Dihydrolevoglucosenone

Dihydrolevoglucosenone (Cyrene) is a bicyclic, chiral, seven-membered heterocyclic cycloalkanone which is a waste derived and fully biodegradable aprotic dipolar solvent. It is an environmentally friendly alternative to dimethylformamide (DMF) and N-methyl-2-pyrrolidone (NMP).

Preparation
Dihydrolevoglucosenone can be prepared through the hydrogenation of unsaturated ketone levoglucosenone (LGO) with heterogenous palladium catalysts under mild conditions. LGO is a chemical building block obtained by acid-catalyzed pyrolysis of lignocellulosic biomass such as sawdust.



Properties
Dihydrolevoglucosenone is a clear colorless, to light-yellow liquid with a mild, smoky ketone-like odor. It is miscible with water and many organic solvents. Dihydrolevoglucosenone has a boiling point of 226 °C at 101.325 kPa (vs 202 °C for NMP), and a vapor pressure of 14.4 Pa near room temperature (25 °C). It has a comparatively high dynamic viscosity of 14.5 cP (for comparison DMF: 0.92 cP at 20 °C, NMP: 1.67 cP at 25 °C).

The compound is stable at temperatures up to 195 °C and weak acids and bases. Dihydrolevoglucosenone can react with inorganic bases via an aldol condensation mechanism. Dihydrolevoglucosenone is readily biodegradable (99% within 14 days) and reacts to oxidants such as aqueous 30% hydrogen peroxide solution even at room temperature.

Dihydroglucosenone as a precursor
Dihydrolevoglucosenone can be used as a renewable building block to produce valuable chemicals such as drugs, flavours and fragrances and specialty polymers.

As dihydrolevoglucosenone is produced as a single enantiomer, it can be used for chiral pool synthesis. For instance, oxidation with peroxy acids such as peroxyacetic acid produces optically pure 5-hydroxymethyldihydrofuranone, from which zalcitabine, formerly a HIV drug, is available.



In a two-step hydrogenation process with a metal catalyst – first at 60 °C then at 180 °C – 1,6-hexanediol is mainly obtained via several intermediates. 1,6-hexanediol can be used as a starting material for the production of polyesters, polyurethanes and diamine 1,6-diaminohexane.

At elevated temperature and in the presence of a palladium catalyst, hydrogenolysis of dihydrolevoglucosenone via levoglucosanol selectively yields tetrahydrofuran-2,5-dimethanol (THF-dimethanol), which is a biodegradable solvent and a bio-based precursor to 1,6-hexanediol (and 1,6-diaminohexane).



Dihydroglucosenone as a safer solvent
The search for alternative "green" solvents made from biomass or low-cost renewable raw materials, which are accessible through high-efficiency processes, in high yields, and meet the performance of conventional solvents, has triggered intensive research activities in industry and academia worldwide.

Dihydrolevoglucosenone is considered a "green" replacement for DMF. Several standard reactions of organic chemistry, e.g. Menshutkin reaction, Sonogashira coupling, Suzuki-Miyaura coupling and the production of ureas have been carried out in dihydrolevoglucosenone.



Production
Circa Group produces dihydrolevoglucosenone from cellulose under the Cyrene brand and has built a 50-tonne demonstration plant with partners in Tasmania. The company estimates that dihydroglucosenone performs better than NMP in 45% and comparably to NMP in 20% of trials to date. Circa received authorization in 2018 from the European Chemicals Agency (ECHA) to produce or import up to 100 tonnes per year of dihydroglucosenone to the EU.

Literature

 * DS van Es: Study into alternative (biobased) polar aprotic solvents. Wageningen University, Wageningen 2017 (wur.nl [PDF]).
 * JH Clark, A. Hunt, C. Topi, G. Paggiola, J. Sherwood: Sustainable Solvents: Perspectives from Research, Business and Institutional Policy . Royal Society of Chemistry, London 2017, ISBN 978-1-78262-335-9.
 * Dickson Kong and Anton V. Dolzhenko. "Cyrene: A Bio-Based Sustainable Solvent for Organic Synthesis." Sustainable Chemistry and Pharmacy 25 (April 1, 2022): 100591. https://doi.org/10.1016/j.scp.2021.100591