Síntese e otimização de novos núcleos 2-amino-7,7-dimetil-4-fenil-3-(1H-tetrazol-5-il)-4,6,7,8-tetrahidro-5H-cromen-5-ona

Abstract

In medicinal chemistry, heterocyclic compounds are very important because of their biological activities. Among them are 4H-chromene derivatives, which stand out for possessing relevant pharmacological properties, such as antioxidant, anti-inflammatory, and antitumor actions. In this scenario, the introduction of new heterocycles, such as the tetrazole ring, has been studied as an approach to alter the physicochemical and biological properties of molecules, helping to improve the pharmacological profile. The objective of this study was to develop and improve synthetic techniques for the production of 4H-chromene and chromene-tetrazole derivatives, using effective reaction strategies in accordance with the principles of Green Chemistry. First, an optimization study of the multicomponent reaction for the synthesis of 4H-chromene derivatives was conducted. In this study, different parameters were analyzed, such as reaction conditions, catalytic systems, and heating techniques, including conventional heating and microwave radiation. Subsequently, the obtained chromenes were used as substrates in the production of chromene-tetrazole derivatives, analyzing variables such as solvent, temperature, and reaction duration. Spectroscopic techniques, particularly ¹H and ¹³C Nuclear Magnetic Resonance (NMR), were employed for the structural characterization of the compounds. Optimization tests showed that the CuSO₄/N(Et)₃ catalytic system combined with microwave radiation presented the best performance, offering higher yields and a considerable reduction in reaction time compared to conventional heating. The use of these conditions allowed the production of several substituted chromenes with satisfactory yields. Following this, the synthesis of chromene-tetraazoles occurred after the analysis of the variables, where ethanol was used as the best solvent, a temperature of 50ºC, and a reaction time of 8h. After this, the suggested structures were confirmed through spectroscopic analyses. The methodology developed proved to be effective in the synthesis of the analyzed derivatives, contributing to the advancement of more efficient synthetic strategies for heterocyclic compounds relevant to pharmacology.