Correlation analysis of carbonyl carbon 13C NMR chemical shifts, IR absorption frequencies and rate coefficients of nucleophilic acyl substitutions. A novel explanation for the substituent dependence of reactivity

Abstract

Rate coefficients of nucleophilic acyl substitutions, carboxylate carbon 13 C NMR chemical shift values and ν(C᎐ ᎐ O) frequencies of several series of aryl and acyl substituted aryl acetates or alkyl benzoates have been investigated. An increasing electron-withdrawal by the acyl or aryl substituents results in higher reaction rates, upfield 13 C NMR chemical shifts and higher frequencies of the C᎐ ᎐ O stretching. Good correlations are observed for the log k versus δ C (C᎐ ᎐ O) plots. The increase of the reaction rate with increased electron density at the C᎐ ᎐ O carbon (as proved by 13 C NMR shifts) contradicts the previous concept of increased electrophilicity of the carbonyl carbon by electronwithdrawing substituents. The rate increase is now attributed to the decrease of the ester ground state resonance stabilization caused by electron-withdrawing substituents. The use of log k versus δ C (C᎐ ᎐ O) correlations is presented as a practical method to evaluate rate coefficients especially for compounds for which Hammett type correlations cannot be used.

Ketone–Alcohol Hydrogen‐Transfer Equilibria: Is the Biooxidation of Halohydrins Blocked?

“…the rates observed for a series of structurally related compounds. [22] They observed that the IR absorption frequencies of the ester carbonyl group unexpectedly increased with the reaction rate. Therefore, esters bearing EWGs showed higher frequencies (higher double-bond character), which contradicted the tacit assumption of increased electrophilicity of the carbonyl carbon.…”

Epoxy‐Amine Resins with Controlled Reactivity

“…They were selected to cover a broad range of Hammett's σ ‐values, which is a classical method to estimate electron density of aromatic systems depending on the aromatic substituents. However, to determine electron densities, NMR spectroscopy is the accepted method of choice . It was expected that the electron‐density of the arylsulfonamide‐moiety could influence the reactivity of the oxirane system.…”

In silico prediction of acyl glucuronide reactivity

“…These simpler derivatives enabled study of a wider selection of substructures across diverse physicochemical property space demonstrating the importance of both electronic and steric factors to the rate of ester hydrolysis. Additionally, the 13 C NMR shift of the ester carbonyl carbon was measured as previous reports have illustrated a good correlation between ester hydrolysis rates and the corresponding 13 C NMR shifts [16,17]. The methyl ester hydrolysis rates/ 13 C NMR shift (measured) correlation for this new data set is shown in Fig.…”