KINETICS AND MECHANISM OF AMINOLYSIS OF SOME NITRO ACTIVATED O-ARYL OXIMES IN ORGANIC SOLVENTS

Abstract

Aminolysis reactions of nitro activated aromatic substrates have been investigated in a number of solvents. A second order dependence is generally shown by these reactions in dipolar solvents whereas a third order dependence has been observed in nonpolar solvents, though some reactions with second order dependence on amine are also known even in nonpolar solvents. Bunnett's mechanism has been accepted by most workers to explain reactions showing second order dependence on amine. However, controversy still exists with regard to reaction mechanism in nonpolar solvents and four different mechanisms are invoked to explain such reactions showing third order dependence on amine. They are: (i) Cyclic transition state mechanism, (ii) Nudelman's mechanism involving attack of amine dimer, (iii) Forlani's molecular complex mechanism and (iv) Jack Hirst's mechanism involving electrophilic catalysis by conjugate and homoconjugate acids. As no agreement has emerged so far amongst various workers in this field, further information is still required on different aspects of these reactions to firmly establish any mechanism. For this purpose, a detailed study of aminolysis of nitro activated O-aryl oximes in benzene as a function of temperature and amine concentration was, therefore, undertaken and the analysis of kinetic data lend support to Jack Hirst's mechanism. The studies were further extended in mixed solvents and in presence of micelles to have additional data in support of the reaction mechanism. Finally, the aminolysis of O-aryl oximes was also investigated with a (i) number of primary amines of different structures so as to elucidate the effect of the nature of nucleophile on the course of reaction. The results of these investigations are summarized here. Three new nitro activated O-aryl oximes viz. 0-(2,4- dinitrophenyl)P,p'-dimethoxybenzophenone oxime (DNPMBO), 0-(2,4- dinitrophenyl)p,P'-difluorobenzophenone oxime (DNPFBO) and 0-(2,4- dinitrophenyl)p,p' -dichlorobenzophenone oxime (DNPCBO) were synthesized and characterized by C,H,N analysis, IR and 1H NMR spectroscopy. Aminolysis of DNPMBO, DNPFBO and DNPCBO was then investigated with two secondary amines viz. pyrrolidine and Piperidine in benzene at three different temperatures under pseudofirst- order condition. The reactions were monitored spectrophotometrically at A_ of the aminolysis product. Pseudo-first-order rate constants (kQ) were calculated by regression analysis from the plots of ,n(Am-At) versus time. The reactivity sequence for different substrates was found to be in the order DNPCBO > DNPFBO > DNPMBO which has been explained on the basis of leaving group departure ability. Further pyrrolidinolysis reactions were found to be faster compared to piperidinolysis owing to smaller size of pyrrolidine. The values of second order rate constant (kA) were calculated by dividing kQ by [amine]. The plots of kA versus"[amine] show an upward curvature and pass through the origin indicating the reactions are wholly base catalysed with order in amine being more than two. Further, the plots of k^B]"1 versus [B] (B =amine) were found to be linear which is an indication of third order dependence on amine. The analysis of these plots show that both (ii) pyrrolidinolysis and piperidinolysis proceed through two routes and the rate of one route increases and of the other decreases with rise in temperature. The results can be explained by invoking Jack Hirst's mechanism involving electrophilic catalysis by conjugate (BH +) and homoconjugate acids (BH +B). The increase in rate of first route supports catalysis by nonhydrogen bonded species (BH +) and decrease in rate of second route indicates the involvement of hydrogen bonded species (BH +...B) in catalytic step which tend to break down at higher temperatures causing a decrease in rate. The relative contribution of both the routes to overall rate has been found to vary with temperature, nucleofugicity of the substrate and nucleophilicity as well as concentration of the amine. As a result, temperature effect on overall rate for some reactions is positive and for others negative. As the results obtained are consistent with Jack Hirst's mechanism, it finds support from these investigations. Other mechanisms do not explain these results as they predict decrease in the rate of both the routes with rise in temperature. Piperidinolysis of DNPCBO has been studied in binary mixtures of benzene with acetonitrile, dimethyl sulphoxide (DMSO) and methanol. In benzene-acetonitrile and benzene-DMSO mixtures, the overall rate increases continuously with increasing amount of acetonitrile and DMSO, respectively. In presence of lesser amount of acetonitrile and DMSO, the piperidinolysis is catalysed by BH+, BH +B and heteroconjugate BH +S, formed due to hydrogen bonding between BH+ and hydrogen bond acceptor solvent, S. However, with increase in concentration of acetonitrile and DMSO in the respective mixtures, 111 uncatalytic route becomes operative and the participation of BH +B decreases and that of BH +S increases. The results have shown that above 30% of acetonitrile and 1.5% (v/v) of DMSO content in the respective mixtures, BH +Bdo not exist and the order with respect to amine changes from three to two. This change in order occurs at very small concentration of DMSO (1.5%) because of its higher hydrogen bond acceptor ability compared to acetonitrile. On the other hand in benzene-methanol mixtures, the overall rate was found to decrease upto 25% (v/v) methanol content and then increases with increasing methanol content. The decrease in rate at lower methanol content could be due to decrease in nucleophilicity of amine as a result of interaction with methanol through hydrogen bonding. At higher concentrations of methanol, the polarity effect of the media overcomes the other effects and the overall rate increases. In benzene-methanol mixtures, reaction shows a third order dependence on amine even at higher methanol content (80%) which has been ascribed to methanol having both hydrogen bond acceptor as well as donor ability. Thus, these results clearly demonstrate that the rate and mechanism of aminolysis reactions depend not only on the dielectric constant of the solvents but also to a great extent on their hydrogen bond acceptor/donor ability. Piperidinolysis of DNPCBO has also been studied over a wide concentration range (both below and above CMC) of two nonionic surfactants viz. Span-60 and lecithin in benzene at 25°C. The less polar nonionic micelles were found to have negligible effect on the reaction rate. However, when the same reaction was carried out in (iv) presence of more polar cationic micelles of cetylpyridinium chloride in 1% (v/v) methanol-benzene mixture at 40°C, the rate increased significantly with concentration of the surfactant above CMC. The observation that more polar environment within the micelles enhance the reaction rate points out to the participation of charged species, BH+ and BH +B, in the catalytic step of the reaction. Lastly, the aminolysis of O-aryl oximes in benzene was studied at different temperatures with three primary amines viz. npropylamine, isopropylamine and cyclopropylamine which have same molecular formula but different structures. For n-propylaminolysis and isopropylaminolysis, the plots of k versus [amine] have been A found to be linear with positive intercepts. This response indicates that the dependence on amine is of second order and the reactions also proceed through an uncatalytic route in addition to the catalytic one. The uncatalytic decomposition of the zwitterionic intermediate formed occurs through intramolecular hydrogen bonding involving second ammonium proton and the oxygen of the leaving group. Unlike n-propylaminolysis and isopropylaminolysis, the reaction of DNPCBO with cyclopropylamine has been found to be wholly base catalysed with order in amine remaining two. The different behaviour of cyclopropylamine in the reaction has been attributed to its rigid structure which prevents the formation of intramolecular hydrogen bond between the ammonium proton and the leaving group. Thus, the studies on aminolysis of O-aryl oximes in benzene, mixed solvents and in presence of micelles have helped in elucidation of the reaction mechanism and provided enough support to Jack Hirst's

concept that electrophile involved in catalytic steps are conjugate acids and their homo-/heteroconjugates depending on the system and experimental condition. Further, primary aminolysis studies demonstrate that the structure of amine affects the course of reaction.