Nucleophilic Substitution, Metallation, and Halogen-Metal Exchange

Nucleophilic Substitution, Metallation, and Halogen-Metal Exchange.—Direct nucleophilic displacement of the 7-chloro-group of 7-chloro-3-methyl-benzo[b]thiophen has been achieved. 3-Bromobenzo[b]thiophen was reduced to the 3-deuterio-derivative by the reaction with sodium borodeuteride and palladium chloride. Meisenheimer complexes were formed in the reaction of methoxide ion with 2-methoxy-3-nitro- and 3-methoxy-2-nitrobenzo[b]thiophen. Rate and equilibrium data were determined in methanol at 25 C. On treatment of 2-bromobenzo[b]thiophen with potassium amide in liquid ammonia, bromine migration to the adjacent carbon atom was observed. Considerable evidence for the occurrence of an intermolecular transbromination was obtained. The reaction of 3-bromo-benzo[b]thiophen with piperidine has been reinvestigated and found to give primarily the normal, but also some of the cine-substitution product, which is the only product obtained in the reaction of 2-bromobenzo[b]thiophen. Possible mechanisms for some of these reacticms are suggested. 

Some benzo[b]thiophen derivatives of biological interest have been selectively deuteriated or tritiated at position 2 by reaction with butyl-lithium and HzO or 

---