**3.5 Ethers**

*Solvents, Ionic Liquids and Solvent Effects*

the synthesis of drugs, pesticides and other chemicals. Their use as fuels varies depending on the length of the carbon chains. Generally C3 and C4 alkanes are used as liquefied petroleum gas for cooking and in cigarette lighters, respectively, while

Benzene, toluene and xylene (BTX) can be derived from wood and agricultural waste [84]. Anellotech, a US-based company, has scaled up a process that converts biomass, using their Bio-TCat™ technology, into BTX mixtures. Benzene, toluene and xylene have identical properties as their fossil-derived counterparts [85]. Benzene is used in the manufacture of resins, rubber lubricants, synthetic fibers, detergents, pesticides, drugs and plastics. Toluene is used in printing and leather tanning processes and as a solvent in paint, a nail polish remover, thinners and glues, while xylene finds use as a cleaning agent, ingredient in pesticide manufacturing, disinfectants, paints, paint thinners, polishes, waxes and adhesives. An elegant multistep route to renewable *p*-xylene was proposed. It begins with (1) the conversion of glucose to fructose, (2) followed by dehydration of the fructose to HMF, (3) hydrodeoxygenation of HMF to 2,5-dimethylfuran (2,5-DMF) and (4) subjecting the resultant 2,5-DMF to Diels-Alder cycloaddition with ethylene

Terpenes are a class of natural solvents obtained from essential oils found in plants. They have C5H8 isoprene units and can be acyclic, bicyclic or monocyclic; therefore, they have varying physical and chemical properties. Extraction using water hetero-azeotropic distillation at low temperatures affords terpenes, and they in turn have been utilized as green alternative solvents for the extraction of oils

D-Limonene is extracted from citrus peels and pulp by steam distillation and alkali treatment [88]. Industrially, limonene is used as a solvent in place of various halogenated hydrocarbons. By 2023, the demand of D-limonene is expected to be 65 kilotons/year [88]. It is also used as solvent to degrease and grease wool and cotton wool and in the dissolution of cholesterol stone, where its performance is better than chloroform and diethyl ether (DEE) in the latter. The catalytic isomerization

C5–C18 alkanes are used in gasoline, diesel and aviation fuel.

*Synthetic steps for straight-chain alkanes from bio-derived furan compounds.*

*3.4.2 Benzene, toluene and xylenes*

to afford the product [86].

from microalgae [87].

*3.4.3 Terpenes*

**Figure 4.**

**10**

Bio-derived ethers are produced by the dehydration of bio-alcohols, mainly ethanol and methanol to form diethyl ether and dimethyl ether, respectively. These ethers are usually used as fuel additives to improve its octane rating and reduce emissions (NOx and ozone) and engine wear.

2-Methyltetrahydrofuran (2-MeTHF) is a biodegradable, non-toxic, non-ozonedepleting, easy-to-recycle ether solvent with a good preliminary toxicology report [91]. It is produced from either furfural or levulinic acid *via* catalytic processes. For instance, the successive hydrogenation of furfural over Ni-Cu, Fe-Cu, Cu-Zn or Cu-Cr produces 2-MeTHF as illustrated in **Figure 5** [92, 93].

The first two hydrogenations have been reported to quantitatively convert furfural alcohol to 2-methylfuran using Ni-based catalysts followed by 2-methylfuran conversion over a Cu-Zn catalyst. 2-MeTHF can also be prepared from levulinic acid *via* consecutive hydrogenation and dehydrogenation steps. Here, Ru-based catalysts are the most active.

Pfizer, USA, has reported the application of 2-MeTHF as a solvent in two-phase reactions due to the poor solubility of water in 2-MeTHF [94]. This bio-derived solvent has also been used in place of dichloromethane (that has unfavourable environmental effects) because of its low boiling point, which makes it difficult to contain on a large scale. Using 2-MeTHF, high yields of product were afforded for amidations, alkylations and nucleophilic aromatic substitutions reactions.

Another pharmaceutical company, Actelion Pharmaceuticals Ltd. in Switzerland, uses 2-MeTHF as solvent in the synthesis of 5-phenylbicyclo-[2.2.2] oct-5-en-2-one [95], an intermediate during the preparation of an important preclinical candidate. Furthermore, the reaction was successfully upscaled to kilogram scale, and the reaction still gave excellent yields (98%) in 2-MeTHF.
