7-Substituted benzo[b]thiophenes and 1,2-benzisothiazoles. Part 1. Hydroxy- or methoxy-derivatives

Abstract

Readily available 2-hydroxy-3-methoxybenzaldehyde (orthovanillin) is converted, via thermal rearrangement (Newman–Kwart) of the O-aryl-NNdimethylthiocarbamate, into 2-mercapto-3-methoxybenzaldehyde (3). This thiol undergoes base-catalysed condensation with compounds of the type ClCH2X (e.g. X = CO2H, Ac, or CN), to give the appropriate 2-(X-substituted)-7-methoxybenzo[b]thiophene. Successive demethylation and decarboxylation of 7-methoxybenzo[b]thiophene-2-carboxylic acid provides a convenient route to 7-hydroxybenzo[b]thiophene. 7-Methoxybenzo[b]thiophene undergoes bromination and nitration at the 4-position; the structure of the 4-bromo compound is confirmed by an unambiguous synthesis. 2-Mercapto-3-methoxybenzaldehyde (3) reacts with chloramine to provide a simple synthesis of 7-methoxy-1,2-benzisothiazole. 2-Mercapto-3-methoxybenzonitrile, obtained as above from the corresponding 2-hydroxy compound, gives 2-acetyl-3-amino-7-methoxybenzo[b]thiophene when treated with chloropropanone, and 3-amino-7-methoxy-1,2-benzisothiazole when treated with chloramine.