Reactivity of N-thioamido amidines with halogenated alkyl derivatives: synthesis of 4,5-disubstituted 2-alkylaminothiazoles

Abstract

2-Bromoacetate ethyl ester 4, 2-chloroacetonitrile 5, 2-bromo-1-(4-nitrophenyl)ethanone 6, and 2-chloroacetone 7 react with N-thioamido amidines 3 to yield the corresponding 4,5-disubstituted 2-alkylamino thiazoles 8, 9, 10, and 11 after the release of an amine molecule. The reaction of the amidines 3 with benzyl bromide 12, 4-chlorobutyronitrile 13, 3-bromopropionate ethyl ester 14, 3-chloropropionate ethyl ester 15, and 4-nitrobenzyl chloride 16 does not lead to the cyclic derivatives but gives opened-ring intermediates 17, 18, 19, 20, and 21. The cyclization mechanism is discussed on the basis of the study of the opened-ring intermediates which have been isolated in some cases and the AM1 and PM3 semi-empirical energetic calculations.

Keywords:

• N-thioamido amidines
• 4,5-disubstituted 2-alkylamino thiazoles
• opened-ring intermediates
• cyclization
• AM1 and PM3 semi-empirical calculations

Acknowledgements

The authors thank MESRST (Ministère de l'Enseignement Supérieur, la Recherche Scientifique et la Technologie) (Lab CH–02) for the financial support.