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29
2.2.2 Synthesis of Quinoxalines and Fluorinated 1, 5-benzodiazepines using
Aromatic Diamines with 1, 2 and Fluorinated 1, 3 Diketones,
respectively.
The quinoxaline framework is an important nitrogen containing
heterocyclic component of various biologically important molecules. Quinoxalines
are widely used in the pharmaceutical industry and are extensively used as dyes and
insecticides.38 Among the strategies for the construction of quinoxaline moiety,
treating an aryl 1, 2-diamine with a 1, 2-dicarbonyl under reflux in ethanol or acetic
acid is most common.39 Recently, there have been reports of the use of molecular
iodine as a catalyst in either acetonitrile or dimethyl sulfoxide40 allowing for the
reaction to take place at room temperature. Even more recently, Heravi et al. have
reported the use of o-iodobenzoic acid (IBX) in acetic acid at room temperature for
the same transformation.41 While all these methods do eliminate the need for
reflux, they introduce other challenges. In the former case, the use of solvents that
are difficult to remove undermines its utility while in the latter case; IBX is known
to explode on heating making its preparation non-trivial.
To further extend this methodology, we explored the use of fluorinated
diketones. As fluorinated 1, 2 diketones are not readily accessible; we turned our
attention to fluorinated 1, 3 diketones, which are commercially available. Thus, we
were able to extend this methodology to synthesize fluorinated 1, 5-benzodiazepine
derivatives. The 1, 5-benzodiazepine core has many applications in both
pharmaceuticals as well as in industry. In the pharmaceutical arena they are
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 43 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 29 2.2.2 Synthesis of Quinoxalines and Fluorinated 1, 5-benzodiazepines using Aromatic Diamines with 1, 2 and Fluorinated 1, 3 Diketones, respectively. The quinoxaline framework is an important nitrogen containing heterocyclic component of various biologically important molecules. Quinoxalines are widely used in the pharmaceutical industry and are extensively used as dyes and insecticides.38 Among the strategies for the construction of quinoxaline moiety, treating an aryl 1, 2-diamine with a 1, 2-dicarbonyl under reflux in ethanol or acetic acid is most common.39 Recently, there have been reports of the use of molecular iodine as a catalyst in either acetonitrile or dimethyl sulfoxide40 allowing for the reaction to take place at room temperature. Even more recently, Heravi et al. have reported the use of o-iodobenzoic acid (IBX) in acetic acid at room temperature for the same transformation.41 While all these methods do eliminate the need for reflux, they introduce other challenges. In the former case, the use of solvents that are difficult to remove undermines its utility while in the latter case; IBX is known to explode on heating making its preparation non-trivial. To further extend this methodology, we explored the use of fluorinated diketones. As fluorinated 1, 2 diketones are not readily accessible; we turned our attention to fluorinated 1, 3 diketones, which are commercially available. Thus, we were able to extend this methodology to synthesize fluorinated 1, 5-benzodiazepine derivatives. The 1, 5-benzodiazepine core has many applications in both pharmaceuticals as well as in industry. In the pharmaceutical arena they are |
