Reaction Mechanism from Structure-Energy Relations. 1. Base-Catalyzed Addition of Alcohols to Formaldehyde

Article abstract of DOI:10.1021/ja00302a018

There is a long-standing evidence that in the general base catalyzed addition of alcohols to formaldehyde, C...O bond formation and proton transfer occur simultaneously.Structure-energy relations for this reaction are complicated.The slopes of Bronsted plots vary greatly, even for structurally similar alcohols, and plots of log k vs. pK_a of the alcohols go through minima.The data thus provide good material for testing the author's recent theory of structure-energy relations for concerted reactions.The theoretical equations are nonlinear and depend specifically on the reaction mechanism.Of four mechanisms, only that favored by previous independent work fits the data well, even onto reproducing the rate-constant minima.The rate-determining step of this mechanism is R'CH2COO(-) + RCH2OH + H2C=O -> R'CH2COOH + RCH2OCH2O(-).R ranges in electronegativity from CH3 to CF3, R' from H to CN.Assuming this mechanism to be correct, progress of C...O bond formation (u^<*>) and proton transfer (v^<*>) were deduced from the theoretical equations.The results show that mean progress at the transition state, (u^<*> + v^<*>)/2, varies only sightly with substitution, but that disparity of progress of the two reaction events, (v^<*>-u^<*>)/2, varies markedly both with R and R' and changes sign within the series.Rate-constant minima occur near points where u^<*> = v^<*>, thus proving the effectiveness of disparity at lowering the free energy of activation.