KINETIC STUDIES ON THE AMINOLYSIS OF SOME O-ARYL OXIMES

Abstract

Experimental results of kinetic studies on the aminolysis of four oxime ethers having structural variations in their oxime moiety viz.0-(2,4- dinitrophenyl)substituted cyclohexanone oxime(DNPCHOX), acetophenone oxime(DNPAPOX), benzophenone oxime (DNPBPOX) and 4'-bromo benzophenone oxime (DNPBrBPOX) with several primary alkylamines ,CH-,NH~—CrHinNH^, o 2 b 1J 2 and two secondary amines, (CH3)2NH and C5H,QNH, in 1:1 wateracetonitrile( v/v) as well as in five non-aqueous solvents (DMSO,DMF, MeCN, MeOH and 1:1 MeOH-MeCN) have been reported and interpreted. Reactions proceed to give the expected aminolysis product without accumulation of any substantial concentra tion of stable intermediate during the reaction in all sol vents. Rates were measured spectro-photometrically as a func tion of several factors such as amine concentration, ionic strength, solvent, polarity, temperature, pH, added NaOH and micellar concentration. Pseudo - first, order conditions were maintained in all runs. When the reactions are run in aqueous acetonitrile, rates increase with increase in ionic strength and solvent polarity. The reactions follow Arrhenius relationship. Thermo dynamic parameters have been calculated. Entropy of activation (A S^ ) values are high and negative indicating congested nature of the transition state. -11- The aminolysis reactions of the oxime ethers are often prone to base catalysis which is found to be a sensitive function of leaving group, attacking amine and nature of reaction medium. Reactions with methylamine in 1:1 wateracetonitrile( v/v) are very weakly sensitive to general base catalysis at 35±0.1°C. Reactions with higher amines, C^HCNH0— 2 b 2 C6H13NH2 are not base catalysed. Change of pH within the range of 10.0-11.2 has no significant effect on the reaction rate of primary amines. Work in non-aqueous media reveals much information. Reactions with n-propylamine, n-butylamine, n-pentylamine and n-hexylamine are strongly catalysed by general base in dimethyl sulphoxide. Reactions of n-butylamine are also strongly catalysed when the reactions are run in two other aprotic solvents, dimethyl formamide and acetoni trile. On the other hand reactions in protic solvent methanol as well as in a mixture of protic and aprotic solvents, 1:1 methanol-acetonitrile(v/v), are not base catalysed. Sensi tivity to base catalysis in different, solvents has been inter preted by considering the hydrogen bond donor-acceptor proper ties of solvents. Secondary amines have been found to promote base catalysis in both protic and aprotic solvents. Reactions with dimethylamine and piperidine in 1:1 water-acetonitrile are strongly catalysed by general base as well as by hydroxide ion. Reactions of all substrates with piperidine in dimethyl sulphoxide are wholly catalysed by piperidine. -111- The discriminating behaviour of the two class of amines pertaining to occurrence of base catalysis has been explained considering intramolecular hydrogen bonding between the ammonium proton of the zwitterionic intermediate to the ortho-nitro group. The same explanation is perhaps valid to account for inhibition of participating a H.B.D. solvent molecule, thus enrouting a base catalytic path even in H.B.D. solvents in the reactions with secondary amine. i The overall reactivity order of the substrates to wards any of the amines in protic or aprotic solvents has been evaluated to be DNPBrBPOX > DNPBPOX > DNPAPOX> DNPCHOX. However, extent of base catalysis is observed in the reverse order: DNPCHOX > DNPAPOX > DNPBPOX > DNPBrBPOX. These orders have been interpreted taking into account the properties of leaving groups. DNPCHOX has been approximated to be the one possessing poorest leaving group among the four subs trates . Among the primary alkylamines, the apparent reactivity decreases from methylamine to n-propylamine and then gradually increases right, up to n-hexylamine. The slightly higher reac tivity of .long chain amine has been sought to explain as a consequence of hydrophobic interactions between the subs trate and long chain amine. Hydrophobic interactions appear to overcome the steric effects. Cationic micelles of cetyl -IVtrimethyl ammonium bromide(CTAB) also enhance the rate of aminolysis which has been explained by considering the dis tribution of the reactants between the micellar and bulk phase. Product, analysis and kinetic data including obser vation of base catalysis are in conformity with the reported data on aromatic substitution by amine nucleophiles, thus unitizing i the site of nucleophilic attack to the nitroactivated aromatic carbon attached to the oxime oxygen. Consequently, cleavage of C-0 bond has been claimed. The kinetic results have been discussed in terms of the inter mediate complex mechanism of nucleophilic aromatic substi tution reactions.