Evidence for two concurrent mechanisms and a kinetically significant proton transfer process in acid-catalyzed O-methyloxime formation

Abstract

A mechanism for Omethyloxime formation from benzaldehydes in aqueous solution is proposed that involves three sequential kinetically significant steps; namely (1) formation of an unstable zwitterionic tetrahedral intermediate, TA(2) protonation of T* in a diffusion-controlled reaction, and (3) hydronium ion catalyzed dehydration of a neutral tetrahedral intermediate that is in rapid equilibrium with the protonated species formed in step 2. The following evidence is presented in support of this mechanism. (1) The pH-rate profiles at zero buffer concentration for the reaction of methoxyamine free base with three substituted benzaldehydes show two negative breaks in the pH region below neutrality. ( 2) A change in ratedetermining step that cannot be accounted for by a transition from rate-determining carbinolamine formation to dehydration is observed in the presence of increasing concentrations of general acid catalysts with pmethoxybenzaldehyde at pH 2-3.(3) Absolute rates for the hydronium ion catalyzed proton transfer process, calculated from observed rate constants and estimated equilibrium constants for formation of TA are 7 X 109-1010 M~1 sec-1, in the range expected for a diffusion-controlled proton transfer. Absolute rates for the uncatalyzed conversion of T* to a neutral tetrahedral intermediate are 106-107 sec-1, consistent with a solvent-mediated intramolecular proton transfer. (4) Structure-reactivity correlations for three substituted benzaldehydes are consistent with the proposed mechanism; in particular, a logarithmic plot of the observed rate constants for the hydronium ion catalyzed proton transfer step against the equilibrium constants for formation of the neutral tetrahedral intermediates has a slope of 0.9 in satisfactory agreement with the expected value of 1.0 for a diffusion-controlled reaction of TA (5) The Br{fnsted plot for general acid catalysis of the reaction of p-methoxybenzaldehyde undergoes a transition from slope 0 to -1.0 at pK ~8.6, which is in good agreement with the estimated pK of ~9 for the hydroxyl group of the protonated tetrahedral intermediate. In addition to the mechanism involving a stepwise proton transfer, a second, concurrent mechanism for catalysis by the hydronium ion, which is ascribed to a proton transfer that is more-or-less "concerted" with carbon-nitrogen bond formation, is observed at high acidity.' for the addition step (extrapolated where necessary to zero methoxyammonium ion concentration), are plotted against acidity in Figure 2. The correction for the contribution of the dehydration step at these low pH values never exceeded 5% of the observed rate constants.A similar small break in the pH-rate profile for p-nitrobenzaldehyde occurs at pH ~4.0, such that the rate con-

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Theoretical and experimental investigation of the formation of E- and Z-Aldimines from the reaction of methylamine with acetaldehyde

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Kinetics and mechanism for oxime formation from 4-dimethylaminobenzaldehyde and 4-trimethylammoniobenzaldehyde iodide

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