A study on the reaction of 3-alkyl(aryl)imidazo[1,5-a]pyridines with ninhydrin

The reaction of 3-alkyl(aryl)imidazo[1,5-a]pyridines (1) with ninhydrin in dichloromethane at room temperature delivered good yields of the respective 2-hydroxy-2-(imidazo[1,5-a]pyridine-1-yl)indene-1,3-diones. In the presence of dimethyl acetylenedicarboxylate (DMAD), this uncatalyzed electrophilic substitution reaction, involving C-1 (in 1) and the central C=O (in ninhydrin), takes precedence over the three-component 1,4-dipolar cycloaddition reaction. This selectivity is probably due to the higher electrophilicity of the carbonyl carbon-2 in ninhydrin as compared to that of the sp-carbon atoms in DMAD, augmented with the high nucleophilicity of carbon-1 in 1.