A Continuous Protodecarboxylation of Heteroaromatic Carboxylic Acids in Sulfolane.

Abstract

A versatile, scalable method for the decarboxylation of indole-2-carboxylic acids has been found. With one equivalent of DBU in sulfolane, indole-2-carboxylic acid derivatives were cleanly decarboxylated in a 316 stainless steel tube reactor at 300 °C within 20 min. The corresponding indole derivatives were obtained in good yields. It was also found that indole-2-carboxylic acid (1) can be decarboxylated in either pure sulfolane or sulfolane with 3% water at 300 °C within 20 min. (1) The decarboxylation with one equivalent of DBU could successfully be transferred to benzo[b]thiophene-2-carboxylic acid derivatives if a prolonged reaction time was used. (2) Picolinic acid could also be decarboxylated in sulfolane with 3% water, and thiophene-2-carboxylic acid was smoothly decarboxylated with DABCO instead of DBU. (3) Benzoic acid derivatives were either inert or decomposed under the reaction conditions.