INTRODUCTION Isatin is present in the brain and other tissues in humans and the oxindole moiety is also found in natural products in some plants 1 . The metabolism of isatin in humans is not yet well elucidated. It has been suggested that tryptophan and/or phenylalanine is converted by intestinal bacteria into indole, which is then absorbed and metabolized in the liver to isatin via 3-hydroxyindole 2 . N-Mannich bases have gained impor- tance due to their application in pharmaceutical chemistry. Isatin, chemically known as 1H-indole-2,3-dione, has become a popular topic due to its various uses. The chemistry of isatin and its derivatives is particularly interesting because of their potential application in medicinal chemistry. Isatins are very important compounds due to their antifungal properties 3 . Schiff and Mannish bases of isatin derivatives were reported to show variety of biological activities like antibacterial 4 , antifungal 5 , anticonvulsant 6 , anti HIV 7 , antidepressant 8 and antiinflamma- tory 9 activities. Because of the importance of the subject and as our continuation studies in the field of solvent effect on reaction rate 10-18 , it was, therefore, as a matter of interest to submit this reaction to kinetic studies. The kinetics were measured in mixed solvent media of water with ethanol and water with acetonitrile (up to 70 %), where, pH of the medium was ca. 9 at different temperatures. This type of study will assist in highlighting on the correlations based on thermody- namic and extra-thermodynamic analysis of the kinetic data obtained; in addition, on the linear free energy relationships Solvent Effects on the Kinetic and Mechanism of N-Mannich Bases of 3-Hydrazonoindole-2-one TAHANI SAAD AL-GARNI, AMEL M. ISMAIL *,† , MAHA AL-ZABEN and AYMAN EL-FAHAM Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia † Permanent address: Department of Chemistry, Faculty of Science, Alexandria University, P.O. 426, Ibrahimia, Alexandria 21321, Egypt *Corresponding author: E-mail: amelmostafa@yahoo.com Received: 11 February 2013; Accepted: 11 June 2013; Published online: 26 December 2013; AJC-14471 N-Mannich base reaction of 3-hydrazonoindolin-2-one with piperidine in presence of formaldehyde was followed spectrophotometri- cally in a wide range of water-acetonitrile and water ethanol (10-70 v/v) and at different temperatures (40-60 ºC). The reaction obeys pseudo-first order kinetics. Addition of organic solvent to water decreases the rate of the reaction. A non-linear relation was observed for the plot of log kobs versus the reciprocal of the dielectric constant for the solvent used which suggested that there is a selective solvation by the higher polar solvent, i.e., by water molecules. The thermodynamic parameters ΔH * , ΔS * and ΔG * were calculated and discussed in terms of solvation effects. The determined isokinetic temperatures in both systems, revealed the existence of compensation effect arising from the strong solute-solvent interaction. Finally a suggested mechanism was proposed. Keywords: Solvent effects, Kinetics, Mechanism, N-Mannich base, 3-Hydrazonoindole-2-one. (LFER). The phenomenon of solvation is an important part concerning this study. The dissolution of a substance requires two factors to be overcome, the interaction energy of the solute molecules (for crystals the lattice energy) and the interaction energy between the solvent molecules themselves. This is compensated by the gain in Gibbs energy of solvation (ΔGºsolv). This thermodynamic function is the result of superimposition of principle components of energy of different nature concer- ning the solute and the solvent 19 . The situation with respect to aqueous mixtures is usually more complicated, since there are inter-and intra-component interactions to consider in the solvent mixtures. A recent study 20 has been done and revealed a deep picture about the structure of the solvation sheath, by measuring the solvent relaxation times of anthracene fluorescent probe, one may conclude that : (i) the solvent molecules in the solvation sheath are labile, so they could be exchanged with the solvent molecules in the bulk, (ii) the stability of clusters in the solvation sheath depends on the energy released due to such exchange and depends on the nature of the replaced solvent molecules. EXPERIMENTAL 3-Hydrazonoindole-2-one was prepared as a recom- mended method 21 . Formaldehyde (B.D.H grade), piperidine (B.D.H grade) and pure solvents (spectroscopic grade) were used. The solvent water binary mixtures were prepared by using double distilled water. Asian Journal of Chemistry; Vol. 26, No. 1 (2014), 48-52 http://dx.doi.org/10.14233/ajchem.2014.15316