Regio- and stereo-selective halogen-induced cyclization of terminal alkynyl thioethers of 3-phenylquinazoline-4-one

Abstract

The present work reports the results of the study of the electrophilic heterocyclization of terminal alkynyl thioethers of quinazoline-4-one under the action of halogens. Starting 2-(but-3-in-1-ylthio)-3-phenylquinazolin-4(3H)-one and 2-(pent-4-in-1-ylthio)-3-phenylquinazolin-4(3H)-one were prepared by alkylation of 2-thioxoquinazolin-4-one with butynyl and pentynyl bromide in an alcoholic-alkaline medium, respectively. It was determined that the interaction of 2-(but-3-in-1-ylthio)-3-phenylquinazoline-4(3H)-one with bromine, iodine and iodine bromide is regio- and stereo-selective and leads to the formation of 1-(halogenomethylidene)-6-oxo-5-phenyl-2,3,5,6-tetrahydro-1H-[1,3]thiazino[3,2-a]quinazolinium halides of angular structure as E-isomers. On the contrary, the halogen-induced heterocyclization of 2-(pent-4-in-1-ylthio)-3-phenylquinazolin-4(3H)-one leads to the annelation of thiazepine cycle to quinazoline core with formation of E-1-(bromomethylidene)-7-oxo-6-phenyl-1,2,3,4,6,7-hexahydro-[1,3]thiazepino[3,2-a]quinazolinium tribromide and E-1-(iodomethylidene)-7-oxo-6-phenyl-1,2,3,4,6,7-hexahydro-[1,3]thiazepino[3,2-a]quinazolinium monobromide. It was found that an increase in the carbon length of the terminal alkynyl substituent by one methylene group affects the regioselectivity of the halocyclization process, but does not affect the stereoselectivity.