Kinetics of acylation of cyclohexylamine with substituted phenyl benzoates

Abstract

Kinetics of acylation of cyclohexylamine with nitro-substituted phenyl benzoates is studied in water solutions of 2-propanol and dioxane. By means of RHF/6-31G* method quantum-chemical simulation of ester molecules and of cyclohexylamine solvatocomplexes was carried out. On the basis of correlation of rate constants and LUMO energies of esters and population of 2p z -orbitals of carbon atom of the acyl group a conclusion on the orbital control of the reactions was made.An interest to the products of acylation of amines is caused by their wide use as polymers, dyes, surfactants, biologically active compounds, and drugs of wide spectrum of action. Optimization of conditions of the industrial synthesis of these substances requires performing kinetic studies and establishing quantitative dependences of rate constants of the abovementioned processes on the structure of reagents and the effect of medium. In the series of studies kinetics is explored and the mechanisms are established of the reactions of aromatic and aliphatic amines with different acylating agents, among them with the carboxylic acid esters in the aprotic non-polar media. Kinetic data on the aminolysis of esters in water and some water-organic solvents are also mentioned [1][2][3][4][5][6][7].In the course of years we study the acyl transfer reactions with the participation of different amines (aromatic, aliphatic including α-amino acids, and mixed). Aroyl and sulfonyl chlorides and also phenyl carboxylates were used as acylating agents. Specific feature of aminolysis of esters in water-containing media is the possibility of parallel proceeding of hydrolysis. The most important factor affecting the rate of aminolysis and hydrolysis is the pH of medium [8][9][10][11]. Note that adequate attention to the consideration of these factors rather scarce [6,7]. We have developed procedures permitting strict accounting for the effect of pH and hydrolysis of acylating agents while calculation of acylation rate constants. Together with these studies quantum-chemical simulation of the reaction mechanisms and state of reagents in solution [12] was carried out. The aim of these studies is the investigation of structure of acylating agents like 2-,3-, and 4-nitrophenyl I-III; 2,4-, 2,5-, and 2,6-dinitrophenyl IV-VI, and 2,4,6-trinitrophenyl VII benzoates on the kinetics of their reaction with cyclohexyl amine. Binary mixtures of water (molar fraction 0.73) with 2-propanol (i-PrOH) and dioxane (Diox) were used as solvents.Reaction of cyclohexylamine with esters under the conditions of kinetic experiments (pH 8.8) proceeds according to Eqs. (1)-(4) where R 1 is mono-, di-or trinitrosubstituted phenyl, k ac , k(H 2 O), and k OH -are rate constants of the processes (1)-(3). fast According to the Eqs. (1)-(4) the rate of change in the concentration of ester (c es ) in the kinetic experiment is described by Eqs. (5), (6).-(dc ef )/(dτ) = k ac с а с ef + k(H 2 O)c(H 2 O)c ef + k OH -с OH -с ef = k obs c ef ,k obs = k ac с а + k(H 2 O)c(H 2 O) + k OH -c OH -.

Acylation of piperidine and morpholine with phenyl benzoates in the mixtures water-2-propanol and water-dioxane

“…For equal amounts of water in the system the values of k for all studied reactions in the mixture water-dioxane are considerably larger than the k values for the same reactions in aqueous 2-propanol (Tables 1-3). The accelerating effect of aqueous dioxane as compared to aqueous 2-propanol on the rate constants of Nacylation was observed also in other reactions, for example, in the reactions of ammonia, aliphatic amines and α-amino acids with esters and sulfonyl chlorides [7,[10][11][12][13].…”

“…2), which is indicative of an important role of specific solvation of amines and transition states of the reaction of acylation. The solvation of the acylation reagents in the reaction of the acyl group transfer, according to the available data [7,[10][11][12][13], plays a subordinate role. Table 3 presents the results of the kinetic study of the reactions of piperidine and morpholine with compounds I and II in the system water (40 wt %)dioxane.…”