Uso de planejamento experimental na síntese de 1,8‐dioxo-octaidroxanteno

Abstract

Organicsynthesis is a fundamental area in the study of organic chemistry, enabling the investigation of various syntheses according to the desired final product. A prominent reaction in these studies is the multicomponent reaction (MCR). This methodology is recognized for its sustainability and environmental compatibility, as it involves the addition of three or more reagents in a single reaction vessel, resulting in a product that incorporates most of the atoms from the reagents, eliminating the need for additional processes such as the purification of intermediates. Among the various classes of molecules that can be synthesized through this reaction, xanthenes stand out due to their potential antibacterial, antimalarial, and antifungal activities, among others. Xanthene is a class of heterocyclic compounds whose basic structure consists of a central pyran ring fused with two benzene rings at each end. In many syntheses, the procedure can be tedious and time-consuming, often requiring numerous experiments, which leads to significant consumption of time and resources. Therefore, the main role of experimental design is to establish and conduct the fewest number of experiments without compromising the reliability of the results obtained. The present work aimed to apply a full factorial experimental design with a central point in the synthesis of 1,8-dioxo-octahydro xanthene and analyze three important variables: concentration, time, and temperature. Three variables were analyzed: catalyst concentration, temperature, and reaction time, using three different catalysts—zinc chloride (ZnCl₂), cobalt chloride (CoCl₂), and hydrochloric acid (HCl). The experimental design was carried out using the Chemoface software, with 11 syntheses performed for each catalyst, three of which were done in triplicate. For each synthesis, the yield was calculated before and after the recrystallization process. These yields were used to generate Pareto charts and response surface plots, evaluating the relationship between the variables. Additionally, the products were characterized using Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (¹H and ¹³C NMR), and differential scanning calorimetry (DSC). The yield of syntheses using CoCl₂ ranged from 26.49% to 90.14%. For ZnCl₂, the yield ranged from 63.85% to 93.67%, while for HCl, it ranged from 2.59% to 77.85%. The results demonstrated that the syntheses were successful with the use of the catalysts, as the desired product was obtained and the characterizations were satisfactory. Based on the calculated yields and the experimental conditions applied in this study, CoCl₂ was identified as the most efficient catalyst. On the other hand, HCl did not reach its catalytic range, while ZnCl₂ exceeded its catalytic range, resulting in a decrease in yield with increasing catalyst concentration. The data presented in the Pareto charts and response surface plots indicated that the variable with the greatest influence on synthesis yields was temperature, followed by concentration and, lastly, time. The product obtained with ZnCl₂ showed differences in the FTIR spectrum and also in the DSC plot compared to the other catalysts.