Studies on the Mechanism of Acid-Catalyzed Bromination of a Hindered Alkyl Aryl Ketone: 2,4,6-trimethylacetophenone. Rate Dependence on Bromine Concentration

Article abstract of DOI:10.1021/ja00321a023

According to the generally accepted Lapworth mechanism for halogenation of ketones, where the rate of reaction is independent of halogen concentration, the slow, rate-determining step is the formation of enol or enolate.The rate of reaction of bromine with 2,4,6-trimethylacetophenone (1) was found to depend on bromine concentration at moderately high concentrations.In the proposed mechanism, reaction of bromine with enol is rate determining - the enolization step being faster.A carbocation (4) instead of a bromonium ion is proposed as the intermediate from reaction of enol with bromine.Rates were determined by following the decrease in bromine concentration at 449 nm under these conditions: 50percent acetic acid (v/v), HBr catalysis, and ionic strength adjusted with sodium perchlorate at 25 deg C.With excess ketone, the average pseudo-first-order rate constant was 1.82x10^-3 s^-1.At a fixed bromine concentration and at varying equal concentrations of both ketone and bromine, k₂ values were 4.34x10^-2 and 4.39x10^-2 L mol^-1 s^-1, respectively.In studies on the effect of bromide ion on the rate, molecular bromine was found to be the active brominating agent with Br3^- contributing to only 0.6percent of the rate constant.Added chloride ion increased the rate; this was explained by Br2/Cl^- interchange to form Br-Cl, a more effective brominating agent.Only bromo ketone was isolated in a preparative-scale reaction containing chloride ions.Added acetate ions decreased the rate as a result of a decrease in proton concentration by formation of acetic acid.Perchloric acid increased the rate.From variable-temperature studies, E_a=61.5 kJ mol^-1 and ΔH(excit.)=59.0 kJ mol^-1.The rate of reaction of bromine with hindered ketone, 1, was nearly 900 times as fast as that with the unhindered analogue, acetophenone, under comparable conditions.