Studies on Sustainable Oxidation, Azidation, Rearrangement, and Annulation Reactions towards Heterocyclic Scaffolds under Batch and Continuous Flow

Abstract

Chemistry paved the path for making modern society livable by fulfilling the basic needs of daily life through rapid industrialization. However, the toxic waste produced by chemical industries vitiates the environment profoundly and affects the ecosystem. Still, industrialization is the only way to cope with the plenty of resources of society. Hence, the quest for new sustainable methods that eliminates hazardous waste generation or delivers useful waste is required in the chemical industry. In this context, twelve green chemistry principles play a pivotal role in making the process sustainable. Therefore, the selection of reactions, chemicals, and processes, which are sustainable and green at the same time, should be preferred for the design and innovation of any chemical operation. Therefore, the utilization of green chemistry tools such as green solvents, green catalysis, solvent free-catalyst free reactions (SF-CF), or the use of alternative technologies (microwave, flow, mechanochemistry, photochemistry, etc.) can be an ideal choice for making the process sustainable. To this direction, we investigated continuous-flow oxidation of methylene group by using TBHP and magnetically retrievable manganese catalysts for the synthesis of carbonyl derivatives such as ketones and esters. Subsequently, studies were carried out on the direct azidation of alcohols by using a solid acid catalyst in the presence of an azidation source for safer multigram scale applications under continuous flow. Furthermore, this azidation reaction was subjected to the peroxides to a sequential reaction that involves skeletal rearrangement and azide incorporation to generate a hitherto unknown library of azides. Further application of the azides to the various heterocyclic compounds under continuous flow via click reaction and thermal rearrangement were investigated. To the direction of waste free catalysis for the synthesis of heterocycles, the acceptorless dehydrogenation (AD) concept has been exploited with the amino alcohols and dicarbonyl compounds for the antipsychotic drug Molindone.