Substitution reactions of benzo[b]thiophen derivatives. Part VII. Reactions of 4-hydroxybenzo[b]thiophen, its 3-methyl derivative, and related compounds

Abstract

Electrophilic substitution reactions of 4-hydroxybenzo [b]thiophen and its 3-methyl derivative are described. Formylation under modified Gattermann conditions and bromination with N-bromosuccinimide gave the 5-substituted product in each case, whereas treatment with bromine in carbon tetrachloride gave the corresponding 5,7-dibromo-compound. Nitration in acetic acid gave a mixture of the 5-nitro-, the 7-nitro-, and the 5,7-dinitro-compounds, of which the 5-nitro-compound was the major component in each case. Claisen rearrangement of 4-allyloxybenzo[b]thiophen and its 3-methyl derivative gave the appropriate 5-allyl-4-hydroxy-compound. Fries rearrangement of 4-acetoxybenzo[b]thiophen with aluminium chloride in boiling benzene gave a mixture of 7-acetyl-4-hydroxybenzo[b]thiophen (90%) and its 2,3-dihydro-derivative (7%). Similar treatment of 4-acetoxy-3-methylbenzo[b]thiophen gave a mixture of 7-acetyl-4-hydroxy-3-methylbenzo[b]thiophen (21%) and the 2-acetyl isomer (68%). Bromination of 4-methylsulphonyloxybenzo[b]thiophen in acetic acid gave a mixture of 3-bromo-(60%) and 5-bromo-4-methylsulphonyloxybenzo[b] thiophen (20%) and the corresponding 5,7-dibromo-compound (6%), together with two unidentified products. 3-Bromomethyl-4-methylsulphonyloxybenzo[b]thiophen, obtained by treatment of the corresponding 3-methyl compound with N-bromosuccinimide. was used as a key intermediate in the synthesis of 2-(4-hydroxy-3-benzo[b]thienyl)ethylamine, the sulphur analogue of 4-hydroxytryptamine.