Thiazoles derived carbanions

Nucleophilic attack at sulfur is implicated in many reactions of 1,2,4-thiadiazoles <84CHEC-I(6)463> and in general soft nucleophiles attack at sulfur. For example, reaction of 3-hydroxy-5-phenyl-1,2,4-thiadiazole (23) with acetic anhydride in the presence of dbu at 130°C gives the thiazoles (31) and (32) <85JHC1497>. These products may be reasonably explained by the mechanism outlined in Scheme 9 in which the thiadiazole ring is opened by the acetic anhydride carbanion. There is some evidence that (32) may arise from attack of the carbanion on the A-acylated derivative (30a) (Scheme 9) <85JHC1497>. 

The electron-withdrawing effect of the benzotriazole nucleus has profound effect on the diverse reactions that oenzotriazole-based synthons undergo. For example, carbanions of 1-methyl- and 2-methylbenzotriazole reacted with 2-(methylthio)benzo-thiazole to afford the 1-substituted-benzotriazole (91) and the corresponding 2-substituted benzotriazole [94H(38)1041]. Immonium cations derived from 1-hydroxy-methylbenzotriazole (92) are also effective acceptors for ketones, 1,3-dicarbonyl and select enamine synthons under Lewis acid reaction conditions [94JHC(31)917]. 

This reasoning is supported by the observation that the reaction of 2-nitrofuran with trichloromethyl carbanion proceeds in both 3- and 5-positions, because in this case the base-induced p-elimination of HCl from the intermediate o adducts is a fast process [54]. Also the VNS reactions of nitro derivatives of other 5-membered heterocycles, imidazoles [20, 56] and thiazoles [34], with a variety of a-halogeno carbanions have been shown to proceed efficiently. 

According to Breslow, the active aldehyde intermediate in the decarboxylation of pyruvate could be an a-hydroxyethyl derivative of thiamine pyrophosphate, the substituent being attached in position 2 to the thiazole ring . His starting point was the observation that thiazolium salts easily lose a proton at C-2. Thus a stable and reactive zwitterion results that could be capable of forming an acyl carbanion derivative. The near-by amino-pyrimidine ring would have an inductive effect upon electron withdrawal at C-2. Breslow pictures the formation of acetoin from pyruvate and acetaldehyde as follows ... 

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