Three Component Divergent Reactions: Base-Controlled Amphiphilic Synthesis of Benzimidazole-Linked Thiazetidines and Fused Thiadiazines

A divergent
reaction of 2-aminobenzimidazole with isothiocyanates
and dihalomethanes has been developed for the selective synthesis
of benzoimidazothiazetidine and benzoimidazothiadiazine. A single-pot
reaction of 2-aminobenzimidazole in the presence of sodium hydride
delivers benzoimidazothiazetidine, whereas triethylamine promotes
the formation of benzoimidazothiadiazine via a sequential stepwise
fashion. The reaction sequence involves the initial formation of thiourea
followed by regioselective nucleophilic addition and intramolecular
ring-closing with dihalo electrophiles. The observed regioselectivity
of this reaction is governed by the nature of bases and the reaction
sequence.