A catalyst‐free, greener and highly efficient method for the synthesis of a series of quinoxaline derivatives involving simple liquid assisted hand‐grinding in a mortar and pestle has been developed. The mechanochemical agitation under LAG was sufficient enough for the smooth condensation of both aromatic and heteromatic 1,2‐diamines with a variety of 1,2‐dicarbonyl compounds to afford the corresponding quinoxalines in high yields. Several of these quinoxaline derivatives inhibit the growth of Mycobacterium smegmatis in moderate to good effect. Simple substitution in the quinoxaline ring was found to be more effective in antibacterial agents than bulky substitution. In particular, pyrido[2,3‐b]pyrazines with an additional N‐atom in the scaffold showed better activity than others. Overall, the key advantages of this method are simplicity of operation, catalyst‐free condition, solvent‐less synthesis, low E‐factor, cleaner reaction profile, devoid of work‐up step, easy purification and shorter reaction times, and the new series of pyrido[2,3‐b]pyrazines are good antibacterial agents against M. smegmatis.
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