Click chemistry: Studies on the synthesis of novel fluorous tagged triazol-4-yl substituted quinazoline derivatives and their biological evaluation – Theoretical and experimental validation

The formation of N- and O-propargylated quinazoline derivatives 2, 3 from quinazol-4-ones 1 was theoretically predicted by optimizations at B3LYP/6-31G* level, analysed kinetically and thermodynamically. Theoretical predictions are validated by experiment to observe the trends and found deviation. Thus, compound 1 was propargylated in basic media to obtain compound 2 and 3 in definite proportions. Each compound was further subjected to [3 + 2] cycloaddition using perfluoroalkyl azides through Click reaction under Sharpless conditions, and obtained a series of novel perfluoroalkyl-1H,1,2,3-triazol-4-yl substituted quinazolines 4, 5, and 6. All the compounds were screened for antimicrobial activity and identified potential compounds.

Graphical abstractA series of novel perfluoroalkyl-1H, 1, 2, 3-triazol-4-yl substituted quinazolines 4, 5, and 6 were synthesized through Click reaction under Sharpless conditions and screened for antimicrobial activity to identify potential compounds. The formation of products predicted by optimizations at B3LYP/6-31G∗ level, analysed kinetically and thermodynamically.Figure optionsDownload full-size imageDownload as PowerPoint slide