A Kinetic Study of the Solvent Effect of DMF on the Medicinal Efficiency of Salicylate Ester

Abstract

For highlighting the solvent effect of a peculiar dipolar aprotic solvent, DMF, on the medicinal efficiency of Salicylate ester, the kinetic studies of the alkali catalysed solvolysis of Butyl salicyate in aquo-DMF medium of various compositions starting from 30 to 80 vol. % of DMF at temperatures ranging from 20 to 40°C have been carried out. The specific rate constant values were found to decrease with increasing proportion of DMF at all the temperatures and thus the prediction of Parker has not been found applicable. The numerical values of iso-composition activation energy EC and iso-dielectric energy ED were found to be changed in opposite direction to each other. The values of iso-composition energy of the reaction are found to increase with increasing concentration of DMF in the reaction media. On the other hand, the values of iso-dielectric activation energy were found decreasing with increasing the dielectric constant value of the reaction media. These changes observed in the two types of activation energies have been interpreted in the light of solvation and desolvation of initial and transition states to different extent. Variations in thermodynamic activations parameters ?S*, ?H* and ?G* have also been evaluated and interpreted on the basis of specific solvation taking place in the reaction media. From the evaluated value of Iso-kinetic temperature of the reaction, which is 336.7, it is inferred that there is strong solvent-solute interaction in water-DMF media.

Introduction

This study investigates how dimethylformamide (DMF), a dipolar aprotic solvent, affects the alkali-catalysed hydrolysis of butyl salicylate in water-DMF mixtures at temperatures between 20°C and 40°C.

Previous studies on solvent effects in ester hydrolysis have produced conflicting results. While some theories predict that lower dielectric constants reduce reaction rates, others suggest that dipolar aprotic solvents such as DMF or DMSO should enhance them through solvation effects. Since little research had been conducted on medicinally important salicylate esters, this study aimed to clarify the influence of DMF.

The reaction followed second-order kinetics. Experimental results showed that increasing the proportion of DMF (30–80% v/v) significantly decreased the reaction rate at all temperatures. This reduction is attributed to the lower dielectric constant of DMF and the desolvation of the transition state, making its formation less favourable and increasing the activation energy.

As temperature increased, the reaction rate increased according to the Arrhenius equation. The iso-composition activation energy (EC) increased with higher DMF concentrations, indicating greater energy requirements due to increased desolvation. Conversely, the iso-dielectric activation energy (ED) decreased as the dielectric constant of the medium increased.

Thermodynamic analysis revealed that ΔH‡, ΔG‡, and ΔS‡ all increased with increasing DMF concentration. The greater increase in enthalpy than entropy indicates that the reaction is enthalpy-controlled, while the rise in Gibbs free energy supports the conclusion that the transition state becomes less solvated.

The reaction also obeyed the Barclay–Butler rule, with an isokinetic temperature of 336.70 K, suggesting strong solvent–solute interactions and significant structural changes in the reactants, solvent, or both. Finally, the reaction rate was found to be largely independent of ionic strength, confirming that the hydrolysis proceeds through an ion–molecule mechanism rather than an ion–ion mechanism.

References

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Copyright

Copyright © 2026 Dr. Kumari Priyanka. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.