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Design and synthesis of a new phosphine pincer porphyrin
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Design and synthesis of a new phosphine pincer porphyrin
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Content
DESIGN AND SYNTHESIS
OF A NEW
PHOSPHINE PINCER PORPHYRIN
by
Marc Hombeck
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
M aster of Science
(Chemistry)
December 1994
Copyright 1994 Marc Hombeck
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UNIVERSITY O F S O U T H E R N C A L IFO R N IA
T H E G R A D U A TE S C H O O L
U N IV E R S IT Y P A R K
L O S A N G E L E S . C A L IF O R N IA 9 0 0 0 7
This thesis, written by
under the direction of h is. Thesis Committee,
and approved by all its members, has been pre
sented to and accepted by the Dean of The
Graduate School, in partial fulfillment of the
requirements for the degree of
D tan
Date.. N ° .Y e5 ? b e r 30 , 1994
THESIS COMMITTEE
Ch.aXfm.an
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Meiner Familie Friedrich, Christel undJan Hombeck
und Marie-Annette
ii
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Life is so unlike Theory
Anthony Trollope
Phineas Finn
iii
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Acknowledgement
This work would never have been accomplished without the great help of so many people
who I all would like to thank. Although I am not able to mention everybody I will never
forget their support. Very special thanks to...
...my advisor Christopher A. Reed for his general enthusiasm about chemistry and
his steady helpful interest in and support of my research - even if it did not work.
I
\
s
...my labmate, Professor Peter D.W. Boyd whose practical and theoretical
knowledge about porphyrins helped me very much in this work. Thank you for the
chemical discussions and the insight in the New Zealand way of life (I will clean
my bench soon!!).
J .
...Robert W. Reed, my sometimes sole postdoc, who eased my first steps into
the laboratory work, led me to the secrets of NMR and has always been helpful
answering my uncountable questions. Thank you for never getting tired of
questioning my results to prevent me from becoming lazy and for taking so
much time to "rip up" my various thesis versions.
...Kristel Heerwegh for getting excited about my research when it came to por
phyrin chemistry, introducing me to UV-VIS and joining me in several enjoyable
opera evenings.
..Bob Bolskar and Raj Mathur for their delightful, controversial discussions
about virtually everything.
..Janet Manning for lending me her computer for the thesis.
...Zuowei Xie for having a critical look at my too small crystals.
...Tatiana Drovetskaya and Yongping Sun, the "inhabitants of the last lab" on this
floor, for always giving me a smile when I asked them for glassware.
i v
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...my roomates Holger Henke (Praktizierte Innerdeutsche Vereinigung) and Klaus
Weber for making L.A. a home.
..Jim Merritt, who always repaired my glassware in time to help me becoming
"Rich and Famous."
...our graduate advisor Paul Langford, without whom the USC-bureaucracy would
have been an inpenetrable jungle.
...Allan Kershaw who helped iqie in my NMR work.
s
...Jay Struckhoff for several neccessary coffee breaks.
...Christian Mult, Siephun Beifuss, Muriin Eberharui and Andreas Fugmann, the
"Ulmers", who initiated football-mania and were my emotional support on many
J.
grey days. Thanks for several unexpected dinners.
...Arwed Burrichter, die old "Adenauer", for easing my first weeks in LA.
...Herwig Heegewald, the new "Adenauer", for interesting discussions and
keeping the ballance between chemistry and life outside die lab.
...my parents and my brother for never stopping to believe in me and sharing my
experiences and problems here. Thank you for the wonderful vacation.
...my girlfriend Marie-Annette, who waited for me to come home, for her long
distance support and encouraging hugs and love.
...the Konrad Adenauer Stiftung for giving me the opportunity and financial
support to come to USC.
v
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Table of Contents
page
Dedication ii
Acknowledgments iv
List of Figures x
List of Spectra xii
Abstract xiii
C hapter 1. Introduction 1
Porphyrins 2
J
Oxygen Storage and Transport. 2
Oxidation of Organic Compounds 3
Bimetallic Porphyrins 5
Cytochrome c Oxidase 5
Model Compounds 7
Oxygen Reduction 7
Oxygen Reduction via Cofacial Porphyrins 8
Nitrogen Reduction 9
Dihydrogen Activation 9
Peroxide Disproportionation and Water Oxidation 9
Electron Transfer 10
Iridium(I) and Rhodium(I) Complexes 11
Mononuclear Compounds 11
Binucleating Ligands 12
v i
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Binucleating Ligands 12
Hydroformylation Reactions 13
Interaction with other metals 13
Our Approach 14
Phosphine Ligand 14
Porphyrin Formation 14
Linkage of the Ligand System 15
Ligand Design 15
Goal 16
References 17
Chapter 2. aaaa-5,10,15,20-tetra-(rj-arhinophenyl)porphyrin 22
Procedure 22
Reaction Scheme 23
Experimental Procedure 24
References 25
Chapter 3. The Acid Production and the Bromine-Diphenylphosphorous
Exchange 26
The 5-Bromo-isophthalic Acid 26
Oxazolines as Protective Groups 27
Production by Dean Stark Method 27
Production via an Acid Chloride 28
Production by Triphenylphosphine 29
Production by Using the Aminoalcohol as Solvent 30
Bromine - Phosphorous Exchange 30
vt t
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Direct Treatment with /i-Butyllithium 30
Palladium Cross Coupling 31
Ester Formation 32
Formation of the other Starting Materials 32
The Coupling Reaction 33
Mechanism 35
Monitoring the Reaction 35
* H-NMR Monitoring 36
31p-NMR Monitoring 37
The Ester Cleavage 38
Experimental Procedures 38
References 42
Chapter 4. Linkage of DPPIA with the Porphyrin 44
Coupling by DCC 44
Coupling by Active Esters 45
Coupling by Acid Chlorides 45
The Reaction Procedure 47
1 H-NMR of the Phosphine- and Phosphine oxide
Pincer Porphyrin 48
^H-COSY of the Phosphine Pincer Porphyrin 49
Assignment of the Proton - NMR 50
Experimental Procedures 51
References 53
viii
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C hapter 5. Metal Complexation and Future Outlook 54
Rhodium Complexation 54
Iridium Complexation 55
Experimental Procedures 55
Future Outlook 57
Expected Chemistry 57
Oxygen Reduction 57
Hydroformylation Reactions 58
References 58
ix
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List of Figures
page
Figure 1.1 Schematic View of a Pincer Porphyrin 1
Figure 1.2 Porphyrin in a Flat View 2
Figure 1.3 Proposed Reaction Cycle of Cytochrome P450 Monooxygenase 4
Figure 1.4 Scheme of a Strapped Porphyrin
j
5
Figure 1.5
* \
Schematic View of Cytpcliroine c Oxidase 6
Figure 1.6 Proposed Reduction Pathway of Cytochrome c Oxidase 6
Figure 1.7 Scheme of a Cofacial Porphyrin 8
Figure 1.8 Schematic View of the Bismanganese Porphyrin 10
Figure 1.9
fl.
Four Characteristic Reactions of Vaska's Compound 12
Figure 1.10 Schematic View of Common Bisphosphine Ligands 13
Figure 1.11 Ortho Functionalized Tetraphenylporphyrin 15
Figure 1.12 Schematic View of the Desired Pincer Porphyrin Ligand 17
Figure 2.1 Reaction Scheme of the Porphyrin Formation 23
Figure 3.1 Oxidation of 5-bromo-w-xylene 26
Figure 3.2 Oxazoline Formation via Dean Stark method 27
Figure 3.3 Oxazoline Formation via an Acid chloride Intermediate 28
Figure 3.4 Oxazoline Formation via Triphenylphosphine Activation 29
Figure 3.5 Oxazoline Formation via Using Aminoalcohol as Solvent 30
Figure 3.6 Bromine - Diphenylphosphorous Cross Coupling 31
Figure 3.7 Ester Formation 32
Figure 3.8 Preparation of the Dibenzonitrile-palladium(II)-dichloride 32
Figure 3.9 Preparation of Trimethylsilyl-diphenylphosphine 33
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Figure 3.10 Proposed Mechanism of the Cross-Coupling Reaction 34
Figure 3.11 Cleavage of the 5-Diphenylphosphino-isophthaloyl diethylester 38
Figure 4.1 Reaction Scheme of DCC 44
Figure 4.2 Reaction Scheme of the Succinimide Ester 45
Figure 4.3 Reaction Scheme of Oxalyl Chloride 46
Figure 4.4 Reaction Scheme of the Coupling Reaction 47
Figure 4.5 Schematic View of one Part of the Ligand 50
Figure 5.1 Schematic Formation'of the Rhodium Complex 54
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List of Spectra
page
Spectrum 1 ^H-NMR Monitoring 36
Spectrum 2 3lp-NMR Monitoring 37
Spectrum 3 1 H-NMR spectra of the Phosphine and Phosphine
oxide Pincer Porphyrin 48
k
t
Spectrum 4 ^H-COSY of the Pnqsphine Pincer Porphyrin 49
Spectrum 5 31p_NMR of the Rhodium Inserted
Pincer Porphyrin 56
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Abstract
The synthesis and characterization of a novel phosphorous pincer porphyrin are
v
t
described. Herein aaaa-(5,10,15,2!0)-o-aminophenyl porphyrin (TAP) and 5-diphenyl-
phosphino-isophthalic acid (DPPIA) are linked via amide bonds.
The TAP is produced through a literature method. For preparation of DPPIA first
5-bromo-isophthalic acid is formed by the oxidation of 5-bromo-m-xylene. After failure
of protecting die carboxylic acid groups by bisoxazoline formation, the diediylester is pre
pared, followed by a palladium cross coupling reaction of the 5-bromo-isophthalic acid
with trimethylsilyl-diphenylphosphine. Cleavage of the 5-diphenylphosphino-isophthaloyl
diethyl ester leads to DPPIA. DPPIA is transformed to its acid chloride and then linked to
the porphyrin. This compound has been fully characterized by ^H-, 31p.NM R,
UV-VIS and FAB-mass.
Rhodium and Iridium-metal complexation was attempted.
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1. Introduction
This thesis describes the synthesis of a pincer porphyrin. Pincer porphyrins
contain two bridged ligands - like the pincers on a crab - which can coordinate a second
metal atom above the porphyrin plane.
— L —
V
M
Figure 1.1: Schematic View of a Pincer Porphyrin.
Thus, pincer porphyrins can bind two metais in close proximity. In some pincer por
phyrins these two metals have electronic interactions and such compounds have been used
to mimic biological systems with bimetallic active sites. *
The ligand synthesized in this project links together two phosphine iigands and a
porphyrin. These ligands allow the access to platinum group complexes which are
normally not encountered in biological, porphyrin-containing systems. Stiil there are
similarities in their chemistry: Vaska’s compound, Ir(CO)Cl(PPh3)2, binds oxygen, as do
some porphyrin metal complexes which occur in biological systems. Of these biological
systems some of them reduce oxygen to water, whereas their monoporphyrin mimics just
reduce it to hydrogenperoxide. The combination of both metals in a mutual ligand might
improve the binding and reduction of oxygen.
This chapter is a summary of metal porphyrins and platinum group metal com
plexes with special emphasis on the chemistry they have in common. Some of these
1
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similarities include the binding of small molecules like dihydrogen and dinitrogen and their
reactions with oxygen.
1.1. Porphyrins
The study of metallo-porphyrin systems is a large area of research. In this
introduction only a few selected areas related to this work will be discussed.
Porphyrins consist of four pyrrole rings in a conjugated ring system that is able to
complex metals in its core. This porphyrin ring can easily be modified at its pyrrole or
meso-positions. These modifications lead to the large variety of known substituted
porphyrins.2
1.1.1. Oxygen Storage and Transport
One important area of porphyrin utilization is in the storage and transport of
oxygen. The most important example for this type of chemistry is found in nature. The
proteins hemoglobin and myoglobin bind oxygen in the lungs and transport it to the
muscle tissues where it is released. The binding site, consisting of an iron porphyrin, has
to undergo structural changes, causing cooperative changes in the protein, in order to bind
or release oxygen. The structure and function of these heme proteins has been widely
Pyrrole-positions Mcso-position
Figure 1.2: Porphyrin in a Flat View.
2
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explored and is quite well u n d e r s t o o d . ^ a series of model compounds^ starting with the
“picket fence” porphyrin^ helped in the understanding of the basic principles that the
oxygen binding heme must have a sterically hindered fifth ligand and a vacant site. This
site must be protected against autoxidation by a hydrophobic pocket. Recently a com
pound produced by Collman et alP was even able to mimic the enhanced preference of
oxygen binding versus carbon monoxide binding.
1.1.2. Oxidation of Organic Compounds
Iron porphyrins mediate the stereospecific oxidation of organic compounds. In
nature cytochrome P450, which occurs in the liver of many animals, oxidizes suitable
substrates to alcohols thus making them water soluble and therefore excretable7 The
active site, an iron porphyrin, binds molecular oxygen and the substrate through a
hydrophobic pocket in close proximity . Due to this proximity the oxidation, which is
believed to proceed via a radical mechanism, can be stereospecific.^ According to this
mechanism, the substrate is first bound to the vacant side of the iron porphyrin. Addition
of oxygen and supply of one electron forms a low spin oxygen adducL This turns into an
active intermediate by the addition of another electron and the loss of one water molecule.
Expelling of the oxidized substrate returns the enzyme to the resting state (figure 1.3).
Recently Collman et al. were able to build a model compound for this reaction site which
mimicked this close proximity binding of oxygen and a substrate well.6
3
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Substrate Sub (R-H)
En-Feln Us.
resting state
Sub-OH XO
By-pass
"Shunt"
En*-Sub-KcIV= 0
active oxygen intermediate
e' (Fe2S2) H ,0
Figurel.3: Proposed Reaction Cycle of Cytochrome P450 M onooxygenase.*
Synthetic models of this system have many applications.
Inoue et al. managed to carry out an enantiomerically specific epoxidation by catalysis
with a strapped p o rp h y rin .9 The strap makes the prochiral dihexyldeuteroporphyrin chiral
and so one enantiomer is preferentially epoxidized (figure 1.4).
Another reaction of this type is reported by Traylor et al. 10. They use a highly
halogenated porphyrin to catalyze the hydroxylation of norbomene in high yields. Due to
the loss of stereochemistry and a large isotope effect they propose a free radical cage pro
cess similar to the reaction catalyzed by the enzyme cytochrome P450 monooxygenase.
4
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Figure 1.4: Schem e of a Strapped Porphyrin.
1.2. Bim etallic Porphyrins
Monomeric porphyrins undergo a great variety of reactions. The introduction of a
second metal center in close contact may dramatically change or enhance such reactivity.
1.2.1. Cytochrome c Oxidase
Chemists have been interested in the structure and mechanism of cytochrome c
oxidase for a long time. This enzyme has been drawing a lot of attention to porphyrin
chemistry due to its unique oxygen reduction and its yet unsolved mechanism.
Cytochrome c oxidase is a membrane-incorporated enzyme that catalyzes the ter
minal reaction of the so called respiratory chain; the reduction of oxygen to water follow
ing the equation:
4 Cyt c2+ + 02 + (4+n) K+ ==> 4 Cyt c3+ + 2 H2O + r.H+
The energy gained by this exergonic reaction is used to form a pH-gradient by pumping
protons^ ’1 -2 which drives the ATP p r o d u c t i o n . ^ Each cytochrome c oxidase is sub
divided into several subunits. The four redox metal centers which are thought to be
involved in the final steps of electron transfer are confined in the heaviest 3 s u b u n i t s . 14
5
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( H i s ) N F ' . N (H is )
H *
+ o -
-O ;
C u 1
Fc"-0. C u 1
H* + [ Fc!V=Q lr/C u '
C om pound A
C om pound C (607 nm )
Cupric hydroperoxide
(Cu EPR Signal)
Ferry! (580 nm)
OHjCu
Pulsed
Figure 1.5: Schematic View Figurel.6: Proposed Reduction Path-
of Cytochrome c Oxidase.^® way of Cytochrome c Oxidase.^®
Of these four redox metal centers only the (CuA)-copper atom which is ligated to
two cysteine and at least one h i s t i d i n e ^ , 16,17 js found jn subunit 2, the other heme and
the binuclear center are located in subunit 1. This active, binuclear site consists of a
histidine ligated heme with an EPR silent C u ^ (surrounded by 3 His) which is held at a
distance of approximately 3 A. 19
The reaction proceeds via a 4-electron reduction of oxygen, possibly including a
(Fe-O -O Cu) and a (Fe=0) intermediate, directly to water.^O Normally oxygen
reduction, proceeding via one-electron steps, first forms H0 2 ' which disproportionates to
oxygen and H2Q2, the product of the 2 electron reduction. This II2O2 is transformed (in
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the presence of Fe^+) to the very reactive -OH radical,^ 1 which can destroy organic
materia’ : if Icfi uuirappeu. Tlierefore nature proceeds via a 4-electron reduction or provides
catalase or peroxidase to destroy H2O2 before it can do any harm.
1.2.2. M odel Compounds
Model compounds have been devised to mimic the structure, spectra and reactivity
of cytochrome c oxidase using bimetal centers in a number of ways. One way was the re
action of a heme and a nitrogen-ligated Cu that fonned |l-0 complexes. Due to the congru
ency of their spectroscopic data with that of cytochrome c oxidase, the X-ray structures of
these compounds provides insight into a possible structure of the binuclear c e n t e r . 2 2 , 2 3
Another way to model this center was to provide a binucleating pincer ligand that
was able to ligate copper in the top as well as zinc in the porphyrin plane and to hold them
at close distance.24
1.2.3. Oxygen Reduction
These attempts have helped to rationalize the structure of the binuclear center but
oxygen reduction was not achieved in these models.
In an attempt to model the four electron releasing centers in cytochrome c oxidase, Anson
et al. 25 coordinated a cobalt porphyrin with four ruthenium(II) centers. These are able to
provide the four electrons needed for the reduction of oxygen to water. He also empha
sizes the importance of having three or four electron-releasing centers as only one or two
favors the two-electron reduction to H2O2.-6
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1.2.4. Oxygen Reduction via Cofacial P o r p h y r i n s 2 7 a
Several groups have reported a similar approach towards oxygen reduction. They
use cofacial porphyrins, through a system that links two porphyrins planar to each other.
Anthracene- Biphenylene-bridged
Figurel.7: Scheme of a Cofacial Porphyrin.
„ . 0 -7 K . . ~ - . . . .
to llm an et a i reported tne tirst oxygen reduction activity ot a cotacial
biscobalt porphyrin. This very rigid bisazabridged porphyrin produced mainly H2O2. In
contrast studies on a more flexible biphenylene- (or anthracene-) linked biscobaltporphyrin
show significant water p r o d u c t i o n .28 in this case the four electron reduction was
achieved. Besides the biscobaltporphyrin they also show four-electron reduction of
oxygen to water by one redox metal center combined with: a l u m i n u m ^ , j ust a free
porphyrin base^O or even just a single iridium complexed porphyrin.31 Surprisingly this
last example shows similar activity to the biscobaltporphyrin. This is not fully understood.
Chang et al. were Uie first to produce the flexible ant’ nracene-32 and bipnenylene-
linked33 cofacial bisporphyrin systems. Insertion of two cobalt atoms in the latter34
affords a catalyst which mediates a significant oxygen reduction. In C02FTF4, another
face-to-face porphyrin, whose porphyrins are linked in the pyrrole positions via two
amide bridges, two cobalt atoms were inserted. This complex catalyzed the reaction of
oxygen to water via one of the clearest cases of four electron reductions.35
Bruice et al. produced several cofacial tetra-aza linked tetraphenyl p o r p h y r i n s 3 6
which were, after cobalt insertion, able to reduce oxygen to water. By varying the plane to
8
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plane distance they postulated that geometry and center-to-center distance, but not the
reduction potential, determine the four-electron versus die two-electron r e d u c t i o n .37
1.2.5. N itrogen Reduction
Another incorporation and reduction of a small molecule, dinitrogen, has been
achieved by a cofacial bismetallo porphyrin. Interestingly, it is the same ligand system
Collman et o/.38,39 use(j for oxygen reduction, but metal-complexed with ruthenium in
stead of cobalt. In modelling die reactivity of nitrogenase^O they were able to characterize
several complexes with reduction intermediates from dinitrogen to bis ammonia as
ligands. Based on cyclic voltammetry measurements they proposed a mechanism involv
ing both metal centers. Unfortunately, the complex is not able to expel ammonia.
1.2.6. Dihydrogen Activation
The same bisruthenium cofacial porphyrin is also able to bind dihydro-
g e n . ^ l >42,43 js not able, however, to reduce it to its hydride. This is achieved by the
monomer Ru(OEP)(THF)2, which dimerise pairwise on the electrode surface forming
pseudo-cofacial porphyrins. In this active form, it is able to bind and to deprotonate dihy
drogen to yield [Ru(OEP)(THF)H]'. This is a good one-electron reductant which is able
to reduce a NAD+ analogue; thus, it is a good model for hydrogenase.
1.2.7. Peroxide Disproportionation
The importance of two instead of only one metal centers for binding and reacting
with small molecules is emphasized by Naruta et al. 44 They show this dependence for
peroxide disproportionation by their catalase-modeling cofacial, anthracene-bridged, di
manganese porphyrin, as only the bismetallo porphyrin disproportionates peroxides.
9
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Another bismanganese bisporphyrin, catalyzes tlie oxidation of water to oxygen. Naruta
et al. 45 again emphasize the importance of two metal centers. Whereas the corresponding
mono-meric porphyrin complexes did not show any reaction, the o-phenyl bridged
bismanganese porphyrin dimers displayed oxygen production. The dependence on short
metal to metal distance for a reaction, proposed by Bruice et a L p is supported by this
result.
M L n
Mn
Figure 1.8: Schematic View of the Bismanganese Porphyrin.** 5
1.2.8. Electron Transfer
Another field of reactions using bismetalloporphyrins is electron transfer reactions.
Many electron transfers towards an Fe(lII)-containing heme are known in nature. In sul
fite reductase, for example, an Fe4S4 cluster donates six electrons via a sulfite-bridge to
the h .e m e .4 6 This heme binds sulfite at the side opposite to the cluster and reduces it to
sulfide.
To model this site Holm et al.47 coupled an Fe4S4 cluster with Fe(OEP) via a
sulfur-bridge and formed a complex which sustains two electron reduction. The X-ray
structure of their compound helps with the understanding of the natural reductase.
Other groups have reported the electron transfer from a porphyrin to a quinone-analog or
porphyrin respectively and discussed the potential of photoelectric reactions mediated by
p o r p h y r i n s . 4 8 , 4 9 , 5 0
10
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1.3. Iridium (I) and Rhodium(I) Complexes
The discussion thus far has dealt with the presentation of some porphyrin
chemistry and its enhanced reactivity in binuclear complexes. The other class of
compounds this survey focuses on are square planar d^-platinum-group-metal complexes
and their mono and bimetallic complexes.
1.3.1. M ononuclear Compounds
Platinum-group-metal complexes of rhodium and iridium, represented by Vaska’s
compound, IrCl(CO)(PPH3)2, ^ are planar complexes which can act with their free elec
tron pair as a base forming five coordinated compounds with Lewis acids (e.g. boron
tri fluoride).^
The main reaction type is oxidative addition. The square planar complex can form
octahedral complexes with many molecules: oxygen, hydrogen, halogens, alkenes,
alkane-halides, ketones and even C70 (figure 1.9).53 While the iridium compounds are
more stable in their octahedral form, the less basic rhodium complexes show an equi
librium that lies more at the four coordinate side. This gives the rhodium compounds more
enhanced catalytic activity.
Both metal complexes are easily transformed into cationic or anionic analogues, of
which the cationic phosphine-containing species have been intensively studied, due to
their reactions with dihydrogen and alkanes.^4
11
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u . ^ c o
C t" '" r^ L
O,
s i
Ref.: 55,56
u .
^ I r ^ .
o , o c
I
a
Ref.: 55,56
111
k k
IrCI(CO)L2, H ,
/
Ref.: 57
- 4
2 COOH I‘ ~CI(CO)L2,4Q°C 2 £ q H + q 2 Ref.: 58
Figure 1.9: Four Characteristic Reactions of Vaska’s Compound.^3 ( L=PPh3)
1.3.2 Binucleating Ligands
The reactivity of these compounds can be enhanced in binuclear compounds. With
bifunctional phosphines, three classes of compounds are known, namely side-by-side, A-
frame and face-to-face complexes (figure 1.10).59
12
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A A
-W l M-
s
%
K
V V
A
1 *
4 4
v
Side by-side A frame Face to face
Figure 1.10: Schematic View of Common Bisphosphine Ligands.^^
Their reactions include the oxidation of the metal resulting in metal-metal bond
formation, addition of neutral molecules and formation of bridge groups such as {i-oxygen
or p-CH2. A-frames are important for the bridging of a small ligand to the vacant site
which can undergo various reactions. To highlight recent achievements some examples are
I.3 .2 .I. H ydroform ylation Reactions
Two recent publications report rhodium complexes showing hydroformylation activity.
Stanley et al. 60 report a tetraphosphine ligand that coordinates two rhodium(I) atoms in a
racemic way close to each other. A mechanism that involves both metals leads to high
reactivity and high regioselectivity toward unbranched aldehydes.
Bulkowski et al. 61 show a Vaska-type rhodium complex in close connection to a
zinc atom giving a hydroformylation catalyst without induction period for initiation.
I.3.2.2. Interaction with Other Metals
A planar rhodium complex was combined with a c r y p t a n d 6 2 or a morpholine
ring63 t0 give, after complexion, a close distance of rhodium to copper respectively to
1 3
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zinc or lithium. Another compound by Balch et al. 64 places aVaska’s compound analog
near a crown ether which easily complexes tin, lead, potassium and sodium in close
proximity, showing new electron absorption spectra resulting from iridium-tin / lead
interaction.
1.4. Our Approach
1.4.1. Phosphine Ligand
The goal of this research project is to form a bifunctional ligand that contains both,
a porphyrin ring and a ligating device which is capable of forming square planar d& metal
complexes with platinum group metals. Rhodium(I) and iridium(I) almost exclusively
form their complexes with soft ligands like alkenes, phosphines or carbon m o n o x i d e .5 9
Among these, the phosphine ligands are the easiest to modifiy and, as shown ear
lier,1 60^61,62 (his methodology of linking a platinum group metal in a binuclear complex
is not uncommon. Therefore, phosphine ligands were chosen.
1.4.2. Porphyrin Formation
In general, there are several ways to produce a derivatized porphyrin. One is to
form the porphyrin and then react this with functionaiizing g r o u p s . 6 5 Alternatively, one
can form two substituted pyrroles which may then be reacted to form the porphyrinogen
ring, which is then oxidized to the conjugated p o r p h y r i n .6 6 T]ie first route was chosen,
due to the fact that the pincer phosphines can easily be oxidized to phosphine oxides and
thus lose their capability of complexing a platinum metal.
14
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Figure 1.11: Ortlio Kunctionali/.ed Tetraphenylporphyrin.
1.4.3. L inkage of the Ligand System
The decision to connect the pincer ligand system through phenyl groups in the
meso positions of the porphyrin in favor of the pyrrole positions was made because of
their greater ease of functionalization. The other question concerning the linkage was
whether to connect each of the two ligands via one or two linkages. Due to the fact that the
ligand, if linked to only one of the four sites of attachment, could isomerize by phenyl
group rotation, the more rigid system of two links was chosen.
1.4.4. L igand Design
In the design of the binucleating ligand system, a way was needed to connect two
phosphine-containing moieties via a double linkage to a porphyrin. A variety of strapped
porphyrins in the literature^ follow this methodology. Some of them consist of a a a a a -
-5,10,15,20-tetra-(o-aminophenyl)porphyrin (TAP) and an isophthalic acid derivative
which are coupled via isophthalic acid chloride as the active intermediate. Thus, the
15
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phosphine ligands were chosen to be isophthalic acid derivatives. This means that the
distance between the phosphine complexed platinum metal and the iron in the porphyrin
are sufficiently close for cooperative interactions.
The remaining question was the environment of the phosphine. One of the three
substituents of the phosphorous was set to be the phenyl group of the isophthalic acid.
Due to the fact that a triphenylphosphine is the least oxygen sensitive and that it is present
in Vaska’s compound, it was decided to produce a triphenylphosphine derivative.
1.4.5. Goal
The goal of this research project was to produce a a a a - 5 ,10,15,20-tetra-(o-
amino-phenyl)porphyrin and 5-diphenylphosphino-isophthalic acid and to combine them
in a single molecule. Thus, the formation of the porphyrin is outlined in chapter two,
followed by the preparation of the isophthalic acid derivative in chapter three. Chapter four
describes their coupling while chapter five deals with the metal complexation. The final
chapter gives a brief future outlook.
16
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® Carbon ^ Phosphorous
© Nitrogen © Chlorine
© Oxygen @ Iridium
Figure 1.7: Schematic View of the Desired Pincer Porphyrin Ligand.
1.5. References
1.) M.J. Gunther, K.J. Berry, K.S. Murray, J. Am. Chem. Soc., 1 9 8 4 ,106, 4227.
2.) M. Momenteau, C.A. Reed, Chem. Rev., 1994, 94, 659 (And references therein).
3.) M.F. Perutz, Acc. Chem. Res., 1987, 20, 309.
4.) T. Takano, J. Molec. Biol., 19 7 7 ,110, 561.
1 7
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5.) J.P. Collman, R.R. Gagne, C.A. Reed, T.R. Halbert, G.Lang,W.T. Robinson,
J. Am. Chem. Soc., 1975, 97, 1427.
6.) J.P. Collman, X. Zhang, P.C. Herrmann, E.S. Uffelman, B. Boitrel,
A. Straumanis, J.I. Brauman, J. Am. Chem. Soc., 1 9 9 4 ,116, 2681.
7.) T.C. Poulos, B.C. Finzel, I.C. Gunsalus, G.C. Wagner, J. Kraut,
J. Biol. Chem., 1985, 260, 16122.
8.) J.T. Groves, J. Chem. Edu., 1985, 62, 928.
9.) K. Konishi, K. Oda, K. Nishida, T. Aida, S. Inoue, J. Am. Chem. Soc.,
1 9 9 2 .114, 1313.
10.) T.G. Traylor, K.W. Hill, W.-P. Fann, S. Tsuchiya, B.E. Dunlap,
J. Am. Chem. Soc., 1992, 114, 1308.
11.) G.T. Babock, P.M. Callahan, Biochemistry, 1983, 22, 2314.
10 'n t n ^ i i p e r \ n p i m r q t P i m n m Pip»>/imc a i q q /« s c ?
x. . j o • luti v>.i. wuuii) iuc i ieot • n/yy j . i ici>y * y w o, ^
13.) G.T. Babcock, M. Wikstroem, Nature, 1992, 356, 301.
14.) G. Palmer, Pure & Appl. Chem., 1987, 59, 749.
15.) B.G. Malmstroem, Chem. Rev., 1990, 90, 1247.
16.) C.T. Martin, C.D. Scholes, S.I. Chan, J. Biolog. Chem., 1984,263, 8420.
17.) L. Holm, M. Sarast, M.Wikstroem, EMBO, 1987, 6, 2819.
18.) T. Ogura, S. Takashasi, S.Hirota, K. Shinzawa-Itoh, S. Yoshikawa,
E.H. Appelman, T. Kitagawa, J. Am. Chem. Soc., 1 9 9 3 ,115, 8527.
19.) J. Cline, B. Reinhammer, P. Jensen, R. Venters, B. Hoffman, J. Biol. Chem.,
1983,253, 8065.
20.) S.I. Chan, P.M. Li, Biochemistry, 1990, 29, 1.
21.) R.J.P. Williams, Chem. Sripta., 1988, 28A, 5.
22.) A. Nanthakamur, S. Fox, N.N. Murthy, K.D. Karlin, N. Ravi, B.H. Huynh,
R.D. Orosz, E.P. Day, K.S. Hagen, N.J. Blackburn, J. Am. Chem. Soc.,
1 9 9 3 .115, 8513.
23.) S.C. Lee, R.L. Holm, J. Am. Chem. Soc., 1993, 115, 5833.
24.) S.J. Rogers, C.A. Koch, J.R. Tate, C.A. Reed, C.W. Eigenbrot, W.R. Scheidt,
Inorg. Chem., 1987, 26, 3649.
25.) C. Shi, F.C. Anson, Inorg. Chem., 1992,37, 5078.
18
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26.) B. Steiger, C. Shi, F.C., Anson, Inorg. Chem., 1993, 32, 2107.
27.) a) J.P. Collman, P.S. Wagenknecht, J.E. Hutchison, Angew. Chem. 1994,
106, 1620.
b) J.P. Collman, P. Denisevich, Y. Konai, M. Marrocco, C. Koval, F.C. Anson,
J. Am. Chem. Soc., 1980, 102, 6027.
28.) J.P. Collman, J.E. Hutchison, M.A. Lopez, A. Tabard, R. Guillard, W.K. Seok,
J.A. Ibers, M. L'Her, J. Am. Chem. Soc., 1 9 9 2 ,114, 9869.
29.) J.P. Collman, N.H. Hendricks, K. Kim, C.S. Bencosme,
J. Chem. Soc., Chem. Commun., 1987, 1537.
30.) R.R. Durand Jr., C.S. Bencosme, J.P. Collman, F.C. Anson,
J. Am. Chem. Soc., 1983, 105, 2710.
31.) J.P. Collman, K. Kim, J. Am. Chem. Soc., 1986, 108, 7847.
11 \ n v Olmnn T I /“ > .•„ 1O01 /I Q Z 1 Q Q
. J A. 4 kUUUllllUI IU A y J . I ^ , CMLin., A , T U ,
33.) C.K. Chang, I. Abdalmuhdi, Angew. Chem., 1984,96, 154.
34.) C.K. Chang, H.Y. Liu, I. Abdalmuhdi, J. Am. Chem. Soc., 1984, 106, 2725.
35.) H.Y. Liu, M.J. Weaver, C.-B. Wang, C.K. Chang, J. Electroanal. Chem.,
1 9 8 3 ,145, 439.
36.) R. Karaman, A. Blasko, O. Almarson, R. Arasasingham, T.C. Bruice,
J. Am. Chem. Soc., 1992,114, 4889.
37.) R. Karaman, S. Jeon, O. Almarson, T.C. Bruice, J. Am. Chem. Soc.,
1 9 9 2 .114, 4899.
38.) J.P. Collman, J.E. Hutchison, M.A. Lopez, R. Guillard, J. Am. Chem. Soc.,
1 9 9 2 .114, 8066.
39.) a) J.P. Collman, J.E. Hutchison, M.S. Ennis, M.A. Lopez, R. Guillard,
J. Am. Chem. Soc., 1992,114, 8074.
b) J.P. Collman, J.E. Hutchison, M.A. Lopez, R. Guillard, R.A. Reed,
J. Am. Chem. Soc., 1991, 113, 2794.
40.) J. Kim, D.C. Rees, Nature, 1992,360, 553.
41.) J.P. Collman, J.E. Hutchison, P.S. Wagenknecht, N.S. Lewis, M.A. Lopez,
R. Guillard, J. Am. Chem. Soc., 1990,112, 8206.
42.) J.P. Collman, P.S. Wagenknecht, J.E. Hutchison, N.S. Lewis, M.A. Lopez,
R. Guillard, M. L'Her, A.A. Bothner-by, P.K. Mishra, J. Am. Chem. Soc.,
1990, 112, 8206.
1 9
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43.) J.P. Collman, P.S. Wagenknecht, N.S. Lewis, J. Am. Chem. Soc., 1992,
114, 5665.
44.) Y. Naruta, K. Maruyama, J. Am. Chem. Soc., 1991, 113, 3595.
45.) Y. Naruta, M. Sasayama, T. Sasaki, Angew. Chem., Int. Ed. Engl.,
1994,53, 1839.
46.) J. Tan, J.A. Cowan, Biochemistry, 1991, 30, 8910.
47.) L. Cai, R.H. Holm, /. Am. Chem. Soc., 1994, 116, 7177.
48.) a) K. Kamioka, R.A. Cormier, T.W. Lutton, J.S. Connally, J. Am. Chem. Soc.,
1992, 114, 4414.
b) F. Lendzian, J. Schluepmann, J. v. Gersdorff, K. Moebius, H. Kurreck,
Angew. Chem., Int. Ed. Engl., 1991,3 0 , 1461.
49.) a) H.A. Staab, M. Tercel, R. Fischer, C. Krieger, Angew. Chem., Int. Ed. Engl.,
100/4 3? 1 AC'i
1 / / T , , 1*TUJ.
b) H.A. Staab, T. Carell, Angew. Chem., Int. Ed. Engl., 1994, 33, 1466.
50.) a) A. Helms, D. Heiler, G. McLendon, J. Am. Chem. Soc., 1992, 114, 6227.
b)B.C. Bookser, T.C. Bruice, J. Am. Chem. Soc., 1991, 113, 4208.
51.) L. Vaska, D.W. DiLuzio, J. Am. Chem. Soc., 1961, 83, 2784.
52.) R.N. Scott, D.F. Shriver, D.D. Lehmann, Inorg. Chim. Acta, 1970, 4, 73.
53.) F.A. Cotton, G.Wilkinson, Comprehensive Organometallic Compounds,
Volume V, pp. 441-628.
54.) R.H. Crabtree, Acc. Chem. R e s ., 1979,12, 331 (and references herein).
55.) C.A. Reed, W.R. Roper, J. Chem. Soc., Dalton Trans., 1973, 1370 .
56.) L.Vaska, L.S. Chen, J. Chem. Soc., Chem. Com., 1971, 1080 .
57.) W. Strohmeier, M. Lucacs, J. Organometal. Chem., 1977, 133, C47 .
58.) B.C. Booth, R.N. Hazeldine, G.R.H. Neuss, J. Chem. Soc., Perkin Trans.1,
1975, 209.
59.) F.A. Cotton, G. Wilkinson, "Advanced Inorganic Chemistry", 1988,
5th edition, p. 900 - 908.
60.) M.E. Broussard, B. Juma, S.G. Train, W.-J. Peng, S.A. Laneman, G.G. Stanley,
Science, 1993, 260, 1784.
20
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61.) J.R. Lockemeyer, A.L. Rheingold, J.E. Bulkowski, Organometallics, 1993,72,
256.
62.) A. Carroy, J.-M. Lehn, J. Chem. Soc., Chem. Commun., 1986, 1232.
63.) K.H. Langrick, D. Parker, Inorg. Chim. Act., 1986, III, L29.
64.) A.L. Balch, F. Neve, M.M. Olmstead, Inorg. Chem., 1991,;W, 3395.
65.) J.P. Collman, X. Zhang, K. Wong, J.I. Brauman, J. Am. Chem. Soc.,
1994, 116, 6245.
66.) D. Reddy, T.K. Chandrashekar, J. Chem. Soc., Dalton Trans. I, 1992, 619.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
2. ocaaa-5,lO,15,2O-tetra-(0-aminophenyI)
Porphyrin
As discussed in the introduction part of this thesis, the first step towards the
formation of the ligand system consists of the formation of the porphyrin ring. In this
chapter the utilized literature procedure is outlined.
2.1. Procedure
» t »i • t i i r . • i .*10 • . < » « ■» •
inis long Known ana ouen nnprovea reaction*’* - consists or tnree steps, in tne
first step, pyrrole and o-nitrobenzaldehyde react in glacial acidic acid at 85°C to form
5,10,15,20-tetra-(o-nitrophenyl) porphyrin.
After isolation the nitro groups are reduced to amino groups by tin dichloride,
forming (5,10,15,20)-tetra-o -aminophenyl porphyrin. This reaction leads to a mixture of
isomers due to the possibility of phenyl group rotation in the meso position. There are
four possible isomers, namely the a a a a - , aaa(3-, a p a P - and aaPp-porphyrins.
In the final step this isomeric mixture is enriched towards the aocaa-isom er by
refluxing the porphyrin absorbed on silica gel in toluene for 24 h o u r s . xiie product is
then separated from the other isomers by chromatography. This procedure leads to pure
aaaa-5,10,15,20-tetra-(fl-aminophenyl)-porphyrin. The coupling with the isophthalic
acid derivative will be described in chapter four.
22
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2.3. Reaction scheme
aaxm
aaa|3
apaP
aapp
PhN O
NO
N glacial acidic acid . . . _ .
v Z— .------ — ----- N 0 2Ph
H reflux, 15 min *
PhN O
o
PhNH
PhN O
SnCI2
PhNH
HN
NH
AT
NH
NH
NH
NH
NH
Figure 2.1: Reaction Scheme of the Porphyrin F orm ation.
23
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2.3. Experim ental Procedures
2.3.1. 5,10,15,20-tetra-(o-n itrop h en yl)p orp h yrin
In a 2-neck, 5-liter flask, equipped with a dropping funnel and a reflux con
denser, lOOg of o-nitrobenzaldehyde (0.662 mol) were dissolved in 1.5 liters of glacial
acidic acid. This solution was then heated to reflux. The heat was removed and while still
refluxing 46 mL of freshly distilled pyrrole (0.663 mol) were added within 20 minutes.
The addition of the pyrrole causes an exothermic reaction, thus only small amounts were
added at one time. The mixture was then refluxed for 15 minutes, cooled to 50°C and
then diluted with 800 mL of chloroform. The solution was then filtered to give a part of
the product. Repeating the filtration after allowing the solution to stand overnight, gave
more product. The product was then washed with 50 mL portions of cold chloroform.
After drying the material via pumping under vacuum, the product remained as a fine
crystalline, purple powder. The yield was 23.1g (15 percent theoretical yield).
2.3.2. 5,10,15,20-tetra-(o-am in op h en yl)p orp h yrin
To reduce the nitro groups on the porphyrin, 5,10,15,20-tetra-(o-nitrophenyl)
porphyrin (23.lg, 29 mmol) was combined with an excess of tin dichloride (85g, 377
mmol) and dissolved in 2L of concentrated hydrochloric acid. The mixture immediately
turned green. It was then heated to 65 - 70°C and manually stirred for 15 minutes at this
temperature. The initiation of the reaction caused extreme foaming of the solution there
fore strong stirring was required. The solution was cooled to -10°C with a salt ice bath
and neutralized with approximately 1.5 L of concentrated ammonium hydroxide solution
until the solution turned brown. The product precipitated and was filtered off with a
BUchner funnel. One liter of chloroform was added to the filtrate. The solution was
stirred overnight and then allowed to separate into two layers. Separation from the water
24
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layer and evaporation of the solvent gave another 2g of the product. The product was a
fine crystaline, purple material. The yield was 15g (76.4 percent of the theoretical yield).
2.3.3. Enrichment of the a a a a -I so m e r
This 5,10,15,20-tetra-(r?-aminophenyl) porphyrin was dissolved in 100 mL of
dichloromethane. Then 200 mL of dry silica gel (mesh 100) were added. Eventually
another portion of dichloromethane was added to the flask to make a complete solution.
Then the silica gel was pumped to complete dryness over 4 hours. After that he material
was placed into a 2000 mL flask together with 600 mL of toluene and a 300 mL portion
of silica gel. This mixture was then refluxed under argon for 20 hours. After the removal
of the solvent the remaining solid was pumped to absolute dryness for 10 hours. A
90mm diameter column was filled 300 min high with a slurry of silicagel (mesh 100) in
chloroform. The silica gel coated porphyrin was loaded on the top of this column. This
column was first eluted with chloroform until the first band, the aPa(3-isomer, came off.
The eluting solvent was changed to a 1:1 mixture of chloroform and diethylether. Ap-
proximatlely 3-4 liters of solvent was required to elute the second (aafifi) and third
(a a a P ) band. The a a a a - isomer is then eluted with 2.5 liters of a 1:1 mixture of ace
tone and diethylether. The final solution was immediately evaporated at room temperature
to prevent further isomerisation. The final yield was 9.5 g of the aaaa-isom er.
2.4. R eferences
1.) J.P. Collman, R.R Gagne, C.A. Reed, T.R. Halbert, G. Lang, W.T. Robinson,
J. Am. Chem. Soc., 1975, 97, 1427
2.) T.N. Sorrell, Inorg. Synth., 1980,20, 161
3.) C M . Elliott, Anal. Chem., 1980, 52, 666
4.) J.J. Lindsey, J. Org. Chem., 1980,45, 5215
25
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3. The Acid Production and the Bromine-
Diphenylphosphorous Exchange
In this chapter the formation of 5-bromoisophthalic acid is described. Several
methods of the exchange of bromine for diphenylphosphorous were tried. The successful
method via palladium coupling is described. The other methods are briefly outlined and
rationalized.
3.1. T he 5-B rom o-isophthalic Acid
In order to produce 5-diphenylphosphino-isophthalic acid, an isophthalic acid
derivative with a good leaving group in the 5-position is necessary. This leaving group is
then exchanged for a diphenylphosphorous group in a later reaction. Common exchange
reactions include an aryllithium or a Grignard-type intermediate for which bromide was
proven to work very well as a leaving group. Thus, the first step towards the triphenyl
phosphine derivative was the production of 5-bromoisophthalic acid.
Br Br
1. KMn04 2. HCI
H20, reflux 12h
HOOC
Figure 3.1: Oxidation of 5 -b ro m o -m -x y le n e.*
In a known procedure, 1 5-bromo-m -xylene was oxidized by boiling in an aque
ous potassium permanganate solution until the permanganate color disappeared. This
gave the desired product although the yields of this reaction were surprisingly low. This
26
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was rationalized by the insolubility of the 5-bromo-ni-xylene in the reaction solvent,
water. Even larger amounts of potassium permanganate and longer reaction times were
only able to increase the yield slightly. Therefore a phase transfer catalyst was added to
the reaction mixture. Both, tetra-«-butylamonium iodide and 18-crown-6, failed to
increase the yield.
3.2. Oxazolines as Protective Groups
After having formed 5-bromo-isophthalic acid, the next step consists of the
exchange of bromine for a diphenylphosphorous group. The two common procedures
include the formation of a Grignard reagent- (by reacting the bromine group with
magnesium) or an aryl-lithium^ (by treatment with n-butyllithium) as an intermediate.
This would then be reacted with chlorodiphenylphosphine. Both of the reagents are
capable of attacking the acid group. Therefore, the acid group must be protected against
reduction. It is well known that the protection of carboxylic acid groups by their
conversion into oxazolines, via the condensation with 2-amino-2methyl-propanol,
permits the reactions of lithium- or Grignard reagents to proceed unhindered.^ Thus, the
production of 5-bromo-isophthaloyl bisoxazoline was attempted.
3.2.1. Production by Dean Stark method
toluene, -H20
Figure 3.2: Oxazoline Form ation via Dean S tark Method/*
27
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The first method of oxazoline production included the heating of the acid under
Dean-Stark conditions.^ Herein the acid and the amino alcohol are refluxed in toluene
utilizing a Dean-Stark apparatus. The water produced by the condensation reaction is
removed by azeotropic destination and collected in a graduated tube. The heating is
continued until no more water is produced.
This reaction failed as 5-bromo-isophthalic acid was insoluble even in refluxing
toluene. After four hours of refluxing no water formation could be detected, thus this
way of oxazoline formation was abandoned. The insolubility of the 5-bromo-isophthalic
acid in toluene can be attributed to strong and extensive hydrogen-bonding between the
different carboxylic acid groups. This leads to dimers, oligomers or even polymers.
4
3.2.2. Production via an Acid Chloride
SOC1
•CGOH
CH2CI
COCi
Figure 3.3: Oxazoline Form ation via an Acid C hloride Interm ediate.^
28
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Another publication reports the production of oxazolines via intermediate acid
c h lo r id e s .^ The carboxylic acid is converted to its acid chloride by treatment with an
excess of thionyl chloride followed by the removal of all volatiles in vacuo. After redis
solving the acid chloride in dichloromethane two equivalents of the protective group are
added. The isolated amide is then cyclized by further treatment with thionyl chloride.
Even though in my reactions the formation of the acid chloride was verified by IR-spec-
troscpy and the amide was formed, the cyclizing step repeatedly produced a greenish oily
material, whose composition could not be resolved by NMR.
3.2.3, Production by Triphenylphosphine
HOOG
Figure 3.4: Oxazoline Formation via T riphenylphosphine Activation.
Literature reports of bis-oxazolines and their formation are rare.6 According to
this procedure a solution of triphenylphosphine/triethylamine/carbon tetrachloride in pyri-
dine/acetonitrile was added dropwise to a solution of the acid and the aminoalcohol in the
same solvents. After the workup a 50 percent yield was reported. When this procedure
was applied to the 5-bromo-iscphthalic acid, only intractable products were produced and
this procedure was abandoned.
29
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3.2.4. Production by Using the Aminoalcohol as Solvent
X S / V 2 .240°C, -H2dT
H2N OH
OOH
1. 170°C, -H20
Figure 3.5: Oxazoline Form ation via Using Aminoalcohol as Solvent.^
Mislorin et a l l have reported the formation of oxazolines by heating the acid with
the aminoalcohol as the solvent. Thus, 5-bi'oinuisupiuhiaiic acid was heated in 2-amino
2-methylpropanol at reflux and the excess of aminopropanol was distilled off. Although
several unsuccesful reactions it was concluded that the material was the amide and the
insolubility arose from the free alcohol groups. To force the cyclization of this amide the
material was treated with thionyl chloride. Another attempt at cyclization using hexa-
methyl-disilazane was also tried. Unfortunately, no cyclisation and therefore no change
in solubility was detected. This failure of the cyclization is not fully understood.
At this point the use of oxazolines as protecting groups for the 5-bromo-isophthalic acid
was discontinued.
3.3. Bromine - Phosphorous Exchange
3.3.1. Direct Treatment with n-butyllithium
Due to the fact that the desired oxazoline protective groups for the acid could not
be produced, alternative methods for the introduction of a diphenylphosphorous group
the ^H-NMR looked promising the material was only soluble in ethanol or water. After
30
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were investigated. Issleib et al.% have reported the preparation of m - and p -diphenyl-
phosphino-benzoic acids. Instead of protecting the carboxylic acid, they used two equiv
alents of H-butyllithium. One forms the unreactive carboxylate anion that protects the acid
group against reduction and the second exchanges bromine for lithium. In a second step
this aryllithium was treated with chlorodiph'.nylphosphine and the diphenylphosphino-
benzoic acid was formed upon acidification.
Thus, 5-bromoisophthalic acid was dissolved in THF and treated with three
equivalents of /i-butyllithium at various temperatures. At -78°C an orange solution was
formed which was then treated with one equivalent of chlorodiphenylphosphine. Subse
quent acidification should have given the desired 5-diphenylphosphino isophthalic acid,
but 31p-NMR showed no significant product formation. It is not understood why the
reported preparation of p -diphenylphospliino-benzoic acid was successful while the same
reaction failed to produce diphenylphosphino-isophthalic acid. It may be that the double
negative charge of the molecule prevents an attack on the bromine in the wie/cr-position.
3.3.2. Palladium Cross Coupling
(C6 H 6 CN)2PdCI2
Toluene, 75°C
EtOOC COOEt
Figure 3.6: Brom ine - D iphenylphosphorous Cross C oupling.! 0
Other ways to exchange a halogen for different groups proceed via a palladium
cross coupling reaction. Many examples are known in the literature.^ In this reaction a
31
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palladium(O) complex mediates as a catalyst normally slow metathesis reaction between an
akyl or aryl halide and an alkene, an organometallic compound of another nucleophile.
3.3.2.1. E ster F orm ation
Br Br
HOOC
OOH
EtOH, HCI-gas
reflux, 10 h
EtOOC 0 0 Et
Figure 3.7: Ester form ation.1 *
Tunney et al}® reported the transformation of a bromine substituent to a diphenyl-
phosphino group on a methyl-benzoate vid a palladium coupling. To carry out this proce
dure with the 5-bromo-isophthalic acid the corresponding diester must first be prepared.
Due to the fact that methyl esters require drastic conditions for cleavage, the diethyl ester
was prepared as they are generally easier to form and to cleave. Thus, in a known
procedure,H the 5-bromo-isophthalic acid was dissolved in dry ethanol and HC1 gas was
bubbled through the solution. After extraction with diethyl ether the 5-bromo-isophthaloyl
diethylester was formed with very h igh yield.
3.3.2.2. F orm ation of the other S tarting M aterials
reflux
PdCI2(PhCN)2
F igure 3.8: P reparation of the D i(benzonitrile)-palladium (II)-dichloride.lO
32
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Si(MehCI
F igure 3.9: P reparation of T rim ethylsilyl-diphenylphosphineJ®
The other starting materials, trimethylsilyl-diphenylphosphine (TMSDP) and the
catalyst precursor bisbenzonitrile-palladium-dichloride were formed by known proce
dures JO
TMSDP was produced by the treatment of triphenylphosphine with lithium
forming lithium-diphenylphosphine followed by its reaction with trimethylsilyl chloride.
The resulting liquid was then purified by distillation JO
Bisbenzonitrile-palladium-dichloride was chosen in favor of the reported bis-
diphenylphosphino-palladium-dichloride as the catalyst precursor to avoid other sources
of phosphorous than TMSDP. This was formed by boiling palladium dichloride in ben-
zonitrile for twelve hours and subsequent crystallisation of the material.
3.3.2.3. T h e coupling r e a c t i o n 1 0
In this experiment the ester and the palladium complex were dissolved in toluene
under argon atmosphere and TMSDP is syringed through a septum into the flask. The
solution was then stirred at 75°C under argon for four days. After the first experiment a
large amount of hydrolysis product, diphenylphosphine, as well as the desired product
and other phosphorous conaining materials were detected by 31p{ 1h )-NMR. Subsequent
experiments were optimized to reduce the presence of trace moisture.
33
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(PhC N )2PdC I2
L2Pd(PPh2)2
ister-Br
L2Pd(PPh2)(ester)
Me3Si-Br Ph2PSiWle3
Figure 3.10: Proposed Mechanism of the Cross-Coupling Reaction.1®
34
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3.3.2.4. Mechanism
This reaction is proposed to proceed via the following mechanism. ^
First the catalyst is activated by the reduction reaction of the palladium complex with
TMSDP. This reaction produces tetraphenyl-diphosphine, identified by its characteristic
31p chemical shift of -16.1 ppm.Through a series of steps the acid and TMSDP add to the
palladium and through a reductive elimination 5-diphenylphosphino-isophthaloyl diethyl-
ester is produced.
3.3.2.5. Monitoring the reaction
The reaction was easily monitored by removing aliquots and running ^H-NMR
and 31p-NMR spectra. By this method the disappearance of starting materials and the
formation of the desired product were conveniently followed. Then the mixture was
worked up by chromatography. Relativley high yields (70 percent) and a pure compound
were obtained by this method.
35
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3.3.2.6. ^H-NMR M onitoring
EtOOC
P (P h)2
H
Hr
p p C O O Et EtOOC COOEtlj
36
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3.3.2.7. 3Ip_N M R M onitoring
vtw *
3 days
j
w «
2 days
1 day
HP(Q)(Ph)2 Product P2Ph4 HP(Ph)2 TMSDPP
100 80 60
-20 -60
F P M
37
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without permission.
3.3.3. The Ester Cleavage
1.K0H, 2.HCI
Me0H/H20
EtOO C CO O Et H O O C ' 'C O O H
Figure 3.11: Cleavage of the 5'Diphenylphosphino-isophtlialoyl d ieth y lester.^
The 5'diphenylphosphino-isophthaloyl diethylester was fully characterized by
^H-, ^ C - and ^lp-NM R and by elemental analysis. For the linkage to the porphyrin ring
the free acid and not the ester was required. Thus, the ester was cleaved in a mild reaction
reported by Yamamoto et a l In this reaction the ester was refluxed in a potassium
hydroxide solution of methanol and water. Acidification gives the clean product in high
yields.
3.4. Experimental Procedures
3.4.1. 5-Bromoisophthalicacid
5-Bromo-m-xylene (30g, 0.162 mol) was filled in a 2L 3-necked flask equipped with a
refluxcondenser and a mechanical stirrer. One liter of an aqueous solution of 15 g
Na2 C0 3 and 120g of potassium permanganate was added. The mixture was slowly
heated to refluxed and left at this temperature until the purple colour disappeared (At least
6 hours). Then the still hot solution was filtered through a Buchner funnel. The black fil
ter residue was washed three times with hot water. The combined solutions were acidified
with HC1 solution until a white material percipitated. This suspension was cooled in fridge
38
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for at least 4 hours before filtration. The material is recrystallized from water containing a
small amount of ethanol.
Product: Fine, white needles.
MP.: 17CTC.
iH-NMR: 8.59 (t, 1H, 1.6Hz), 8.33 (d, 2H, 1.6Hz) ppm.
J3C ^H J-N M R : 165.5, 137.0, 134.0, 130.1, 122.9 ppm.
IR: 3050 (m), 1760(s), 1560 (m), 1260 (s), 1240 (s), 1150 (s),
%
1010 (s), 996{ s) c m '1.
3.4.2. 5-Bromo-isophthaloyl diethylester
5-Bromoisophthalic Acid (4.90g, 0.02 mol) were placed into a two neck flask
equipped with a reflux condenser, an argoh inlet and an HC1 gas inlet Dry ethanol (20ml)
was directly distilled into the flask. Then die suspension was wanned and for two minutes
HC1 gas was bubbled through the suspension (exothennic reaction). After all the acid
dissolved the solution was refluxed for 20 minutes. Then the HC1 bubbling was repeated
and the solution was refluxed for 4 hours. Next, the excess ethanol was distilled off and
the solution cooled to room temperature. The cloudy solution was extracted three times
with ether. The ether fraction was neutralized with a Na2C0 3 solution and dried over
Na2S C > 4. Then the ether was evaporated and die product was dried under high vacuum. It
was then recrystalized from pentane.
Product: White crystaline material.
Yield: 3.46g (60%).
MP.: 39-41°C.
*H-NMR: 8.57 (t, 1H, 1.4Hz), 8.32 (d, 2H, M H z), 4.38 (q, 4H, 7.2Hz),
1.39 (t, 6H, 7.2Hz)ppm.
39
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!3C {iHJ-NMR: 164.3, 136.5, 132.6, 129.2, 122.5, 61.7, 14.8 ppm.
IR: 3070(m), 2980(m), 1725(s), 1600(m), 1280(s) cm*1.
3.4.3. Trimethylsilyl-diphenylphosphine
Li-metal (7g, 1.01 mole) was added in small pieces to a solution of 50g of triph-
enylphosphine in 500mL of THF. The solution turned red after a few minutes. After
stirring overnight the solution became dark brown and was canulated into another flask
separating it from the excess of Li-metal. Then, 60 ml of trimethylsilylchloride were
dropped into the solution in smali portions under cooling. After stirring overnight most
of the solvent was evaporated and the residue was vacuum-distilled twice.
Product: Colorless oil.
B.P.: 88°C, 300 mtorr, (lit!: 126-127°C, l.OmmHg)13-
iH-NMR: 8.98 (m, 5H), 8.83 (m, 5H), 1.75 (d, 9H,-4.8Hz) ppm.
31P { 1H)-NMR: -57.47 ppm.
3.4.4. Bishenzonitri!e-pa!ladium(II)-dichloride
Palladium(II)-dichloride (0.3g, 1.6mmole) was refluxed in 25mL of benzonitrile
for four hours, hot filtered and cooled in the freezer for 24 hours. The orange crystalline
product was collected by filtration and washed with pentane.
3.4.5. 5-Diphenylphosphino-isophthaIoyl diethylester
4.78g of dry 5-bromo-isophthaloyl-diethylester (0.0155 mol) were placed in a
100 mL 2-neck flask equipped with a reflux condenser, septum and an argon inlet. Then
0.09g of bisbenzonitrile-palladium(II)-chloride (1.5 mol-%) was added and the flask was
pumped under vacuum for 1 hour. After filling with argon, 30 ml of toluene were freshly
40
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distilled directly into the reaction flask. The solution turned orange. Under continuous
stirring, 4.2g of trimethylsilyl-diphenylphosphine (0.017 mol) were syringed through the
septum into the solution. The solution immediately turned dark purple-brown. Then the
solution was heated to 75°C for four days. During that time it was monitored by *H-
NMR and ^Ip-NM R to check the product formation and the amount o f starting material.
Additional TMSDP was added to the reaction mixture as required. After NMR showed a
yield of 80 - 90%, the reaction was stopped. The solvent was pumped off in vacuum
leaving a dark brown, tarlike material. This was redissolved in 40 ml of CHCI3 ,
approximately 20 g of neutralized silica gel (60-200) was added and then it was pumped
to dryness. For neutralization the silica gel was suspended into pentane, 1 mL of
trimethylamine was added and the silica gel was pumped to dryness.
The silica gel was put on the top of a 30mm diameter column which was loaded
under argon with 150 mm of neutralized 60-200 silica gel. First the column was eluted
with 75 mL of pentane to wash off the unreacted 5-bromo-isophthalic diethylester. Then
it was eluted with 400 mL of hexane and with another 200 mL of hexane/chloroform
(19:1). Both fractions contained major portions of the product. A final elution with
CHCI3 yielded more of the desired product. The individual elution volumes were
evaporated to afford oils which crystallized upon cooling in the freezer overnight. Further
purification was unnecessary.
Product: White crystalline material.
MP.: 82-83°C.
iH-NMR: 8.61 (t, 1H, 1.6Hz), 8.13 (dd, 2H, 1.6Hz, 5.3 Hz),
7.34 (m, 10H), 4.32 (q, 4H, 7.14Hz),
1.34 (t, 6H, 7.14Hz)ppm.
4 1
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13c {1h }-NMR: 138.6, 138.3, 133.90 133.6, 131.1, 131.2, 130.7, 129.2,
128.8, 128.7, 61.4, 14.2 ppm.
31P {*H}-NMR: -6.9 ppm.
Elemental Anal, calcd.: C, 70.93; H, 5.7; P, 7.62.
Found: C, 69.38; H, 5.6; P, 6.89.
3.4.6. 5-Diphenylphosphino-isophthalic acid
To a mixture of 5g KOH in 45mL of methanol and 5 mL of water, 4.82g (0.0I2mol) of
5-diphenylphosphino isophthaloyl diethylester was added and the suspension heated to
reflux. After the solution reached its boiling point the ester dissolved completely. Then
the solution was refluxed for four hours and then slowly cooled, diluted with 40 mL of
water and acidified with concentrated HC1.'A white material precipitated.
The suspension was extracted 3 times with diethylether. The ether layer was neutralized
with a saturated Na2C0 3 -solution, dried over MgS04 and evaporated to dryness.
The white material was then pumped to absolute dryness by heating it under high vacuum
at 100OC.
Product:
DP.:
iH-NMR:
*3C {*H}-NMR:
31P ^H J-N M R :
IR:
White powdery material.
241°C.
8.64 (t, 1H, 1.6Hz), 8.15 (dd, 2H, 1.6Hz, 5.3Hz),
7.43 (m, 5H), 7.35 (m, 5H) ppm.
166.2, 140.5, 140.3, 138.8, 138.6, 136.7, 136.6, 134.5,
134.23, 132.07, 131.42, 130.04, 129.60, 129.52 ppm.
-1.6 ppm.
3550(m), 3450(m), 3100-3000(w), 1720(s), 1700(s), 1620(m),
1470(m), 1290(s)(3), 900(m) cm '1.
42
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Elemental anal. Calcd.: C: 68.57, H: 4.32, P: 8.84.
Found: C: 64.46, H: 4.46, P: 7.94.
3.5. References
1.) H.G.O. Becker, Organikum, 1990, vol. 18., p.350.
2.) a) M. Reumun, A.I. Meyers, Tetrahedron, 1985, 41, 837.
b) A.J. Meyers, E.D. Mihelich, Angew.Chem., 1976, 88, 321.
3.) M. Fieser, C.F. Fieser, “Reagents for Organic Synthesis”, vol. 6, p. 20.
4.) H.L. Wehrmeister, J. Org. Chem., 1961, 26, 3821.
5.) A.I. Meyers, D.L. Temple, D. Haidukewych, E.D. Mihelich, J. Org. Chem.,
1974, 39, 2787.
6.) H. Vorbrueggen, K. Krolikiewicz, Tetrahedron Lett., 1981, 22, 4471.
4
7.) D.H.R. Barton et al.,J. Chem. Soc. Perkin Trans. 1, 1985, 1865.
8.) K. Issleib, H. Zimmermann, Z. Anorg. Allgem. Chem., 1961,353, 197.
9.) F.A. Carey, R.J. Sundberg, Advanced Organic Chemistry, 3rd Ed., 414-422.
10.) S.E. Tunney, J.K. Stille, J. Org. Chem., 1987,52, 748.
11.) H.G.O. Becker, Organikum, 1990, vol. 18, 403.
12.) K. Furuta, K. Iwanaga, H. Yamamoto, Organic Synthesis, Vol.69, 55.
13.) W. Kuchen, H. Buchwald, Chem. Ber., 1959, 92, 227.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
4. Linkage of DPPIA with the Porphyrin
This chapter describes the the coupling condensation of 5-diphenylphosphino
isophthalic acid (DPPIA) and the aaaa-(5,10,15,20)-tetra-o-am inophenyl porphyrin
(TAP) via the formation of amide bonds. There is a variety of known procedures of this
type* and the following sections outline these procedures and their use in this work.
4.1. C oupling by DCC
One very common method uses dicyclohexyldicarbodiimide (DCC) to trap the
water arising from the formation of a bond between an acid and an a m i n e . ^ During this
4
reaction DCC is transformed to an urea which must then be separated from the desired
product.
R’ — COOH + H2NR R*— COHN—R
THF
rigure 4.1: Reaction Scheme of uCC.^ rigure 4.1: Reaction Scheme of uCC.^
Several reactions of the porphyrin with the acid by the addition of an excess of
DCC were attempted in dry dichloromethane. The temperature and amounts of DCC were
varied, but even refluxing the solution with a large excess of DCC for several hours
caused no change as monitored by UV-VIS and by TLC. This methodology of coupling
was abandoned.
44
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4.2. Coupling by Activated Esters
Active esters are used as intermediates in another very common method of peptide
bond formation.^ One such active ester is the hydroxysuccinimide ester.4 It can readily be
formed by the condensation of a carboxylic acid with hydroxysuccinimide.
DCC
H OO
R’-N H
Hydroxy
succinimide
4
ONH R'
Figure 4.2: Reaction Scheme of the Succinimide Ester.4
In this reaction DPPIA was transformed into this active ester by treating a solution
of DPPIA and the hydroxysuccinimide with DCC. The formation of the disuccinimide
ester was verified by ^H-NMR. However, the treatment of the ester with the porphyrin in
dry dichloromethane did not show the desired reaction according to UV-VIS and TLC.
4.3. Coupling by Acid Chlorides
A method of amide bond formation that is commonly applied in porphyrin
chemistry uses acid chlorides as the reactive intermediates.* To form the acid chloride a
huge excess of thionyl chloride together with DMF and a base are normally used. These
are pumped off after die reaction is complete. In this reaction the conditions were slightly
different.
45
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Due to the oxidation sensitivity of the phosphines, the milder reagent oxalyl
chloride was chosen. One mole of it converts one mole of a carboxylic acid group to an
acid chloride group. Through this reaction it conveniently decomposes into carbon
monoxide, carbon dioxide and hydrogen chloride gases.
Figure 4.3: Reaction Scheme of Oxalyl Chloride.
Departing from the standard procedure, the solvent was not pumped off after the
preparation of the acid chloride due to the fact that the next reaction step requires the same
solvent. Freshly added solvent may have introduced traces of moisture lowering the
overall yield dirough hydrolysis of the acid chloride groups
In the first part of the reaction the 5-diphenylphosphino-isophthaloyl dichloride
was generated by the precise stoichiometric reaction of oxalyl chloride with the diacid.
Great care was taken to ensure the absence of excess oxalyl chloride which could have
complicated further reaction chemistry. The second step of the reaction involving the
combination of the diacid chloride and the TAP was performed with a ten percent deficit of
the porphyrin in order to allow for inevitable trace moisture.
46
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4.3.1. The Reaction Procedure
(COCl)2
CIOC COCI HOOC COOH
/ H
11
Figure 4.4: Reaction Scheme of the Coupling Reaction.
To carry out this reaction oxalyl chloride was syringed into a dichloromethane
solution of the acid, dried DMF and distilled pyridine. This was transfered into a constant
dropping funnel after the acid chloride formation was complete. Then it was added
dropwise into a flask at the same speed as an equal volume of the porphyrin solution.
Stirring the solution was followed by the removal of the solvent. The separation from
other materials was managed by chromatography. A pure product in considerable yield
was routinely obtained and fully characterized by ^H-, 31p-NMR, FAB-mass and
UV-VIS.
4 7
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4.3.1.1. ^H-NMR spectra of the Phosphine* and Phosphineoxide Pincer
Porphyrin
1 1 !\
tl| I
* S ' j ' i
'H
j I* ! I
i M
+ On
1 1
I .> - p V
I I S *
I I ! ! r t i :
j - • T - - - - - - - - - - T —
9.0
-> - - r -i | i — i — i — i — p— .— r — ,— r — p
8.5 8.0 7.5 7.0 ppm
48
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4.3.1.2. *H-COSY of the Phosphine Pincer Porphyrin
49
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4.4. Assignment of the Proton - NMR
By comparing the spectra of the oxidized and the unoxidized material and by ex
amining the 2-D-COSY spectrum, the assignment of the protons was achieved. Compar
ison with similar compounds confirmed these assignments.^
121
6
Figure 4.5: Schematic View of one Part of the Ligand.
J U
2 4 3‘
.r V _ . J V
13 5
' i t i I f
9 8 12 1110
9.0
1 I !-
8.5 8.0
* 1 r 1 ----- [-----1 ----- r
7.5 7.0 ppm
50
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4.5. Experimental Procedures
4.5.1. 5-Diphenylphosphino-isophthaloyl dichloride
An apparatus consisting of a Claissenhead equipped with a septum on the one side
and a reflux condenser topped with an argon-inlet on the other side, was taken out of the
oven and cooled under argon. 5-diphenylphosphino-isophthalic acid (0.5785g, 0.0016
mol), which had been pumped for 5 hours under vacuum, was put in a 300mL flask.
Then 175 mL of twice distilled CH2CI2 are freshly distilled into the flask. A white
suspension occured. The flask was then attached to the apparatus. After that five drops of
predried DMF and 0.5mL of pyridine, freshly distilled from potassium hydroxide, were
syringed through the septum. After stirring for 20 minutes the solution became totally
clear. Under continous stirring 0.286 mL,of Oxaloyl-chloride (0.0033 mol) were slowly
(!) syringed through the septum in the flask. The reaction mixture started to bubble and
turned slighdy yellow. After stirring for one more hour it was ready for further use.
4.5.2. Phosphorous Pincer Porphyrin
A 500 mL 3-neck flask, equipped with two constant dropping funnels and an
argon inlet, was taken out of the oven and cooled under argon. The acid chloride solution
was then cannuiated from the reaction flask into one of the dropping funnels. A solution
of the dried porphyrin in freshly distilled dichloromethane was cannuiated in the other
dropping funnel. After addition of 0.5 mL pyridine into the flask, the two solutions were
added together at the same speed. This took about 3 hours. The solution was then left
stirring for another hour to complete the reaction. Then the solvents were removed under
vacuum and the compound was pumped to complete dryness.
A column (70mm) was filled with a slurry of dichloromethane and TLC graded
silicagel, which had been neutralized with lmL of triethylamine. After the column had
51
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settled overnight its height was 90mm. To separate the pincer porphyrin from the other
compounds the solid material from. the. former reaction was dissolved in a small amount of
dichloromethane and gently put on the top of the column. The column was then eluted
under argon with degassed dichloromethane/diethylether (97% / 3%).
The first band eluted off the column contained the product and the solvent was
immediately pumped off. The product was a purple to brownish colored, shiny powder.
Spectroscopical data:
UV-VIS (e):
*H-NMR:
31p {iHJ-NM R:
FAB-mass:
( M + + 02 )
52
426.2 (Soret), 522.4( ), 557.6(.), 595.2(), 652.0( ) nm.
9.09 (s, 4H), 8.90 (dd, 4H, 8.4Hz, 1.0Hz), 8.77 (s, 4H),
8.34 (dd, 4H, 7.6Hz, 1.5Hz), 8.04 (s, 4H),
7.90 (td, 4H, 8.6Hz, 1.5Hz), 7.65 (td, 4H, 7.6Hz, 1.0Hz),
7.43 (dd, 4H, 6.5HZ; 1.5Hz),7.23 (m, 2H), 7.00 (m, 4H),
6.91(td, 8H, 6.4Hz, 1.4Hz), 6.83 (td, 8H, 8.0Hz, 1.2Hz) ppm.
164.4, 154.3, 142.1 (d, 17.3Hz), 140.2, 139.1, 135.8 (d, 19.7Hz),
135.3 (d, 5.4Hz), 134.92 (d, 6.5Hz), 133.4 (d, 20.3Hz),
130.8, 129.1 (d, 3.9), 128.4 (d, 7.3), 123.1, 122.4, 118.9,
115.43 ppm.
-6.5 ppm.
1335.3.
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4.6. References
1.) M.Bodanszky, A.Bodanszky, The Practice o f Peptide Synthesis, Springer Verlag,
Heidelberg, 1984.
2.) H.G.O. Becker, Organikum, 1990, l6.Ed., 413.
3.) M.Bodanszky, A.Bodanszky, The Practice o f Peptide Synthesis, Springer Verlag,
Heidelberg, 1984, 113-142.
4.) G.W. Anderson, J.E. Zimmerman, F.M. Callahan, J. Am. Chem. Soc., 1964,
86, 1839. ,
5.) J.P. Collman, R.R. Gagne, C.A: Reed, T.R. Halbert, G.Lang, W.T. Robinson,
J. Am. Chem. Soc., 1975, 97, 1427.
6.) D.Reddy, T.K. Chandrashekar, J. Chem. Soc., Dalton Trans. I, 1992, 619.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
5. Metal Complexation and Future Outlook
After the production and characterization of the phosphine pincer porphyrin
ligand system, complexation with a square planar platinum group metal was attempted.
5.1. R hodium (I) C om plexation
(Rh(CO)2Cl)2
/
OC-
Y
Figure 5.1: Schematic Formation of the Rhodium Complex.
According to the literature, a common way of complexing rhodium with a phos
phine ligand consists of the slow warming of a solution that contains [Rh(CO)2Cl]2 and
the phosphine ligand J To attempt this method [Rh(CO)2Cl]2 was prepared by the
literature method.^
The rhodium complex of the pincer ligand was formed by the addition of a
concentrated solution of [Rh(CO)2Cl]2 in dichloromethane to an ice-cold dichloro
methane solution of the porphyrin ligand. After warming the solution to room temper
ature, the solvent was removed in vacuo. Evidence for the formation of the desired metal
complex was found in the 31p-NMR spectrum by the appearance of a new peak at
28.78 ppm with a characteristic coupling constant 1 JRhP = 128.3 Hz. This matches
values in the literature quite well.
54
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5.2. Iridium(I) Complexation
In an NMR tube experiment a solution of the ligand in dichloromethane was
treated with a solution of Vaska’s compound in the same solvent. Possible exchange
reactions due to a chelating effect of the ligand were attempted to be monitored by 31p.
NMR. Due to the low solubility of Vaska’s compound in dichloromethane, the com-
plexed porphyrin precipitated as rhombic crystals. Unfortunately these crystals were too
small for X-ray defraction.
5.3. Experimental Procedures
5.3.1. Dichloro-tetracarbonyl-dirhodium
A 50 cm glass tube equipped with a medium frit was attached via an inlet to a
carbon monoxide lecture bottle and placed into an oil bath. Rhodium(III)-chloride 3-
hydrate (1.2g, 4.3mmol) was pulverized and placed on the top of the fritt. The tube was
then purged with carbon monoxide at 85°C for 24 hours. Orange needles of
[Rh(CO)2Cl)2 sublimed up the tube. Allowing the tube to cool to room temperature, the
needles were scraped off and dissolved in a mixture of dichloromethane and pentane.
This solution was gravity filtered to remove any insoluble starting material. Removing
the solvent in vacuo yielded 0.7g (74 percent theoretical yield) of [Rh(CO)2Cl]2-
5.3.2. Rhodium Complexed Ligand
An apparatus including a 200 mL flask, a dropping funnel and an argon inlet is
taken out of the oven and cooled under argon. The pincer porphyrin (21.6 mg, 0.016
mmole) is placed in this flask, dissolved in 50 mL of twice distilled dichloromethane and
the solution is cooled in an ice bath. Then the rhodium-complex, [Rh(CO)2Cl]2 (3.3
mg, 0.008 mmole), is dissolved in 20 mL of freshly distilled dichloromethane and
55
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cannuiated into the dropping funnel. Within the next 30 minutes this rhodium solution is
slowly added into the porphyrin solution. The solution is allowed to warm to room
temperature and then the volatiles are pumped off in vacuo. The product remained as a
purple powder.
31P {iHJ-NM R: 28.78 ppm, ijpRh = 128.3 Hz.
CM
c r >
CM
''K iw i li
i
.j’
W f l / W I l ’ *!/' ' a " ' " f r - . T h j i
i li i ’ j ii 9 1/1 1 > i
i r n r i t 1 1 i y j V i V i i r y T- T T ' ; 'i i “ r y r i — j -|— t " t " r — |
! 30.5 30.0 29.5 29.0 28.5 28.0 27.5 ppmj
31p-NM R of the Rhodium complexed Phosphine Pincer Porphyrin
56
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5.4. Future Outlook
This thesis has shown the design and preparation of a pincer porphyrin which is
expected to hold a metal containing porphyrin and a square planar platinum group metal
at close proximity. The preparation of the ligand has so far been verified by various
methods, although the exact structure is yet unknown. Thus, growing of a single crystal
and obtaining an X-ray structure is a further step in this project.
The next goal includes the complete metal complexation of the ligand, e.g. the
ligation of a platinum-group metal by the phosphine ligands as well as the insertion of a
metal such as cobalt in the porphyrin. Such metal insertions in the porphyrin plane are
known reactions.^ After successful metalation the metal complex will be fully charac
terized by NMR, UV-VIS, FAB-mass and crystal structure.
With this complex several reactions could 'be tried.
5.5. Expected Chemistry
This ligand combines the features of two totally different systems. On the one
side diere is a metallated porphyrin ring which is used in many reactions with biological
background. These include oxygen and nitrogen fixation plus reduction, oxidation
reactions and several others.^ On the other side there is a platinum group metal that is
mostly found in homogenous, catalytic reactions, including oxygen fixation and hydro-
formylation reactions.^ Combination of both in one ligand could produce a system with
new catalytic properties. Two of the expected reactions are outlined below.
5.5.1. Oxygen Reduction
One possible catalytic reaction of this complex may be the four electron reduction
of oxygen to water. Vaska’s compound itself is able to bind oxygen reversibly,^
Co(TPP) also binds and reduces oxygen.^ Both centers together may have enough re-
57
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duction potential to push the oxygen reduction beyond the metastable hydroperoxide
formation and, attached to an electrode, catalyze its reduction to water.
5.5.1. H y d roform ylation R eactions
In the literature many planar, phosphine-containing rhodium complexes are
known to catalyze hydroformylation reactions of alkenes. Introduction of another metal
center in close proximity to the rhodium often caused the preferential formation of only
one possible product.4 Thus the catalysis of a regiospecific hydroformylation reaction
will not be unexpected.
5.6. R eferences
1.) K.V. Katti, R.G. Cavell, Organomet'allics, 1988, 7, 2236.
2.) J.A. Cleverly, G.Wilkinson, Inorg. Synth., vol. VIII, 211.
3.) J.-H. Fuhrlop, K.M. Smith, Laboratony Methods in Porphyrin and Metallo-
porphyrin Research, 1975, 39-56.
4.) See: Introduction.
5.) H. Jahnke, M. Schonborn, G. Zimmermann, Top. Curr. Chem., 1976, 61, 133.
6.) J.R. Lockemeyer, A.L. Rheingold, J.E. Bulkowski, Oranometallics, 1993,
12, 256.
58
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Asset Metadata
Creator
Hombeck, Marc
(author)
Core Title
Design and synthesis of a new phosphine pincer porphyrin
School
Graduate School
Degree
Master of Science
Degree Program
Chemistry
Degree Conferral Date
1994-12
Publisher
University of Southern California
(original),
University of Southern California. Libraries
(digital)
Tag
chemistry, inorganic,OAI-PMH Harvest
Language
English
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Digitized by ProQuest
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Advisor
Reed, Christopher (
committee chair
), [illegible] (
committee member
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