S_N2 Mechanism for Alcoholysis, Aminolysis, and Hydrolysis of Acetyl Chloride

Abstract

First-order solvolysis rate constants are reported for solvolyses of acetyl chloride in methanol and MeOD, and in binary aqueous mixtures with acetone, acetonitrile, ethanol, methanol, and trifluoroethanol at 0 degrees C. Product selectivities (S = [MeCOOR]/[MeCOOH] x [water]/[alcohol]) are reported for solvolyses in ethanol/ and methanol/water at 0 degrees C. Solvolyses of acetyl chloride show a high sensitivity to changes in solvent ionizing power, consistent with C-Cl bond cleavage. As the solvent is varied from pure ethanol (or methanol) to water, S values and rate-rate profiles show no evidence for the change in reaction channel observed for solvolyses of benzoyl and trimethylacetyl chlorides. However, using rate ratios in 40% ethanol/water and 97% trifluoroethanol/water (solvents of similar ionizing power but different nucleophilicities) to compare sensitivities to nucleophilic attack, solvolyses of acetyl chloride are over 20-fold more sensitive to nucleophilic attack than benzoyl chloride. The solvent isotope effect of 1.29 (MeOH/MeOD) for acetyl chloride is similar to that for p-methoxybenzoyl chloride (1.22) and is lower than for benzoyl chloride (1.55). Second-order rate constants for aminolyses of acetyl chloride with m-nitroaniline in methanol at 0 degrees C show that acetyl chloride behaves similarly to p-methoxybenzoyl chloride, whereas benzoyl chloride is 40-fold more sensitive to the added amine. The results indicate mechanistic differences between solvolyses of acetyl and benzoyl chlorides, and an S(N)2 mechanism is proposed for solvolyses and aminolyses by m-nitroaniline of acetyl chloride (i.e. these reactions are probably not carbonyl additions, but a strong sensitivity to nucleophilic attack accounts for their high rates).

Ferrocenoyl‐Substituted Pyrimidine Nucleobases: An Experimental and Computational Study of Regioselective Acylation of Uracil, Thymine, and 5‐Fluorouracil

“…This supports earlier theoretical and experimental results that corroborate that nucleophilic addition to the carbonyl group of acid chlorides proceeds by a concerted S N 2-like mechanism with the absence of the generally assumed tetrahedral intermediate. [7][8][9] The one-step mechanism is operative in the reaction between other pyrimidine bases, thymine (1 N1 , R = Me) or 5-fluorouracil (1 N1 , R = F), and FcCOCl, as evidenced by our computational results. However, if a poor leaving group is incorporated in the acylating agent, then the "classical" two-step mechanism becomes operative.…”

Sixty Years of the Grunwald–Winstein Equation: Development and Recent Applications

“…An analysis on terms of Equation (7b) of the specific rates of solvolysis of acetyl chloride in 20 solvents led to values of 0.79 for l and 0.67 for m. 82,83 Both these values are intermediate when compared to those for conventional S N 1 and S N 2 attack. The best description is probably that the pathway is near the borderline between S N 2 attack with a loose transition state 82 and a strong nucleophilic solvation assistance to an ionisation (S N 1) process. Support for the nucleophilic solvation hypothesis comes from the observation that the solvolyses of carbomoyl chlorides, which are internally assisted by the lone pair of electrons on the nitrogen and are generally believed to follow an ionisation mechanism, also involve relatively high l values of 0.4 to 0.7 in their solvolyses.…”

Influence of Sulfur for Oxygen Substitution in the Solvolytic Reactions of Chloroformate Esters and Related Compounds

“…The situation can be simplified by use of MeOH and MeOD as the two solvents for comparison [36]. Addition-elimination (association-dissociation) substitution processes tend to involve a second nucleophilic molecule acting as a general-base [37] and this tends to raise the values for the k MeOH / k MeOD ratio above the values for either conventional bimolecular or unimolecular pathways.…”