Computational study on the reaction pathway of α-bromoacetophenones with hydroxide ion: possible path bifurcation in the addition/substitution mechanism.

The reaction of an α-haloketone with a nucleophile has three reaction channels: carbonyl addition, direct substitution, and proton abstraction. DFT calculations for the reaction of PhCOCH(2)Br with OH(-) showed that there exists an addition/substitution TS on the potential energy surface, in which OH(-) interacts with both the α- and carbonyl carbons. The intrinsic reaction coordinate calculations revealed that the TS serves as the TS for direct substitution for XC(6)H(4)COCH(2)Br with an electron-donating X or a X less electron-withdrawing than m-Cl, whereas the TS serves as the TS for carbonyl addition for derivatives with a X more electron-withdrawing than m-CF(3). Trajectory calculations starting at respective TS indicated that the single TS can serve for the two mechanisms, substitution and addition, through path bifurcation after the TS for borderline substrates. The reaction is the first example of dynamic path bifurcation for fundamental reaction types of carbonyl addition and substitution.