Eucalyptol: New solvent for the synthesis of heterocycles containing oxygen, sulfur and nitrogen

Significance 

Global push for sustainable development agenda has coerced firms into seeking alternative material sources. In particular, the need to avert materials/compounds from non-renewable resources has become a priority. In this context, researchers have been seeking alternative active pharmaceutical ingredients following the high environmental impact that solvents have. As such, solvents derived from biomass, such as; limonene, have shown promising results. Limonene can efficiently replace non-polar petroleum-based solvents used in extraction processes or cleaning applications.

Another bio-solvent is eucalyptol or 1,8-cineole. Eucalyptol is insoluble in water but miscible with ether, ethanol and chloroform. It has been demonstrated that this bio-solvent does not generate peroxides and does not require the addition of an inhibitor such as butylated hydroxytoluene, a powerful antioxidant. This promotes its use because it is, in addition, cheaper than 2-Methyltetrahydrofuran.Unfortunately, there is no report in the literature to date on the use of Eucalyptol in organic synthesis.

In this view, University of Orléans researchers Dr. Joana F. Campos and Prof. Sabine Berteina-Raboin together with Prof. Marie-Christine Scherrmann Paris-Sud University in France explored the feasibility of using eucalyptol as the new solvent for organic transformations. Their objective was to evaluate limonene and eucalyptol as solvents for some of the most prevalent transformations at both process development and manufacturing scale, i.e. the synthesis of heterocycles and cross-coupling reactions. Their work is currently published in the research journal, Green Chemistry.

With reference to their previous work on the development of new methodologies and greener approaches in the synthesis of heterocycles, they focused on heterocycles containing oxygen, sulfur or nitrogen. This way, heterocycles containing oxygen, sulfur and nitrogen were chosen as targets or as starting materials for widely used palladium-catalyzed cross-coupling reactions. In short, they compared limonene and eucalyptol: the latter being the candidate for the new solvent.

The authors showed that eucalyptol could be an interesting alternative to conventional solvents for the one-pot synthesis of 2,3-diarylimidazol [1,2-a] pyridines involving a condensation between 2-aminopyridine and bromoacetophenones, followed by a C-H activation at C-3. In addition, the solvent derived from the biomass was also seen to be effective for various transformations of heteroatom-containing heterocycles such as oxygen, sulfur or nitrogen. Moreover, they reported that it was possible to recover the solvent from the reaction media by simple distillation, using a standard equipment, which is very important environmentally and economically.

In summary, the team demonstrated for the first time that eucalyptol could be used as solvent for organic synthesis. Generally, the use of eucalyptol as a green solvent was also related to its safety and pharmacological profiles: Eucalyptol is considered to be a safe chemical when taken in normal doses. Altogether, Eucalyptol turned out to be a viable sustainable alternative to common solvents.

Reference

Joana F. Campos, Marie-Christine Scherrmann, Sabine Berteina-Raboin. Eucalyptol: New solvent for the synthesis of heterocycles containing oxygen, sulfur and nitrogen. Green Chemistry, 2019, volume 00, page 1-3

Go To Green Chemistry

Check Also

New perspectives of ZnO nanorods as efficient water splitting and O2 evolution photo-electrocatalyst - Advances in Engineering

New perspectives of ZnO nanorods as efficient water splitting and O2 evolution photo-electrocatalyst