The kinetics and mechanism of the acid-catalysed hydrolysis of substituted 4-alkyl-4-methyl-2-aryl-4,5-dihydro-1,3-oxazol-5-ones to the corresponding 2-alkyl-2-benzoylaminopropanoic acids were studied. The Taft correlation of rate constants of the acid-catalysed hydrolysis with alkyl substitution at the 4-position of the 1,3-oxazol-5-one ring is non-linear. In the Hammett correlation, the value of decreases with increasing steric demand of the alkyl substituent. With the 4-isopropyl and tert-butyl derivatives, ¼ À0.63 and À0.32, respectively. The protonated 4-isopropyl and tert-butyl derivatives undergo nucleophilic attack by water at the carbonyl carbon atom at the 5position of the 1,3-oxazol-5-one ring to the extents of ca 70% and 60%, respectively. Another reaction path consists in nucleophilic attack by water at the 2-position of the 1,3-oxazol-5-one ring. The reaction kinetics of aminolyses of substituted 4-isopropyl-4-methyl-2-phenyl-1,3-oxazol-5(4H)-ones (1a, 1b, 1f) giving substituted N-{1,2-dimethyl-1-[(propylamino)carbonyl]-propyl}benzamides (3a, 3b, 3f, 4a) was studied in aqueous propylamine buffers. In the case of the aminolysis of 1a and 1b with propylamine, the rate-limiting step consists in the decomposition of the intermediate In AE catalysed by both the acidic and the basic buffer components. The base-catalysed route is four times faster in both cases. In the case of the aminolysis of 1f with propylamine and that of 1a with ethylenediamine, the ratelimiting step is the formation of the intermediate In AE , the subsequent reaction step being accelerated by substitution and/or intramolecular catalysis.
EXPERIMENTAL MaterialsThe new dialkyl-2-aryl-4,5-dihydro-1,3-oxazol-5-ones were prepared by a known method 11 of ring closure and
The reaction of substituted phenyl isocyanates with 2-amino-2-phenylpropanenitrile and 2-amino-2-(4-nitrophenyl)propanenitrile has been used to prepare substituted 1-(1-cyanoethyl-1-phenyl)-3-phenylureas. In anhydrous phosphoric acid the first products to be formed from 1-(1-cyanoethyl-1-phenyl)-3-phenylureas are phosphates of 4-methyl-4-phenyl-2-phenylimino-5-imino-4,5-dihydro-1,3-oxazoles, which on subsequent hydrolysis give the respective ureidocarboxylic acids. On prolongation of the reaction time, the phosphates of 4-methyl-4-phenyl-2-phenylimino-5-imino-4,5-dihydro-1,3-oxazoles rearrange to give phosphates of 5-methyl-4-imino-3,5-diphenylimidazolidin-2-ones, and these are subsequently hydrolysed to the respective substituted 5-methyl-3,5-diphenylimidazolidin-2,4-diones. The ureidocarboxylic acids were also prepared by alkaline hydrolysis of 5-methyl-3,5-diphenylimidazolidin-2,4-diones. The 5-methyl-3,5-diphenylimidazolidin-2,4-diones and ureidocarboxylic acids were characterised by their 1 H and 13 C NMR spectra. Structure of the 5-methyl-5-(4-nitrophenyl)-3-phenylimidazolidine-2,4-dione was verified by X-ray d i ffraction. The alkaline hydrolysis of individual imidazolidine-2,4-diones was studies spectrophotometrically in sodium hydroxide solutions at 25 °C. The rate-limiting step of the base catalysed hydrolysis consists in decomposition of the tetrahedral intermediate. The reaction is faster if electron-acceptor substituents are present in the 3-phenyl group of imidazolidine-2,4-dione cycle. The pK a values of individual 5-methyl-3,5-diphenylimidazolidine-2,4-diones have been determined kinetically.
Kinetics and mechanism of desulfurization reaction of 1-methyl-2-(substituted phenyl)-quinazoline-4(1H)-thiones in sodium methoxide solutions have been studied, giving the corresponding 1-methyl-2-(substituted phenyl)quinazolin-4(1H)-ones. The reaction proceeds in two steps. The first step involves splitting off of sulfur in the form of SH- and is much faster than the second step, whose rate is almost independent of the concentration of water in methanol. At lowest concentrations of methoxide, the rate of the first step increases linearly, but at higher concentrations a gradual decrease in the rate takes place. The rate of the second step, i.e. the transformation of the intermediate formed In into 1-methyl-2-(substituted phenyl)quinazolin-4(1H)-one (2a-2e), is independent of the methoxide concentration but increases with increasing concentration of water in methanol. On the basis of the kinetic dependences, the mechanism for both steps of desulfurization and the structure of intermediate In were proposed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.