Abnormal Fischer Indolization and its Development to a New Synthetic Method.

Abstract

Fischer indolization of ο-methoxyphenylhydrazone derivatives provides various types of unexpected indole products under several condition. These abnormal results were well-established. The representative case has been shown by the formation of ethyl 6-chloro- and 6-ethoxyindole-2-carboxylate in treatment of ethyl pyruvate 2-methoxyphenylhydrazone with ethanolic hydrogen chloride. Formation of these products are explainable by cyclization of the starting hydrazone to the orthoposition occupied by a methoxy group. This abnormal Fischer indolization has been developed to a new synthetic method for 6-substituted indole. For example, treatment of 2-methoxyphenylhydrazone with TsOH in the presence of ethyl acetoacetate, an enolizable dicarbonyl compound, gave an indolic product having ethyl acetoacetate group at the C₆ position with other indole derivatives. The new reaction was applied to synthesis of two natural indole products having an alkene side chain at the C₆ position.
Fischer indolization of other ortho substituted phenylhydrazones have been studied.