Synthesis of Novel 6, 8-Distributed-Chromone-3-Carboxamides and their evaluation as potential anti-tuberculosis agents

Abstract

This project focusses on the synthesis of novel 6,8-disubstituted-chromone-3-carboxamides and their evaluation as potential anti-tuberculosis agents. In this study, four 3-iodo-5-substituted-2-hydroxyacetophenones (58A-D) and three 3-bromo- 5-substituted-2-hydroxyacetophenones (63A-C) were successfully synthesized from 5- substituted-2-hydroxyacetophenones (57A-D). The Vilsmeier-Haack reaction was used to synthesize the 8-iodo-6-substituted-chromone-3-carbaldehydes and 8-bromo-6-substitutedchromone- 3-carbaldehydes from the 3-iodo/bromo-5-substituted-2-hydroxyacetophenones. These compounds were treated with sodium chlorite and sulfamic acid to afford corresponding chromone-3-carboxylic acids. Recrystallization with either ethanol or methanol was used to purify the synthesized compounds. All compounds were synthesized in good to excellent yields. The yields of the 3- iodo-5-substituted-2-hydroxyacetophenones (58A-D) ranged from 55 - 75 %, the 3-bromo-5- substituted-2-hydroxyacetophenones (63A-C) were synthesized with yields from 66 - 87 %, the percentage yields are significantly different probably because different methods were used. The yields of the 8-iodo-6-substituted-chromone-3-carbadehydes (59A-D) ranged from 78 – 90 %, the 8-bromo-6-substituted-chromone-3-carbaldehydes (64A-C) with yields from 85 - 87 %, 8-bromo-6-substuted-chromone-3-carboxylic acids from 47 – 52 %, and chromone-3- carboxylic acid afforded a yield of 57 %. 1H NMR, 13C NMR and FTIR spectroscopic techniques were used to characterize synthesized compounds and also confirmed by melting points for compounds reported in literature.