Extensive Biginelli reaction: Activated charcoal promoted green approach for one pot synthesis of 4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate derivatives
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Methyl 2-methyl-4-phenyl-4H-pyrimido [2,1-b][1,3] benzothiazole-3-carboxylate (4a):To a mixture of benzaldehyde (2g; 18.8 mmol), 2-aminobenzothizole (2.83g; 18.8 mmol), methyl acetoacetate (2.19g; 18.8 mmol) in water added acetic acid (0.23g; 3.8 mmol) and activated charcoal (0.2g; 10% of aldehyde) into a round-bottom flask. Then the reaction mass heated up to 90-95 °C with continuous stirring at 90-95 °C for 2 h. The progress of reaction was monitored using TLC. On completion of the reaction (absence of aldehyde), reaction mass cooled to ambient temperature gently. Reaction mass diluted with methylene chloride and stirred for about 30 min. Reaction mass filtered through celite pad and then layers separated. Organic layer recovered completely under reduce pressure to get oily residue which further purified by column chromatography by eluted with ethyl acetate/hexane. Isolated material finally recrystallized in methanol, and dried under vacuum to afford yellowish solid (5.51g; 87%). Rf =0.6 (TLC mobile phase ethyl acetate: hexane = 4:6 v/v); M.pt 146.2 °C.