Diethyl Malonate → 1,2-Benzisoxazole

Participants

Reaction Steps

The benzisoxazole-, benzisoxazole-, and benzothiazolecarboxylic acids were prepared using similar strategies outlined for the indazole acids. For example, ethyl 6-bromobenzisoxazole-3-carboxylate was prepared from 2,5-dibromonitrobenzene by reaction with diethyl malonate, saponification and decarboxylation, and reaction with isoamylnitrite. Ethyl benzisoxazole-3-carboxylate was obtained by hydrogenolysis of the 6-bromo derivative. 4-Benzothiazolecarboxylic acid was prepared from 2-amino-4-chloro-benzothiazole by reaction with isoamyl nitrite followed by metal-halogen exchange and trapping with carbon dioxide. 5-Benzothiazolecarboxylic acid was prepared from 4-chloro-3-nitrobenzoic acid by reaction with Na2S and sodium hydroxide followed by reduction with zinc in formic acid. 3-Benzisothiazolecarboxylic acid was prepared from thiophenol by reaction with oxalyl chloride and aluminum chloride followed by treatment with hydroxylamine, hydrogen peroxide, and sodium hydroxide.

Provenance & Evidence