetato- complexes. Attempts to synthesize this monomethyl compound by adding one (or several) equivalents of acid in a CH 2 Cl 2 lead only to partial conversion to the monomethyl complex. Attempts to obtain it via anion exchange with Pt(bpym)(CH 3 )Cl, or via conproportionation of corresponding dimethyl- and diacetato- complexes were unsuccessful as well. Monomethyl trifluoroacetato- analog could be synthesized in pure form, however (see below). Pt(bpym)(CH 3 )TFA. To a solution of 80 mg (0.209 mmol) of 2 in 8 mL of CH 2 Cl 2 , 16 mL (0.209 mmol) of H TFA was added at -78 °C. The red solution immediately turned black and suspension was formed. The reaction mixture was allowed to warm up to room temperature, warming up was accompanied by gas evolution and dissolution of the suspension, giving an orange solution. After addition of 50 mL of hexanes a bright-yellow solid precipitated, which was filtered off and dried in vacuo. Yield 90%, 1 H NMR (360.1 MHz, CD 2 Cl 2 ): d 1.12 (s+d, 3 H, 2 J Pt-H = 79.5 Hz, -CH 3 ), d 7.60 (dd, 1 H, bpym H 5 or 5’ ), d 7.81 (dd, 1 H, bpym 95 H 5 or 5’ ), d 8.93 (dd, 1 H, bpym H 4 or 4’ ), d 9.25 (dd, 1 H, bpym H 4 or 4’ ), d 9.29 (dd, 1 H, bpym H 6 or 6’ ) d 9.32 (dd+dd, 1 H, 3 J Pt -H = 60.0 Hz, bpym H 6/6’ ). 13 C NMR (90.6 MHz, CD 2 Cl 2 ): d -13.5 (s+d, 1 J Pt-C = 787.1 Hz, -CH 3 ), d 115.8 (q, -OCOCF 3 , 1 J C-F = 290.2 Hz), d 124.4 (s+d, 3 J Pt-C = 48.3 Hz, bpym C 4/4’ ), d 125.3 (s, bpym C ? ), d 154.4 (s, bpym C ? ), d 157.0 (s+d, 4 J Pt -C = 42.8 Hz, bpym C ? ), d 158.0 (s, bpym C ? ), d 159.7 (s, bpym C ? ), d 160.7 (s, bpym C 2/2’ ), d 162.7 (q, -OCOCF 3 , 2 J C-F = 36.3 Hz), d 164.2 (s, bpym C 2/2’ ). 19 F NMR (470.6 MHz, CD 2 Cl 2 ): d -74.6 (s, - OCOCF 3 ). Anal. Calcd for C 11 H 9 F 3 N 4 O 2 Pt (M r = 481.29): C, 27.45; H, 1.88; N 11.64. Found: C, 27.10; H, 2.12; N 11.55. X-ray quality orange needles of Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 were obtained by crystallization from dichloromethane. The crystal structure of this complex is shown on Figure 3.19 (hydrogens and CH 2 Cl 2 molecule have been omitted for clarity). 96 Figure 4.19. ORTEP drawing of Pt(bpym)(CH 3 )(TFA). Pt(bpym)(CH 3 )(Cl)I 2 . 20 mg [Pt(CH 3 )(Cl)(bipym)] (0.0495 mmol) and 13 mg I 2 (0.0495 mmol) were dissolved in 3 ml dichloromethane each and the latter was added slowly to the complex-solution at room temperature. First, the initial suspension of a brown-orange solid dissolved to give a yellowish-orangebrown solution, then an orange precipitate was formed. NMR: Mixture of products. 1 H NMR of in situ reaction with I 2 (500.1 MHz, CD 2 Cl 2 ): d 3.26 (s+d, 3 H, 2 J Pt-H = 72.5 Hz, -CH 3 ), d 7.95 (dd, 1 H, bpym H 5/5’ ), d 7.98 (dd, 1 H, bpym H 5/5’ ), d 9.16 (dd+dd, 1 H, 3 J Pt-H = 33.0 Hz, bpym H 4/4’ ), d 9.28 (dd, 1 H, bpym H x ), d 9.33 (dd, 1 H, bpym H x ) d 9.62 (dd, 1 H, bpym H x ). 13 C NMR (125.8 MHz, CD 2 Cl 2 ): d -15.8 (s, -CH 3 ), d 125.5 (s, bpym C x ), d 125.7 (s, bpym C x ), d 155.6 (s, bpym C x ), d 156.7 (s, bpym C x ), d 161.9 (s, bpym C x ), d 162.0 (s, bpym C x ) Pt(bpym)(CH 3 )(TFA)I 2 . To a solution of 32 mg (0.125 mmol) of I 2 in 4 mL CH 2 Cl 2 , 30 mg (0.062 mmol) of solid 4 was added. After stirring for 20 min at room temperature, a brown-red solution was obtained. This solution was evaporated to minimal volume and the product was precipitated with 15 mL of pentane. Precipitate was filtered off, washed with pentane to remove excess iodine and dried in vacuo, resulting in a brown solid. Yield: 75%. 1 H NMR (500.1 MHz, CD 2 Cl 2 ): d 3.57 (s+d, 3 H, 2 J Pt-H = 72.5 Hz, -CH 3 ), d 7.88 (dd, 1 H, bpym H 5/5’ ), d 7.96 (dd, 1 H, bpym H 5/5’ ), d 9.04 (dd+dd, 1 H, 3 J Pt-H = 41.3 Hz, bpym H 4/4’ ), d 97 9.22 (dd, 1 H, bpym H x ), d 9.30 (dd, 1 H, bpym H x ) d 9.60 (dd, 1 H, bpym H x ). 13 C NMR (125.8 MHz, CD 2 Cl 2 ): d -0.2 (s+d, 1 J Pt-C = 463.0 Hz, -CH 3 ), d 112.5 (q, - OCOCF 3 , 1 J C-F = 289.8 Hz), d 125.2 (s+d, 3 J Pt-C = 32.0 Hz, bpym), d 125.4 (s, bpym), d 157.7 (s, bpym), d 157.9 (s, bpym), d 160.0 (s, bpym), d 161.6 (s, bpym), d 161.9 (s, bpym), d 162.0 (s+d, 2 J Pt-C = 58.0 Hz, bpym), d 162.4 (q, -OCOCF 3 , 2 J C-F = 38.3 Hz). 19 F NMR (470.6 MHz, CD 2 Cl 2 ): d -74.6 (s, -OCOCF 3 ). Anal. Calcd for C 11 H 9 F 3 I 2 N 4 O 2 Pt (M r = 735.10): C, 17.97; H, 1.23; N, 7.62. Found: C, 17.73; H, 1.21; N, 7.33. Pt(bpym)(CH 3 )(TFA)Cl 2 . 50 mg (0.131 mmol) of 4 was dissolved in 20 mL CH 2 Cl 2 at -78 °C, and excess Cl 2 gas was added to the reaction flask. On stirring reaction mixture changed color from orange-red to pale yellow, at which point stirring was stopped and excess chlorine and solvent were removed in vacuo (10 mTorr) while still maintaining the reaction mixture at low temperature. Light- yellow solid was obtained, which was only stable at temperatures below -30 °C, and above this temperature quickly decomposing unless excess Cl 2 is present. Yield: 95%. 1 H NMR (500.1 MHz, CD 2 Cl 2 ): d 3.05 (s+d, 3 H, 2 J Pt-H = 68.2 Hz, - CH 3 ), d 7.84 (dd, 1 H, bpym H x ), d 7.92 (dd, 1 H, bpym H x ), d 8.87 (dd+dd, 1 H, 2 J Pt-H = 35.7 Hz, bpym H 4 ), d 9.20 (dd, 1 H, bpym H x ), d 9.28 (dd, 1 H, bpym H x ), d 9.56 (dd, 1 H, bpym H x ); coordinated CH 2 Cl 2 molecule observed in DMSO - 1 H NMR (DMSO-d 6 ): d 3.05 (s+d, 3 H, 2 J Pt-H = 60.5 Hz, -CH 3 ), d 5.76 (s, 1 H, ½ CH 2 Cl 2 ), d 8.18 (dd, 1 H, bpym H x ), d 8.33 (dd, 1 H, bpym H x ), d 9.32 (dd, 1 H, 98 bpym H x ), d 9.44 (dd+dd, 2 H, bpym H x + bpym H x ), d 9.55 (dd, 1 H, bpym H x ); 13 C NMR (125.8 MHz, CD 2 Cl 2 ): d 15.5 (s+d, 2 J Pt-C = 465.7 Hz, -CH 3 ), d 113.8 (q, -OCOCF 3 , 1 J C-F = 290.7 Hz), d 125.5 (s+d, 3 J Pt-C = 27.6 Hz, bpym C 4/4’ ), d 125.9 (s, bpym C ? ), d 155.1 (q, -OCOCF 3 , 2 J C-F = 41.3 Hz), d 156.9 (s, bpym C ? ), d 157.5 (s, bpym C ? ), d 158.6 (s, bpym C 2/2’ ), d 161.7 (s, bpym C ? ), d 161.9 (s, bpym C 2/2’ ), d 162.6 (s, bpym C ? ). 19 F NMR (470.6 MHz, CD 2 Cl 2 , C 6 F 6 ref.): d -77.0 (s, - OCOCF 3 ). Elemental analysis and nmr spectra consistent with the formula Pt(bpym)(CH 3 )(TFA)Cl 2 ⋅0.5CH 2 Cl 2. Anal. Calcd for C 11.5 H 10 Cl 3 F 3 N 4 O 2 Pt (M r = 594.67): C, 23.23; H, 1.69; N, 9.42. Found: C, 23.18; H, 1.68; N, 9.22. DOSO 2 F/SbF 5 (deuterated magic acid). A mixture of 98%-d-D 2 SO 4 and triple distilled HOSO 2 F was distilled at 165 °C to give d-enriched fluorosulfuric acid. Triple distillation of 1:1 mixtures leads to 86 % deuterium incorporation (as estimated by GCMS analysis of CH 4 /CH 3 D mixtures obtained from the reaction of CH 3 Li with HOSO 2 F/DOSO 2 F (for known d-98% D 2 SO 4 a value of d-97% was found by GCMS). Then a 1:1 mixture of DOSO 2 F/SbF 5 was prepared. Deuteration grade found: 71% (probably due to hydrolysis of SbF 5 ). Table 3.3. Crystal data and structure refinement for Pt(bpym)Cl 4 ⋅0.5DMF. Identification code ptcl4m Empirical formula C9.50 H9 Cl4 N4.50 O Pt Formula weight 539.10 Temperature 133(2) K 99 Wavelength 0.71073 Å Crystal system Orthorhombic Space group Pbcn Unit cell dimensions a = 17.908(5) Å α= 90°. b = 13.152(3) Å β= 90°. c = 12.165(3) Å γ = 90°. Volume 2865.3(12) Å 3 Z 8 Density (calculated) 2.499 Mg/m 3 Absorption coefficient 10.539 mm -1 F(000) 2012 Crystal size 0.15 x 0.15 x 0.02 mm 3 Theta range for data collection 1.92 to 27.48°. Index ranges -22<=h<=23, -16<=k<=17, -11<=l<=15 Reflections collected 16230 Independent reflections 3258 [R(int) = 0.0668] Completeness to theta = 27.48° 99.1 % Transmission factors min/max ratio: 0.481 Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 3258 / 0 / 178 Goodness-of-fit on F 2 1.037 Final R indices [I>2sigma(I)] R1 = 0.0444, wR2 = 0.1051 R indices (all data) R1 = 0.0715, wR2 = 0.1138 Largest diff. peak and hole 1.836 and -1.378 e.Å -3 Table 3.4. Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)Cl 4 ⋅0.5DMF. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. _______________________________________________________________________________ x y z U(eq) _______________________________________________________________________________ Pt(1) 1866(1) 1527(1) 1483(1) 25(1) 100 Cl(1) 3017(1) 2109(2) 2067(2) 41(1) Cl(2) 672(1) 990(2) 1012(2) 42(1) Cl(3) 2294(1) 1289(2) -279(2) 34(1) Cl(4) 2215(1) -105(2) 1906(2) 36(1) C(1) 1489(6) 3490(6) 262(7) 38(2) C(2) 1147(5) 4445(7) 237(9) 44(3) C(3) 849(6) 4820(7) 1186(9) 45(3) C(4) 1159(5) 3400(6) 2096(7) 30(2) C(5) 1151(5) 2763(6) 3118(7) 29(2) C(6) 841(5) 2504(7) 4869(9) 45(3) C(7) 1183(6) 1549(7) 4854(8) 41(2) C(8) 1489(5) 1239(6) 3897(7) 30(2) C(9) 513(7) 1264(11) 8148(11) 77(4) N(5) 0 1809(11) 7500 56(3) C(10) 0 2890(20) 7500 94(7) O(1) 343(13) 3336(17) 8189(18) 220(10) N(1) 1482(4) 2977(5) 1227(5) 23(2) N(2) 848(4) 4318(5) 2130(6) 36(2) N(3) 1477(4) 1852(5) 3007(6) 27(2) N(4) 823(4) 3118(6) 4008(6) 33(2) _______________________________________________________________________________ Table 3.5. Bond lengths [Å] and angles [°] for Pt(bpym)Cl 4 ⋅0.5DMF. _____________________________________________________ Pt(1)-N(3) 2.026(7) Pt(1)-N(1) 2.052(6) Pt(1)-Cl(4) 2.293(2) Pt(1)-Cl(3) 2.298(2) Pt(1)-Cl(1) 2.309(2) Pt(1)-Cl(2) 2.324(3) C(1)-N(1) 1.353(10) C(1)-C(2) 1.398(12) C(2)-C(3) 1.364(14) 101 C(3)-N(2) 1.325(12) C(4)-N(1) 1.327(11) C(4)-N(2) 1.330(10) C(4)-C(5) 1.499(12) C(5)-N(4) 1.318(11) C(5)-N(3) 1.340(10) C(6)-N(4) 1.322(12) C(6)-C(7) 1.398(13) C(7)-C(8) 1.349(13) C(8)-N(3) 1.350(11) C(9)-N(5) 1.408(14) N(5)-C(9)#1 1.408(14) N(5)-C(10) 1.42(3) C(10)-O(1) 1.19(2) C(10)-O(1)#1 1.19(2) N(3)-Pt(1)-N(1) 80.1(3) N(3)-Pt(1)-Cl(4) 94.9(2) N(1)-Pt(1)-Cl(4) 174.50(19) N(3)-Pt(1)-Cl(3) 175.6(2) N(1)-Pt(1)-Cl(3) 95.55(18) Cl(4)-Pt(1)-Cl(3) 89.47(8) N(3)-Pt(1)-Cl(1) 87.4(2) N(1)-Pt(1)-Cl(1) 92.2(2) Cl(4)-Pt(1)-Cl(1) 89.90(9) Cl(3)-Pt(1)-Cl(1) 91.99(8) N(3)-Pt(1)-Cl(2) 88.5(2) N(1)-Pt(1)-Cl(2) 86.3(2) Cl(4)-Pt(1)-Cl(2) 91.25(9) Cl(3)-Pt(1)-Cl(2) 92.04(9) Cl(1)-Pt(1)-Cl(2) 175.82(9) N(1)-C(1)-C(2) 117.5(9) C(3)-C(2)-C(1) 118.6(9) 102 N(2)-C(3)-C(2) 123.6(8) N(1)-C(4)-N(2) 126.0(8) N(1)-C(4)-C(5) 115.5(7) N(2)-C(4)-C(5) 118.5(8) N(4)-C(5)-N(3) 126.4(8) N(4)-C(5)-C(4) 119.3(8) N(3)-C(5)-C(4) 114.4(7) N(4)-C(6)-C(7) 123.3(9) C(8)-C(7)-C(6) 117.4(9) C(7)-C(8)-N(3) 120.4(8) C(9)#1-N(5)-C(9) 118.7(17) C(9)#1-N(5)-C(10) 120.6(9) C(9)-N(5)-C(10) 120.6(9) O(1)-C(10)-O(1)#1 121(3) O(1)-C(10)-N(5) 119.3(17) O(1)#1-C(10)-N(5) 119.3(17) C(4)-N(1)-C(1) 119.1(7) C(4)-N(1)-Pt(1) 114.5(5) C(1)-N(1)-Pt(1) 126.3(6) C(3)-N(2)-C(4) 115.2(8) C(5)-N(3)-C(8) 117.4(7) C(5)-N(3)-Pt(1) 115.5(6) C(8)-N(3)-Pt(1) 127.1(6) C(5)-N(4)-C(6) 115.1(8) _____________________________________________________________ Symmetry transformations used to generate equivalent atoms: #1 -x,y,-z+3/2 Table 3.6. Anisotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)Cl 4 ⋅0.5DMF. The anisotropic displacement factor exponent takes the form: -2π 2 [ h 2 a* 2 U 11 + ... + 2 h k a* b* U 12 ] ______________________________________________________________________________ U 11 U 22 U 33 U 23 U 13 U 12 103 ______________________________________________________________________________ Pt(1) 33(1) 16(1) 28(1) -1(1) 0(1) 1(1) Cl(1) 45(2) 36(1) 41(1) -3(1) 2(1) -5(1) Cl(2) 43(1) 34(1) 49(1) -3(1) -3(1) -2(1) Cl(3) 44(1) 27(1) 32(1) -5(1) 3(1) -1(1) Cl(4) 48(1) 17(1) 44(1) 0(1) 1(1) 9(1) C(1) 58(6) 26(5) 29(5) 10(4) -1(4) -8(4) C(2) 38(6) 31(5) 64(7) 19(5) -2(5) -7(4) C(3) 56(7) 17(4) 62(7) 5(4) -4(5) 6(4) C(4) 29(5) 21(4) 39(5) -1(4) -3(4) -2(4) C(5) 27(5) 22(4) 40(5) -4(4) -1(4) -9(4) C(6) 47(6) 41(6) 48(6) -13(5) 5(5) -6(5) C(7) 56(7) 40(5) 26(5) 3(4) -5(4) -11(5) C(8) 44(6) 18(4) 29(5) -2(3) -8(4) 1(4) C(9) 75(10) 89(11) 66(9) 0(7) 18(7) 9(8) N(5) 55(9) 66(9) 46(8) 0 7(7) 0 C(10) 120(20) 109(19) 57(13) 0 52(13) 0 N(1) 34(4) 10(3) 26(4) 4(3) -3(3) 2(3) N(2) 39(5) 17(4) 53(5) 5(3) 6(4) 7(3) N(3) 29(4) 16(3) 36(4) -8(3) 2(3) -2(3) N(4) 34(5) 31(4) 33(4) -6(4) 3(3) 1(3) ______________________________________________________________________________ 104 Table 3.7. Hydrogen coordinates ( x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)Cl 4 ⋅0.5DMF. _______________________________________________________________________________ x y z U(eq) _______________________________________________________________________________ H(1) 1718 3211 -374 45 H(2) 1122 4824 -426 53 H(3) 630 5478 1169 54 H(6) 610 2724 5530 54 H(7) 1199 1134 5493 49 H(8) 1713 586 3850 36 H(9A) 814 1741 8581 115 H(9B) 841 863 7671 115 H(9C) 242 808 8645 115 Table 3.8. Crystal data and structure refinement for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . Identification code bpmptmem Empirical formula C12 H11 Cl2 F3 N4 O2 Pt Formula weight 566.24 Temperature 143(2) K Wavelength 0.71073 Å Crystal system Monoclinic Space group P2(1)/c Unit cell dimensions a = 8.9805(13) Å α= 90°. b = 23.393(3) Å β= 96.713(2)°. c = 7.7775(11) Å γ = 90°. Volume 1622.7(4) Å 3 105 Z 4 Density (calculated) 2.318 Mg/m 3 Absorption coefficient 9.022 mm -1 F(000) 1064 Crystal size 0.14 x 0.13 x 0.01 mm 3 Theta range for data collection 2.28 to 27.48°. Index ranges -11<=h<=11, -29<=k<=15, -9<=l<=10 Reflections collected 9838 Independent reflections 3619 [R(int) = 0.0444] Completeness to theta = 27.48° 97.2 % Transmission factors min/max ratio: 0.584 Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 3619 / 0 / 208 Goodness-of-fit on F 2 1.027 Final R indices [I>2sigma(I)] R1 = 0.0401, wR2 = 0.0947 R indices (all data) R1 = 0.0547, wR2 = 0.1005 Largest diff. peak and hole 2.030 and -1.260 e.Å -3 Table 3.9. Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. _______________________________________________________________________________ x y z U(eq) _______________________________________________________________________________ Pt(1) 3932(1) 7887(1) 6790(1) 25(1) Cl(1) 8403(3) 9544(1) 8323(3) 54(1) Cl(2) 10063(3) 8980(1) 11292(3) 49(1) F(1) 3919(11) 9891(5) 6197(13) 133(3) F(2) 1564(9) 9946(4) 5767(10) 96(2) F(3) 2613(9) 9745(3) 8215(8) 85(2) O(1) 3624(6) 8737(2) 7066(6) 33(1) O(2) 1687(8) 8845(3) 4987(8) 56(2) N(1) 5959(7) 7996(2) 5769(8) 24(1) 106 N(2) 7835(7) 7452(3) 4592(8) 31(2) N(3) 4482(7) 7069(3) 6490(7) 27(1) N(4) 6252(7) 6473(3) 5306(8) 29(1) C(1) 6718(9) 8480(3) 5512(10) 31(2) C(2) 8041(8) 8472(4) 4803(10) 33(2) C(3) 8566(9) 7936(4) 4348(10) 36(2) C(4) 6584(8) 7500(3) 5314(9) 25(2) C(5) 5722(8) 6979(3) 5704(9) 27(2) C(6) 5468(9) 6022(4) 5744(10) 37(2) C(7) 4204(9) 6068(4) 6552(10) 37(2) C(8) 3729(9) 6609(4) 6922(9) 32(2) C(9) 1963(9) 7722(4) 7705(10) 32(2) C(10) 2617(9) 9012(3) 6113(10) 33(2) C(11) 2687(10) 9645(4) 6567(13) 47(2) C(12) 9371(10) 8929(3) 9079(10) 38(2) _______________________________________________________________________________ Table 3.10 Bond lengths [Å] and angles [°] for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . _____________________________________________________ Pt(1)-N(3) 1.996(6) Pt(1)-C(9) 2.019(7) Pt(1)-O(1) 2.022(5) Pt(1)-N(1) 2.085(6) Cl(1)-C(12) 1.748(9) Cl(2)-C(12) 1.764(8) F(1)-C(11) 1.309(12) F(2)-C(11) 1.325(11) F(3)-C(11) 1.312(11) O(1)-C(10) 1.274(9) O(2)-C(10) 1.203(10) N(1)-C(1) 1.348(9) N(1)-C(4) 1.354(9) 107 N(2)-C(4) 1.319(9) N(2)-C(3) 1.333(10) N(3)-C(8) 1.334(10) N(3)-C(5) 1.348(10) N(4)-C(5) 1.326(9) N(4)-C(6) 1.335(10) C(1)-C(2) 1.367(10) C(2)-C(3) 1.400(11) C(4)-C(5) 1.493(10) C(6)-C(7) 1.365(11) C(7)-C(8) 1.378(12) C(10)-C(11) 1.522(12) N(3)-Pt(1)-C(9) 95.5(3) N(3)-Pt(1)-O(1) 173.4(2) C(9)-Pt(1)-O(1) 90.8(3) N(3)-Pt(1)-N(1) 80.4(2) C(9)-Pt(1)-N(1) 175.7(3) O(1)-Pt(1)-N(1) 93.3(2) C(10)-O(1)-Pt(1) 122.1(5) C(1)-N(1)-C(4) 116.7(6) C(1)-N(1)-Pt(1) 129.6(5) C(4)-N(1)-Pt(1) 113.7(5) C(4)-N(2)-C(3) 116.6(7) C(8)-N(3)-C(5) 117.3(7) C(8)-N(3)-Pt(1) 127.1(6) C(5)-N(3)-Pt(1) 115.5(5) C(5)-N(4)-C(6) 115.6(7) N(1)-C(1)-C(2) 121.8(7) C(1)-C(2)-C(3) 116.7(7) N(2)-C(3)-C(2) 122.6(7) N(2)-C(4)-N(1) 125.7(7) N(2)-C(4)-C(5) 120.3(7) 108 N(1)-C(4)-C(5) 113.9(7) N(4)-C(5)-N(3) 125.7(7) N(4)-C(5)-C(4) 118.1(7) N(3)-C(5)-C(4) 116.1(7) N(4)-C(6)-C(7) 123.2(8) C(6)-C(7)-C(8) 117.6(8) N(3)-C(8)-C(7) 120.7(7) O(2)-C(10)-O(1) 130.2(8) O(2)-C(10)-C(11) 119.4(8) O(1)-C(10)-C(11) 110.4(7) F(1)-C(11)-F(3) 106.1(9) F(1)-C(11)-F(2) 106.2(9) F(3)-C(11)-F(2) 104.0(8) F(1)-C(11)-C(10) 113.0(9) F(3)-C(11)-C(10) 113.3(8) F(2)-C(11)-C(10) 113.6(9) Cl(1)-C(12)-Cl(2) 112.1(5) _____________________________________________________________ Symmetry transformations used to generate equivalent atoms: Table 3.11. Anisotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . The anisotropic displacement factor exponent takes the form: -2π 2 [ h 2 a* 2 U 11 + ... + 2 h k a* b* U 12 ] ______________________________________________________________________________ U 11 U 22 U 33 U 23 U 13 U 12 ______________________________________________________________________________ Pt(1) 25(1) 26(1) 23(1) -2(1) 2(1) 3(1) Cl(1) 76(2) 36(1) 48(1) 7(1) 0(1) -2(1) Cl(2) 44(1) 49(1) 52(1) 6(1) -2(1) -5(1) F(3) 156(7) 46(4) 51(4) -18(3) 4(4) 12(4) 109 O(1) 35(3) 31(3) 33(3) -7(2) 0(2) 6(2) O(2) 66(4) 43(4) 51(4) -6(3) -19(3) 15(3) N(1) 25(3) 21(3) 26(3) 1(2) 0(2) 2(2) N(2) 30(3) 40(4) 23(3) -2(3) 4(3) 4(3) N(3) 30(3) 30(4) 21(3) 6(3) 1(2) 0(3) N(4) 30(3) 23(3) 35(3) 2(3) 4(3) 6(3) C(1) 33(4) 27(4) 34(4) -7(3) 1(3) 3(3) C(2) 28(4) 38(5) 33(4) -4(4) 3(3) -10(4) C(3) 29(4) 46(5) 32(4) -1(4) 2(3) -2(4) C(4) 26(4) 26(4) 21(3) 4(3) 0(3) 3(3) C(5) 31(4) 28(4) 21(3) -2(3) -2(3) -4(3) C(6) 42(5) 33(5) 35(4) 3(4) 1(4) -1(4) C(7) 43(5) 30(5) 38(4) 1(4) 3(4) -8(4) C(8) 36(4) 33(5) 24(4) 3(3) 2(3) 0(4) C(9) 32(4) 35(4) 32(4) 11(3) 13(3) 2(3) C(10) 37(4) 30(4) 34(4) 3(3) 10(4) 5(4) C(11) 38(5) 41(5) 65(6) 5(5) 16(4) 8(4) C(12) 52(5) 31(5) 35(4) -1(4) 16(4) -8(4) ______________________________________________________________________________ Table 3.12. Hydrogen coordinates ( x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for Pt(bpym)(CH 3 )(TFA)⋅CH 2 Cl 2 . _______________________________________________________________________________ x y z U(eq) _______________________________________________________________________________ H(1) 6322 8836 5831 38 H(2) 8578 8813 4628 40 H(3) 9479 7916 3845 43 H(6) 5806 5651 5479 44 H(7) 3671 5738 6850 45 H(8) 2856 6656 7490 38 110 H(9A) 1258 7557 6780 49 H(9B) 1547 8078 8112 49 H(9C) 2127 7450 8669 49 H(12A) 10219 8864 8396 46 H(12B) 8691 8595 8905 46 111 3.6 Chapter Three References 1 Shilov, A.E.; Shul’pin, G.B. Activation and catalytic reactions of saturated hydrocarbons in the presence of metal complexes Kluwer Academic Publishers: New York/Boston/Dordrecht/London/Moscow, 2002. 2 a) Süss-Fink, G.; Stanislas, S.; Shul’pin, G.B.; Nizova, G.V. Appl. Organomet. Chem. 2000, 14, 623; b) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633; c) Labinger, J.A.; Bercaw, J.E. 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Rev. 2005, 105, 2471; and references cited therein. 16 Goldshleger, N.F.; Moiseev, I.I.; Khidekel, M.L.; Shteinman, A.A. Dokl. Akad. Nauk SSSR 1972, 206, 106. 17 For example, see the following: a) Morton, M.S.; Lachicotte, R.J.; Vicic, D.A.; Jones, W.D. Organometallics 1999, 18, 227; b) Albrecht, M.; Rodriguez, G.; Schoenmaker, J.; van Koten, G. Org. Lett. 2000, 2, 3461. 18 Puddephatt, R. J. Coord. Chem. Rev. 2001, 219-221, 157. 19 Stahl, S.S.; Labinger, J.A.; Bercaw, J.E. J. Am. Chem. Soc. 1996, 118, 5961. 20 a) Sommer, J.; Goeppert, A. Carbocation Chemistry Eds.: Olah, G.A.; Prakash, G.K.S. John Wiley & Sons, Inc.: Hoboken, NJ, 2004, 309; b) Walspurger, S.; Goeppert, A.; Haouas, M.; Sommer, J. New J. Chem. 2004, 28, 266. 21 Luinstra, G.A.; Wang, L.; Stahl, S.S.; Labinger, J.A.; Bercaw, J.E. J. Organomet. Chem. 1995, 504, 75. 22 a) Labinger J.A.; Herring A.M.; Lyon D.K.; Luinstra G.A.; Bercaw J.E. Organometallics 1993, 12, 895; b) DeVries N.; Roe D.C.; Thorn D.L. J. Mol. Cat. 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Organometallics 1986, 5, 1538. 115 4 Chapter Four: C 6 H 6 Activation in Weakly Acidic Media via 6-Membered Cyclic Transition State 4.1 Introduction Organometallic coordination catalysts based on the C-H activation reaction currently show the greatest potential for the development of new, selective, hydrocarbon hydroxylation chemistry. 1 Figure 4.1. Hydrocarbone reactivity through CH activation mechanism. Previously we reported on a platinum catalyst, Pt(bpym)Cl 2 (bpym=η 2 -{2,2'- bipyrimidyl}), that converts methane to methanol in concentrated sulfuric acid with a 70% one-pass yield. 2g The practically of this system is limited as the average catalyst rate, TOF ~ 10 -3 s -1 , is below the commercially viable target of ~ 1 M-(Hydrocarbon) + X - Hydrocarbon + M-X M-R + HX Multiple Opportunity for Functionalization . 116 s -1 . This is due to severe inhibition of the CH activation step (which is the rate determining step for oxidation in the presence of 1M water or methanol) by the reaction products, resulting in a maximum methanol concentration to ~1M rather than the ~5M required for efficient separation. Figure 4.2. Water/methanol inhibition as result of sulfuric acid dilution during reaction course. The development of highly active catalyst for CH activation in less acidic media is crucial. To achieve improved reactivity two approaches can be applied: a) stabilization of transition state; b) destabilization of ground state. In chaper 3 the mechanism investigation of the Pt(bpym)Cl 2 /H 2 SO 4 system was presented. Based on our understanding of the mechanism of the M-X M-(Hydrocarbon) Hydrocarbon Coordination TS C-H Bond Cleavage TS M-R Resting State in 100% H 2 SO 4 Inhibition by water Dilute H 2 SO 4 Resting State due to water binding 117 Pt(bpym)Cl 2 /H 2 SO 4 system, 1h,2 we identified two key steps that contribute to the overall CH activation barrier of ~32 kcal/mol: A) ~27 kcal/mol for coordination of the hydrocarbon (RH) and B) ~5 kcal/mol for cleavage of the coordinated CH bond. Figure 4.3. Two approaches to reactivity: resting state destabilization or transition state stabilization. In designing improved catalysts it is important that both steps be explicitly considered to ensure that catalyst modifications that decrease the energy requirements for one step does not proportionately increase the other. This should be possible since the bonding in the ground state and cleavage transition state should be different. 1h M-X M-(Hydrocarbon) Hydrocarbon Coordination TS C-H Bond Cleavage TS M-R Ground State Destabilization Transition State Stabilization 118 4.2 Results and Discussion. I now report new recipie for efficient H/D exchange in weak acid media. U sing an interplay between computational and experimental methods new highly effient transition state geometry was identified. The resulting reactivity is believe to came entirely from an efficient 6-membered cyclic transition state that reduce rate determining C-H cleavage barrier without a corresponding increase in the energetics for hydrocarbon coordination. Figure 4.4. CH activation by internal electrophilic substitution through 6- membered cyclic transition state versus external electrophilic substitution. We postulated that the neutral bipyrimidine in Pt(bpym)(X) 2 with use of bi- dentate TFA ligands in lieu of Cl is competent in benzene/triflouroacetic acid H/D exchange reaction. Furthermore, calculations predicted that ligands could facilitate M- X M-(Hydrocarbon) Hydrocarbon Coordination TS C-H Bond Cleavage TS M- R Resting State External Electrophilic Substitution Internal Electrophilic Substitution through 6-membered cyclic TS 119 CH cleavage via a 6-membered cyclic transitions state that is not proportionately higher in energy relative to that for the Pt(bpym)(X) 2 system. It is necessary to underline that Pt(bpym) catalyze CH activation by new mechanism in weak acidic media compare to concentrated sulfuric acid conditions. One of the reasons for such changes is an appropriate geometry due to C-O bonds versus S-O bonds. N N N N Pt C O H O CF 3 N N N N Pt C H O CF 3 O O O CF 3 Figure 4.5. 6-Membered cyclic and less favorable electrophilic substitution transition states. Similar 6-membered, cyclic transition states have previously and independently from our research been postulated by Ryabov 3 based on unusual thermodynamics properties of reaction yet in 1985 and was supported by DFT in a recent, 2006, computational study for cyclometalation of dimethylbenzylamine. 4 In present study, the bipyrimidine ligand was chosen because it shows high acid and thermo stability as well as high affinity to Platinum in sulfuric acid at 220 o C. In hot sulfuric acid, it is competent in dissolving Platinum black. At the same time 120 bipyrimidine Platinum complex in sulfuric acid facilitate the C-H activation reaction as well as selective functionalization of the M-R intermediate. 5 Except for the scienfitic reasons, there was a practical one as well. The synthesis can be a critical point in research of organic chemist. We have built significant amount of knowledge and expertise in reactivity of bipyrimidine toward different platinum complexes. It was logical and appropriate to use that expertise for fast progress in research. Active catalyst, Figure 4.6, were prepared by treatment of the known Pt(bpym)(Ph) 2 with 2 equivalent of HTFA in dichloromethane, and has been characterized by 1 H and 13 C NMR, high-resolution electrospray ionization mass spectrometry, and elemental analysis. N N N N Pt O O CF 3 O CF 3 O N N N N Pt CH 2 Cl 2 + + 2 HTFA 2 C 6 H 6 Figure 4.6. Preparation of active catalyst, (bpym)Pt(TFA) 2 . In-situ NMR studies of active catalyst in TFA also showed that 1 was thermally stable in CF 3 CO 2 H at 150 o C for weeks in air. Upon heating a mixture of benzene (0.1 ml) and CF 3 CO 2 D (1 ml) containing 4 mM of 1 to 70 o C, catalytic incorporation of deuterium into benzene was observed. Analysis by GC/MS shows 4.6 after 20h, TOF ~ 6.4 x 10 -5 s -1 . Based on the temperature dependence a ?G ‡ of 121 ~27 kcal/mol was estimated. Control experiments without catalyst did not lead to any observable H/D exchange (< 0.5%, usual GCMS accuracy) under the same reaction conditions. Deuterium Insersion Study during HD Exchange Reaction between Benzene and TFA-d1 by (bpym)Pt(TFA)2/AgOAc 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00 90.00 100.00 0 5 10 15 20 25 30 35 Time (hours) % Figure 4.7. Study of isotopologes appearance in H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by (bpym)Pt(TFA) 2 /AgOAc at 150 o C. Black – C 6 H 6 ; Dark blue – C 6 H 5 D; Blue – C 6 H 4 D 2 ; Light blue – C 6 H 3 D 3 ; Green -– C 6 H 2 D 4 ; Orange – C 6 HD 5 ; Red – C 6 D 6 . Study of isotopologes appearance during H/D exchange reaction suggests that the hydrocarbon coordination is not the rate-determining step (RDS). Instead C-H cleavage is one. By establishing RDS It would be possible to connect our 122 experimental results to our theoretical estimates and to observe the proximity of theory to experiment. This area of science is still on the innovative stage. Figure 4.8. Thermodynamics of Calculated Mechanism for the Benzene C -H Activation by Pt(bpym). The theoretical calculations of CH activation with these systems (Figure 4.8) are consistent with the experimental results. According to our calculations, 1 activates benzene C -H bonds with a ?H ‡ ~27 kcal/mol calculated for Pt(bpym)TFA 2 and comparable to the experimental activation barrier of ? G ‡ ~27 kcal/mol obtained. H/D exchange proceed without catalyst with barrier of ?H ‡ ~38 kcal/mole, which cannot be observed experimentally due to insaficient reactivity. However, insaficient background reactivity was observed. 0 10 20 30 0.0 14.1 27 21 Arene coordination CH Cleavage Pt TFA N TFA N Pt C 6 H 6 N N TFA Pt Ph N N HTFA 0 10 20 30 0.0 14.1 27 21 Arene coordination CH Cleavage Pt TFA N TFA N Pt C 6 H 6 N N TFA Pt Ph N N HTFA 123 As can be seen in Figure 4.7, the calculated resting state of the Pt(bpym) system is a bis-TFA – complex with an overall neutral charge, Pt(bpym)TFA 2 . Loss of TFA – generates a cationic species that coordinates benzene with ?H of ~14 kcal/mol. The ?H ‡ for the subsequent CH cleavage step, leading to the phenyl complex, is ~13 kcal/mol. Ligand exchange between Pt-HTFA and solvent DTFA is expected to be facile, as the three coordinate phenyl species is only uphill by 18.2 kcal/mol (not shown). While a five-coordinate ligand exchange, associative transition state cannot be ruled out, the 18.2 kcal/mol can be considered an upper bound. Figure 4.9. C-H cleavage transition state TS1. The C-H cleavage occurs through a six-membered transition state, TS1, Figure 5.5, where the covalent Pt-O and C-H bonds are broken while the Pt-C and O -H 124 bonds are created. Both C-O bonds are 3/2 bond order, with the p-bond transforming into a s -bond. The reaction is best described as an electrophilic substitution proceeding via addition of the Pt center to the arene ring (as opposed to a sigma-bond metathesis involving only the sigma-framework). Similar transition states have been implicated in other theoretical works, 4,6 but this is to the best of our knowledge the first time this kind of solvent participation has been included by design for CH activation. 4.3 Conclusion In summary, I have demonstrated that a strong interaction between experimental and theoretical research can lead to deeper understanding as well as fast practical progress. Enhanced C-H activation reactivity was observed experimentally for a bipyrimidine platinum system. A novel, facile transition state for C-H cleavage has been identified theoretically. Specifically, I demonstrated a well-defined, late metal, N,N-ligated complex, which is competent for arene C-H activation, exhibits thermal and protic stability and is an efficient catalyst for H/D exchange. Results suggest that rate of hydrocarbone activation can be improved based on transition state stabilization as well as ground state destabilization effects. 125 4.4 Experimental Section General consideration: Unless otherwise noted, all reactions and manipulations were performed in a M -Braun circulating Argon atmosphere glovebox or using standard Schlenk techniques. Glassware was dried in an oven at 150 °C before use. Unless otherwise noted, reagents were purchased from commercial suppliers and used without further purification. Neutral alumina was used in chromatography unless otherwise noted. Diethyl ether, THF and benzene were distilled from sodium/benzophenone ketyl under Argon prior to use. Hexanes and pentane were dried with P 2 O 5 under Argon and kept refluxing under flow of Argon. CH 2 Cl 2 was purified from stabilizer by stirring with concentrated H 2 SO 4 for 4 hours, mixture was separated, organic phase was neutralized with KHCO 3 , dried with MgSO 4 and P 2 O 5 , and refluxed under flow of Argon for 3 days. Organic acids were distilled from P 2 O 5 . Deuterated solvents were degassed by freezing, evacuating, and thawing (3x), and were then dried over 4 Å sieves and stored under Argon. Unless otherwise indicated, NMR spectra were obtained using a Variant Mercury-400 MHz spectrometer (400 MHz for 1 H spectra, 100.6 MHz for 13 C{ 1 H} spectra, 376.5 MHz for 19 F spectra). Chemical shifts are reported in parts per millio relative to residual protiated solvent, coupling constants are reported in Hertz (Hz), and integrations are reported in number of protons. Unless otherwise noted, samples for NMR analysis were prepared using CDCl 3 as the solvent. 126 Kinetic studies were performed using a Shimadzu-QP5000 GCMS or by NMR spectroscopy using a Variant Mercury-400 spectrometer (see above). All reaction mixtures were prepared under Argon and kept under static Ag during the kinetic analyses. For GCMS experiments, ethane standard was introduced. The compounds [(Et 2 S)Pt(Ph) 2 ] 2 7 were prepared using literature procedures. N Pt N N N Figure 4.10. (Bpym)Pt(Ph) 2 complex. (Bpym)Pt(Ph) 2 . Method A. In a 100 m L Schlenk flask containing 0.79 g (5.0 mmol, 400% excess) of bipymidine was added 20 mL of CH 2 Cl 2 and vigorously stirred. In another 100 mL Schlenk flask containing 1.76 g (2.0 mmol) of [(Et 2 S)Pt(Ph) 2 ] 2 was added in 80 mL of CH 2 Cl 2 to complete solid dissolving and added drop-wise to the first flask. The solution color changed from slight yellow to deep red during reaction and black solid of bi-adduct to ligand precipitate. The volume was reduced to 50 mL and the solid was precipitated with methanol (200 mL) to leave excess of free ligand in solution. The solid was washed three times 127 with methanol, dried in vacuo over 1 day and a red crystalline solid formed (1.6 g, 80% yield). Method B. In a 100 mL Schlenk flask containing 0.79 g (5.0 mmol, 20% excess) of bipymidine was added 20 mL of CH 2 Cl 2 , cooled to –50 o C and vigorously stirred. In another 100 mL Schlenk flask containing 1.76 g (2.0 mmol) of [(Et 2 S)Pt(Ph) 2 ] 2 was added in 80 mL of CH 2 Cl 2 to complete solid dissolving and added drop-wise to the first flask. The reaction mixture was allowed to warm up till room temperature for 5 hours. The solution color changed from slight yellow to deep red during reaction at 0 o C. The volume was reduced to 30 mL and the solid was precipitated with methanol (100 mL) to leave excess of free ligand in solution. The solid was washed with methanol, dried in vacuo over 1 day and a red crystalline solid formed (1.8 g, 90% yield). 1 H NMR (400 MHz, CDCl 3 , 298 K): 9.20 (dd, 2H, H-6, 3 J = 4.9 Hz, 4 J = 2.2 Hz), 8.79 (dd, 2H, H-4, 3 J = 5.5 Hz, 4 J = 2.3 Hz), 7.50 (t, 2H, H-4, 3 J = 5.3 Hz), 7.38 (dd, 2H, H-orto, 3 J = 8.2 Hz, 4 J = 1.6 Hz, w/Pt satellites 3 J Pt-H = 35 Hz), 7.00 (t, 2H, H-meta, 3 J = 7.4 Hz), 6.87 (tt, 1H, H-para, 3 J = 7.4 Hz, 4 J = 1.4 Hz). HRMS (Electro-spray) Calcd for C 20 H 17 N 4 Pt (M+H): 508.1101. Found: 508.1114. N Pt N O N O CF 3 N 128 Figure 4.11. (Bpym)Pt(Ph)(TFA) complex. (Bpym)Pt(Ph)(TFA). In a 100 mL Schlenk flask containing 202.8 mg (0.40 mmol) of (bpym)Pt(Ph) 2 was added in 50 mL of CH 2 Cl 2 to complete dissolving, and added 32.0 µL (0.41 mmol, slight excess) of trifluoroacetic acid. The solution was allowed to react at room temperature for 2 hours. The volume was reduced to 10 mL and the solid was precipitated with methanol (50 mL) to leave trace of (bpym)Pt(TFA) 2 in solution. The solvent residue was dried in vacuo over 1 day and a red crystalline solid formed (207 mg, 95% yield). 1 H NMR (400 MHz, CD 2 Cl 2 , 298 K): 9.77 (dd, 1H, H-6, 3 J = 5.4 Hz, 4 J = 2.2 Hz), 9.27 (dd, 1H, H-4, 3 J = 4.8 Hz, 4 J = 2.2 Hz), 9.24 (dd, 1H, H-4, 3 J = 4.8 Hz, 4 J = 2.2 Hz), 8.86 (dd, 1H, H-6, 3 J = 5.8 Hz, 4 J = 2.2 Hz, w/Pt satellites 3 J Pt-H = 28.2 Hz), 7.84 (t, 1H, H-5, 3 J = 5.1 Hz), 7.46 (t, 1H, H-4, 3 J = 5.3 Hz), 7.35 (dd, 2H, H-orto, 3 J = 8.0 Hz, 4 J = 1.2 Hz, w/Pt satellites 3 J Pt-H = 17.6 Hz), 7.09 (t, 2H, H-meta, 3 J = 7.4 Hz), 1.39 (tt, 1H, H-para, 3 J = 7.4 Hz, 4 J = 1.2 Hz). 13 C NMR (101 MHz, CDCl 3 , 298 K): 159.9 (s), 157.7 (s), 157.3 (s), 155.3 (s), 137.5 (s), 128.0 (s), 124.9 (s), 124.7 (s), 124.2 (s). 19 F NMR (101 MHz, CD 2 Cl 2 , 298 K, with C 6 F 6 as standard -164.9): -77.6 (s). Anal. Calcd for C 16 H 11 N 4 O 2 PtF 3 : C, 35.37; H, 2.04; N, 10.31; F, 10.49. Found: C, 36.53; H, 1.93; N, 9.84; F, 10.06. 129 N Pt N O N O CF 3 N O O CF 3 Figure 4.12. (Bpym)Pt(TFA) 2 complex. (Bpym)Pt(TFA) 2 . In a 100 mL Schlenk flask containing 108.6 mg (0.20 mmol) of (bpym)Pt(Ph) 2 was completely dissolved in 50 mL of CH 2 Cl 2 to complete dissolving, and added 24.0 µL (0.3 mmol, excess) of trifluoroacetic acid. The solution was allowed to react at room temperature for 2 hours. The solvent was dried in vacuo over 1 day and a yellow crystalline solid formed (115 mg, 100% yield). 1 H NMR (400 MHz, CD 2 Cl 2 , 298 K): 9.32 (dd, 2H, H-6, 3 J = 5.0 Hz, 4 J = 1.9 Hz), 8.89 (dd, 2H, H-4, 3 J = 5.9 Hz, 4 J = 2.0 Hz), 7.84 (t, 2H, H-5, 3 J = 5.4 Hz). 13 C NMR (101 MHz, acetone-d6, 298 K): 163.43 (s, -CO2-), 162.56 (s, pym), 161.57 (s, pym), 157.07 (s, pym), 125.58 (s, pym), 117.24 (s, -CF 3 ). 19 F NMR (101 MHz, CD 2 Cl 2 , 298 K, with C 6 F 6 as standard - -164.9): -75.26 (s, CF 3 ). Anal. Calcd for C 12 H 6 N 4 O 4 PtF 6 : C, 25.07; H, 1.10; N, 9.32; F, 19.34. Found: C, 24.88; H, 1.04; N, 9.67; F, 19.68. MS (Electro-spray) Calcd for C 10 H 6 O 2 N 4 F 3 Pt (M-TFA): 466.0091. Found: 466.0092. 130 Deuterium insertion study. In a 3 mL Schlenk flask containing 1mg (2 µmol) of (bpym)Pt(TFA) 2 , 0.5mg (2 µmol) of silver acetate was added 1mL of TFA-d1 and 0.1 mL of benzene. The mixture was heated at 70 o C and analyzed by GC/MS as above. Table 4.1. Deuterium insertion study by (bpym)Pt in C 6 H 6 /DTFA reaction. isotop\time(h) 0 0.33 0.68 1.01 20 42 60 TOF 0 0 0 0 6.4E-05 6.2E-05 5.6E-05 TON 0.0 0.0 0.0 0.0 4.6 9.4 12.1 D 0 99.6 99.9 99.3 99.6 98.8 97.4 96.8 D 1 0.4 0.1 0.7 0.4 0.8 1.8 2.1 D 2 0.0 0.0 0.0 0.0 0.3 0.5 0.8 D 3 0.0 0.0 0.0 0.0 0.1 0.2 0.3 D 4 0.0 0.0 0.0 0.0 0.0 0.1 0.1 D 5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 D 6 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Deuterium insertion study. In a 3 mL Schlenk flask containing 1mL of TFA-d 1 and 0.1 mL of benzene and 0.5mg (2 µmol) of silver acetate was heated at 70 o C and analyzed by GC/MS as above. Table 4.2. Deuterium insertion study in C 6 H 6 /DTFA reaction without any catalyst. 131 Isotop\time(h) 0 0.33 0.68 1.0 20.0 42.0 60.0 TOF 0 0 0 0 0 0 0 TON 0.0 0.0 0.0 0.0 0.0 0.0 0.0 D 0 100.0 99.8 99.5 99.7 99.3 99.3 99.9 D 1 0.0 0.2 0.5 0.3 0.7 0.7 0.1 D 2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 D 3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 D 4 0.0 0.0 0.0 0.0 0.0 0.0 0.0 D 5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 D 6 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Deuterium insertion study. In a 3 mL Schlenk flask containing 5mg (0.01 mmol) of (bpym)Pt(TFA) 2 , 3mg (0.02 mmol) of silver acetate was added 1mL of TFA-d1 and 0.1 mL of benzene. The m ixture was heated at 150 o C analyzed by GC/MS every 15 minutes as above. 132 turn over number (TON) versus time(hours) of HD exchange between Benzene-h6 and DTFA-d1 in bpymPt(TFA)2/AgOAc/C6H6/DTFA system 0.0 50.0 100.0 150.0 200.0 250.0 300.0 350.0 400.0 0 5 10 15 20 25 30 35 time, hr TON TON (multip. D) Figure 4.13. Turn over number versus time(hours) of H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by (bpym)PtCl 2 /AgOAc at 150 o C. Table 4.3. DFT estimation of thermodynamic data of (bpym)Pt(TFA)(Ph) intermediate. t (h) d 0 d 1 d 2 d 3 d 4 d 5 d 6 TON 0 92.51 7.26 0.22 0.01 0.00 0.00 0.00 7.7 0.25 84.80 11.44 2.58 0.88 0.25 0.05 0.01 20.5 0.5 78.28 14.66 4.64 1.73 0.55 0.12 0.02 32.1 0.75 73.87 16.79 6.02 2.34 0.77 0.18 0.03 40.0 1 67.98 19.39 7.93 3.23 1.12 0.29 0.05 51.2 1.25 62.73 21.41 9.70 4.17 1.51 0.41 0.07 61.8 1.5 56.94 23.38 11.61 5.33 2.05 0.59 0.11 74.4 133 1.75 52.36 24.77 13.21 6.30 2.48 0.73 0.14 84.5 2 47.09 25.88 15.06 7.65 3.16 0.97 0.19 97.6 2.25 43.67 26.56 16.22 8.53 3.65 1.15 0.22 106.2 2.5 40.89 27.24 17.17 9.20 3.97 1.28 0.26 113.0 2.75 38.56 27.44 18.06 9.92 4.36 1.39 0.28 119.4 3 35.08 27.75 19.34 11.02 4.96 1.57 0.28 128.8 3.25 32.28 27.69 20.18 11.97 5.61 1.88 0.39 138.1 3.5 29.99 27.58 20.96 12.84 6.11 2.08 0.43 145.4 3.75 27.92 27.56 21.78 13.58 6.53 2.20 0.43 151.6 4 25.89 27.12 22.36 14.43 7.18 2.51 0.52 159.5 4.25 24.22 26.96 22.81 15.11 7.63 2.71 0.56 165.3 4.5 23.00 26.46 23.30 15.72 8.03 2.89 0.60 170.4 4.75 21.75 26.17 23.60 16.25 8.49 3.08 0.66 175.4 5 19.93 25.64 24.07 17.12 9.13 3.39 0.72 182.9 5.25 18.89 25.09 24.29 17.68 9.63 3.64 0.78 188.1 5.5 17.46 24.46 24.61 18.44 10.24 3.93 0.85 194.7 5.75 16.43 23.91 24.70 19.02 10.83 4.18 0.92 200.1 6 15.44 23.37 24.81 19.55 11.39 4.45 1.00 205.4 7 12.26 20.77 24.75 21.40 13.64 5.82 1.35 226.3 7.25 11.56 20.38 24.71 21.83 14.08 6.03 1.37 230.1 7.5 10.93 19.73 24.58 22.34 14.57 6.32 1.50 234.9 8 10.03 18.83 24.59 22.86 15.27 6.78 1.61 241.3 8.25 9.62 18.35 24.40 23.14 15.74 7.04 1.69 244.9 8.5 9.06 17.83 24.02 23.45 16.26 7.39 1.78 249.4 8.75 8.75 17.48 23.97 23.68 16.68 7.57 1.85 252.2 9.25 7.87 16.42 23.64 24.40 17.50 8.15 2.00 259.7 10 7.06 15.40 23.25 24.83 18.44 8.80 2.19 267.4 10.25 6.84 15.02 23.15 24.92 18.84 8.96 2.24 269.8 11.333 5.68 13.24 22.01 25.52 20.47 10.36 2.69 283.7 134 12.333 5.03 12.24 21.40 25.94 21.47 11.03 2.85 291.1 13.333 4.57 11.32 20.69 26.22 22.34 11.70 3.07 297.8 14.333 4.22 10.67 20.06 26.24 23.12 12.39 3.28 303.7 15.333 3.9 10.00 19.43 26.30 23.78 13.07 3.49 309.3 16.333 3.64 9.52 19.05 26.34 24.33 13.46 3.62 313.1 30.667 2.66 6.74 15.62 25.41 27.26 17.05 5.22 339.9 All calculations utilized the Jaguar 6.5 suite, using B3LYP/LACVP**++ with ZPE and solvent corrections for the TFA medium (Poisson-Boltzmann continuum solvent, with e = 8.42 and radius probe = 2.479). 8,9 Diffuse functions were not used for solvents. Furthermore, due to inaccuracies of free energy calculations in solvents, no ? G results have been included. Table 4.4. DFT estimation of thermodynamic data of (bpym)Pt(TFA)(Ph) intermediate. bpym.Pt.TFA.TFA Gas phase Energy: -1699.06522961581 hartrees Solvation Energy: -1699.10667693293 hartrees Zero Point Energy: 122.345 kcal/mol Coordinates: Pt1 -0.0001930497 0.0006646731 -0.3502959436 O2 1.5656885409 -0.1440188960 0.9263090704 C3 1.5422386601 -0.8814676322 2.0056223061 C4 2.9357494327 -0.8304326925 2.6857233437 F5 3.2335332964 0.4076939685 3.1157198312 F6 3.9004971134 -1.1949872070 1.7971020563 135 F7 3.0062963939 -1.6667823967 3.7249925917 O8 0.6453514330 -1.5549277511 2.4632610308 N9 1.2966215441 -0.1854104877 -1.8967437911 C10 2.7293794474 -0.3899873835 -4.1761489409 C11 0.7357585082 -0.1029112562 -3.1344197769 C12 2.6238948945 -0.3772372149 -1.7965351001 C13 3.3896920660 -0.4862194310 -2.9502395998 N14 1.4077565484 -0.1992424186 -4.2707647460 H15 3.0119112775 -0.4395437620 -0.7836202643 H16 4.4604451755 -0.6423242691 -2.8900502146 H17 3.2721426693 -0.4688047499 -5.1147612150 N18 -1.2967126304 0.1889536931 -1.8961645753 C19 -2.7298531546 0.3972882193 -4.1747283242 C20 -0.7359714219 0.1089290042 -3.1340682747 C21 -2.6238880413 0.3801539382 -1.7952399800 C22 -3.3899248046 0.4909400549 -2.9484203389 N23 -1.4081880288 0.2072090375 -4.2700874206 H24 -3.0118024751 0.4404053369 -0.7822887902 H25 -4.4607176619 0.6464184649 -2.8876839806 H26 -3.2727808177 0.4776144251 -5.1131018019 O27 -1.5661007747 0.1419659356 0.9267347079 C28 -1.5456126383 0.8892152631 1.9985458705 O29 -0.6528070816 1.5749807714 2.4463075893 C30 -2.9362789801 0.8323867615 2.6844422323 F31 -3.2246936578 -0.4061007221 3.1182018401 F32 -3.9061093534 1.1897797357 1.7984428841 F33 -3.0084254756 1.6706533459 3.7225882235 136 Table 4.5. DFT estimation of thermodynamic data of (bpym)Pt(TFA)(Ph) intermediate. bpym.Pt.TFA.C6H6+ Gas phase Energy: -1404.90071027875 hartrees Solvation Energy: -1404.97776156501 hartrees Zero Point Energy: 168.603 kcal/mol Coordinates: Pt1 -8.3752566511 -3.5913463051 1.8076362701 O2 -7.7279478402 -3.8821609140 3.7067966765 C3 -8.6378098305 -3.7259138957 4.6398371054 C4 -8.0606406028 -4.1184989253 6.0219709015 F5 -6.9414208449 -3.4246197829 6.2946841354 F6 -7.7470757207 -5.4367405067 6.0082830310 F7 -8.9452488059 -3.9042105251 6.9920936923 O8 -9.7930351983 -3.3752797356 4.5078451888 N9 -9.1198227050 -3.6037294648 -0.1289680283 C10 -10.3195938418 -4.0045690043 -2.5402473741 C11 -9.7501529236 -4.7634749432 -0.4745333127 C12 -9.0975347707 -2.6181618850 -1.0467748800 C13 -9.6955116703 -2.7819848798 -2.2882500545 N14 -10.3414996481 -4.9874614444 -1.6347045644 H15 -8.5959639875 -1.6978620052 -0.7735121676 H16 -9.6739451477 -1.9855589601 -3.0229443897 H17 -10.8133519323 -4.2059234391 -3.4872648232 N18 -9.0969443785 -5.5088535834 1.7096438338 C19 -10.2228634853 -7.9284446324 1.2734333345 C20 -9.7340878400 -5.8323110903 0.5557995742 C21 -8.9972921862 -6.4428206723 2.6744348479 C22 -9.5657194599 -7.6956226625 2.4829196533 137 N23 -10.2976359720 -7.0012891625 0.3105385700 H24 -8.4600547735 -6.1628430704 3.5728192953 H25 -9.4970464574 -8.4557632108 3.2525122937 H26 -10.6991753986 -8.8824410354 1.0629439904 H27 -8.9197990079 -0.9686370210 1.2971240961 C28 -8.1181232480 -1.2409914048 1.9771193194 C29 -5.8700796742 -1.3601235726 3.6558068390 C30 -8.2039783851 -0.7835133765 3.3214309941 C31 -6.8765939613 -1.7429938078 1.4876417873 C32 -5.7559102952 -1.8041208334 2.3528599302 C33 -7.0939239695 -0.8426820856 4.1392636598 H34 -9.1422766306 -0.3796489982 3.6854493857 H35 -6.7144847965 -1.8925073671 0.4244307700 H36 -4.8094240494 -2.1758033889 1.9749213791 H37 -7.1547642896 -0.4853338490 5.1625573805 H38 -5.0091781575 -1.3948059245 4.3161492568 Table 4.6. DFT estimation of thermodynamic data of (bpym)Pt(TFA)(Ph) intermediate. ts_bpym.Pt.Ph-H-TFA+ Gas phase Energy: -1404.88927933728 hartrees Solvation Energy: -1404.95724370283 hartrees Zero Point Energy: 165.507 kcal/mol Coordinates: Pt1 -6.4268866452 -3.2154594379 1.8606988540 O2 -6.3300330917 -5.1415022652 2.5572014327 C3 -6.3042747996 -5.4676067588 3.7912180502 C4 -6.1913892938 -6.9905092401 4.0491316020 F5 -4.8904831084 -7.3157473631 4.1041854024 138 F6 -6.7649578963 -7.6799965893 3.0521224651 F7 -6.7748486872 -7.3168576219 5.1994399897 O8 -6.3183501762 -4.6988209508 4.7677202741 N9 -6.5274972976 -1.4715415975 0.7852959984 C10 -6.6721362260 0.5982999183 -0.9784940540 C11 -6.5939018394 -1.6373161448 -0.5698178225 C12 -6.5327173665 -0.2085808009 1.2550705324 C13 -6.6056855513 0.8726969149 0.3865571382 N14 -6.6649472612 -0.6536168535 -1.4480192218 H15 -6.4790135974 -0.0845528932 2.3276781134 H16 -6.6104158246 1.8871545293 0.7679916055 H17 -6.7323698384 1.3929699343 -1.7176825042 N18 -6.5129481264 -3.9784391157 -0.0756090758 C19 -6.6318927069 -4.5960381989 -2.7024279909 C20 -6.5839226006 -3.0434690727 -1.0515251663 C21 -6.5044350854 -5.2763640699 -0.4245467669 C22 -6.5638952412 -5.6306395318 -1.7667726544 N23 -6.6432360843 -3.3053621251 -2.3465618046 H24 -6.4516423962 -5.9926623856 0.3886240518 H25 -6.5573291247 -6.6721228986 -2.0666093061 H26 -6.6795423298 -4.8024766101 -3.7685147231 H27 -4.1799491608 -2.0801635857 3.8208405137 C28 -5.1121380310 -1.6088688490 4.1204751287 C29 -7.5136405424 -0.4382191324 4.9768035161 C30 -5.0795952485 -0.4284715529 4.8542271350 C31 -6.3463001143 -2.2369250752 3.7819373738 C32 -7.5455476764 -1.6169815505 4.2402542560 C33 -6.2807172433 0.1568290342 5.2764838803 H34 -4.1310392534 0.0316191653 5.1138441701 139 H35 -8.4990371658 -2.0962537952 4.0345950215 H36 -6.2550403708 1.0729684567 5.8604155643 H37 -8.4349632803 0.0134024876 5.3319917207 H38 -6.3345096021 -3.4171815078 4.2404389392 Table 4.7. DFT estimation of thermodynamic data of (bpym)Pt(TFA)(Ph) intermediate. bpym.Pt.TFA.Ph grep: bpym.Pt.TFA.Ph.tfasolv.out: No such file or directory Gas phase Energy: -1404.51995530512 hartrees Zero Point Energy: 160.759 kcal/mol Coordinates: Pt1 -6.6211582892 -2.0083261542 0.8294262878 O2 -6.1640323516 -3.9954448115 0.7676290498 C3 -7.1215698399 -4.8775548260 0.7942872469 C4 -6.5454244344 -6.2807340281 0.4735664136 F5 -5.4785469635 -6.5885316629 1.2323345418 F6 -6.1404378549 -6.3060736571 -0.8287388371 F7 -7.4605708757 -7.2431055624 0.6292287974 O8 -8.3173708496 -4.7318163345 0.9561447673 N9 -6.9113052650 -0.0001264001 0.5755071900 C10 -7.2675418316 2.6175657867 -0.0838490552 C11 -6.9939764046 0.4482779654 -0.7135096382 C12 -6.9919012188 0.9202704852 1.5567526559 C13 -7.1733132056 2.2638979652 1.2603966306 N14 -7.1739947398 1.7140369882 -1.0637718247 H15 -6.9204026811 0.5400455890 2.5690037155 H16 -7.2383521169 2.9998824280 2.0536153454 H17 -7.4168299654 3.6502777047 -0.3899799453 140 N18 -6.5710124221 -1.8262514492 -1.3248676332 C19 -6.7970915830 -1.2205979057 -3.9482427407 C20 -6.8405810987 -0.5830105101 -1.7758142294 C21 -6.4002915848 -2.8077594377 -2.2223335807 C22 -6.5090844768 -2.5366421497 -3.5811234804 N23 -6.9604800154 -0.2395300875 -3.0542676876 H24 -6.1847904876 -3.7929716640 -1.8187272772 H25 -6.3790655759 -3.3188947541 -4.3201434671 H26 -6.9017474658 -0.9405684315 -4.9940502631 H27 -8.7270982981 -1.1314373756 2.9312518740 C28 -7.9087757995 -1.5653957834 3.5022569007 C29 -5.8858447841 -2.7494541477 5.0023630853 C30 -8.0172569446 -1.6313032584 4.8952125727 C31 -6.7839513537 -2.0837299933 2.8339186933 C32 -5.7823121663 -2.6913921744 3.6106693599 C33 -7.0019840593 -2.2174437773 5.6510135325 H34 -8.9030592127 -1.2352355227 5.3865590268 H35 -4.9188205801 -3.1334220876 3.1219597443 H36 -7.0844278948 -2.2699963551 6.7334392652 H37 -5.0943826467 -3.2198316211 5.5813097389 141 4.5 Chapter Four References 1 (a) Periana, R. A.; Taube, D. J.; Gamble, S.; Taube, H.; Satoh, T.; Fujii, H. Science 1998, 280, (b) Shilov, A. E.; Shul’pin, G. B. Activation and Catalytic Reactions of Saturated Hydrocarbons in the Presence of Metal Complexes Kluwer Academic; Dordrecht, 2000.560 (c) Jia, C.G.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 633 and references therein. (d) Crabtree, R. H. J. Chem. Soc., Dalton Trans. 2001, 19, 2437. (e) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507. (f) Jones, W. D. Acc. Chem. Res. 2003, 36, 140. (g) Periana, R. A.; Mironov, O.; Taube, D.; Bhalla, G.; Jones, CJ. Science 2003, 301, 814. (h) Conley, B. L; Tenn III, W. J.; Young, K. J. H.; Ganesh, S. K.; Meier, S. K; Ziatdinov, V. R.; Mirinov, O.; Oxgaard, J.; Gonzales, J.; Goddard III, W. A. Periana, R. A. J. Mol. Cat. A 2006, in press. 2 (a) Xu, X.; Kua, J.; Periana, R. A.; Goddard, W. A. Organometallics 2003, 22, 2057 (b) Kua, J.; Xu, X.; Periana, R. A.; Goddard, W. A Organometallics 2002, 21, 511. 3 Ryabov, A. D.; Sakodinskaya, I. K.; Yatsimirsky, A. K. J. Chem. Soc., Dalton Trans. 1985, 2629. 4 Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem. Soc. 2005, 127, 13754. 5 Bhalla, G.; Liu, X. Y.; Oxgaard, J.; Goddard, W. A.; Periana, R. A. J. Am. Chem. Soc. 2005, 127, 11372. 6 Kragten, D. D.; van Santen, R. A.; Neurock, M.; Lerou, J. J. J. Phys. Chem. A 1999, 103, 2756. 7 Steele, B. R.; Vrieze, K. Transition Metal Chemistry 1977, 2, 140. 8 Dannhauser, W.; Cole, R. H. J. Am. Chem. Soc. 1952, 74, 6105. Harris, F. E.; O'Konski, C. T. J. Am. Chem. Soc. 1954, 76, 4317. 9 Jaguar, version 6.5, Schrodinger, LLC, New York, NY, 2005. For further details, see supporting information 142 5 Chaper Five: Fast C 6 H 6 Activation in Weakly Acidic Media via Resting State Destabilization 5.1 Introduction Organometallic coordination catalysts based on the C-H activation reaction currently show the greatest potential for the development of new, selective, hydrocarbon hydroxylation chemistry. 1. In chapter 4, I reported on a platinum catalyst, Pt(bpym)(TFA) 2 (bpym=η 2 -{2,2'-bipyrimidyl}), that competent in benzene CH activation in trifluoroacetic acid which is observed by H/D exchange reaction between hydrocarbon and acid. The practically of this system is limited as the catalyst rate, TOF ~ 10 -5 s -1 for benzene CH activation, is way below the commercially viable target of ~ 1 s -1 for methane activation. Based on study of the Pt(bpym)(TFA) 2 /HTFA system, I identified that 6- membered cyclic transition state provides significant advantage in cleavage of CH bond compare to the external electrophilic substitution efficient for Pt(bpym)Cl 2 /H 2 SO 4 system. 2 From the understanding of the overall CH activation mechanism , the total barrier comes from : A) coordination of the hydrocarbon (RH) and B) cleavage of the coordinated CH bond. In designing improved catalysts it is important that both steps be explicitly considered to ensure that catalyst modifications that decrease the energy requirements for one step does not proportionately increase the other. This should be possible since the bonding in the 143 ground state and cleavage transition state should be different. 1h We now report that using an interplay between computational and experimental methods an efficient system has been designed which catalyzes H/D exchange magnitudes faster than the Pt(bpym)Cl 2 system. This improvement results from a reduction in the energetics for coordination without a corresponding increase in the energetics for cleavage. Figure 5.1. Effect of anionic ligand on resting state of catalyst. 5.2 Results and Discussion We postulated that replacing the neutral bipyrimidine in Pt(bpym)(X) 2 with a mono-anionic ligand such as η 2 -N,O-picolinate (pic) would yield a complex which would have reduced energetics for RH coordination due to the increased electron density at the metal center. Furthermore, calculations predicted that use of M-X M-(Hydrocarbon) Hydrocarbon Coordination TS C-H Bond Cleavage TS M-R New Resting State Internal Electrophilic Substitution through 6-membered cyclic TS Destabilization by Anionic Ligand Old Resting State 144 bi-dentate TFA ligands in lieu of Cl ligands could facilitate CH cleavage via a 6- membered cyclic transitions state that is not proportionately higher in energy relative to that for the Pt(bpym)(X) 2 system, resulting in a predicted lower overall barrier for CH activation for the K[Pt(pic)(TFA) 2 ] system . N O O H Figure 5.2. Picolinic acid. The picolinate ligand was chosen because it is a commercially available mono- anionic, chelating N and O-donor ligand that is stable to protic, thermal and oxidizing conditions. We have recently shown that O-donor ligands can facilitate the C-H activation reaction as well as selective functionalization of the M-R intermediate, 3 and computational screening indicated that C/H activation should be facile, using this ligand. Solutions of 1 were prepared by treatment of the known K[Pt(pic)Cl 2 ] with silver acetate in TFA, Scheme 1, and has been characterized by 1 H and 13 C NMR, as well as high-resolution electrospray ionization mass spectrometry. Due to the anionic character of 1 we were unable to isolate it as a pure material without contamination from AgOAc, either by recrystallization or extraction. However, the 145 neutral derivative, Pt(pic)(Me)(Et 2 S), has been prepared and fully characterized by 1 H and 13 C NMR as well as elemental analysis. Furthermore, in-situ NMR confirms that all acetate is present as free HOAc in the TFA solution. Figure 5.3. Preparation of active catalyst. In-situ NMR studies of 1 in TFA also showed that 1 was thermally stable in CF 3 CO 2 H at 70 o C for several days in air. At 100 o C a slow reaction occurs to quantitatively generate Pt(pic) 2 and a black precipitate (believed to be Pt black), with a t 1/2 of ~10 days. As reactions with methane were found to require temperatures above 100 o C, the CH activation studies were conducted with benzene where reaction could be readily observed at 70 o C. Upon heating a mixture of benzene (0.1 ml) and CF 3 CO 2 D (1 ml) containing 4 mM of 1 to 70 o C, catalytic incorporation of deuterium into benzene was observed. Analysis by GC/MS shows 43 turnovers after 1h (TOF of ~1.2 x 10 -2 s -1 ). Based on the temperature dependence a ?G ‡ of ~23 kcal/mol was estimated. Control experiments without catalyst did not lead to any observable H/D exchange (< 0.5%) under the same reaction conditions. To compare the catalytic activity of 1 to the Pt(bpym) system, Pt(bpym)TFA 2 was prepared and characterized by elemental analysis, high- 146 resolution mass spectroscopy, 1 H and 13 C NMR. H/D exchange with Pt(bpym)TFA 2 shows that this complex is 300 times less active (TON of 4.6 after 20h, TOF ~ 6.4 x 10 -5 s -1 ) than 1 under similar conditions. Unfortunately, direct comparison with (bpym)PtCl 2 is not possible as it is not soluble in TFA. Our theoretical calculations of CH activation with these systems (Figure 1) are consistent with the experimental results. According to our calculations, 1 activates benzene C-H bonds with a ?H ‡ ~21 kcal/mol, which is significantly lower than the ~27 kcal/mol calculated for Pt(bpym)TFA 2 but comparable to the experimental activation barrier of ~23 kcal/mol obtained for 1. Figure 5.4. Thermodynamics of Calculated Mechanism for the Benzene C -H Activation: Pt(pic) – solid line; Pt(bpym) – dashed line. 0 10 20 30 Pt TFA O N TFA Pt C 6 H 6 O N TFA Pt Ph O N HTFA 0.0 0.0 5.0 14.1 21 27 14 21 Arene coordination CH Cleavage TS1 Pt TFA N TFA N Pt C 6 H 6 N N TFA Pt Ph N N HTFA 147 As can be seen in Figure 5.4, the calculated resting state of the Pt(bpym) system is a bis-TFA – complex with an overall neutral charge, Pt(bpym)TFA 2 . Loss of TFA – generates a cationic species that coordinates benzene with ?H of ~14 kcal/mol. The ?H ‡ for the subsequent CH cleavage step, leading to the phenyl complex, is ~13 kcal/mol. The calculations also show that the resting state of the picolinate system is a bis-TFA complex but in this case this species is anionic, Pt(pic)TFA 2 – . Here, consistent with our original expectation that increasing the electron density at Pt could facilitate substrate binding, the ?H for loss of a TFA - and coordination of benzene is considerably less than that for the neutral Pt(bpym)(TFA) 2 complex at ~5.0 kcal/mol; a factor of almost three times lower! Furthermore, the ?H ‡ for CH cleavage shows only a slight increase to ~16 kcal/mol, leading to an overall decrease in the rate of CH activation for the picolinate complex. Ligand exchange between Pt-HTFA and solvent DTFA is expected to be facile, as the three coordinate phenyl species is only uphill by 18.2 kcal/mol (not shown). While a five-coordinate ligand exchange, associative transition state cannot be ruled out, the 18.2 kcal/mol can be considered an upper bound. The C-H cleavage occurs through a six-membered transition state, TS1, Figure 5.5, where the covalent Pt-O and C-H bonds are broken while the Pt-C and O -H bonds are created. Both C-O bonds are 3/2 bond order, with the p-bond transforming into a s -bond. The reaction is best described as an electrophilic substitution proceeding via addition of the Pt center to the arene ring (as opposed 148 to a sigma-bond metathesis involving only the sigma-framework). Similar transition states have been implicated in other theoretical works, 4,4 but this is to the best of our knowledge the first time this kind of solvent participation has been included by design for CH activation. Figure 5.5. C-H cleavage transition state TS1. Bond lengths in Å. It is not clear why the ?H ‡ for CH cleavage for the Pt(pic) and the Pt(bpym) systems are similar given the dramatic differences in the ?H for benzene coordination, Figure 1. We are carrying out further studies to understand the fundamental basis for these differences in order to design CH activation based oxidation catalysts that have low barriers for both coordination and CH cleavage in coordinating media such as water. O O Pt C C H 1.30 1.25 1.26 2.06 2.18 1.35 2.32 149 5.3 Conclusion. In summary, it has been demonstrated that a strong interaction between experimental and theoretical research can lead to deeper understanding as well as fast practical progress. A novel, facile transition state for C-H cleavage has been identified. Enhanced C-H activation reactivity was predicted conceptually for the class of compounds, supported theoretically and shown experimentally for a picolinate platinum system. Specifically, I demonstrated a well-defined, late metal, N,O-ligated complex, which is competent for arene C-H activation, exhibits thermal and protic stability and is an efficient catalyst for H/D exchange. 5.4 Experimental. General Considerations: Unless otherwise noted, all reactions and manipulations were performed in a M-Braun circulating Argon atmosphere glovebox or using standard Schlenk techniques. Glassware was dried in an oven at 150°C before use. Unless otherwise noted, reagents were purchased from commercial suppliers and used without further purification. Neutral alumina was used in chromatography unless otherwise noted. Diethyl ether, THF and benzene were distilled from sodium/benzophenone ketyl under Argon prior to use. Hexanes 150 and pentane were dried with P 2 O 5 under Argon and kept refluxing under flow of Argon. CH 2 Cl 2 was purified from stabilizer by stirring with concentrated H 2 SO 4 for 4 hours, mixture was separated, organic phase was neutralized with KHCO 3 , dried with MgSO 4 and P 2 O 5 , and refluxed under flow of Argon for 3 days. Organic acids were distilled from P 2 O 5 . Deuterated solvents were degassed by freezing, evacuating, and thawing (3x), and were then dried over 4 Å sieves and stored under Argon. Unless otherwise indicated, NMR spectra were obtained using a Variant Mercury-400 MHz spectrometer (400 MHz for 1H spectra, 100.6 MHz for 13 C{ 1 H} spectra, 376.5 MHz for 19 F spectra). Chemical shifts are reported in parts per millio relative to residual protiated solvent, coupling constants are reported in Hertz (Hz), and integrations are reported in number of protons. Unless otherwise noted, samples for NMR analysis were prepared using CDCl 3 as the solvent. Kinetic studies were performed using a Shimadzu-QP5000 GCMS or by NMR spectroscopy using a Variant Mercury-400 spectrometer (see above). All reaction mixtures were prepared under Argon and kept under static Ag during the kinetic analyses. For GCMS experiments, ethane standard was introduced. The compounds [(Et 2 S)Pt(Ph) 2 ] 2 5 , K(pic)PtCl 2 6 were prepared using literature procedures. 151 N Pt O O CH 3 S Figure 5.6. (Pic)Pt(Me)(Et 2 S) complex. (Pic)Pt(Me)(Et 2 S). In a 50 mL Schlenk flask containing 189.0 mg (0.3 mmol) of dimmer [(Et 2 S)Pt(Me) 2 ] 2 was added 73.8 mg (0.6 mmol) of picolinic acid and CHCl 3 (20 mL). The solution was stirred and heated at 70 o C for 1 hour. The crystalline solid was precipitated with pentane (60 mL) and filtered. At this point NMR show small presence of Platinum starting material that was removed by column chromatography with pentane/EtOAc 1:1 mixture as solvent. The solvent has been removed in vacuo over 1 day and a white crystalline solid formed (240 mg, 91% yield). 1 H NMR (400 MHz, CDCl 3 , 298 K): 8.62 (d, 1H, H-6, 3 J = 5.6 Hz, w/Pt satellites 3 J Pt-H = 24 Hz), 8.17 (dd, 1H, H-3, 3 J = 7.9 Hz, 4 J = 1.4 Hz), 8.05 (dt, 1H, H-4, 3 J = 7.8 Hz, 4 J = 1.3 Hz), 7.52 (ddd, 1H, H-5, 3’ J = 7.4 Hz, 3’’ J = 5.8 Hz, 4 J = 1.6 Hz), 3.10 (bm, 2H, S-CH 2 -Me), 2.85 (bm, 2H, S-CH 2 -Me), 1.39 (t, 6H, S-CH 2 -CH 3 , 3 J = 7.5 Hz) and 0.73 (s, 3H, Pt-CH 3 , w/Pt satellites, 2 J Pt-H = 41.4 Hz). 13 C NMR (101 MHz, CDCl 3 , 298 K): 172.5 (s, -CO 2 -), 153.5 (s, py), 144.64 (s, py), 139.2 (s, py), 128.3 (s, py), 127.5 (s, py), 30.7 (s, -CH 2 -), 13.2 (s, -CH 3 ), 152 and -22.2 (s, Pt-Me). Anal. Calcd for C 11 H 17 NO 2 PtS: C, 31.28; H, 4.06; N, 3.32; S, 7.59. Found: C, 31.52; H, 3.81; N, 3.23; S, 7.86. N Pt O O N O O Figure 5.7. (Pic) 2 Pt complex. (Pic) 2 Pt. In a 50 mL Schlenk flask containing 415.0 mg (1.0 mmol) of K 2 PtCl 4 was added 246.2 mg (2.0 mmol) of picolinic acid and water (10 mL). The solution was stirred and heated at 70 o C for 5 minutes to dissolve all starting materials. The white precipitate was formed, filtered, washed with water, MeOH and dried in vacuum (420 mg, 96% yield). 1 H NMR (400 MHz, trufluoroacetic acid-d 1 , 298 K): 8.61 (d, 1H, H-6, 3 J = 5.7 Hz), 8.23 (t, 1H, H-4, 3 J = 8.3 Hz), 8.01 (d, 1H, H-3, 3 J = 7.9 Hz), 7.72 (t, 1H, H-5, 3 J = 6.6 Hz). 13 C NMR (101 MHz, trufluoroacetic acid- d 1 , 298 K): 182.01 (s, -CO2-), 150.76 (d, py), 143.79 (s, py), 132.27 (s, py), 130.20 (s, py). Anal. Calcd for C 12 H 8 N 2 O 4 Pt: C, 32.75; H, 1.96; N, 6.22. Found: C, 32.81; H, 1.84; N, 6.38. 153 N Pt O O O O O O Figure 5.8. K(Pic)Pt(OAc) 2 complex. K(Pic)Pt(OAc) 2 in solution. In a 15 mL Schlenk flask containing 42.7 mg (0.1 mmol) of KpicPtCl 2 was added 33.4 mg (0.2 mmol) of silver acetate and TFA (5 mL). The solution was stirred and heated at 70 o C for 5 minutes to dissolve all starting materials. The white precipitate of AgCl was formed, filtered out and the solution was analyzed. 1 H NMR (400 MHz, trufluoroacetic acid-d 1 , 298 K): 8.78 (s, 1H), 8.72 (s, 1H), 8.51 (s, 1H), 8.20 (s, 1H), 2.70 (s, 6H). 13 C NMR (101 MHz, trufluoroacetic acid-d 1 , 298 K): 183.10 (s, -OC(O)py), 180.72 (s, -OC(O)Me), 149.94 (d, py), 143.79 (s, py), 131.82 (s, py), 130.52 (s, py), 20.58 (s, -CH 3 ), 20.40 (s, -CH 3 ). HRMS (Electro-spray) Calcd for C 10 H 10 NO 6 Pt (M-K): 435.0156. Found: 435.0156. Stability study. In a NMR tube containing 1mg (2 µmol) of (pic)PtCl 2 , 0.5mg (0.02 µmol) of silver acetate was added 1mL of TFA-d 1 . The mixture was heated at 100 o C and analyzed by NMR. 154 Figure 5.9. 1 H NMR of Platinum picolinate in trifluoroacetic acid after one day at 100 o C. Deuterium insertion study. In a 3 mL Schlenk flask containing 1mg (2 µmol) of (pic)PtCl 2 , 0.5mg (2 µmol) of silver acetate was added 1mL of TFA-d 1 and 0.1 mL of benzene. The mixture was let to react and AgCl was removed by filtration. The mixture was heated at 70 o C, cooled down to room temperature and 1 µL of reaction solution was injected to GC/MS. After separation on column and ionization the mass distribution of ions of injected sample was collected. The deconvolution program converts the mass distribution of ion to benzene isotope concentration. This program used experimental data of different isotopes of benzene to construct the system of linear equations, by solving which the isotope distribution of benzene in sample was determined. According to test experiments 155 this approach can be reliable to within 2%.” The same procedure was used for 150 o C. Table 5.1. Deuterium insertion study by (pic)Pt in C 6 H 6 /DTFA reaction. isotop\time(min) 0 20 40 60 80 100 TOF 0 .0155 .0127 .0120 .0102 .0093 TON 0 18.6 30.5 43.3 49.0 55.9 D 0 99.4 96.7 94.3 91.4 89.7 88.0 D 1 0.1 2.3 3.6 5.6 6.8 8.1 D 2 0.1 0.1 0.5 0.8 1.0 1.2 D 3 0.0 0.1 0.3 0.5 0.6 0.7 D 4 0.0 0.0 0.3 0.5 0.6 0.7 D 5 0.0 0.1 0.3 0.5 0.6 0.7 D 6 0.4 0.7 0.7 0.7 0.5 0.6 Deuterium insertion study. In a 3 mL Schlenk flask containing 5mg (0.01 mmol) of (pic)Pt(Cl) 2 , 3mg (0.02 mmol) of silver acetate was added 1mL of TFA-d 1 and 0.1 mL of benzene. Mixture was heated at 100 o C and analyzed by GC/MS every 15 minutes as above. 156 Table 5.2. Kinetic of deuterium insertion by (pic)Pt in C 6 H 6 /DTFA reaction. time(h) d 0 d 1 d 2 d 3 d 4 d 5 d 6 TON 0.00 92.99 6.76 0.22 0.02 0.01 0.00 0.00 7.3 0.27 59.79 26.54 9.32 3.06 0.98 0.26 0.05 59.9 0.45 49.41 30.54 13.19 4.82 1.56 0.41 0.08 80.1 0.63 41.54 32.20 16.56 6.70 2.29 0.60 0.10 98.2 0.82 36.24 32.78 18.87 8.25 2.94 0.79 0.14 111.8 1.02 31.95 32.55 20.75 9.87 3.69 1.02 0.17 124.5 1.27 28.02 31.87 22.56 11.53 4.51 1.28 0.23 137.4 1.43 25.74 31.41 23.52 12.53 5.07 1.47 0.26 145.2 1.60 24.09 30.88 24.19 13.35 5.57 1.63 0.29 151.5 1.77 22.64 30.27 24.73 14.15 6.06 1.82 0.33 157.5 1.93 21.30 29.76 25.12 14.94 6.51 2.01 0.36 163.1 2.13 19.99 29.12 25.63 15.68 7.05 2.16 0.37 168.6 2.35 18.80 28.37 25.86 16.53 7.62 2.39 0.43 174.7 2.60 17.67 27.67 26.23 17.21 8.14 2.60 0.47 180.2 2.83 16.66 26.94 26.46 17.93 8.68 2.83 0.50 185.5 3.15 15.40 25.64 26.82 18.78 9.53 3.20 0.62 193.5 3.55 14.26 24.68 26.92 19.56 10.26 3.62 0.70 200.5 3.82 13.33 24.03 27.11 20.14 10.83 3.81 0.75 205.6 4.38 12.44 23.30 26.81 21.00 11.50 4.15 0.80 211.5 5.00 11.60 22.31 26.72 21.63 12.26 4.57 0.91 218.0 5.33 11.44 22.10 26.55 21.77 12.52 4.69 0.93 219.6 6.07 10.56 21.19 26.50 22.44 13.21 5.06 1.05 225.9 24.00 6.71 15.82 24.49 25.57 17.78 7.83 1.80 262.6 157 Deuterium Insertion Study during HD Exchange Reaction between Benzene and TFA-d1 by K(pic)Pt(Cl)2/AgOAc 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00 90.00 100.00 0.00 5.00 10.00 15.00 20.00 25.00 30.00 Time, hours % C6H5D C6H4D2 C6H3D3 C6H2D4 C6HD5 C6D6 C6H6 Figure 5.10. Study of isotopologes appearance in H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by K(pic)PtCl 2 /AgOAc at 100 o C. Turn over number (TON) versus time(hours) of HD exchange between Benzene-h6 and DTFA-d1 in picPtCl2/AgOAc/C6H6/DTFA system 0.0 50.0 100.0 150.0 200.0 250.0 300.0 0.00 5.00 10.00 15.00 20.00 25.00 30.00 time, hr TON TON (multip. D) Figure 5.11. Turn over number versus time(hours) of H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by K(pic)PtCl 2 /AgOAc at 100 o C. 158 All calculations utilized the Jaguar 6.5 suite, using B3LYP/LACVP**++ with ZPE and solvent corrections for the TFA medium (Poisson-Boltzmann continuum solvent, with e = 8.42 and radius probe = 2.479). 7,8 Diffuse functions were not used for solvents. Furthermore, due to inaccuracies of free energy calculations in solvents, no ? G results have been included. Table 5.3. DFT estim ation of thermodynamic data of (pic)Pt(TFA) 2 - . pic.Pt.TFA.TFA- Gas phase Energy: -1607.95753971431 hartrees Solvation Energy: -1608.03977580633 hartrees Zero Point Energy: 94.588 kcal/mol Coordinates: Pt1 1.5560163298 1.6284756520 -1.0090403502 N2 1.3040974245 3.3759407281 -0.0453862472 C3 1.0592373989 5.9304299601 1.0005689383 C4 1.6372850969 4.4516310147 -0.7967887918 C5 0.8420259667 3.5423198028 1.2083277442 C6 0.7114552192 4.8117305166 1.7605702385 C7 1.5257554516 5.7431359608 -0.2986042346 H8 0.3403960030 4.9120173839 2.7752346358 H9 1.8104940061 6.5576063825 -0.9552764892 H10 0.9647344250 6.9297458215 1.4162501278 C11 1.0342559214 -0.5027480272 -2.9048580214 C12 1.5648477233 -1.7493534638 -3.6658072519 159 O13 1.9348425306 -0.0661601909 -2.0875708997 F14 1.9160066587 -2.7424473364 -2.8177271481 F15 0.6370338732 -2.2504301371 -4.5038689076 F16 2.6550283763 -1.4508580807 -4.4083498320 H17 0.5813016550 2.6339826103 1.7391749708 O18 -0.0913313800 -0.0965904762 -3.1429127513 O20 0.8499829208 0.5191842969 0.5754616528 C21 1.6729666158 -0.0047921129 1.4262485847 C22 0.8727194013 -0.5903725828 2.6220597252 O23 2.8902241470 -0.0421390936 1.4505765245 F24 -0.1169083547 -1.4192361502 2.2390420254 F25 1.6609214744 -1.2650736774 3.4756201363 F26 0.2958482107 0.4236728399 3.3295213093 C27 2.1247557467 4.1547877288 -2.2054872254 O28 2.4449270996 5.0881767578 -2.9337316063 O29 2.1501220071 2.8898654040 -2.5111984815 Table 5.4. DFT estimation of thermodynamic data of (pic)Pt(TFA)(C 6 H 6 ) intermediate. pic.Pt.C6H6.TFA Gas phase Energy: -1313.91393796719 hartrees Solvation Energy: -1313.93740481069 hartrees Zero Point Energy: 141.424 kcal/mol Coordinates: Pt1 0.5225334064 -1.5552974124 -1.8953703414 N2 0.9119615468 0.1603627549 -2.9203782471 C3 1.5577928245 2.2887103477 -4.5544304917 160 C4 1.4874392038 -0.0664197481 -4.1229239273 C5 0.6505299413 1.4123300652 -2.5046830402 C6 0.9646997765 2.5030447836 -3.3085659591 C7 1.8237252349 0.9838944840 -4.9661192523 H8 0.7428563246 3.5037275607 -2.9540965367 H9 2.2824719699 0.7420667417 -5.9183115155 H10 1.8081141724 3.1294970255 -5.1943076799 C11 0.6384240022 -3.4179469982 -0.5040834231 C12 0.6050276975 -5.2442453703 -2.6360688170 C13 1.8012477738 -4.1785369892 -0.8169667480 C14 -0.5431593339 -3.5968280531 -1.2749014070 C15 -0.5372028569 -4.5274711031 -2.3464591315 C16 1.7804300093 -5.0674766957 -1.8702601492 H17 2.6944057434 -4.0563027070 -0.2122624502 H18 -1.4727406917 -3.1369054182 -0.9537061665 H19 -1.4421205354 -4.6704795637 -2.9283539119 H20 2.6694897340 -5.6402507338 -2.1165348736 H21 0.6080456865 -5.9511537545 -3.4604205486 H22 0.5939572388 -2.8765243006 0.4358501409 O23 -2.3305323669 -1.2201244389 -0.2406618482 C24 -1.4173159823 -0.4843597772 0.0890536749 C25 -1.6726132263 0.6735425069 1.0892813985 O26 -0.1713549893 -0.4789228776 -0.2821004110 F27 -1.4157485441 1.8653094398 0.4893871352 F28 -2.9402639117 0.6930093629 1.5094284401 F29 -0.8708207976 0.5799478186 2.1661441194 H30 0.1900169282 1.5042692635 -1.5277403513 C31 1.7363470236 -1.5175947865 -4.4768557980 O32 2.2543059632 -1.8081092489 -5.5415098823 161 O33 1.3552400302 -2.3759116869 -3.5574590291 Table 5.5. DFT estimation of thermodynamic data of 6-membered cyclic CH cleavage transition state (pic)Pt(TFA-H-C 6 H 5 ) with TFA- ion around. tsPtNO.C6H5HAF.AF- Gas phase Energy: -1840.16369455891 hartrees Solvation Energy: -1840.27863716960 hartrees Zero Point Energy: 154.601 kcal/m ol Coordinates: Pt1 -6.3162814431 -2.9906716473 1.8042543016 O2 -5.9137335291 -4.7713867707 2.7282483698 C3 -6.8958020010 -5.4686142778 3.2008526739 C4 -6.3551243842 -6.7935216619 3.8046780641 F5 -5.4544435842 -6.5512762620 4.7887141718 F6 -5.7376300848 -7.5543143071 2.8758798949 F7 -7.3408077977 -7.5351353373 4.3412279680 O8 -8.0905878268 -5.2338906862 3.2463529172 N9 -6.7100818276 -1.3945312063 0.5804305969 C10 -7.4865412504 0.5054779152 -1.3054666723 C11 -7.2406135194 -1.7801054557 -0.6082735189 C12 -6.5186809768 -0.0805468753 0.8176282269 C13 -6.8985467043 0.8913023699 -0.1019646588 C14 -7.6465914516 -0.8531577798 -1.5602068762 H15 -6.0140159875 0.1738932534 1.7410079860 H16 -6.7175628719 1.9346374617 0.1333786332 H17 -7.7956542804 1.2487920227 -2.0351729042 O18 -6.8210042698 -4.0182471889 0.0495956169 162 C19 -7.3191613739 -3.2752329215 -0.8854456576 O20 -7.8000574661 -3.6495253749 -1.9520939803 O21 -2.6960573300 0.1754283614 1.4403139078 C22 -3.2359638862 -0.7127497620 2.0780821193 O23 -4.2890564703 -0.5855625806 2.8283940060 C24 -2.5773672319 -2.1183139486 2.0076704209 F25 -1.2490728945 -2.0183337492 2.2279865393 F26 -2.7488460436 -2.6581905143 0.7846687836 F27 -3.0635710468 -2.9901094906 2.9148837132 H28 -7.5644803501 -0.5223982441 3.2727612256 C29 -7.0657027389 -1.0906838806 4.0528862852 C30 -5.8434906768 -2.5271084584 6.0935428939 C31 -7.3969732620 -0.8241322409 5.3787708734 C32 -6.1092269039 -2.0749178534 3.6917772763 C33 -5.5235393542 -2.7941031056 4.7652638231 C34 -6.7844356704 -1.5436189006 6.4070352654 H35 -8.1412880271 -0.0659609500 5.6112617873 H36 -5.0895205414 -1.4877128508 3.0805184253 H37 -4.8058855455 -3.5727875366 4.5372853306 H38 -7.0414221207 -1.3418679007 7.4442084863 H39 -5.3680433549 -3.0980128016 6.8873746889 H40 -8.0668705644 -1.2464767795 -2.4788422470 Table 5.6. DFT estimation of thermodynamic data of (pic)Pt(Ph)(HTFA) intermediate. pic.Pt.Ph.HTFA Gas phase Energy: -1313.89835939865 hartrees iterations: 14 Solvation Energy: -1313.91923963653 hartrees 163 Zero Point Energy: 141.052 kcal/mol Coordinates: Pt1 0.3045134267 0.9137113056 -1.1457777110 N2 0.3669624830 2.8825273593 -0.2825639019 C3 0.5358560034 5.5716064597 0.3622573503 C4 0.4166751939 3.8117328280 -1.2579874300 C5 0.3935774531 3.2611901728 1.0045481383 C6 0.4790944892 4.6027641364 1.3654770158 C7 0.5012946217 5.1694910533 -0.9704645670 H8 0.5015060144 4.8769195538 2.4136816987 H9 0.5395220714 5.8645191726 -1.8001921045 H10 0.6058698012 6.6237712066 0.6183313607 C11 0.3144044687 -0.7955699208 -2.2378696866 C12 0.3602007745 -3.0881459675 -3.9050721283 C13 1.3167046705 -1.7744336356 -2.1118935318 C14 -0.6563994808 -0.9992682015 -3.2357118431 C15 -0.6352665874 -2.1275605750 -4.0535815353 C16 1.3372231699 -2.9093607814 -2.9337060229 H17 2.1022615477 -1.6446879319 -1.3727192184 H18 -1.4224148204 -0.2511431840 -3.3824096017 H19 -1.3950845543 -2.2546624686 -4.8153070030 H20 2.1237303827 -3.6429776380 -2.8153823982 H21 0.3738262563 -3.9647299815 -4.5448537212 C22 -0.2618442047 -1.1172684136 1.0636343589 C23 -0.5174353966 -1.4242725166 2.5510437364 O24 0.1984389760 -0.0146821586 0.7521215323 F25 -0.3369320583 -0.3242418011 3.2870238373 F26 -1.7724951824 -1.8616105237 2.7165909652 F27 0.3329386719 -2.3735280279 2.9639147234 164 H28 0.3412956930 2.4647592291 1.7388672966 O29 -0.5710547360 -2.1015488437 0.2819375406 H30 -0.3079191185 -1.8913819670 -0.6648413061 C31 0.3767930883 3.3066929170 -2.6896509174 O32 0.3902631921 4.1065007173 -3.6101880357 O33 0.3268103347 1.9957437437 -2.8338910272 165 5.5 Chapter Five References 1 (a) Periana, R. A.; Taube, D. J.; Gamble, S.; Taube, H.; Satoh, T.; Fujii, H. Science 1998, 280, (b) Shilov, A. E.; Shul’pin, G. B. Activation and Catalytic Reactions of Saturated Hydrocarbons in the Presence of Metal Complexes Kluwer Academic; Dordrecht, 2000.560 (c) Jia, C.G.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 633 and references therein. (d) Crabtree, R. H. J. Chem. Soc., Dalton Trans. 2001, 19, 2437. (e) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507. (f) Jones, W. D. Acc. Chem. Res. 2003, 36, 140. (g) Periana, R. A.; Mironov, O.; Taube, D.; Bhalla, G.; Jones, CJ. Science 2003, 301, 814. (h) Conley, B. L; Tenn III, W. J.; Young, K. J. H.; Ganesh, S. K.; Meier, S. K; Ziatdinov, V. R.; Mirinov, O.; Oxgaard, J.; Gonzales, J.; Goddard III, W. A. Periana, R. A. J. Mol. Cat. A 2006, in press. 2 (a) Xu, X.; Kua, J.; Periana, R. A.; Goddard, W. A. Organometallics 2003, 22, 2057 (b) Kua, J.; Xu, X.; Periana, R. A.; Goddard, W. A Organometallics 2002, 21, 511. 3 Bhalla, G.; Liu, X. Y.; Oxgaard, J.; Goddard, W. A.; Periana, R. A. J. Am. Chem. Soc. 2005, 127, 11372. 4 Kragten, D. D.; van Santen, R. A.; Neurock, M.; Lerou, J. J. J. Phys. Chem. A 1999, 103, 2756. 5 Steele, B. R.; Vrieze, K. Transition Metal Chemistry 1977, 2, 140. 6 Annibale, G.; Cattalini, L.; Chessa, G.; Marangoni, G.; Pitteri, B.; Tobe, M. L. Gazzetta Chimica Italiana 1985, 115, 279. 7 There is a discrepancy in the literature regarding the dielectric of TFA, where it is alternative reported as 8.42 (Dannhauser, W.; Cole, R. H. J. Am. Chem. Soc. 1952, 74, 6105. Harris, F. E.; O'Konski, C. T. J. Am. Chem. Soc. 1954, 76, 4317) and 39.0 (Simons, J. H.; Lorentzen, K. E. J. Am. Chem. Soc. 1950, 72, 1426). As there exists a possibility that the higher dielectric could be a better measure of the polirizability of the TFA, we performed control calculations of bpymPt at both dielectrics. However, the high dielectric yielded unrealistic barriers, and were thus discarded. 8 Jaguar, version 6.5, Schrodinger, LLC, New York, NY, 2005. For further details, see supporting information 166 6 Chapter Six: CH 4 Activation in Weakly Acidic Media via Transition State Stabilization 6.1 Introduction. Organometallic coordination catalysts based on the C-H activation reaction currently show the greatest potential for the development of new, selective, hydrocarbon hydroxylation chemistry. 1 Previously we reported on a platinum catalyst, Pt(bpym)Cl 2 (bpym=η 2 -{2,2'-bipyrimidyl}), that converts methane to methanol in concentrated sulfuric acid with a 70% one-pass yield. 2g The practically of this system is limited as the average catalyst rate, TOF ~ 10 -3 s -1 , is below the commercially viable target of ~ 1 s -1 . This is due to severe inhibition of the CH activation step (which is the rate determining step for oxidation in the presence of 1M water or methanol) by the reaction products, resulting in a maximum methanol concentration to ~1M rather than the ~5M required for efficient separation. Based on our understanding of the mechanism of the Pt(bpym)Cl 2 /H 2 SO 4 system, 1h,2 we identified two key steps that contribute to the overall CH activation barrier of ~32 kcal/mol: A) ~27 kcal/mol for coordination of the hydrocarbon (RH) and B) ~5 kcal/mol for cleavage of the coordinated CH bond. In designing improved catalysts it is important that both steps be explicitly considered to ensure 167 that catalyst modifications that decrease the energy requirements for one step does not proportionately increase the other. This should be possible since the bonding in the ground state and cleavage transition state should be different. 1h Recently we report a reduction in the energetics for coordination without a corresponding increase in the energetics for C-H bond cleavage. 3 Unfortunately effective destabilization of resting state leads to the low stability of anionic Pt(pic)TFA 2 – complex and the incompetence to methane CH activation. At the same paper we reported the observation of very efficient 6-membered cyclic transition state. Here we report that using an interplay between computational and experimental methods an efficient system has been designed. New catalyst is more efficiently apply 6-membered cyclic interaction to CH activation catalysis by ligand assistance, highly stable and is competent in catalytic methane CH activation. ~17 kcal/mole 6-member ring - ON N N N N Pt O O HO O CF 3 CF 3 6-member ring - OFF N N N N Pt O O O O CF 3 H CF 3 168 Figure 6.1. Strong 6 -membered cyclic interaction present in intermediates as well as in transition states. The improvement results from a reduction in the energetics for C-H bond cleavage step without a corresponding increase in the energetics for the resting state. The strong 6-membered cyclic interaction is a driving phenomenon for this improvement. 6.2 Results and Discussion. We postulated that replacing the neutral bipyrimidine in Pt(bpym)(X) 2 with a neutral 2-(2-Pyridinyl)-1,8-naphthyridine ligand would yield a complex which would have reduced energetics for C-H cleavage due to the efficiency of the interactions in ligand-assisted 6-membered cyclic transition state. M-X M-(HR) Hydrocarbon Coordination TS C-H Bond Cleavage TS M-R Resting State Internal Electrophilic Substitution through 6-membered cyclic TS with enhanced acid-base properties 6-membered cyclic intermediate is the new limiting factor L n Pt L L X H L n Pt L L R H 169 Figure 6.2. Energy shift of 6-membered cyclic interactions compare to the resting state by controlling of acid-base properties of proton acceptor. Efficiency was achieved by choosing geometry as well as acid-base properties of ligand. This ligand-assisted TS phenomenon is an independent to resting state destabilization phenomenon published previously for Pt(pic) system. 3 The addictiveness of two phenomenons is still a question. All calculations utilized the Jaguar 6.5 suite, using B3LYP/LACVP**++ with ZPE and solvent corrections for the TFA medium (Poisson-Boltzmann continuum solvent, with e = 8.42 and radius probe = 2.479). 4,5 Diffuse functions were not used for solvents. Furthermore, due to inaccuracies of free energy calculations in solvents, no ?G results have been included. The 2-(2-Pyridinyl)-1,8-naphthyridine ligand was chosen because it a) can be made analytically pure by Friedlander condensation 6 in one step; b) is a neutral ligand; c) is a thermally and acid stable; d) computational screening indicated that CH activation should be facile, using this ligand. To the best of our knowledge, there are not Platinum complexes reported with this ligand. A compound with stoichiometry close to Pt(nap)Cl 2 can be prepared by treating K 2 PtCl 4 or (PtCl 2 ) n with 1 equivalent of nap ligand in acetic acid. The presence of multiple, equivalent, highly-Platinum-affinic, pyridine-type ligands leads to multiple isomers at equilibrium. The equilibration was supported by observing the characteristic temperature dependence of isomers ratio 170 (N=N 0 exp(-?G/kT)). Major attempt to purify Pt(nap)Cl 2 decrease ligand concentration of complex, which suggest presence of dimmers or even oligomers. Solutions of 1 were prepared by treatment of Pt(nap)Cl 2 mixture with silver TFA in TFA, Figure 6.3. Multiple isomers at equilibrium point were observed b y 1 H NMR (at least three). N N N Pt Cl Cl N N N Pt Cl Cl N N N N N N Pt TFA TFA (PtCl 2 ) n + Acetic Acid 70 o C, 12h AgTFA + + AgCl (+ isomers) (+ isomers) (+ isomers) HTFA Figure 6.3. Synthesis of active catalyst - “(nap)Pt(TFA) 2 ”. In-situ NMR studies of 1 in TFA also showed that 1 was thermally stable in CF 3 CO 2 H at 150 o C for weeks in air. Catalyst exhibits H/D exchange reaction between CH 4 and DTFA at 160 o C. Analysis by GC/MS shows 7 turnovers after 3 hours (TOF of 0.65 x 10 -3 s -1 ). Pt(bpym)TFA 2 system does not show any activity to CH 4 and barely activate benzene at similar conditions (however Pt(bpym)Cl 2 in significantly more acidic D 2 SO 4 exhibits TOF of 0.50 10 -3 s -1 at higher 169 o C). To 171 quantify naphthyridine-donor ligand effect we choose more reactive hydrocarbone, benzene. Upon heating a mixture of benzene (0.1 ml) and CF 3 CO 2 D (1 ml) containing 6 mM of 1 to 130 o C, catalytic incorporation of deuterium into benzene was observed. Analysis by GC/MS shows 450 turnovers after 5 min (TOF of ~1.5 s -1 ). Based on the temperature dependence a ?G ‡ of ~24 kcal/mol was estimated. Control experiments without catalyst did not lead to any observable H/D exchange (< 0.5%) under the same reaction conditions. -1 0 1 2 3 4 5 6 7 0 10 15 21 25 30 time(minutes) % Figure 6.4. Study of isotopologes appearance in H/D exchange reaction between C 6 H 6 and DTFA-d 1 catalyzed by (nap)PtCl 2 /AgOAc at 115 o C. Dark blue – C 6 H 5 D; Blue – C 6 H 4 D 2 ; Dark green – C 6 H 3 D 3 ; Green -– C 6 H 2 D 4 ; Orange – C 6 HD 5 ; Red – C 6 D 6 . 172 H/D exchange between benzene and trifluoroacetic acid does not observed, if 1 was exposed to 500 psi of methane at 160 o C for 12 hours. Despite of CH activation reactivity to methane, catalyst is subject to deactivation processes by methane. The mechanism of such deactivation is part of outgoing investigation. Figure 6.5. Methane C-H cleavage transition state. Bond lengths in Å. Our theoretical calculations of CH activation with these systems, Figure 6.6, are consistent with the experimental results. According to our calculations, 1 activates methane C-H bonds with a ?H ‡ ~26.7 kcal/mol and benzene with a ?H ‡ ~17.5 kcal/mol, which is significantly lower than Pt(bpym)TFA 2 does: methane C- H activation barrier ~40 kcal/mol and benzene ~27 kcal/mol. At the same time 173 calculated barriers are not contradict to the experimental data. It is necessary to take in account that CH cleavage is not the rate determining step for 1 in case of benzene CH activation. Methane CH activation compete with unknown deactivating process. Figure 6.6. Thermodynamics of postulated mechanism for the benzene C-H activation: Pt(nap) – solid line; Pt(bpym) – dashed line. As can be seen in Figure 6.6, the calculated resting state of the Pt(bpym) system is a bis-TFA – complex with an overall neutral charge, Pt(bpym)TFA 2 . Protonation generates a cationic species with 6-membered cyclic interaction with ?H of ~14 kcal/mol. (An artificial attempt to break 6-membered cyclic interaction show the Pt N N Ph O O CF 3 H 10 20 30 Pt N N TFA TFA N Pt N N TFA TFA 0.0 – 0.5 14.3 17.5 27.0 10.5 13.7 Pt N N Ph TFA N Pt N N Ph TFA 12.1 14.1 Pt N N O O CF 3 H N TFA Pt N N C 6 H 6 TFA N Pt N N TFA Ph H N Pt N N O O O CF 3 H O CF 3 Pt N N C 6 H 6 TFA 174 energy of 6 -membered cyclic interaction about ~17 kcal/mole) The ?H ‡ for the benzene CH cleavage step, leading to the phenyl complex, is ~27 kcal/mol. On the other hand, the protonation of the Pt(nap)TFA 2 system is almost energy-neutral. 7 Facile protonation is expected due to higher basisity of pyridine-type group over trifluoroacetate group. The ?H ‡ for the benzene CH cleavage step, leading to the phenyl complex, is ~17.5 kcal/mol. Here, consistent with our original expectation, by enhancing proton acceptor basisity and keeping the original geometry, we effectively lower TS for CH cleavage of hydrocarbons. Both Pt(bpym) and Pt(pic) demonstrated a sequential deuterium incorporation in benzene in contrast to Pt(nap) that demonstrate parallel deuterium incorporation. In order to understand nature of such behavior we are distinguishing the TS from the resting state phenomenon’s by considering hydrocarbon coordination as reference point. Naphthyridine did not affect significantly the energetics of hydrocarbon coordination, ?H of ~12 kcal/mole for Pt(nap)(C 6 H 6 )TFA + similar to ?H of ~14 kcal/mole for Pt(bpym)(C 6 H 6 )TFA + . However, it has major effect on C-H bond cleavage making hydrocarbon coordination a RDS for activation benzene. In contrast, Pt(pic)TFA 2 – rate acceleration was based predominantly on the resting state destabilization phenomenon. ?H of Pt(pic)(C 6 H 6 )TFA formation is ~5 kcal/mole. The CH bond cleavage barrier ~16 kcal/mole is similar to ~13 kcal/mole observed for Pt(bpym) system. 175 6.3 Conclusion. A novel phenomenon was conceptually proposed, supported theoretically and shown experimentally. We have demonstrated as well that a strong collaboration between experimental and theoretical research can lead to deeper understanding and fast practical progress. Specifically enhanced C -H activation reactivity was predicted conceptually for the class of compounds, supported theoretically by DFT and shown experimentally for a 2-(2-Pyridinyl)-1,8- naphthyridine platinum system, that exhibits high thermal and protic stability and is an efficient catalyst for methane CH activation. 6.4 Experimental. General Considerations: Unless otherwise noted, all reactions and manipulations were performed in a M-Braun circulating Argon atmosphere glovebox or using standard Schlenk techniques. Glassware was dried in an oven at 150 o C before use. Unless otherwise noted, reagents were purchased from commercial suppliers and used without further purification. Neutral alumina was used in chromatography unless otherwise noted. Diethyl ether, THF and benzene were distilled from sodium/benzophenone ketyl under Argon prior to use. Hexanes and pentane were dried with P 2 O 5 under Argon and kept refluxing under flow of 176 Argon. CH 2 Cl 2 was purified from stabilizer by stirring with concentrated H 2 SO 4 for 4 hours, mixture was separated, organic phase was neutralized with KHCO 3 , dried with MgSO 4 and P 2 O 5 , and refluxed under flow of Argon for 3 days. Organic acids were distilled from P 2 O 5 . Deuterated solvents were degassed by freezing, evacuating, and thawing (3x), and were then dried over 4 Å sieves and stored under Argon. Unless otherwise indicated, NMR spectra were obtained using a Variant Mercury-400 MHz spectrometer (400 MHz for 1H spectra, 100.6 MHz for 13 C? 1 H? ? spectra, 376.5 MHz for 19 F spectra). Chemical shifts are reported in parts per millio relative to residual protiated solvent, coupling constants are reported in Hertz (Hz), and integrations are reported in number of protons. Unless otherwise noted, samples for NMR analysis were prepared using CDCl 3 as the solvent. Kinetic studies were performed using a Shimadzu-QP5000 GCMS or by NMR spectroscopy using a Variant Mercury-400 spectrometer (see above). All reaction mixtures were prepared under Argon and kept under static Ag during the kinetic analyses. For GCMS experiments, ethane standard was introduced. The compounds 2-(2-Pyridinyl)-1,8-naphthyridine were prepared using literature procedures 8 and completely characterized by 1 H, 13 C NMR and elemental analysis. 177 N N N Pt Cl Cl Figure 6.7. (nap)Pt(Cl) 2 complex. “(nap)Pt(Cl) 2 ”. In a 100 mL Schlenk flask, 299.0 mg (1.00 mmol) of PtCl 2 , XXX mg (1.00 mmol) of 2-(2-Pyridinyl)-1,8-naphthyridine, and 50 mL of acetic acid were placed. The solution was allowed to react at 70 o C for 12 hours. The yellow precipitate was filtered off, washed with water, diethyl sulfide, diethyl ether several times and dried in vacuo over 1 day at 120 o C (115 mg, 40% yield). Product is barely soluble in organic solvents and exhibits peaks of at least three different complexes that different from free ligand, at the same time peaks of free ligands are completely missing. Anal. Calcd for C 12 H 6 N 4 O 4 PtF 6 : C, 33.00; H, 1.92; N, 8.88; Cl, 14.98. Found: C, 28.73; H, 1.98; N, 7.35; Cl, 17.3. Cleaner product is not known so far. Deuterium insertion study. In a 3 mL Schlenk flask containing 1mg (2 µmol) of “(nap)Pt(Cl) 2 ”, 0.5mg (2 µmol) of silver trifluoroacetate was added 1mL of TFA-d 1 and 0.1 mL of benzene. The mixture was heated at 85 o C, 100 o C, 115 o C and analyzed by GC/MS. 178 Table 6.1. Deuterium insertion study by (nap)Pt(TFA) 2 in C 6 H 6 /DTFA reaction at 85 o C. time(min) D 0 D 1 D 2 D 3 D 4 D 5 D 6 TOF 0 93.700 6.100 0.200 0.000 0.000 0.000 0.000 0.000 5 93.657 6.119 0.189 0.005 0.010 0.007 0.014 0.012 10 93.445 6.258 0.209 0.014 0.016 0.009 0.048 0.018 20 93.240 6.323 0.241 0.030 0.036 0.006 0.125 0.018 30 92.832 6.552 0.258 0.037 0.061 0.036 0.225 0.022 Table 6.2. Deuterium insertion study by (nap)Pt(TFA) 2 in C 6 H 6 /DTFA reaction at 100 o C. time(min) D 0 D 1 D 2 D 3 D 4 D 5 D 6 TOF 0 93.70 6.10 0.20 0.00 0.00 0.00 0.00 0.00 5 93.12 6.34 0.26 0.04 0.05 0.03 0.16 0.10 10 92.93 6.33 0.29 0.04 0.08 0.04 0.29 0.07 15 92.57 6.40 0.29 0.06 0.13 0.06 0.50 0.08 20 92.25 6.47 0.31 0.05 0.17 0.08 0.65 0.07 179 Table 6.3. Deuterium insertion study by (nap)Pt(TFA) 2 in C 6 H 6 /DTFA reaction at 115 o C. time(min) D 0 D 1 D 2 D 3 D 4 D 5 D 6 TOF 0 93.70 6.10 0.20 0.00 0.00 0.00 0.00 0.00 10 90.16 6.33 0.41 0.18 0.54 0.35 2.03 0.44 15 88.10 6.38 0.50 0.28 0.84 0.72 3.17 0.47 21 86.60 6.18 0.58 0.39 1.10 1.03 4.12 0.44 25 85.01 6.21 0.66 0.48 1.31 1.45 4.89 0.45 30 82.26 6.21 0.83 0.65 1.71 1.97 6.37 0.50 Table 6.4. Deuterium insertion study by (nap)Pt(TFA) 2 in C 6 H 6 /DTFA reaction at 130 o C. time(min) D 0 D 1 D 2 D 3 D 4 D 5 D 6 TOF 0 93.70 6.10 0.20 0.00 0.00 0.00 0.00 5 88.33 6.26 0.52 0.32 0.80 0.76 3.01 1.36 10 82.13 6.04 0.90 0.80 1.78 2.19 6.16 1.51 15 76.22 5.90 1.26 1.30 2.84 3.77 8.73 1.53 20 71.94 5.86 1.54 1.73 3.68 5.12 10.13 1.42 All calculations utilized the Jaguar 6.5 suite, using B3LYP/LACVP**++ with ZPE and solvent corrections for the TFA medium (Poisson-Boltzmann continuum solvent, with e = 8.42 and radius probe = 2.479). 9,10 Diffuse functions 180 were not used for solvents. Furthermore, due to inaccuracies of free energy calculations in solvents, no ? G results have been included. Table 6.5. DFT estimation of thermodynamic data of (nap)Pt(TFA)(TFA) intermediate. nap.Pt.TFA.TFA Gas phase Energy: -1836.7537 hartrees Solvation Energy: -1836.7660 hartrees Zero Point Energy: 155.205 kcal/mol Coordinates: H1 0.0788693042 -0.1887049210 0.0655563427 C2 0.0629895936 -0.0531696352 1.1418315950 H3 0.2133815366 2.0925838923 1.1044845215 C4 0.1404585039 1.1935886768 1.7104807117 N5 -0.0642412428 -1.1041593995 3.3120056910 C6 0.1208748793 1.3107065272 3.1232782994 C7 -0.0472148799 -1.1791178007 1.9970970307 C8 0.0368042759 0.1052818902 3.8875557562 C9 0.1704722435 2.5480868937 3.8001993729 H10 -0.1174335275 -2.1818392451 1.5825481325 C11 0.1189173423 2.5620574093 5.1698059797 H12 0.2386341324 3.4729704133 3.2340971177 H13 0.1391108491 3.5007494101 5.7076464100 C14 0.0505449313 1.3437492534 5.8837878900 N15 0.0417205474 0.1452689273 5.2665433420 C16 -0.0265258082 1.3084212231 7.3526646359 C17 -0.1944499459 0.9782270284 10.0840984663 N18 -0.0717536789 0.0592665555 7.8856146976 181 C19 -0.0699392549 2.4335729121 8.1789053442 C20 -0.1598707629 2.2683297787 9.5576112411 C21 -0.1434698670 -0.1082433473 9.2192509507 H22 -0.0367259107 3.4288691051 7.7536668947 H23 -0.1993590576 3.1351271977 10.2094034035 H24 -0.1445494053 -1.1367277528 9.5609097952 H25 -0.2587285007 0.8036432357 11.1522105418 Pt26 0.0587945867 -1.4758125997 6.5762535250 O27 0.1412540196 -2.8238363853 8.0940728257 C28 -0.9256532565 -3.5365000630 8.3414714887 O29 -2.0124942978 -3.5206285676 7.8020244077 C30 -0.6703575836 -4.4300741405 9.5819100064 F31 -0.4804241730 -3.6348345758 10.6713174373 F32 -1.7126922116 -5.2265616937 9.8399296573 F33 0.4236682003 -5.1967829637 9.4444562265 O34 0.2079515043 -3.0968687827 5.3643040334 C35 1.2854747502 -3.2309265883 4.6605549515 O36 2.2821836886 -2.5295130955 4.6130850484 C37 1.1777412418 -4.4761722796 3.7413301849 F38 0.8095424815 -5.5783836130 4.4150256720 F39 2.3414730273 -4.7333095432 3.1264553362 F40 0.2476341744 -4.2640701406 2.7701188463 Table 6.6. DFT estimation of thermodynamic data of (nap)Pt(TFA)(HTFA) + intermediate. nap.Pt.TFA.HTFA + Gas phase Energy: -1837.1324 hartrees Solvation Energy: -1837.2611 hartrees 182 Zero Point Energy: 166.700 kcal/mol Coordinates: H1 0.0058043112 -0.3161201883 0.0532036624 C2 0.0073736814 -0.1719470603 1.1270446871 H3 -0.1194829546 1.9714904333 1.0639708682 C4 -0.0612403417 1.0859648362 1.6903419611 N5 0.0854757533 -1.1505842796 3.2978598183 C6 -0.0565149970 1.2379472137 3.0988484967 C7 0.0823041426 -1.2873537549 1.9736440068 C8 0.0190173294 0.0691575221 3.9008471730 C9 -0.1224377339 2.4859427059 3.7662611487 H10 0.1444371144 -2.3065624135 1.6086599588 C11 -0.1137298824 2.5152315909 5.1375520711 H12 -0.1804526510 3.4034630795 3.1892162979 H13 -0.1668816121 3.4623431117 5.6576869707 C14 -0.0388953192 1.3107094422 5.8779107966 N15 0.0302074146 0.1075991858 5.2628437813 C16 -0.0378052325 1.2749382828 7.3473011192 C17 -0.0351381901 0.9617753754 10.0863585035 N18 0.0200892781 0.0256996208 7.8946123268 C19 -0.0965549134 2.4022864799 8.1662530393 C20 -0.0962374212 2.2451198596 9.5518659919 C21 0.0234399319 -0.1352872223 9.2279693074 H22 -0.1424588474 3.3955042726 7.7377411042 H23 -0.1437980087 3.1147649736 10.1988515641 H24 0.0701732115 -1.1611930927 9.5771004052 H25 -0.0332319457 0.7939273208 11.1576654825 Pt26 0.0999928501 -1.4981185093 6.5853142174 O27 0.2135606199 -2.7825550779 8.1213473530 183 C28 -0.7790309843 -3.6308232883 8.2915603703 O29 -1.7559179949 -3.7883906050 7.5944037682 C30 -0.5751702771 -4.4015286308 9.6201182481 F31 -0.5732661219 -3.5034594550 10.6433508828 F32 -1.5633563794 -5.2674349324 9.8303737984 F33 0.5929584732 -5.0533517113 9.6432304531 O34 0.1538008646 -2.9053277557 5.0749730532 C35 0.4507721849 -4.2032373488 5.1256097934 O36 0.8179040136 -4.8488478672 6.0663270850 C37 0.2451461212 -4.8275625553 3.7210403637 F38 -1.0444992656 -4.7553611666 3.3500564738 F39 0.6536944382 -6.0818871977 3.6687121977 F40 0.9588712450 -4.1039072687 2.7959413079 H41 0.1334757826 -2.0444500893 3.9539326227 Table 6.7. DFT estimation of thermodynamic data of (nap)Pt(TFA)(C 6 H 6 ) + intermediate. nap.Pt.TFA.C 6 H 6 + Gas phase Energy: -1542.5722 hartrees Solvation Energy: -1567.6702 hartrees Zero Point Energy: 205.704 kcal/mol Coordinates: H1 -0.7395699022 0.1234443938 -0.1015036372 C2 -0.5890475216 0.1613840494 0.9725266361 H3 -0.2776031298 2.2902905263 1.0924860970 C4 -0.3341733401 1.3456359905 1.6275078453 N5 -0.4774407658 -1.0767913959 3.0480623536 C6 -0.1490986011 1.3344100446 3.0345549418 C7 -0.6548856211 -1.0290958672 1.7387363298 184 C8 -0.2228045364 0.0740779074 3.7047077339 C9 0.0886525272 2.4999582495 3.7979657215 H10 -0.8633616761 -1.9808369856 1.2486091814 C11 0.2080525652 2.3924234040 5.1595053997 H12 0.1588633725 3.4663760562 3.3060688012 H13 0.3705620354 3.2760548671 5.7621447489 C14 0.1224806305 1.1242851112 5.7769674558 N15 -0.0493490888 -0.0127217780 5.0691306085 C16 0.1619769980 0.9774750558 7.2411280127 C17 0.0267297596 0.4702663508 9.9492363810 N18 0.0481629780 -0.3010951168 7.6923626446 C19 0.2428735617 2.0401714251 8.1432977662 C20 0.1822164419 1.7848529391 9.5119192218 C21 -0.0358190114 -0.5546376260 9.0092001590 H22 0.3433455077 3.0601262180 7.7909033897 H23 0.2470384325 2.6047801382 10.2213977630 H24 -0.1506414135 -1.5933040538 9.2930294791 H25 -0.0402649224 0.2264353760 11.0032779008 Pt26 0.1142910806 -1.7504884283 6.2514318862 O27 0.2948518459 -3.1848931019 7.6736767746 C28 1.4808308429 -3.2923363140 8.2253786528 O29 2.5035225923 -2.6872217861 7.9536692795 C30 1.4260884906 -4.2983656445 9.4063883005 F31 0.9372190659 -5.4871879125 9.0119706898 F32 2.6328570068 -4.4792377619 9.9409291631 F33 0.6019164084 -3.8040918488 10.3673653803 H34 1.1921886391 -2.5953091356 3.9222628577 C35 0.8145210824 -3.3327030861 4.6152581790 C36 -0.2071252626 -5.6082523160 5.9034628609 185 C37 -0.5955958068 -3.5198748637 4.7414446187 C38 1.7031285058 -4.3140224160 5.1385749909 C39 1.1933657855 -5.4388623936 5.7593383599 C40 -1.0917534211 -4.6652948562 5.4143990459 H41 -1.2627951614 -2.8769158742 4.1897076669 H42 2.7794630629 -4.1792974084 5.0287616368 H43 1.8677300436 -6.2011388205 6.1428265713 H44 -2.1683671904 -4.8098251874 5.5149614903 H45 -0.5882556375 -6.5009501136 6.3986525865 Table 6.8. DFT estimation of thermodynamic data of (nap-H-Ph)Pt(TFA) + transition state. ts_nap.Pt.Ph-H-TFA + Gas phase Energy: -1542.5514 hartrees Solvation Energy: - 1542.6625 hartrees Zero Point Energy: 202.237 kcal/mol Coordinates: H1 -0.2507558929 -0.5391203569 -0.0417963482 C2 -0.1906123100 -0.3640787451 1.0261895527 H3 -0.1599051789 1.7806058468 0.8946487778 C4 -0.1406318818 0.9121265632 1.5466437415 N5 -0.0881276226 -1.2954688173 3.2252102320 C6 -0.0614372484 1.1008420231 2.9488082881 C7 -0.1591496111 -1.4580003474 1.9131319673 C8 -0.0391513885 -0.0580924309 3.7690975539 C9 -0.0016776087 2.3613158217 3.5929644524 H10 -0.1907472900 -2.4846963404 1.5584554819 C11 0.0731164990 2.4106130239 4.9623655906 H12 -0.0152232644 3.2722226905 3.0024720825 186 H13 0.1194826769 3.3669327449 5.4666477500 C14 0.0898350301 1.2168868861 5.7254573899 N15 0.0339326988 0.0052603145 5.1310441664 C16 0.1623911130 1.2036076822 7.1966612114 C17 0.2655749829 0.9212085956 9.9341573790 N18 0.1535726375 -0.0360023873 7.7537887090 C19 0.2313981836 2.3447206346 7.9971610342 C20 0.2867981742 2.1995752827 9.3832478584 C21 0.1966637132 -0.1825105633 9.0841770418 H22 0.2439320763 3.3343441277 7.5567655828 H23 0.3444561133 3.0763299317 10.0200064990 H24 0.1767690729 -1.2035863153 9.4498391405 H25 0.3038205635 0.7672453199 11.0068185450 Pt26 0.1083973161 -1.6222168952 6.3836059120 O27 0.1264705091 -2.9953552480 7.8775977887 C28 1.2853782597 -3.4978645503 8.2198194803 O29 2.3702041088 -3.3367716933 7.6955662747 C30 1.1398063943 -4.3307307120 9.5179888496 F31 0.1873453572 -5.2688454724 9.4056389851 F32 2.2876317494 -4.9222052851 9.8476107812 F33 0.7877771243 -3.4979983411 10.5333343549 H34 -0.0160104320 -2.2934365333 4.1262070668 C35 0.0821920921 -3.2709298341 5.0577791225 C36 0.1337496437 -6.0051024227 4.3664098943 C37 -1.1153257808 -4.0305519257 4.9634660090 C38 1.3085214330 -3.9434848273 4.8039344299 C39 1.3321296561 -5.2895059883 4.4539070192 C40 -1.0914438765 -5.3763997712 4.6160825018 H41 -2.0689537533 -3.5443612140 5.1533280035 187 H42 2.2416365590 -3.3951985904 4.8875240497 H43 2.2784081862 -5.7865315807 4.2626692872 H44 -2.0168267871 -5.9401305847 4.5456658640 H45 0.1535830668 -7.0579015538 4.0985888990 Table 6.9. DFT estimation of thermodynamic data of (nap)Pt(TFA)(Ph) intermediate. nap.Pt.TFA.Ph Gas phase Energy: -1542.5623 hartrees Solvation Energy: -1542.6910 hartrees Zero Point Energy: 205.791 kcal/mol Coordinates: H1 0.3446020051 -0.1844575742 -0.0842206622 C2 0.2490275949 -0.0950094734 0.9912023102 H3 -0.0604205072 2.0310986531 1.0082879380 C4 0.0241753958 1.1253235975 1.6020082212 N5 0.2483138134 -1.1440388245 3.1192610747 C6 -0.0881664699 1.2168525044 3.0093094025 C7 0.3634296990 -1.2334659853 1.7938319786 C8 0.0249952836 0.0273437536 3.7770734942 C9 -0.2904069716 2.4273165664 3.7175883160 H10 0.5485046869 -2.2279985983 1.4027452904 C11 -0.3265361327 2.3944057858 5.0866003121 H12 -0.3952853790 3.3613350057 3.1756186186 H13 -0.4479876392 3.3143597454 5.6427043665 C14 -0.1918793112 1.1714801353 5.7915443875 N15 -0.0591428008 -0.0130469122 5.1363980246 C16 -0.1427420801 1.1202752301 7.2611487945 C17 0.0823324855 0.7946269208 9.9848049875 188 N18 0.1299888934 -0.1035278985 7.7768739054 C19 -0.3233003887 2.2269130822 8.0969873459 C20 -0.2071451034 2.0584175962 9.4757266627 C21 0.2386103456 -0.2726763443 9.0994617945 H22 -0.5574508979 3.2048066351 7.6949834198 H23 -0.3437123081 2.9052184931 10.1402295028 H24 0.4440868638 -1.2855166019 9.4313015296 H25 0.1822949980 0.6250871835 11.0512257163 Pt26 0.1357103318 -1.6909481439 6.3468164494 O27 0.3566809751 -3.0677194074 7.8122587589 C28 1.5501625749 -3.5797390918 7.9764786202 O29 2.5493451937 -3.4175852201 7.3032820943 C30 1.5878439812 -4.4260884520 9.2731448607 F31 0.6326252839 -5.3670589766 9.2827125222 F32 2.7726502156 -5.0145012915 9.4347711735 F33 1.3764422418 -3.6045624137 10.3361091451 H34 0.2977543826 -2.0162656853 3.7081401125 C35 -0.0780879573 -3.2305107761 5.0293302749 C36 -0.4596503608 -5.4010652763 3.2577878732 C37 1.0178477073 -3.9850095519 4.5607357548 C38 -1.3710301064 -3.6002413854 4.5972842456 C39 -1.5585799618 -4.6759699441 3.7267432454 C40 0.8259220296 -5.0530034390 3.6751396893 H41 2.0167708620 -3.7492946682 4.9147402436 H42 -2.2386817603 -3.0507226712 4.9534994618 H43 -2.5635146726 -4.9506931170 3.4177143091 H44 1.6845642106 -5.6226710231 3.3295390853 H45 -0.6063735933 -6.2368452538 2.5796472524 189 Table 6.10. DFT estimation of thermodynamic data of (nap-H-CH3)Pt(TFA) transition state. ts_nap-H-CH3.Pt.TFA + Gas phase Energy: -1350.7924 hartrees Solvation Energy: -1350.9200 hartrees Zero Point Energy: 168.787 kcal/mol Coordinates: H1 -0.1201659888 -0.2547510778 0.1170253394 C2 -0.1021399424 -0.1023498710 1.1900395004 H3 -0.1854173906 2.0432995838 1.1006219390 C4 -0.1378686537 1.1644363867 1.7369348847 N5 -0.0155168931 -1.0883201270 3.3675489296 C6 -0.1095971605 1.3226109536 3.1453883045 C7 -0.0402324835 -1.2192067465 2.0489004639 C8 -0.0463297279 0.1418786111 3.9243897776 C9 -0.1352235270 2.5583689730 3.8423008960 H10 -0.0098984052 -2.2334449137 1.6600517092 C11 -0.0932660507 2.5619002040 5.2166207808 H12 -0.1847495713 3.4901625093 3.2874499604 H13 -0.1078768820 3.4999039582 5.7574126497 C14 -0.0255928731 1.3412914811 5.9332645564 N15 -0.0079737865 0.1623084806 5.2827025608 C16 0.0374252595 1.2324921981 7.3978418087 C17 0.1649379072 0.7560918605 10.1067071919 N18 0.1222692129 -0.0464859468 7.8628774944 C19 0.0163262004 2.3114028278 8.2800599365 C20 0.0827211047 2.0692861568 9.6524181979 C21 0.1805949858 -0.2864757423 9.1802576143 190 H22 -0.0519158804 3.3272091805 7.9092813737 H23 0.0691087797 2.8977584048 10.3528881125 H24 0.2407256478 -1.3302664772 9.4690484700 H25 0.2172414026 0.5259848003 11.1650356297 Pt26 0.1372903918 -1.5241179477 6.4137802537 C27 0.1603724747 -3.2717018896 5.0628670813 H28 1.1547000549 -3.6591212889 5.2864983854 H29 -0.0303160651 -3.5025139445 4.0030212163 H30 -0.6201538644 -3.8213645564 5.5916161756 H31 0.0478406540 -2.0587383199 4.3199172048 O32 0.2299106624 -2.9603308031 7.8465536108 C33 1.3760701844 -3.5660513964 8.0539639556 O34 2.4000316506 -3.4890941803 7.4069300150 C35 1.2955976690 -4.4212379874 9.3439805237 F36 0.2981194987 -5.3156765332 9.2774808060 F37 2.4385872588 -5.0645941220 9.5700961094 F38 1.0531916857 -3.6023266864 10.4011364564 191 6.5 Chapter Six References 1 (a) Periana, R. 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R.; Oxgaard, J.; Mironov, O. A.; Young, K. J. H.; Goddard III, W. A.; Periana, R. A. J. Am. Chem. Soc. 2006, 128, 7404. 4 Dannhauser, W.; Cole, R. H. J. Am. Chem. Soc. 1952, 74, 6105. Harris, F. E.; O'Konski, C. T. J. Am. Chem. Soc. 1954, 76, 4317. 5 Jaguar, version 6.5, Schrodinger, LLC, New York, NY, 2005. For further details, see supporting information 6 Majewicz, T. G.; Caluwe, P. J. Org. Chem. 1974, 39, 720. 7 Calculations with charge change are still on cutting edge of science and can be corrected later, however, the correction should not exceed 5 kcal/mole. 8 Ezell, E. L.; Thummel, R. P.; Martin, G. E. Journal of Heterocyclic Chemistry 1984, 21(3), 817; Campos-Fernandez, C. S.; Ouyang, X.; Dunbar, K. R. Inorganic Chemistry, 2000, 39(12), 2432; Campos-Fernandez, C. S.; Thomson, L . M.; Galan-Mascaros, J. R.; Xiang, O.; Dunbar, K. R. Inorganic Chemistry 2002, 41(6), 1523. 9 Dannhauser, W.; Cole, R. H. J. Am. Chem. Soc. 1952, 74, 6105. Harris, F. E.; O'Konski, C. T. J. Am. Chem. Soc. 1954, 76, 4317. 10 Jaguar, version 6.5, Schrodinger, LLC, New York, NY, 2005. For further details, see supporting information 192 7 Chapter Seven: CH Activation Perspective in a Weakly Acidic Media 7.1 Introduction The reported degenerate reaction of H/D exchange is a convenient tool for detecting CH activation and does not have longgoing practical applications. The major role of CH activation is to form M -C complex. 1 The last is a very reactive species and useful synthetic intermediate. The complete catalytic cycles were always in mind during CH activation development as the ultimate objects. The significant advantage of CH activation step is an exceptional selectivity based on electronic properties of bond. From selectivity point of view, CH activation does not have an alternative. At the same time, reactivity of plain hydrocarbons is not sufficient for industrial use. The importance of synthetic reactions with plain hydrocarbons allows deeply concentrate on the detailed study of CH activation. Here, the next steps and new directions are presented to fulfill the picture. Four major directions of further study can be persuded: 1) developing new naphthyridine-type ligand with high affinity to metal and high stability to oxidant as well as reaction media and themperature; 2) investigation of naphthyridine-type 193 ligand effect on entropy of CH activation; 3) investigating possibility for new Pd(II)/Pd(I)/Pd(0) catalytic cycle in organic solvents; and 4) developing stereoselective CH activation chemistry. 7.2 Discussion. New naphthyridine-type ligands. The first step in developing new catalyst is to born idea or concept for new phenomenon, reactivity in the presented case. The next step is to support idea by specific system experimentally and theoretically. Even if the idea was supported and high reactivity was indeed achived, it will take a lot of effort as well as luck to develop v aluable catalytic system, which is stable selective and chemically compartible with all reactants. The satisfaction of all these conditions together in one pot would make practical catalyst, which is the ultimate object. In chapter 5 the enhanced CH activation reactivity in weakly acidic media was reported catalyzed by Pt(pic)TFA 2 . It is believed that the catalyst activity was inhenced by resting state destabilization. Such approach to rate acceleration is in logical contradiction with stability requirement on catalyst. At present, it is difficult to imagine the way to overcome such philosophic contradiction. On the other hand, in chapter 6 the enhanced reactivity was reported based on transition state stabilization effect. Having achieved high rate, the idea does not 194 create additional restrictions on complex stability. Therefore, even highly affinic systems would exhibite high rate to CH activation. It was established by engeeners that themperature in a range 150 o C - 200 o C ideal for industrial synthesis. Lower temperatures require complicated cooling system, higher temperatures and pressures increase the capital costs. The catalyst should maintain it reactivity at such temperature for long time, TON > 10 6 . One of the best to day catalytic methane to methanol process by (bpym)PtCl 2 in sulfutic acid, which is highly stable for long time, was born from initial results with unstable (NH 3 ) 2 PtCl 2 according to the authors. It is necessary to employ this positive experience to increase ligand affinity and stability toward multiple challenges of new naphthyridine ligands. It is difficult to predict any specific structures; however, increase of nitrogen content can be one of possible improvement. Due to electrophilic character of CH activation more electron deficient ligand will be less acceptable to CH activation attacks. At the same time, electron-deficient molecules are less susceptible to oxidation and more significantly have higher degree of affinity to methal center compare to electron rich due to favourable p-bonding. It would be interesting to notice, that highly reliable bio-system use nucleotide that are derivatives of bipyrimidine ring and purin two-ring. It suggests that two-ring system can be made highly stable by introducing more nitrogen in ring. Specific details are a part of outgoing investigation. 195 Entropic Effect. The profound investigation of catalytic mechanism , that our group tends to conduct, allows observing unusual features of specific systems. It was found for Pt(bpym)TFA 2 and Pt(pic)TFA 2 unique temperature dependence of CH activation thermodynamics. Specifically, ?S ‡ was huge and negative, ~ -140 eu. The physical meaning of entropy suggests that resting state and rate determining transition step have different degree of freedom . Indeed, it is difficult to organize six atoms at specific positions. Having observed this, Ryabov paper 2 was found that predict 6-membered cyclic transition state geometry based on similar entropic effect in different system. It was attempted to similate entropic effect theoretically, but all our effort failed (we are an experimental group overall). -12 kcal mole -1 rewards in CH activation transition state at 200 o C due to this entropic effect would dramatically improve methane reactivity. In order to preorganized transition state the Pt(nap)TFA 2 system was design. In addition to the entropic effect the last promised enthalpic benefits as described in chapter 6. Benzene/DTFA HD exchange test suggest that CH coordination is a rate determining step. Therefore, the entropic effect is hidden in case of benzene. The experiment cannot be conclusive in case of methane because of complicated kinetics as result of insaficient stability of catalyst. In order to reach deep understanding of the entropic effect and the ways to manipulate it the more stable catalyst is require. Specific details are a part of outgoing investigation. 196 Pd(II)/Pd(I)/Pd(0) catalytic cycle. One successful catalytic system inspire a creation of new mechanistic cycles. It is known for long time that one of the major challenges in catalytic palladium chemistry is precipitation of metal cluster. Formation metal cluster become possible due to different catalytic cycle of Palladium compare to Platinum. The first one tends to reductively eliminate a product from +2 oxidation state in contrast to platinum which require to be oxidized to Pt(IV) to make analogos oxidation step. Reductive elimination produce unstable and labile Pd(0), that tends to form catalytically inactive, solid metal clusters. Present straightforward approach to the problem suggests kinetically fast oxidants to prevent cluster formation. The enhanced rates raise a question about unprecedented selectivity of such oxidation. The oxidation of starting material and even product are undesired side reaction that is difficult to eliminate. At the same time, the compartibility of multiple reagents becomes a significant issue. There is fundamental problem with such approach: by using kinetics, it is not possible to change thermodynamics equilibrium. If Pd cluster remains the resting state of this system, eventually such catalyst will die. For long-lived system one should provide new stable resting state. One of such opportunities can be ligand stabilized Pd-Pd dimmer complex. As soon as Pd(0) will form, it will create complex with Pd(II) in similar maner as Hg(0) is react with Hg(II) to form actual reasting state for mercury methane to methanol process in sulfuric acid. 197 There are multiple dimmer complexes known for Pd and Pt. Naphthyridine–type ligand will significantly stabilize such state. At the same time, we will have better control on this system by controlling stabilization energy. This is impossible to do for mercury system. Ultimately, it will be possible to dissolve Pd clusters by ligand and Pd(II) as catalyst to dimmeric Pd(I)-Pd(I) state and further to monomeric Pd(II) by conventional oxidant as air and Cu(II). Similar mechanism can be potentially applied to nickel as well as Cobalt. Specific details are a part of outgoing investigation. Stereoselective CH activation. Unusual feature of CH activation is selectivity. Indeed, the activation of unpolar methane proceeds faster than polar methanol molecule. Such phenomenons are very rear and attract attention of chemists. Pharmaseutical industry often requires enantiomerically pure substances. Reported examples of the highly enantioselective include hydrogenation, hydrosylation, and hydroboration of unsaturated compounds, eposidation of allylic alcohol, hydrovynilation, hydroformylation, cyclopropanation, and isomerisation of olefins, vicinal hydroxylation, propylene polymerization, organometallic addition to aldehydes, allylic alkylation, organic halide-organometallic coupling, aldol type reactions, and Diels-Alder reactions. Direct application of enantioselective CH activation does not look promising due to 1 o > 2 o > 3 o selectivity of CH activation. However, the catalytic cycles similar to BINAP-type complexes 3 are possible. The significant difference between BINAP and naphthyridine-based system can be in electronic properties. 198 BINAP tend to operate at electronically rich condition under reducing atmosphere of H 2 . Pt(nap)TFA 2 desigh to work at oxidative conditions and electron-deficient acidic media. Useful application may include enantioselective hydroxylation of alkenes. The synthesis of naphthyridine-based ligand with stereochemistry is critical for such catalysis. Specific details are a part of outgoing investigation. 7.3 Conclusion Deeper understanding of the C-H activation and the exploiting the physical nature of C-H bonds leaded to the development of the next generation of hydrocarbon conversion catalysts. The fauther step have a potential to develop new paradigms in energy and petrochemical technologies and ultimately in the quality of human life. 199 7.4 Chapter Seven References 1 (a) Periana, R. A.; Taube, D. J.; Gamble, S.; Taube, H.; Satoh, T.; Fujii, H. Science 1998, 280, (b) Shilov, A. E.; Shul’pin, G. B. Activation and Catalytic Reactions of Saturated Hydrocarbons in the Presence of Metal Complexes Kluwer Academic; Dordrecht, 2000. 560 (c) Jia, C.G.; Kitamura, T.; Fujiwara, Y. 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Asset Metadata

Creator Ziatdinov, Vadim Rinatovich (author)

Core Title Activation of methane by homogeneous catalyst in weakly acidic solvents

School College of Letters, Arts and Sciences

Degree Doctor of Philosophy

Degree Program Chemistry

Publication Date 05/17/2007

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag CH activation,methane,OAI-PMH Harvest,Shylov reaction

Language English

Advisor Periana, Roy A. (committee chair), Olah, George A. (committee member), Steier, William H. (committee member)

Creator Email vadimius@gmail.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-m488

Unique identifier UC1234265

Identifier etd-Ziatdinov-20070517 (filename),usctheses-m40 (legacy collection record id),usctheses-c127-496638 (legacy record id),usctheses-m488 (legacy record id)

Legacy Identifier etd-Ziatdinov-20070517.pdf

Dmrecord 496638

Document Type Dissertation

Rights Ziatdinov, Vadim Rinatovich

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Repository Name Libraries, University of Southern California

Repository Location Los Angeles, California

Repository Email uscdl@usc.edu

Abstract (if available)

Abstract This dissertation describes the latest development in engaging simple hydrocarbons in reaction by CH activation. From initially fuming oleum condition and catalysis like halogens, the trend goes to gold catalyst in 96% sulfuric acid, and later to variety platinum complexes in weak organic acids. The story concentrates on discovery of basic physical phenomenons to enhance reactivity versus specific synthetic applications. -- Chapter One introduces the C-H activation and functionalization of alkanes via the electrophilic mechanism, and discusses the role of non-coordinating solvents and the related problem of inhibition of electophilic catalysts by products such as methanol and water. The simplest iodine and mercury in sulfuric acid catalysts described.