Hydrogen Bromide → 5-Bromoisoquinoline

Participants

Reaction Steps

The procedure described by Osborn AR, et al, J Chem Soc 1956:4191 was used. 5-Aminoisoquinoline (43.6 g, 0.302 mol) was dissolved in 300 ml 48% HBr and 200 mL water and cooled in an ice bath. NaNO2 (21.21 g, 0.307 mol) in 130 mL of water was added dropwise to the HBr solution and the reaction stirred for 1 hour. CuBr (52 g, 0.363 mol) in 500 mL of 48% HBr was heated to 85° C., the diazonium solution added dropwise from an ice-cooled jacketed-addition funnel, and the reaction stirred overnight at 50° C. The reaction mixture was cooled in an ice bath and the acid neutralized by dropwise addition of concentrated NH4OH solution. The solid precipitates were filtered off, washed with concentrated NH4OH until colorless, and then water. The solid was dissolved in ethyl acetate, washed with brine (2×), and dried over magnesium sulfate, filtered, and evaporated. The reside was chromatographed on silica gel (30% ethyl acetate in hexane as eluant) to give 53.7 g (86%) of the product as an off-white solid.

Provenance & Evidence