Acylphosphonate hemiketals - Formation rate and equilibrium. The electron-withdrawing effect of dimethoxyphosphinyl group

Examination of alcoholic solutions of dimethyl acetylphosphonate (1) and dimethyl benzoylphosphonate (2) by ³¹P NMR spectroscopy reveals the presence of considerable amounts of hemiketals. Because of the great difference between the ³¹P chemical shifts of acylphosphonates (ca. 0 ppm) and their hemiketals (17-21 ppm), ³¹P NMR spectroscopy is a uniquely suitable method for studying the rates and equilibria of hemiketal formation of acylphosphonates with different alcohols. The equilibrium constants K_f, K′_f (K′_f = K_f[ROH]), pseudo-first-order rate constants k′_f, the second order rate constants, k_f for hemiketal formation from dimethyl acetylphosphonate with various alcohols, as well as the reverse reaction rate constants, k_r to starting materials, were determined. The kinetic isotope effect of 2.8 for the forward reaction k_f (EtOH addition) and the backward reaction k_r indicates a general catalysis pathway. On the other hand, the calculated values of the enthalpies of activation ΔH^‡ = 10.37 kcal mol^-1 (forward), ΔH^‡ = 13.66 kcal mol^-1 (backward) and the entropies of activation, ΔS^‡ = -17.25 cal mol^-1 K^-1 (forward), ΔS_‡ = -9.82 cal mol^-1 K^-1 (backward) are not in accord with high molecularity of the reaction (1 cal = 4.184 J). Our analysis led to the conclusion that this is probably due to the fact that the transition state is mainly reactant-like with the development of only limited extent of bond formation. Various plausible reaction pathways for hemiketal formation are discussed. In addition, we have calculated the value of 2.65 σ* for the P(O)(OMe)₂ group based on proton affinity obtained from heats of formation (ΔH_f) of applying the MNDO techniques. The following linear correlation between pKa values and PA values of hemiketals of the form (Me)(R)C(OH)(OCH₂X) was developed: pK_a = PA - 356.58 + 9.18 [σ*(Me) + σ*(R) + 0.2σ*(X)].