Extended E1cB Mechanism for Ester Hydrolysis: Allylic Substitution via Carbanion in Ester Hydrolysis

Article abstract of DOI:10.1021/ja00370a033

Studies of E1cB hydrolysis of ester have been extended to the investigation of ester hydrolysis via allylic substitution (eq 2).The hydrolysis of p-nitrophenyl 2-cyano-3-(p-methoxyphenyl)propenoate (1) provides p-nitrophenol (p-NP), 2-cyano-3-(p-methoxyphenyl)propenoic acid (2), p-methoxybenzaldehyde (6), and cyanoacetic acid.The percentage yields of the products varied with pH; below pH 8 hydrolysis of 1 occurs predominantly by way of retro-Knoevenagel reaction to yield p-NP and 6, while above pH 8, the ester hydrolysis of 1 provides 2 and by way of retro-Knoevenagel reaction 6.The pH dependence of the two competing processes (ester hydrolysis and retro-Knoevenagel reaction) were provided by a log (<2>_infinite/<6>_infinite)-pH profile.The rate of hydrolysis of 1 (30 deg C) obeys the first-order rate law, and the carboanion (7) and carbon acid (8) intermediates do not accumulate in the course of hydrolysis.At pH values above 12, two reaction processes, well separated in time, were observed; the initial first-order rate process is associated with the formation of the same products obtained between pH 8 and 12, and the slow reaction is associated with hydrolysis of 2 to 6 cyanoacetic acid (Scheme V).The mechanism of lyate species hydrolysis of 1 was elucidated by use of log k_ly vs. pH and log (<2>_infinite/<6>_infinite) vs. pH profiles and by comparison of ΔS(excit.) and ΔS₂(excit.) - ΔS₆(excit.) with known literature values.The three mechanisms which may be considered for hydrolysis of 1 involve: (i) competitive and parallel first-order decay of 1 by C-C bond scission to provide 6 + p-NP and ester hydrolysis to provide 2 + p-NP (Scheme II); (ii) addition of HO to the C-C double bond of 1 to provide a carboanion 7 which then indergoes parallel first-order decomposition via C-C bond scission to yield p-NP + 6 and ester hydrolysis through a ketene intermediate to provide p-NP + 2 (Scheme III); and (iii) addition of the elements of HO^- plus H⁺ to the C-C double bond of 1 to yield the carbon acid ester 8 which then partitions to p-NP + 2 and p-NP + 6 (Shceme IV).The reactions of Scheme II do not predict the correct pH dependencies for the two hypothetical parallel reaction paths, which may be determined from the pH dependence of k_ly and <2>_infinite/<6>_infinite, nor the values of ΔH(excit.) and ΔS(excit.) for ester hydrolysis typical of the B_AC2 mechanism required by Scheme II.The sequences of Scheme III predict the observed dependencies of k_ly, predict ratios <2>_infinite/<6>_infinite upon pH, and explain the determined values of ΔS(excit.)₂ - ΔS(excit.)₆.The mathematical forms of equations derived from the sequences of reactions of Scheme IV are sufficient to fit the log k_ly vs. pH and log <2>_infinite/<6>_infinite vs. pH profile.However, Scheme IV is strongly disfavored on the basis, among other considerations, that values of the rate constant for the B_AC2 hydrolysis of 8 determined by any of the four possible simplifying kinetic assumptions is more than 100-fold ...