Mechanism of formation of 3-methyl derivatives of imidazo[2,1-b]thiazoles and their benzo analogs in the reactions of 2-mercaptoimidazole and 2-mercaptobenzimidazole with 1,3-dichloroacetone under phase-transfer catalysis conditions

Abstract

Keywords: 3-methyl derivatives of imidazo[2,1-b]thiazoles, phase-transfer catalysis, X-ray structural analysis. Imidazo[2,1-b]thiazoles have a broad spectrum of biological activity [1]. The main method for synthesizing 3-methyl-substituted imidazo[2,1-b]thiazoles and 3-methyl[1,3]thiazolo[3,2-a]benzimidazoles is based on the reaction of 2-mercaptoimidazoles with chloroacetone in ethanol [2] or alkaline ethanol [3]. 3-Methylbenzo[4,5]imidazo[2,1-b]thiazoles have also been obtained through the reaction of 2-mercaptobenzimidazoles with acetone in the presence of I 2 [4] or H 2 SO 4 -AcOH [5]. In addition, 3-methyl[1,3]thiazolo-[3,2-a]benzimidazole is prepared via cyclization of 2-propargylthiobenzimidazole in the system Hg(OAc) 2 -H 2 SO 4 -acetic acid [6] or from 2-(2-bromo-2-propenylthio)benzimidazole under phase-transfer catalytic conditions in the system KOH-benzyltriethylammonium chloride-DMSO [7]. There is also evidence in the literature for the deiodination of 3-iodomethyl-2,3-dihydro[1,3]thiazolo[3,2-a]benzimidazole to 3-methyl[1,3]-thiazolo[3,2-a]benzimidazole in alkaline medium [8].In the reactions of the thiols 1-4 with 1,3-dichloroacetone in the system solid K 2 CO 3 -solid KI-18-crown-6-toluene the single reaction products in place of the expected chloromethyl derivatives are the methyl heterocycles 5-8 which are low melting, crystalline materials (see Experimental).We have carried out several experiments to determine the mechanism of formation of compounds 5-8. In the first we have shown that refluxing 1,3-dichloroacetone with excess solid KI and solid K 2 CO 3 forms 1,3-diiodoacetone. The reaction of transfer of halogens from one molecule of 1,3-dihaloacetone to another

Benzothiazole derivatives augment glucose uptake in skeletal muscle cells and stimulate insulin secretion from pancreatic β-cells via AMPK activation

“…To obtain 3,3 0 -(ethane-1,1-diylbis(sulfanediyl))dipropionic acid ( 16), the free thiol group of 3-mercaptopropanoic acid was conjugated with acetaldehyde in the presence of BF 3 Ádiethylether in chloroform. Three other compounds, 3-methylimidazo[2,1-b]thiazole (17), 3-methylbenzo [4,5]imidazo[2,1-b]thiazole (18) and 3-methyl-7-nitrobenzo [4,5]imidazo[2,1-b]thiazole (19), were synthesized by alkylating thiol groups of their imidazole moiety with 1,3-dichloropropan-2-one, following direct cyclization of the substituted alkyl chain to obtain the corresponding two-or tricycle aromatic derivatives. 19 The effect of these 19 compounds on GSIS was studied in INS-1E b-cells, as described before.…”

“…Three other compounds, 3-methylimidazo[2,1-b]thiazole (17), 3-methylbenzo [4,5]imidazo[2,1-b]thiazole (18) and 3-methyl-7-nitrobenzo [4,5]imidazo[2,1-b]thiazole (19), were synthesized by alkylating thiol groups of their imidazole moiety with 1,3-dichloropropan-2-one, following direct cyclization of the substituted alkyl chain to obtain the corresponding two-or tricycle aromatic derivatives. 19 The effect of these 19 compounds on GSIS was studied in INS-1E b-cells, as described before. 20 Table S1 (ESI †) shows that only the benzothiazole derivatives, 1 and 9, exhibited significant positive effects in this assay.…”