Selective 5-Exo-Dig versus 6-Endo-Dig Cyclization of Benzoimidazole Thiols with Propargyl Alcohols

We describe here the Lewis acid-promoted cyclization reaction of benzomidazole thiols with propargyl alcohols for the selective synthesis of benzoimidazolo thiazines and benzothiazolo imidazoles. The reaction is regioselective and the solvent controls the formation of products. The systematic study to determine the best reaction conditions revealed that the six-membered benzoimidazolo thiazines were obtained by reacting the benzoimidazole thiols with propargyl alcohols in the presence of boron trifluoride etherate, using dichloromethane as the solvent. Replacement of dichloromethane with dimethylformamide, by using the same starting material and reagents, gave selectively the five-membered benzothiazolo imidazoles. The mechanism of this cyclization was proposed based on the results obtained and several control experiments.

Automated summary

The Lewis acid-promoted cyclization reaction of benzomidazole thiols with propargyl alcohols for the selective synthesis of benzoimidazolo thiazines and benzothiazolo imidazoles is described. The reaction is regioselective and controlled by the choice of solvent. The best reaction conditions were determined through systematic study, resulting in the formation of six-membered benzoimidazolo thiazines using boron trifluoride etherate and dichloromethane as the solvent, and five-membered benzothiazolo imidazoles using the same starting material and reagents with dimethylformamide as the solvent. The proposed mechanism of the cyclization reaction is based on experimental results and control experiments.