Bromine → Bromine

Participants

Reaction Steps

Bromination of 7-methoxy-1-naphthonitrile (4) with bromine in acetic acid is a very temperature sensitive reaction. The compound 8-bromo-7-methoxy-1-naphthonitrile is produced rapidly at room temperature with two equivalent of bromine. It produces many poly-brominated impurities when the temperature is above 70° C. In this process of the present invention, 7-methoxy-1-naphthonitrile (4) is di-brominated at 40-70° C. with 2-6 equivalents of bromine in acetic acid. Upon the completion of the reaction, the reaction mixture is quenched with excess sodium bisulfite to reduce excess bromine and the product precipitates and is isolated with an expected yield on the order of 90-95% with high purity. This dibromide, without further purification, is heated with stannous chloride in a mixture of acetic acid and concentrated HCl at 100° C. The bromine in 8 position is selectively reduced. The product, 3-bromo-7-methoxy-1-naphthonitrile (6) is filtered from the reaction mixture after the reaction is complete. Typically, the yield is 70-80% over 2 steps with 95%+HPLC purity.

Provenance & Evidence