Proton transfer between electronegative atoms: rate-determining or not?

Abstract

Several carbonyl group reactions which involve rate—deter— mining proton transfer between electronegative atoms, as evidenced by biphasic Bronsted plots and detailed kinetic analysis, also give kinetic hydrogen isotope effects which change rapidly with the pKa differ— ence between the proton donor and the protonated proton acceptor (ipK) and peak sharply at LpK=O. This indicates that the proton transfer component of the overall proton transfer process (encounter of react— ants, proton transfer, and separation of products) is at least partly rate—determining in these systems, but it is so only over a narrow region of ipK about tpK=O. Kinetic isotope effects on the basecatalyzed decomposition of nitramide as well as the shape of the Bronsted plots for this reaction and the deprotonation of the conjugate acid of 2, 7—dimethoxy—l, 8-bis(dimethylamino)naphthalene indicate that proton transfer involving nitrogen is intrinsically slower than that involving oxygen and is therefore (partly) ratedetermining over a wider, albeit still rather limited, range of LpK. INTRODUCTION It is a tenet of long standing in mechanistic chemistry that proton transfer between electronegative atoms such as oxygen and nitrogen is seldom if ever rate-determining in a reaction where such transfer and changes in bonding between heavy atoms must take place. This idea is stated especially clearly in a Solvation Rule laid down by Swain, Kuhn and Schowen (1), who said: A proton being transferred from one oxygen (or nitrogen) to another in a reaction which requires heavy atom reorganization lie in an entirely stable potential at the transition state and should not form reacting bonds nor give rise to primary isotope effects. The origin of this idea is obscure, but it was undoubtedly fostered by the fact that rates of proton transfer between electronegative atoms, i.e. [in the Eigen sense (2)] acid-base centers, were for a long time too fast to measure. When appropriate fast reaction techniques were invented and the rates of normal acid-base reactions were finally measured and found to be very fast indeed (2), the idea was reinforced. Heavy atom reorganization, however, can also be very fast. An early indication that it might be fast enough to compete with proton transfer between electronegative atoms came from studies of oxygen-18 exchange during the hydrolysis of carboxylic acid esters which suggested that proton transfer from solvent water to the negatively charged oxygen atom of the tetrahedral intermediate formed in this reaction (eq. 1) might in some cases be kinetically significant (3). This requires reversal of tetrahedral intermediate Q HO 0 HO OH 1 2 ' 2 ' RCO +ROH 1 RCOR —Tg' ROR — ROR 2 OH OH formation, which involves bonding changes between oxygen and carbon, to be either faster than or at least of the same velocity as proton transfer between two oxygen atoms. Firm evidence that breakdown of tetrahedral intermediates can be faster than subsequent protonation of these species was