Highly selective aromatic chlorinations. Part 2. The chlorination of substituted phenols, anisoles, anilines, and related compounds with N-chloroamines in acidic solution

Abstract

Phenols, anisoles, anilines, and related compounds are chlorinated in trifluoroacetic acid at room temperature by N-chlorodialkylamines and N-chlorotrialkylammonium salts. With monosubstituted compounds and their 2- and 3-substituted derivatives the reaction occurs efficiently and selectively at the 4-position. The reactivity of these substrates and the selectivity of their chlorinations are determined by electronic rather than steric effects of the substituent. Blocking the reaction with a substituent in the 4-position generally leads to only poor or moderate yields of the 2-chlorinated product. Evidence for radical and cation radical intermediates has been obtained in the reactions of some of the 4-substituted reactants and the mechanism of chlorination is discussed in the light of these findings. The reactions of selected substrates have been scaled up to give laboratory syntheses.