Stereopopulation Control. 8. Rate and Equilibrium Enhancement in the Formation of Homophthalic Anhydrides

Article abstract of DOI:10.1021/ja00347a041

The kinetics of cyclization of α,α,3,4,6-pentamethylhomophthalic acid have been measured in sovent acetonitrile at 28.5 deg C, using as catalysts a series of acids ranging in strength from perchloric to acetic.In the presence of 0.12 M HClO4, t_1/2 for acid anhydride formation = 0.3 s.For the stronger acid catalysts, k_cycl is a linear function of catalyst concentration; for the weak acids, however, a change in rate-limiting step is revealed by curvature in the plots of k^tot_obsd vs. .All the weak acids show the same limiting value, 6.45E-3 min^-1; this value is considered to be the rate constant for uncatalyzed formation of the tetrahedral intermediate.Homoconjugate bases (HA2(-)) of the weak acids show a similar curvature in their dilution plots, and the same limiting rate constant as for weak acids.Two independent and competitive pathways for cyclization are proposed.For strong acid catalysis, an intermediate acylium ion is considered on the basis of Broensted α = -0.79, k_H/k_D ca. 1, and acceleration of anhydride hydrolysis by methyl substituents.A value of ΔS^excit. = -23 eu suggests that cyclization, rather than acylium ion formation, is rate limiting.For weak acid catalysis, α = -0.17, k_H/k_D = 4.3, ΔS^excit. = -31 eu, and methyl groups retard anhydride hydrolysis by electron release; for this pathway, catalyzed breakdown of a tetrahedral intermediate is considered rate limiting.The composite Broensted plot is curved because the two pathways follow different rate laws.In contrast to rate enhancement results for phenolic lactone formation, the pentamethylhomophthalic acid is only sevenfold as reactive as α,α-dimethylhomophthalic acid.For the catalyst acids, pK(acetonitrile) is shown to be a linear function of pK(H2O) over the entire range of acids examined.