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21
Scheme 2.1 Reactions of Benzaldehyde and Ketones with 1,2-
Phenylenediamines
Ph H
O
NH2
NH2
N
N
Ph
CH2Ph
+
N
N
Ph
CH2Ph
H
H
Y
Y Y
R1 CH2R2
O
R1, R2 = alkyl, phenyl N
N
R1
R1
CH2R2
H
R2
Y
1a
2 3
4
However, when ketones (When R1, R2 = alkyl, phenyl) were used under
similar conditions, 1,5 benzodiazepine derivatives 5 were formed as the major
products (Scheme 1).28,29,30,31,32,33,34 This reaction proceeds through the diimine
intermediate 10a, which then undergo an internal Michael type addition reaction to
give rise to the corresponding 1,5-benzodiazepine derivatives 5 (Scheme 2.1).
Reports on the direct synthesis of fluorinated benzimidazolines are very rare.35,36
Funabiki et al.37 have prepared fluorinated benzimidazolines from fluorinated
butynoic acids 5 (Scheme 2.2). Synthesis of more diverse and functionalized
starting materials for this reaction is tedious. Furthermore, the reaction conditions
are harsh and chemical yields are not so significant.
Scheme 2.2 Synthesis of Fluorinated Heterocycles from Fluorinated Butynoic
Acids
NH
X CH3
Rf
Rf C C COOH
NH2
XH
+
EtOH-H2O
Reflux, 1-32 h
X = NH, S, O
Rf = CHF2, CHF2CF2CF2, CF3
22-88 %
5
Object Description
| Title | Synthesis of organofluorine compounds via Lewis/Bronsted acid and base catalysed reactions and related chemistry |
| Author | Vaghoo, Habiba Ebrahim |
| Author email | vaghoo@usc.edu; vaghoo@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program |
Chemistry vinyl fluorides |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2008-06-24 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-10-31 |
| Advisor (committee member) |
Olah, George A. Shing, Katherine S. |
| Abstract | This dissertation describes the development of new and practical methodologies for the synthesis of a broad variety of fluorinated heterocycles and vinyl fluorides via acid and base catalysis, respectively. It also describes efficient cyanosilylation of carbonyl compounds using a variety of nucleophilic catalysts.; Chapter 1 explores the rich history of fluorine and its compounds. Important milestones that have made a significant contribution to the field of chemistry are highlighted with emphasis on fluorine's role in medicinal chemistry. Methods to introduce fluorine are also included in this chapter.; Chapter 2 deals with the use of gallium (III) triflate as a versatile Lewis acid for the synthesis of different fluorinated heterocycles and α-aminonitriles. The condensation-cyclization reactions of various aromatic amino derivatives with fluorinated ketones to afford the corresponding fluorinated benzimidazolines, benzothiazolines, benzoxazolines, and dihydrobenzoxazinones, as well as fluorinated 1, 5 benzodiazepines and quinoxaline derivatives is described. Also included in this chapter are the syntheses of α-aminonitriles and their fluorinated analogs via the multicomponent Strecker reaction using gallium (III) triflate. Monofluoro-, difluoro-, or trifluoromethyl groups have been incorporated into both heterocycles and the α-aminonitrile products by varying the nature of the fluorinated ketones.; In Chapter 3, Nafion^®-H, a perfluoroalkanesulfonic acid resin, is shown to be a suitable solid acid catalyst with high selectivity and catalytic activity for the one-pot synthesis of fluorinated heterocycles. The Nafion-H mediated reactions are easily achieved under mild conditions in high yields and purity. Monofluoro, difluoro and trifluoromethylated derivatives can be prepared and its advantage as a solid superacid is highlighted by the recyclability studies.; Chapter 4 describes a new approach for the stereoselective synthesis of vinyl fluorides using α-substituted fluoro(phenylsulfonyl)methane derivatives under mildly basic reaction conditions. A variety of fluorovinyl sulfones as well as α-fluoro-α,β-unsaturated carbonyls can be synthesized to afford the E-isomer.; Finally, in Chapter 5, cyanosilylation of aldehydes and ketones using various nucleophilic catalysts under mild conditions is portrayed. Use of dimethylformamide (DMF) as solvent, afforded the trimethylsilylated cyanohydrins in good to excellent yields. K2CO3 and (MeO)2P(O)(O^-)(N^+Bu4)3 have been employed as the nucleophilic catalysts for the cyanosilylation using trimethylsilyl cyanide (TMSCN). |
| Keyword | fluorine chemistry; fluorinated heterocycles; fluorinated aminonitriles; cyanosilylation |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m1729 |
| Contributing entity | University of Southern California |
| Rights | Vaghoo, Habiba Ebrahim |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-Vaghoo-2053 |
| Archival file | uscthesesreloadpub_Volume44/etd-Vaghoo-2053.pdf |
Description
| Title | Page 35 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 21 Scheme 2.1 Reactions of Benzaldehyde and Ketones with 1,2- Phenylenediamines Ph H O NH2 NH2 N N Ph CH2Ph + N N Ph CH2Ph H H Y Y Y R1 CH2R2 O R1, R2 = alkyl, phenyl N N R1 R1 CH2R2 H R2 Y 1a 2 3 4 However, when ketones (When R1, R2 = alkyl, phenyl) were used under similar conditions, 1,5 benzodiazepine derivatives 5 were formed as the major products (Scheme 1).28,29,30,31,32,33,34 This reaction proceeds through the diimine intermediate 10a, which then undergo an internal Michael type addition reaction to give rise to the corresponding 1,5-benzodiazepine derivatives 5 (Scheme 2.1). Reports on the direct synthesis of fluorinated benzimidazolines are very rare.35,36 Funabiki et al.37 have prepared fluorinated benzimidazolines from fluorinated butynoic acids 5 (Scheme 2.2). Synthesis of more diverse and functionalized starting materials for this reaction is tedious. Furthermore, the reaction conditions are harsh and chemical yields are not so significant. Scheme 2.2 Synthesis of Fluorinated Heterocycles from Fluorinated Butynoic Acids NH X CH3 Rf Rf C C COOH NH2 XH + EtOH-H2O Reflux, 1-32 h X = NH, S, O Rf = CHF2, CHF2CF2CF2, CF3 22-88 % 5 |
