Demonstration of Green Solvent Performance on O,S,N-Heterocycles Synthesis: Metal-Free Click Chemistry and Buchwald—Hartwig Coupling

Abstract

The development of new and greener approaches to organic synthesis has been a trend in recent years. Continuing the latest publications of our team, in this work, we demonstrate the efficiency of three solvents: eucalyptol (1,8-cineole), cyclopentyl methyl ether (CPME), and 2-methyltetrahydrofuran (2-MeTHF) for the synthesis of O,S,N-heterocyclic compounds.

GreenMedChem: the challenge in the next decade toward eco-friendly compounds and processes in drug design

“…As a specific example, Campos et al 133 showed in their work the potential of solvents 79–81 to efficiently replace petroleum solvents for the synthesis of O,S,N-heterocyclic compounds. Furthermore, they included eucalyptol (1,8-cineol) (81) (Fig.…”

“…The natural origin of the vegetable oils is evident, but to form a connection to CPME, it is necessary to take a look at the building blocks of the solvent, which is formed from furfural, and furfural is derived from pentoses such as xylose, and thus are regenerative raw materials, confirming its seminatural origin. 133 Therefore, a greener approach regarding natural solvents seems feasible at least for some reactions but not yet used in an industrial setting to the best of our knowledge. 132…”

“…Specifically, they developed a one-pot approach to synthesise pyrazole-derivatives (e.g., 137) in water under ultrasonic irradiation (Fig. 32) starting from aromatic aldehydes (134), hydrazine monohydrate (135), ethyl acetoacetate (133) and malononitrile/ammonium acetate (136). They tried some variations in reaction temperature and based on their results, per- 158 formed the reaction at 50 °C.…”

Monitoring of Catalyst-Free Microwave-Assisted MCR-Type Synthesis of 2-Amino-3-cyano-4H-chromene Derivatives Using Raman Spectrometry

“…To overcome these drawbacks, we envisioned the use Raman spectrometry to live-monitor the reaction outcome in the sealed tube. As part of our recent work on the search for sustainable chemistry methods, [29][30][31] the use of some green solvents was also investigated, the results of which are presented here.…”