Facile, Metal‐free, Highly Para ‐Selective Room Temperature Monobromination of Aniline Analogs

Abstract A highly para ‐selective, room temperature, direct bromination of aniline and analogs with N ‐bromosuccinimide is reported herein. Benzylic bromination was not observed in substrates with competing benzylic hydrogens. Cyano, amide, ester, carboxylic acid, methoxy, N ‐alkyl and N , N ‐dialkyl groups, morpholine, and piperazine rings were tolerated. Gram‐scale reaction was demonstrated with selected substrates. This para ‐selective bromination methodology was used in our one‐pot sequential chlorination and iodination demonstrative synthesis of mixed dihalo‐ and trihalo‐aniline analogs. The ortho ‐ para transition states and the corresponding sigma complexes’ energy differences were determined to account for the high para‐selectivity of aniline bromination. Both differences are comparable in values, but the energy difference for the sigma complexes is slightly greater than the energy difference of the transition states.