Hydroxymethylfurfural

Chemical compound

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| GHSSignalWord = Warning It is a white low melting solid (although commercial samples are often yellow) which is highly soluble in both water and organic solvents. The molecule consists of a furan ring, containing both aldehyde and alcohol functional groups. HMF can form in sugar containing food, particularly as a result of heating or cooking. Its formation has been the topic of significant study as HMF was regarded as being potentially carcinogenic to humans. However, so far in vivo genotoxicity was negative. No relevance for humans concerning carcinogenic and genotoxic effects can be derived. HMF is classified as a food improvement agent and is primarily being used in the food industry in form of a food additive as a biomarker as well as a flavoring agent for food products. It is also produced industrially on a modest scale as a carbon neutral feedstock for the production of fuels and other chemicals.

HMF was first reported in 1875 as an intermediate in the formation of levulinic acid from sugar and sulfuric acid. This remains the classical route, with 6 carbon sugars (hexoses) such as fructose undergoing acid catalyzed poly dehydration. When hydrochloric acid is used 5 chloromethylfurfural is produced instead of HMF. Similar chemistry is seen with 5 carbon sugars (pentoses), which react with aqueous acid to form furfural. The classical approach tends to suffer from poor yields as HMF continues to react in aqueous acid, forming levulinic acid. HMF was not produced on a commercial scale until over 90 years later. The first production plant coming online in 2013. continuous liquid liquid extraction, reactive distillation and solid acid catalysts to either remove the HMF before it reacts further or to otherwise promote its formation and inhibit its decomposition.

HMF itself has few applications. It can however be converted into other more useful compounds. HMF can be converted to 2,5 dimethylfuran (DMF), a liquid that is a potential biofuel with a greater energy content than bioethanol. Hydrogenation of HMF gives 2,5 bis(hydroxymethyl)furan. Acid catalysed hydrolysis converts HMF into gamma hydroxyvaleric acid and gamma valerolactone, with loss of formic acid. HMF is a well known component of baked goods. Upon toasting bread, the amount increases from 14.8 (5 min.) to 2024.8 mg/kg (60 min). It is a good wine storage time−temperature marker, especially in sweet wines such as Madeira and those sweetened with grape concentrate arrope. HMF can be found in low amounts in honey, fruit juices and UHT milk. Here, as well as in vinegars, jams, alcoholic products or biscuits, HMF can be used as an indicator for excess heat treatment. For instance, fresh honey contains less than 15 mg/kg—depending on pH value and temperature and age, and the codex alimentarius standard requires that honey have less than 40 mg/kg HMF to guarantee that the honey has not undergone heating during processing, except for tropical honeys which must be below 80 mg/kg. Higher quantities of HMF are found naturally in coffee and dried fruit. Several types of roasted coffee contained between 300 – 2900 mg/kg HMF. Dried plums were found to contain up to 2200 mg/kg HMF. In dark beer 13.3 mg/kg were found, bakery products contained between 4.1 – 151 mg/kg HMF. It can be found in glucose syrup. HMF can form in high fructose corn syrup (HFCS), levels around 20 mg/kg HMF were found, increasing during storage or heating.

A major metabolite in humans is 5 hydroxymethyl 2 furoic acid (HMFA), also known as Sumiki's acid, which is excreted in urine. HMF bind intracellular sickle hemoglobin (HbS). Preliminary in vivo studies using transgenic sickle mice showed that orally administered 5HMF inhibits the formation of sickled cells in the blood. Under the development code Aes 103, HMF has been considered for the treatment of sickle cell disease.

Today, HPLC with UV detection is the reference method (e. g. DIN 10751–3). Classic methods for the quantification of HMF in food use photometry. The method according to White is a differential UV photometry with and without sodium bisulfite reduction of HMF. Winkler photometric method is a colour reaction using p toluidine and barbituric acid (DIN 10751–1). Photometric test may be unspecific as they may detect also related substances, leading to higher results than HPLC measurements. Test kits for rapid analyses are also available (e. g. Reflectoquant HMF, Merck KGaA).

HMF is an intermediate in the titration of hexoses in the Molisch's test. In the related Bial's test for pentoses, the hydroxymethylfurfural from hexoses may give a muddy brown or gray solution, but this is easily distinguishable from the green color of pentoses. Acetoxymethyl furfural (AMF) is also bio derived green platform chemicals as an alternative to HMF.