Solvent-free reactions are an interesting alternative for the chemical industry. which seeks to improve productivity. However, the physical and chemical properties of the reaction mixture evolve continuously during the reaction from pure reagents to final products. This evolution can lead to a modification of kinetic and energetic parameters. As an illustration. we chose to study the esterification of acetic anhydride by methanol, catalyzed by sulfuric acid and using a calorimetric reactor. A slowing down of the reaction rate was observed by recording the rate of energy released by the reaction for each successive addition of acetic anhydride. The kinetic and energetic parameters of the model were estimated thanks to a hybrid method, using a genetic algorithm together with a locally convergent method.