Kut D., Kut M., Onysko M., Lendel V. STUDY OF REGIO- AND STEREO-SELECTIVITY OF HALOGEN-INDUCED CYCLIZATION OF TERMINAL PROPARGYL THIOETHERS OF 3-ALKYL(PHENYL)QUINAZOLINE-4-ONES

Abstract

Polycyclic condensed quinazoline derivatives are biologically valuable compounds that have found their application in pharmaceutical and medicinal chemistry. Their practical use makes such compounds interesting and promising, and their synthesis is an urgent task. In the present work, the regio- and stereo-selectivity of the halocyclic reaction of propargyl thioethers of 2-thioxoquinazoline-4-one with bromine, iodine and iodine bromide, the effect of solvent polarity, acceptor substituent at position 7 of quinazoline, and the steric effect of the substituent at N(3) of quinazoline on the course of the electrophilic heterocyclic reaction were investigated. It was found that the halogenation of 3-alkyl-2-thioxo-2,3-dihydroquinazoline-4(1H)-ones in chloroform or ice-cold acetic acid proceeds regio- and stereo-selectively with the formation of salt-like thiazoloquinazoline halides. On the contrary, the stereoselectivity of halogenation of the 3-phenyl substituted propargyl thioether of quinazoline depends on the polarity of the solvent and in chloroform leads to the formation of a mixture of configurational isomers of thiazoloquinazoline tribromide, while in acetic acid, presumably, one geometric isomer is formed. The structure of the obtained polycyclic systems was proved on the basis of NMR spectroscopy and elemental analysis.
 Keywords: propargyl thioethers; halogenation; stereo-selectivity; regio-selectivity; thiazoloquinazoline halides.