Reaction Mechanism and Effect of Substituent in Direct Bromination of Indoles

Abstract A reaction mechanism for the direct bromination of substituted indoles in dimethylformamide solution at 298.15 K and 1 atm is proposed and studied. It consists of two steps, the first one, in which the lowest unoccupied molecular orbital of Br 2 overlaps with the highest occupied molecular orbital of the substituted indole, is the rate‐determining step. A linear correlation is observed between the electron‐withdrawing power of the substituent (expressed through the relative molecular electrostatic potential) and the Gibbs free energy barrier of the reaction‘s rate‐determining step, . This correlation is suggested for estimating in other unexplored cases. The variation of with a change in substituents is primarily governed by electronic factors, but the presence of itself is due to entropic factors. The rate of the bromination reaction under the studied conditions diminishes with a change in the substituent, R, following the order: R=−OCH 3 , −CH 3 , −H, −CCH 3 CH 2 , −C 6 H 5 , −CH 2 OH, −F, −SCH 2 CH 3 , −Cl, −Br, −COCH 3 , −COOH, −NC, −COH, and −CN.