ORGN 439 |
| Benzoheterocycles such as benzothiazoles, benzimidazoles and benzoxazoles can serve as unique and versatile scaffolds for experimental drug design as exemplified by the structures of riluzole, ® dabigatran® and flunoxaprofen®. For structural elaboration in lead optimization, the points of attachment can be through a number of individual atoms on either the benzene or heterocyclic rings and may be facilitated through ether, sulfide, amide, amine or carbon-carbon bonds. A scheme for the preparation of aldehydes in the benzothiazole, benzoxazole and benzimidazole series is described. Starting with the corresponding methyl-substituted benzoheterocycle, the conversion entails a two-step sequence. The methyl group serves as the carbon from which the formyl group is derived. Hence, adjustment of the oxidation state of the methyl group first involves a free radical dihalogenation followed by a silver nitrite/dimethylsulfoxide-mediated hydrolysis to the aldehyde functionality. Of special note is the survival of multiple BOC-protected amino substituents on the heterocyclic ring during the entire process. Carbon-carbon forming reactions of the heterocyclic carbaldehydes which are compatible with the multiple BOC protection system will be described along with several types of deprotection reactions. |
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Heterocycles and Aromatics, Molecular Recognition and Self Assembly
8:00 PM-10:00 PM, Tuesday, April 8, 2008 Morial Convention Center -- Hall A, Poster
Division of Organic Chemistry |