Indian Journal of Chemistry Vol. 47A, January 2008, pp. 49-54 Kinetics and mechanism of amine-catalysed solvolysis of azlactone in water-dioxan mixtures Amel M Ismail Chemistry Department, Faculty of Science, Alexandria University, P.O.426 Ibrahimia, Alexandria 21321, Egypt Email: amelmostafa@yahoo.com Received 10 June 2007; revised 25 October 2007 The effect of replacing solvent water by dioxan up to 50% v/v on the rate of catalytic-amine solvolysis of azlactone has been measured spectrophotometrically in the temperature range 40-60ºC. Addition of an organic solvent to water largely decreases the rate of ring- opening process. Such an effect was found to diminish in the region of lower relative permittivity. The reaction rate constants are analyzed and discussed in terms of solvent effect and nucleophilicity of amines. ∆G ≠ gradually decreases as a function of increasing [water], due to a complex and quasi-mirror image compensation of ∆H ≠ and ∆S ≠ . The variation of ∆H ≠ versus ∆S ≠ is linear. The catalytic coefficient, k Am , for amine has been estimated from the general linear equation, k obs = k o + k Am [Amine]. The binary solvent mixtures used give an unusual range of properties. The plot of log k Am versus log [H 2 O] show two linear segments with intersection at 33.3 mol dm -3 [H 2 O]. The correlation between log k Am and reciprocal of the relative permittivity is non-linear, while that between log k Am versus pK a is linear. All these observations are consistent with the suggested mechanism. Azlactone of the 4-hydroxybenzylideneimidazolinone is considered as the chromophore of the green fluorescent protein 1 . The photophysical and photochemical properties of the azlactone derivative, 4-(2-furylmethylene)-2-phyenyl-5-oxazolone have been examined in different solvents 2 . Azlactone anions are used as the key intermediate in the classical Erlenmer syntheses of amino acid, which possess aromatic stabilization 3 . The proton sensitive azlactone derivative, 4-[(p-N, N dimethylamine) benzlidene-]-2- phenyloxazol 5-one exhibits high quantum yield, excellent photostability, and high molar absorpitivity in sol–gel 4 . Azlactone has also been selected as the electrophile in the multistep reaction for the synthesis of D (+) – Duocarmycins 5 , which is a prominent and potent antitumor antibiotic, isolated from streptomyces species 6 . However, only a few studies on the kinetics of azlactone ring–opening have been reported 7-9 . The present work reports a study on the effect of solvent on the kinetics of azlactone ring- opening in water-dioxan mixtures. The difference between both constituents, especially with respect to their relative permittivity (ε = 78.5 for pure water and 2.2 for pure dioxan) gives the mixture an unusual range of properties. Thus, many different applications of this solvent may exist because of its versatility. Among these, of importance is the influence of decreased polarity on certain phenomena related with biological macromolecules 10 . Solvation phenomena can be readily accounted for by the thermodynamic properties of the activated complex, and an analysis of the solvent effect on the mechanism of azlactone ring –opening by amines may be made. Materials and Methods Azlactone was prepared as reported 11 , while the solvent used (dioxan) was of reagent grade (BDH) and used after further purification as recommended 12 . Pyridine, 2-methylpyridine, triethylamine and morpholine were purified according to literature methods 13 . The studied reactions of azlactone with amines in dioxan –water mixtures (15-50% v/v) were followed spectrophotometrically in the temperature range 40- 60ºC. The spectra of infinity samples were identical to the spectra of the corresponding authentic samples of the product in the same solvent. Solutions of both the substrate and the mixed solvent with amine were separately allowed to attain the desired temperature ± 0.05 ºC in a thermostatted bath before being mixed. The two solutions were quickly and thoroughly mixed, with the initial concentration for the substrate being 4×10 -5 M. Solutions of the various amines in the concentration range 4×10 -4 -1×10 -2 M were prepared.