Yong-Jin Wu, B. Yang
2009
Citations
0
Influential Citations
5
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Journal
Progress in Heterocyclic Chemistry
Abstract
Publisher Summary This chapter discusses the syntheses and reactions of these 5-membered heterocyclic ring systems containing nitrogen and sulfur (or selenium). The importance of these π-rich heterocycles in medicinal chemistry and natural products is also discussed. The chapter discusses the synthesis of thiazoles, fused thiazoles, and thiazolines. Reactions of thiazoles and fused derivatives are also discussed in the chapter. The first practical, large-scale synthesis of 2-amino-5-fluorothiazole employs the reaction of dilithiated 2-butoxycarbonylaminothiazole with N-fluorobenzenesulfonimide (NFSi). This reaction generates a 70:15 mixture of the desired fluorinated thiazole and the sulphone, and after three consecutive recrystallizations thiazole is isolated in 35–40% yield. This procedure has been utilized to prepare multikilogram quantities of 2-amino-5-fluorothiazole that is a heterocyclic amine component of a series of glucokinase inhibitors. A new methodology for direct phosphonation of thiazoles has been developed. Reaction of substituted thiazoles with dimethyl or diethyl phosphates in the presence of manganese (III) acetate dihydrate provides 5-dimethyl or diethyl-phosphonothiazoles.