Structure‐reactivity correlation in the aminolysis of 4‐fluorophenyl acetate in aqueous medium

Abstract

The reaction of the title substrate with a series of amines of varying pK a , viz. ammonia, ethanolamine, glycine, 1,2-diaminopropane, 1,3-diaminopropane, n-butylamine, piperidine, hydrazine, imidazole, and hydroxylamine is subjected to a kinetic study in aqueous medium, 25 • C, ionic strength 0.1 M (KCl). Pseudo-first-order rate coefficients (k obs ) are found throughout under amine excess at various pH values for each amine. For amines, excluding hydrazine, ammonia, and hydroxylamine the reaction follows clean second-order kinetics and the plots of (k obs − k H ) against free amine concentration are linear at constant pH. The macroscopic nucleophilic substitution rate coefficients (k N ) are obtained as the slopes of these plots and found to be pH independent. For hydrazine, ammonia, and hydroxylamine, a rate dependence on more than first power of the amine is observed, accordingly, the rate constants for the assisted paths have been disseminated for these amines besides k N . The Brönsted-type plot (logk N against amine pK a ) is linear with a slope value of β = 1.02. The magnitude of the slope value is consistent with a stepwise mechanism through a zwitterionic tetrahedral addition intermediate whose breakdown to products is rate-determining (k 2 step). A remarkable reactivity difference is observed among the diamines, the reason for which is discussed in detail.

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

“…We have explored the potential energy surface trying to locate all the relevant stationary points to determine the possible pathways. These calculations have been guided by the results of previous studies on different esters 34,35,45,47,48,63,64 . The different pathways found are shown in Figure 2.…”

“…[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.…”

Chiral recognition of cyclic α‐hydroxyketones by CD‐sensitive zinc tetraphenylporphyrin tweezer

“…In both cases, the ester bonds in 8 and 9 are readily cleaved by inter-or intramolecular aminolysis which is well-documented as general base-catalysis arising from the 1,3-diaminopropane moiety. 41,42 Therefore we examined the employment of milder conjugates that are capable of coordinating with the zinc of the tweezer molecule, to prevent undesirable aminolysis.…”

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.…”