Exploration and Optimization of an Efficient One‐pot Sequential Synthesis of Di/tri‐substituted Thiazoles from α‐Bromoketones, Thioacids Salt, and Ammonium Acetate

Abstract

Exploration of scope of an optimized one‐pot sequential procedure for preparing of 2,4‐di‐ and 2,4,5‐tri‐substituted thiazoles has been accomplished. The synthesis was performed by the initial formation of a β‐keto‐thioester intermediate from nucleophilic substitution of α‐bromoketones with thioacid potassium salts, followed by treatment with ammonium acetate and one equivalent of acetic acid in toluene to form imine intermediate eventually leading to cyclization yielding thiazoles. This procedure should be highlighted with a flexible way to control the substitution pattern around thiazole ring by choosing appropriately substituted α‐bromoketones even containing acid labile functionality and thioacid potassium salts, and thus its applicability is very wide.