KINETIC AND MECHANISTIC STUDIES OF AMINOLYSIS REACTIONS OF SOME 0-(2,4-DINITROPHENYL) DERIVATIVES OF CYCLIC KETOXIMES

Abstract

Aminolysis reactions of nitro activated aromatic substrates have been studied both in nonpolar and dipolar solvents. These reactions have been found to exhibit generally a second order dependence on amine in dipolar solvents which has been explained by well accepted Bunnett's mechanism. However, in nonpolar solvents such as benzene, toluene and cyclohexane, similar reactions tend to show mostly third order dependence on amine, which has been explained in terms of four mechanisms. As the mechanism is yet to be firmly established, more experimental information is needed on different aspects of these reactions. In all the mechanisms, as the reactions mainly proceed through two routes involving the participation of hydrogen bonded/ nonhydrogen bonded species and molecular complexes, it was thought that a detailed study of temperature effect on the rates of separate routes may yield information in support of reaction mechanism. Studies in this direction were, therefore, undertaken and results obtained provided evidence in support of Jack Hirst's mechanism in case of reactions with substrates having good leaving group. In order to generalize the observations, it was thought necessary to have further information on different systems, especially with substrates possessing poor leaving group. Therefore, aminolysis of 0-(2,4-dinitrophenyl) derivatives of cyclic ketoximes was studied as a function of temperature and amine concentration. The results obtained indicate that Jack Hirst's mechanism is operating in these reactions also. The reactions were also studied with a number of primary amines to elucidate the effect of amine structure on the course of reaction. Finally, the reactions were investigated in various solvents and in presence of additives and micelles to have additional information in support of the mechanism. A brief abstract of the work carried out is reported as under. Three nitro activated derivatives of cyclic ketoximes viz. 0-(2,4- dinitrophenyl)cyclopentanone oxime (DNPCPTOX), 0-(2,4-dinitrophenyl)cycloheptanone oxime (DNPCHTOX) and 0-(2,4-dinitrophenyl)cyclooctanone oxime (DNPCOCTOX) have been synthesized and characterized by IR, !H NMR spectroscopy and elemental analysis. The substrates prepared have oxime moiety in the leaving group of increasing size from DNPCPTOX to DNPCOCTOX so that the effect of leaving group size on reaction rate can be determined. The reactions of DNPCPTOX, DNPCHTOX, and DNPCOCTOX with two secondary cyclic amines viz. pyrrolidine and piperidine have been studied under pseudo-first order condition as a function of amine concentration at different temperatures. All the reactions were monitored spectrophotometrically at XmRX of the aminolysis product. The products of the reactions have been identified as N-(2,4-dinitrophenyl)amines by TLC and spectral methods. Pseudo-first order rate constants (k0) were calculated numerically from the plots of h^A^-Af) versus time. Second order rate constants (kA) were then calculated on dividing k0 by the [amine]. The rates of the three substrates are found in the order DNPCPTOX > DNPCHTOX > DNPCOCTOX, which can be ascribed to steric factors. As the size of leaving group increases from DNPCPTOX to DNPCOCTOX, the reactivity of substrate decreases due to steric hindrance felt by the incoming nucleophile. The plots of kA versus [amine] are curvilinear, being concave towards rate axis and also pass through the origin. This indicates that the order of reaction in amine is more than two and they are wholly base catalysed. Further, treatment of data shows that the plots of kA[B]_1 versus [B], B being amine, are linear. The analysis of these plots show that for both pyrrolidinolysis and piperidinolysis, reactions proceed through two routes; route-I, involving two amine molecules and route-II, involving three amine molecules. The rate of route-I is found to increase and that of route-II to decrease with rise in temperature. These results have been satisfactorily explained by assuming Jack Hirst's mechanism which involves electrophilic catalysis by conjugate (BH+) and homoconjugates (BH+B). The increase in the rate of route-I is in agreement by electrophilic catalysis through nonhydrogen bonded species (BH+) and decrease in the rate of route-II supports the involvement of hydrogen bonded species (BH+B) in the catalytic steps. The hydrogen bonded species (BH+B) tend to break down at higher temperatures and thus, causing a decrease in rate of route-II. The increase in rate with rise in temperature for first route and decrease in rate for the second catalytic route is consistent with Jack Hirst's mechanism and thus, support it. On the other hand, the results of effect of temperature on rates of separate routes do not support the other three mechanisms viz. Banjoko's cyclic transition state, Nudelman's dimer and Forlani's molecular complex mechanisms because they all predict decrease in rate for both the routes. The relative contribution of both the routes to overall rate has been found to vary with temperature, nucleofugicity of the substrate and nucleophilicity of the amine. For all the three substrates, the rate decreasing contribution of route-II has been found to predominate the rate increasing effect of route-I and as a result, overall rate of the reactions studied decrease with rise in temperature. Next, aminolysis of the substrates was investigated with three primary amines viz. n-propylamine, isopropylamine and cyclopropylamine which have the same number of carbon atoms but different structures. The studies were undertaken to elucidate the effect of variation in the structure of amine on the rate and mechanism of aminolysis reactions. The results indicate a second order dependence on amine for n-propylaminolysis and isopropylammolysis of all the three substrates. Further, an uncatalytic route is also observed in addition to catalytic step. The uncatalytic decomposition of the intermediate complex formed, possibly occurs through intramolecular hydrogen bonding involving the second proton of the amine. The reaction rate of isopropylammolysis is found to be much smaller than that of in n-propylaminolysis and is ascribed to steric factors. In contrast to n-propylaminolysis and isopropylammolysis, cyclopropylaminolysis reactions are found to be surprisingly wholly base catalysed with a third order dependence. The absence of uncatalytic route in the later case could be attributed to rigid structure of cyclopropylamine which prevents the approach of ammonium proton to the leaving group to form intramolecular hydrogen bond. Pyrrolidinolysis of the three 0-(2,4-dinitrophenyl)cyclic ketoximes was also investigated in two pairs of solvents : (i) benzene and dioxane, and (ii) chlorobenzene and ethyl acetate, which have the same dielectric constant but differing in their hydrogen bond acceptor ability, in order to have additional data in support of role of the hydrogen bonded species in electrophilic catalysis. It was expected that in solvents having high hydrogen bond acceptor ability like dioxane and ethyl acetate, the hydrogen bonded BH+B will be broken down in view of the larger amount of the solvent and instead a hydrogen bonded heteroconjugate BH+S, (S=solvent) will form. The reactions in route-II will then be catalysed by BH+S rather than BH+B, which would mean only a second order dependence on amine. However, surprisingly all the reactions show a third order dependence on amine in all the solvents investigated, indicating the involvement of two molecules of amine in the catalytic step. Third order dependence on amine in dioxane and ethyl acetate has been explained due to the presence of two hydrogen bond acceptor sites in the solvents. It appears that the presence of two hydrogen bond acceptor sites in dioxane and ethyl acetate molecule leads to the formation of a mixed heteroconjugate involving a solvent molecule and two amine molecules. This mixed heteroconjugate appears to catalyse the reaction and thus, leads to a third order dependence on amine in the two hydrogen bond acceptor solvents. Finally, pyrrolidinolysis of DNPCPTOX was also investigated in benzene in IV presence of a number of hydrogen bond acceptor/donor additives viz. chloroform, dimethylfonnamide, acetonitrile and methanol and micelles of surfactants. Investigations have shown that aminolysis rate decreases in presence of a small amounts of dimethylfonnamide and acetonitrile whereas it decreases when the additives are methanol and chloroform. Results have been explained in terms of hydrogen bond acceptor/donor ability of the additives. The studies in the presence of reverse micelles of surfactants have shown that the rate is practically not affected when the core of micelles is less polar and decreases when it becomes more polar indicating the immobilization of charged electrophiles BH+, BH+B of Jack Hirst's mechanism. This incorporation of BH+ and BH+B within the core of micelles make them less accessible for reaction occurring in the bulk. Thus the detailed investigations of aminolysis reactions of 0-(2,4- dinitrophenyl) derivatives of cyclic ketoximes in benzene at different temperatures, in presence of hydrogen bond donor/acceptor additives and micelles of surfactants and in solvents of same dielectric constant but different hydrogen bond acceptor ability provide evidence in support of the concept that in nonpolar solvents, hydrogen bonded electrophiles catalyse the reaction in addition to nonhydrogen bonded electrophile. Thus, Jack Hirst's mechanism is supported by the results of present investigations. Further, primary aminolysis studies demonstrate that the course of reactions does depend on the structure of amines.