Synthesis of a Cyclic Hexaamide Consisting of a Brominated m-Phenylene Repeating Unit.

Aiming to synthesize a cyclic hexaamide, 4-bromo-3-(isobutylamino)benzoic acid was subjected to self-condensation reactions in the presence of either dichlorotriphenylphosphorane in 1,1,2,2-tetrachloroethane or tetrachlorosilane in pyridine. However, instead of the targeted cyclic hexaamide, the cyclic triamide and the cyclic tetraamide were obtained. The cyclic hexaamide was successfully synthesized via the self-condensation of the dimer, which was synthesized in five steps from 4-bromo-3-(isobutylamino)benzoic acid. A thorough screening of the self-condensation conditions was performed to improve the yield of the target macrocycle. In addition, the linear hexamer was synthesized by stepwise deprotection and condensation, and its cyclization afforded the cyclic hexaamide in good yield.