Bovonsombat P.Hocks A.Kittithanaluk P.We J.T.Khanthapura P.Choosakoonkriang S.Srikamhom N.Ploymanee F.Mahidol University2025-05-132025-05-132025-04-25ChemistrySelect Vol.10 No.16 (2025)https://repository.li.mahidol.ac.th/handle/20.500.14594/110069A 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.ChemistryArticleSCOPUS10.1002/slct.2025005442-s2.0-10500371155723656549