Sinenko V. Preparation of new biologically active 1,3-thiazoles using lithiating reagents

Reactions of lithiation in the 1,3-thiazole ring were studied to obtain new thiazole derivatives. A versatile approach to obtaining 1,3-thiazole derivatives containing hydroxyalkyl substituents in positions 2 and 5 of the cycle has been developed. Four isomeric chloromethyl derivatives of 1,3-thiazole containing a latent aldehyde group are synthesized. Their nucleophilic substitution reactions with dimethylamine and sodium methylthyolate have been investigated. New low molecular weight aldehydes of the 1,3-thiazole series were obtained. The lithiation reaction of 2-bromo-4-(1,3-dioxolan-2-yl)-1,3-thiazole with lithium diisopropylamide in position 5 of the thiazole ring and double lithiation with t-butyllithium in positions 2 and 5 were found. Processing formed lithiated and dilithiated thiazoles by various electrophiles yielded a number of trifunctionalized 1,3-thiazoles with high yields. The synthesized isomeric aldehydes were involved in the condensation reaction with phenylhydrazine, isoniazid, and N-substituted rhodanines as well as in a three-component reaction with acetoacetic ester and urea. As a result of these reactions, the corresponding hydrazones, rhodanins and Biginelli reaction products were obtained. Chemical synthesis, IR and NMR spectroscopy (1H, 13C), LCMS, elemental analysis. Preliminary biological studies of a number of synthesized substances were performed. Found substances that have anti-TB and anticancer activity. Scope – bioorganic chemistry.