2-Methylfuran has a mild aromatic odor. This heterocyclic compound is chemically reactive and readily undergoes addition, oxidation, and substitution reactions. It is flammable and explosive, with an extremely low flash point; it ignites easily when exposed to high temperatures or open flames, and its vapors are toxic. It is primarily used as an intermediate in the fine chemicals industry and is widely employed in the synthesis of pharmaceuticals, pesticides, food flavorings, and resin raw materials. It can also serve as a highly effective organic solvent and a component in fuel blends.

Metabolic Activation of 2-Methylfuran to Acetylacrolein

2-Methylfuran (2-MF) is a process-related contaminant found primarily in heat-treated foods, such as coffee or canned food. The oxidative metabolic activation of 2-MF is supposed to follow the pathway established for furan, which is known to generate the highly reactive metabolite butenedial (BDA). In the case of 2-MF, generation of the BDA homologue 3-acetylacrolein (AcA) is to be expected. 2-Methylfuran metabolism to AcA was investigated in two model systems: commercial microsomal preparations and primary rat hepatocytes (pRH). To scavenge the generated 2-MF, two model nucleophils, N-acetyl-l-cysteine (AcCys) and N-α-acetyl-l-lysine (AcLys), were used, and the formation of the corresponding adducts was measured in the supernatants. The metabolic activation of 2-MF to AcA was studied using human liver microsomes as well as rat liver microsomes. Incubation of 2-MF in Supersomes allowed to identify the cytochrome P450 isoenzyme primarily responsible for 2-methylfuran.

In addition, primary rat hepatocytes were incubated with 2-methylfuran or AcA and AcLys adduct of AcA (N-α-acetyl-l-lysine-acetylacrolein, AcLys-AcA) determined in the cell supernatants by UHPLC-MS/MS. In model experiments, AcA formed adducts with AcCys and AcLys. The structures of both adducts were characterized. For incubations in biological activating systems, CYP 2E1 was found to be a key enzyme for the conversion of 2-methylfuran to AcA in Supersomes. When pRH were incubated with 2-MF and AcA, AcLys-AcA was detected in the cell supernatants in a time- and dose-dependent manner. The results showed that AcA was indeed formed at the cellular level. In contrast to the AcLys-AcA adduct, no N-acetyl-l-cysteine-acetylacrolein (AcCys-AcA) adduct could be detected in pRH. AcA was determined as a reactive metabolite of 2-methylfuran in vitro, and its adduct formation with nucleophilic cellular components was evaluated. The metabolites were characterized, and AcLys-AcA was identified as potential biomarker.

Recent Progress in the Conversion of Methylfuran into Value-Added Chemicals and Fuels

In the context of the “dual carbon goal”, lignocellulosic biomass with an annual productivity of over 180 billion tons has been identified as a promising raw material in the search for alternative resources to produce low-carbon future commodity chemicals and transportation fuels. Lignocellulose includes lignin, cellulose, and hemicellulose, which has the potential to be transformed into chemicals and fuels through catalytic conversion. 2-methylfuran is an organic compound with the chemical formula C5H6O. 2-methylfuran is used as a chemical raw material to prepare acetylpropanol, pentadiene, pentanediol, etc. It can also be used in the pharmaceutical field to synthesize vitamin B1 (anti-neuroinflammatory drug), chloroquine phosphate, and primaquine phosphate (anti-dysentery drug). It is also a good solvent. It is an important organic intermediate with important applications in the fields of chemical, pharmaceutical, pesticide, and energy. Meanwhile, 2-methylfuran has a higher octane number and higher energy density than ethanol, making it a biofuel alternative to gasoline. The synthesis of 2-methylfuran involves a selective hydrogenation step of furfural derived from the hydrolysis and dehydration processes of hemicellulose.[2]

2-methylfuran is mainly prepared through processes like hydrolysis, dehydration, and selective hydrogenation of biomass hemicellulose. Due to its special physical and chemical properties, 2-methylfuran can be used as a raw material and intermediate in the production of anti-malaria drugs, and its combustion efficiency is high. It can be mixed with gasoline to reduce gasoline consumption. 2-methylfuran can undergo hydroxyalkylation/alkylation reactions with aldehydes, ketones, and esters derived from biomass to grow carbon chains and then undergo hydrogenation deoxygenation to produce alkane fuels. The aldehydes involved in this article include butyraldehyde, furfural, 5-hydroxymethylfurfural, 5-methylfurfural, benzaldehyde, vanillin, glutaraldehyde, propanal, acetaldehyde, and formaldehyde. The ketones involved include acetone, hydroxyacetone, butanone, 2-pentanone, cyclopentanone, cyclohexanone, and isopropylacetone. The esters involved include ethyl acetate and angelolactone. The catalysts used in hydroxyalkylation/alkylation reactions can be liquid acids, solid acids, or ionic liquids. Liquid acids mainly comprise sulfuric acid and p-toluenesulfonic acid. The solid acids involved include cation exchange resins, zeolite molecular sieves, oxides, and sulfonic-acid-based, carbon-based solid acids.

References

[1]Sch?fer V, Stegmüller S, Becker H, Richling E. Metabolic Activation of 2-Methylfuran to Acetylacrolein and Its Reactivity toward Cellular Proteins. Chem Res Toxicol. 2024 Nov 18;37(11):1807-1820. doi: 10.1021/acs.chemrestox.4c00083. Epub 2024 Sep 6. PMID: 39240537; PMCID: PMC11577422.

[2]Wang W, Yan J, Sun M, Li X, Li Y, An L, Qian C, Zhang X, Shao X, Duan Y, Li G. Recent Progress in the Conversion of Methylfuran into Value-Added Chemicals and Fuels. Molecules. 2024 Jun 22;29(13):2976. doi: 10.3390/molecules29132976. PMID: 38998927; PMCID: PMC11243621.