Kinetic Implications Derived From Competitive Reactions: Buchwald-Hartwig Amination

The Buchwald-Hartwig amination reaction has gained great interest in the last decade in both academic and industrial environments. In the work presented herein, we discuss a very interesting effect in the competitive reaction of two amines (benzophenone hydrazone and n-hexylamine) with 3-bromobenzotrifluoride.The reactions involving either benzophenone hydrazone or n-hexylamine have been studied by reaction calorimetry. The benzophenone hydrazone reaction presents zero order kinetics, while the hexylamine reaction is first order in the aryl halide and zero order in the amine. Under synthetically relevant conditions, at 90 degrees C, the rate of the hexylamine reaction is about 30-fold higher than the rate of the benzophenone reaction.Interestingly, when reacting together, the benzophenone reacts first, and the hexylamine does not start to react until the benzophenone is not completely finished. This behavior can be explained by taking into account the mechanism and by observing that the catalyst intermediate which sits as the catalyst resting state in the benzophenone reaction is more stable than the Pd(BINAP) complex, catalyst resting state for the hexylamine reaction, which forms from the dissociation of BINAP from Pd(BINAP)(2) and exists only fleetingly in stoichiometric and catalytic reaction networks. It is the stability of the major intermediate, in this case, which controls selectivity, and not the relative reactivity.This concept can be used in the study of other parallel reaction networks, and for designing more efficient catalyst systems in kinetic resolutions.