Substituted bisindolines were synthesized from the reaction of 3,5-dimethoxyaniline and vicinal diones (2,3butanedione, benzil, and 4-methylbenzil). The reaction of 3,5-dimethoxyaniline with 2,3-butanedione under polar acidic conditions proceeded with an unanticipated double cyclization reaction forming 2,2 0dimethyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-1. The reaction of 3,5-dimethoxyaniline with benzil under similar conditions did not form a bisindoline, but instead formed cis-1,2-diphenyl-2-[(3,5dimethoxyphenyl)imino]ethanone, 2. When the solvent, acid, and reaction temperature were changed for the reaction of 3,5-dimethoxyaniline with benzil, 3,3-diphenyl-4,6-dimethoxyindolin-2-one, 3 (an isomer of 2), and 2,2 0 -diphenyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-4, were isolated as major and minor products, respectively. Similarly, the reaction of 3,5-dimethoxyaniline with 4-methylbenzil produced a 1 : 1 mixture of cis-1-(4-methylphenyl)-2-phenyl-2-[(3,5-dimethoxyphenyl)-imino]ethanone, 6a, and cis-1- (3,5-dimethoxyphenyl)imino]ethanone, 6b, under polar acidic conditions and 3-(4-methylphenyl)-3-phenyl-4,6-dimethoxyindolin-2-one, (+/À)-7 and 2-(4-methylphenyl)-2 0phenyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-8, under apolar acidic conditions at elevated temperature. We propose the mechanism of bisindoline and indolinone formation to include a Friedel-Crafts type electrophilic attack on the electron rich aryl ring at the ring closing C-C bond forming steps, and further propose a common carbocationic monocyclized intermediate.
