Metalation and halogen–metal exchange in 3-arylthiophens

Abstract

The reactions of n-butyl-lithium with 3-(p-bromophenyl)thiophen and 3-(o-bromophenyl)thiophen have been investigated by studying the products of the reaction of the lithium derivatives formed with carbon dioxide. With the para-isomer a mixture of 3-(p-carboxyphenyl)thiophen, 3-(p-bromophenyl)-2-carboxythiophen and 4-(p-bromophenyl)-2-carboxythiophen was obtained, indicating that metal–halogen exchange competes with metalation of the 2- and 5-positions in the thiophen nucleus. In the case of the ortho-isomer the same molecule undergoes both metal–halogen exchange and metalation of the 2-position of thiophen : treatment with carbon dioxide afforded 2-carboxy-3-(o-carboxyphenyl)thiophen as the main product. Similar results were obtained when the reaction mixture from 3-(o-bromophenyl)thiophen and n-butyl-lithium was treated with benzaldehyde.