Hemiacetals of acetophenone. Aromatic substituent effects in the H+- and general-base-catalysed decomposition in aqueous solution

Abstract

We describe a double-mixing stopped-flow technique for the study of the acid- and base-catalysed breakdown of the unstable methyl hemiacetals of aryl-substituted acetophenones in aqueous solution. The approach takes advantage of the build-up of the hemiacetal during the H⁺-catalysed decomposition of the corresponding dimethyl acetal. Thus, mixing a weakly basic solution of acetal with excess acid provides a solution containing unchanged acetal, the acetophenone product of the hydrolysis and the hemiacetal intermediate. After a short period of time (< 1 s) corresponding to the maximum build-up of hemiacetal, this solution is mixed with a neutral or weakly basic buffer solution. This second pH jump quenches the acetal hydrolysis, but not the hemiacetal breakdown. The kinetics of the hemiacetal can then be monitored spectrophotometrically. Twelve aryl-substituted acetophenone dimethyl acetals ranging from 4-dimethylamino to 3-bromo were synthesised and investigated. Hammett ρ values for the H⁺-catalysed acetal and hemiacetal breakdown are in good agreement with literature data, but our analysis suggests a larger resonance effect component than previously assumed. The corresponding set of Hammett plots for base catalysis of hemiacetal breakdown reveals a relatively weak dependence of the catalytic constants on aromatic substitution, which appears to be inconsistent with much stronger dependences on substitution in the leaving alcohol. We propose a case of non-perfect synchronization or imbalance in the transition state where, in the breakdown direction in a class n mechanism, the degree of C–O bond breakage as measured by β_Ig is considerable, but the change in hybridization of the central carbon (sp³→sp²), as measured by ρ, lags behind in the transition state so that there is less interaction with the aromatic substituents here.