Dihydrolevoglucosenone
Chemical compound
From Wikipedia, the free encyclopedia
Dihydrolevoglucosenone (Cyrene) is a bicyclic, chiral, seven-membered heterocyclic cycloalkanone which is a waste derived and fully biodegradable aprotic dipolar solvent.[4][5][6] It is an environmentally friendly alternative to dimethylformamide (DMF) and N-methyl-2-pyrrolidone (NMP).[7]
| Names | |
|---|---|
| IUPAC name
(1R,5S)-7,8-Dioxabicyclo[3.2.1]octan-2-one | |
| Other names
Cyrene | |
| Identifiers | |
3D model (JSmol) |
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| ChemSpider | |
| ECHA InfoCard | 100.234.612 |
| EC Number |
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PubChem CID |
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CompTox Dashboard (EPA) |
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| |
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| Properties | |
| C6H8O3 | |
| Molar mass | 128.127 g·molâ1 |
| Appearance | clear to yellowish liquid |
| Density | 1.2473 g/cm3 (25 °C) [1] |
| Boiling point | 226 °C (439 °F; 499 K)[2] |
| miscible | |
| Vapor pressure | 12.98 Pa (25 °C) [1]
14.4 Pa (25 °C) [2] |
Refractive index (nD) |
1.4732 (20 °C) [2] |
| Hazards[3] | |
| GHS labelling: | |
| Warning | |
| H319 | |
| P305+P351+P338, P313 | |
| Flash point | 108 °C (226 °F; 381 K) |
| 296 °C (565 °F; 569 K) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Preparation
Dihydrolevoglucosenone can be prepared through the hydrogenation of unsaturated ketone levoglucosenone (LGO) with heterogenous palladium catalysts under mild conditions.[8][9] LGO is a chemical building block obtained by acid-catalyzed pyrolysis[10] of lignocellulosic biomass such as sawdust.

Properties
Dihydrolevoglucosenone is a clear colorless, to light-yellow liquid with a mild, smoky ketone-like odor.[11] It is miscible with water and many organic solvents.[11] Dihydrolevoglucosenone has a boiling point of 226 °C at 101.325 kPa (vs 202 °C for NMP), and a vapor pressure of 12.98 Pa near room temperature (25 °C).[1] 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).[12]
The compound is stable at temperatures up to 195 °C and weak acids and bases.[citation needed] Dihydrolevoglucosenone can react with inorganic bases via an aldol condensation mechanism.[citation needed] Dihydrolevoglucosenone is readily biodegradable (99% within 14 days) and reacts to oxidants such as aqueous 30% hydrogen peroxide solution even at room temperature.[citation needed]
Applications
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.[8]
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,[13] from which zalcitabine, formerly a HIV drug, is available.[14]

]
In a two-step hydrogenation process with a metal catalyst â first at 60 °C then at 180 °C â 1,6-hexanediol is mainly obtained via several intermediates.[15] 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),[8] which is a biodegradable solvent and a bio-based precursor to 1,6-hexanediol (and 1,6-diaminohexane).[16]

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,[17] has triggered intensive research activities in industry and academia worldwide.
Dihydrolevoglucosenone is considered a "green" replacement for DMF.[5] Several standard reactions of organic chemistry, e.g. Menshutkin reaction,[5] Sonogashira coupling,[18] Suzuki-Miyaura coupling[19] and the production of ureas[20] 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.[21]
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
