Enabling mechanochemistry for sustainable synthesis of indoles

Abstract

The high consumption of fossil resources associated with growing environmental problems, generated by their use on a global scale, requires the identification of alternatives for obtaining fuels, chemicals and functional materials. Such alternatives are crucial for the development of modern society. Therefore, biomass presents itself as a renewable and sustainable source of organic carbon, with great potential for the production of fuels, polymeric materials and chemical inputs.This Proposal for Research Internships Abroad is composed of 2 strategic research axes, whose central objective is to explore the benefits of mechanochemistry to obtaining aromatic compounds from furans derived from biomass. Axis 1 aims at synthesizing indole-containing compounds using three furan platforms derived from biomass: 3-acetamide-5-acetylfuran (3A5AF), dihydroxyethyl acetamidefuran (DiHAF), 3-acetamidofuran (3AF) and other lignocellulosic-derived furans. We will explore these reactions under milling conditions and vary parameters such as milling frequency, degree of filling, use of liquid or solid assisted grinding, temperature and time to prospect results that are comparable or superior from those obtained in solution phase. In axis 2, we will study the use of 3-acetamide 2-pyrone (3A2P) and 3-acetamide-6-methyl-2-pyrone (3A6M2P) as building blocks in Diels-Alder reactions targeting its potential platform application in drug synthesis.This proposal is totally related to the goals of the PD project carried out in Brazil and financed by FAPESP. In this context, the partnership with Prof. Duncan L. Browne (affiliated and collaborator in the Young Investigator Grant Phase 2 -2021/06661-5) will contribute substantially for the development of this project. The experience obtained in the host institution in the UK will enable the continuation of the experiments in this research area in Brazil with the acquisition of ball mills by Prof. Julio C. Pastre in our laboratory (one mixer mill is already available) and consequent knowledge transfer after Dr. Camila's return to Brazil. (AU)