Mechanistic change in the reactivity of substituted phenyl acetates over phenyl thiolacetates toward imidazole in aqueous phase

Abstract

The kinetics of aminolysis of several substituted phenyl acetates by imidazole is studied in aqueous medium at 20 • C and an ionic strength of 0.1 M (KCl). By following the leaving groups spectrophotometrically (λ max = 272-401 nm), under excess free imidazole, pseudofirst-order rate constants (k obs ) are obtained. For the esters with good nucleofuges, the reaction follows clean second-order kinetics and the plots of (k obs − k H ) against free imidazole concentration are linear at constant pH. The macroscopic nucleophilic substitution rate constants (k N ) are obtained as the slopes of these plots and found to be pH independent. For the esters with poor nucleofuges, a rate dependence on more than first power of the free imidazole and a linear dependence of k 2 on free imidazole is observed. Accordingly, the microscopic rate constants for the assisted paths viz. k ga and k gb have been disseminated besides for simple bimolecular attack. The Brönsted-type plots and Hammett plots were constructed whose slope values are consistent with a stepwise mechanism through a bipolar tetrahedral addition intermediate whose formation or breakdown being rate determining for various paths. Comparison of this reaction of oxyesters with the earlier reported works on similar reaction of analogue thiolesters under identical reaction conditions showed remarkable mechanistic differences which are discussed in detail. The discussion is extended to include the details on previously studied ammonolysis of these two types of esters wherein thiolesters showed differed reactivity than that reported in the present study. C 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: [211][212][213][214][215][216][217][218][219][220][221] 2005

Mechanistic insights into lysine-targeting covalent inhibition through a theoretical study of ester aminolysis

“…[32][33][34][35][36][37][38][39][40][41][42][43][44][45] However, the mechanism of the aminolysis of activated esters in aqueous solution is not yet fully understood, despite some experimental studies. [46][47][48][49][50][51] Some theoretical calculations are available in acetonitrile solution, 35,41,42 but the reaction mechanism is arguably different in this case since the formation of zwitterionic intermediates was ruled out under these conditions, whereas such process is expected to play a central role in aqueous solution. However, modeling in aqueous environment is more challenging and complicated because of the handicaps in theoretical characterization of the zwitterionic and ion-pair species.…”

Kinetic regularities of resolution of amines racemates in the acylation reaction with chiral N‐protected amino acids esters

“…There are a large number of publications in the literature devoted to both the preparative stereoselective kinetic resolution via the reaction 1 5-10 and the mechanistic regularities of the acylation reaction with the participation of optically inactive NuH and RC(O)X (under achiral conditions). 11- 16 At the same time, successful implementation of kinetic resolution is impossible without obtaining unified comprehensive detailed information about the kinetic and stereochemical regularities of the reactions underlying them. Elucidation of the features of the kinetic resolution makes it possible to theoretically justify the choice of the optimal conditions for the preparation of individual enantiomers of NuH using reaction 1 with a high rate and stereoselectivity.…”

“…Interest in acylation reactions continues to grow. There are a large number of publications in the literature devoted to both the preparative stereoselective kinetic resolution via the reaction 1 5 – 10 and the mechanistic regularities of the acylation reaction with the participation of optically inactive Nu H and RC(O) X (under achiral conditions) 11 – 16 …”

Predicting Reactivities of Organic Molecules. Theoretical and Experimental Studies on the Aminolysis of Phenyl Acetates

“…Sung et al examined the stability of a zwitterionic intermediate in aqueous solution in the aminolysis of phenyl acetate with the aid of theoretical computations. Rajarathnam et al , experimentally investigated the kinetics of the aminolysis of a series of meta- and para-ring-substituted phenyl acetates by imidazole in aqueous medium.…”