General Base Catalysis Of Hydrolysis Research Articles

Differentiation of nucleophilic and general base catalysis in hydrolysis of N-acetylbenzotriazole using the proton inventory technique

Differentiation of nucleophilic and general base catalysis in hydrolysis of N-acetylbenzotriazole using the proton inventory technique

Reaction of amines and oxygen nucleophiles with 5-nitrocoumaran-2-one: nucleophilic and general base catalysis of hydrolysis

The reaction of nitrocoumaranone (1) with bases was studied using aqueous solution. Primary and secondary amines react to yield the 2-hydroxy-5-nitrophenylacetamide. A negligible deuterium oxide solvent isotope effect and a large Bronsted βn confirm the nucleophilic pathway and a class II aminolysis. Carboxylic acids, phosphate, and heterocyclic amines yield the acid product, and the low Bronsted β, deuterium oxide solvent isotope effect of 2–3, and comparison with reactivity against 4-nitrophenyl acetate indicate a general-base catalysed path. Tertiary alkylamines (yielding acid) are more efficient than predicted from the general base Bronsted relationship, are less efficient than the primary amines of similar pKa, and have negligible deuterium oxide solvent isotope effect; these data and comparison with 4-nitrophenyl acetate reactivity indicate a nucleophilic mechanism.Consideration of frontier orbitals and stereoelectronic factors indicates that the E1cB mechanism is an ‘allowed’ process which must be suppressed by the efficiency of trapping of the keten intermediate by the neighbouring hydroxy function.

ChemInform Abstract: THE HYDROLYSIS OF α‐ACETOXYSTYRENES. KINETICS AND INVESTIGATIONS OF OXYGEN‐18 EXCHANGE

The alkaline hydrolyses of ..cap alpha..-acetoxystyrenes 1a-f and 1-acetoxy-1-ethoxy-2-phenylethylene (2) have been shown to proceed by the same mechanism which has been demonstrated for the hydrolysis of alkyl and aryl acetates. Among the pieces of experimental evidence leading to this conclusion are the inverse solvent deuterium isotope effects (0.74 + 0.07 for 1c, 0.80 +- 0.09 for 2), the kinetics of hydrolysis, which are first order in hydroxide ion, and the absence of general base catalysis of hydrolysis. In mildly acidic solution, however, the hydrolysis of 2 proceeds exclusively by a mechanism involving a rate-determining proton transfer to the leaving group double bond, a mechanism which was previously demonstrated for ..cap alpha..-acetoxystyrenes in strongly acidic solution. Carbonyl labeled ..cap alpha..-acetoxystyrene-/sup 18/O as synthesized, and /sup 18/O exchange from the carbonyl position during alkaline hydrolysis was investigated; no /sup 18/O exchange was observed. This behavior is similar to that observed for aryl esters, and contrasts with that observed for hydrolysis of esters with less acidic leaving groups. These observations support our contention that acetophenone enols are about as acidic as phenols, a conclusion which, along with the fraction enol in acetophenone, leads to a carbon pK/sub a/ for acetophenone of 15.8more » +- 1.0.« less

The hydrolysis of .alpha.-acetoxystyrenes. Kinetics and investigations of oxygen-18 exchange

The alkaline hydrolyses of ..cap alpha..-acetoxystyrenes 1a-f and 1-acetoxy-1-ethoxy-2-phenylethylene (2) have been shown to proceed by the same mechanism which has been demonstrated for the hydrolysis of alkyl and aryl acetates. Among the pieces of experimental evidence leading to this conclusion are the inverse solvent deuterium isotope effects (0.74 + 0.07 for 1c, 0.80 +- 0.09 for 2), the kinetics of hydrolysis, which are first order in hydroxide ion, and the absence of general base catalysis of hydrolysis. In mildly acidic solution, however, the hydrolysis of 2 proceeds exclusively by a mechanism involving a rate-determining proton transfer to the leaving group double bond, a mechanism which was previously demonstrated for ..cap alpha..-acetoxystyrenes in strongly acidic solution. Carbonyl labeled ..cap alpha..-acetoxystyrene-/sup 18/O as synthesized, and /sup 18/O exchange from the carbonyl position during alkaline hydrolysis was investigated; no /sup 18/O exchange was observed. This behavior is similar to that observed for aryl esters, and contrasts with that observed for hydrolysis of esters with less acidic leaving groups. These observations support our contention that acetophenone enols are about as acidic as phenols, a conclusion which, along with the fraction enol in acetophenone, leads to a carbon pK/sub a/ for acetophenone of 15.8more » +- 1.0.« less

Intramolecular general base catalysis in the hydrolysis of 3-dimethylaminopropionates

The hydrolysis of p-nitrophenyl 2-dimethylaminobenzoate, and of a series of substituted-phenyl 3-dialkylaminopropionates, is subject to intramolecular catalysis by the dialkylamino group. A general base catalysis mechanism is indicated. General base catalysis of hydrolysis by tertiary nitrogen is characterised by solvent deuterium isotope effects which fall with increasing basicity of the general base, to as low as kH/kD= 1.4. These low values are associated with a significant increase in the sensitivity of the reaction to the basicity of the leaving group, compared with similar reactions catalysed by oxyanions.

The reactivity of phosphate esters. Multiple structure–reactivity correlations for the reactions of triesters with nucleophiles

The reactivities of a wide range of nucleophiles towards the phosphorus centre of a series of dialkyl substitutedphenyl phosphate esters are sensitive to changes in both the nucleophile and the leaving group. The sensitivity parameters, obtained from linear free-energy relationship equations, are themselves sensitive to the reactivity of the system and a single equation, correlating changes in both the nucleophile and the leaving group, is derived for the reactions of oxyanion nucleophiles. The sensitivity to the leaving group of the rate constant for nucleophilic attack is lower for more basic nucleophiles, and reaches a lower limit for nucleophiles much more basic than the leaving group. This and other observations favour, but do not require, an interpretation in terms of a two-step mechanism involving a quinquecovalent addition intermediate. Among several close similarities to the corresponding reactions of carboxylate esters is a change in mechanism from nucleophilic to general base catalysis of hydrolysis as the nucleophile becomes markedly less basic than the leaving group. Neutral hydrolysis involves general base catalysis in this way, and is an unexpectedly slow reaction.

General Base Catalysis of Hydrolysis of Alkylaminoethyl Esters of Carboxylic Acids

General base-catalyzed hydrolysis for several choline salt esters of carboxylic acids as well as succinylcholine chloride was investigated. Acetylcholine chloride, a part of succinylcholine chloride molecule, also was subject to general base-catalyzed hydrolysis. The ratio, kAC- to kOH-, of acetylcholine chloride was almost equal in magnitude to that of succinylcholine chloride. Degree of the influence of catalytic effect of general bases on the overall rate constant of ester hydrolysis was discussed. Imidazole was a less effective catalyst than phosphate dianion for the hydrolysis of the choline salt esters of carboxylic acids. The general base-catalyzed hydrolysis for these esters appears to represent classical general base catalysis rather than nucleophilic catalysis, as shown in the catalytic hydrolysis for the esters activated in acyl portion, enthyl haloacetates.5) An attempt was made to compare the effect of acetate ions on the hydrolytic rate constants of the Choline salt esters with that of the corresponding tertiary aminoesters. The catalytic contribution of acetate ions for the latter esters became less pronounced. The logarithms of rate constants of alkaline hydrolysis and acetate ion catalysis were not linearly related.