Mechanistic observations in the gewald syntheses of 2‐aminothiophenes

Abstract

Abstract The Gewald syntheses were employed to prepare a series of 2‐amino‐3‐carboethoxythiophenes, and the syntheses of two of these, namely, the 3,4‐trimethylene ( 1f ) and 3,4‐tetramethylene ( 1g ) derivatives, were examined in detail. In two preparations of 1f , octahydro‐6a‐(4‐morpholinyl)‐2‐thioxocyclopenta[ b ]pyrrole‐3‐carboxylic acid ( 7 ) was a co‐product. The structure of 7 was ascertained from its 300 MHz 1 H nmr and 13 C nmr spectra, and by its conversion to 1,4,5,6‐tetrahydro‐2‐mercaptocyclopenta[ b ]pyrrole‐3‐carboxylic acid ethyl ester ( 8 ). Isolation of 7 and other observations led to postulated mechanisms for three of the Gewald thiophene syntheses.