Bromination of Isoquinoline, Quinoline, Quinazoline and Quinoxaline in Strong Acid

Abstract

Bromination of benzazines and benzodiazines most often gives a mixture of products. In this paper, we show that isoquinoline (1) may be regioselectively monobrominated in concentrated H₂SO₄ using NBS or in CF₃SO₃H using N,N’-dibromoisocyanuric acid (DBI) to give 5-bromoisoquinoline (2). The bromination was found to be highly sensitive to the choice of brominating agent, acid, temperature and concentration. Quinoline, quinazoline and quinoxaline may be brominated likewise, although with the strong regioselectivity reserved to isoquinoline.

bromination - electrophilic aromatic substitution - regioselective - benzazines - benzodiazines

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This expected doublet of doublet was observed as a triplet with the given coupling constant.