2,5-Furandicarboxylic acid
Encyclopedia
2,5-Furandicarboxylic acid (FDCA), also known as dehydromucic acid, is an oxidized furan
derivative. This organic compound
was first obtained by Fittig and Heinzelmann in 1876. The first review by Henry Hill was already published in 1901. FDCA has also been detected in human urine. A healthy human produces 3-5 mg/day. Numerous studies were undertaken to establish the metabolism of this compound and to determine the quantity, which is produced depending on the healthiness of the human. It was demonstrated that the individual quantity of produced FDCA increased after the injection of fructose. FDCA was also detected in blood plasma. FDCA was more than 125 years later identified by the US Department of Energy as one of 12 priority chemicals for establishing the “green” chemistry industry of the future. Furan-2|,5-dicarboxylic acid (FDCA) has been suggested as an important renewable building block because it can substitute for terephthalic acid
(PTA) in the production of polyesters and other current polymers containing an aromatic moiety. Avantium has announced plans to produce 40 ton/year of FDCA monomer at a pilot plant in the second half of 2011.
(mucic
) acids. This reaction requires severe conditions (highly concentrated acids, temp > 120 °C, React time > 20h) and all the methods were non-selective with yields < 50%. The process has also been patented by the French company Agro Industrie Recherches et Developements.
(HMF) with air over different catalysts have been reported. Oxidation of HMF under strongly alkaline conditions over noble metal catalysts gives almost quantitative formation of FDCA. HMF and methoxymethylfurfural
(MMF) oxidation was also studied with a series of conventional metal bromide catalysts (Co, Mn, Br) used for the oxidation of para-xylene to terephthalic acid
. Also, the direct, one pot dehydration and oxidation of fructose to FDCA via intermediate HMF has been investigated with good selectivities, unfortunately this system does not work in water.
and the latter was subsequently converted to its methyl ester. The ester was then converted via chloromethylation at position 5 to give 5-chloromethylfuroate. The latter was oxidized with nitric acid to form dimethyl 2,5-furandicarboxylate, which, after the alkaline hydrolysis gave FDCA in 50% yield. Andrisano reported that potassium 2-furoate, when heated up to 300 ºC in a nitrogen atmosphere, underwent decarboxylation to furan with simultaneous carboxylation at position 5 to di-potassium 2,5-furandicarboxylate.
basilensis HMF14. This enzyme is able to convert HMF to FDCA using molecular oxygen. A Pseudomonas putida
strain that was genetically engineered to express this enzyme can completely and selectively convert HMF to FDCA. This biocatalysis
is performed in water, at ambient temperature and pressure, without toxic or polluting chemicals, making it very environmentally friendly.
applications has been extensively reviewed by Gandini. Examples of polyesters, polyamides and polyurethanes have been described in literature. The company Avantium claims to have developed a cost effective route to produce FDCA and the derived polyesters via so-called YXY Building Blocks
. FDCA has also been applied in pharmacology. It was demonstrated that its diethyl ester had a strong anaesthetic action similar to cocaine. Dicalcium 2,5-furandicarboxylate was shown to inhibit the growth of Baccillus megatorium. Screening studies on FDCA-derived anilides showed their important anti-bacterial action. The diacid itself is a strong complexing agent, chelating such ions as: Ca2+, Cu2+ and Pb2+, it is utilized in medicine to remove kidney stones. Interestingly, HMF is metabolized via FDCA in mammals including humans. A very diluted solution of FDCA in tetrahydrofuran is utilized for preparing artificial veins for transplantation. At the beginning of this chapter, it was mentioned that FDCA is a chemically stable compound. This property has been well benefited in industry – FDCA as most of polycarboxylic acids can be an ingredient of fire foams. Such foams help to extinguish fires in a short time caused by polar and non-polar solvents.
(HMF) as intermediate are generally nonselective, unless, immediately upon their formation, the unstable intermediate products can be transformed into more stable materials such as methoxymethylfurfural
(MMF). Necessary R&D will include development of selective dehydration systems and catalysts. FDCA formation will require development of cost effective and industrially viable oxidation technology that can operate in concert with the necessary dehydration processes.
Furan
Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen. The class of compounds containing such rings are also referred to as furans....
derivative. This organic compound
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
was first obtained by Fittig and Heinzelmann in 1876. The first review by Henry Hill was already published in 1901. FDCA has also been detected in human urine. A healthy human produces 3-5 mg/day. Numerous studies were undertaken to establish the metabolism of this compound and to determine the quantity, which is produced depending on the healthiness of the human. It was demonstrated that the individual quantity of produced FDCA increased after the injection of fructose. FDCA was also detected in blood plasma. FDCA was more than 125 years later identified by the US Department of Energy as one of 12 priority chemicals for establishing the “green” chemistry industry of the future. Furan-2|,5-dicarboxylic acid (FDCA) has been suggested as an important renewable building block because it can substitute for terephthalic acid
Terephthalic acid
Terephthalic acid is the organic compound with formula C6H42. This colourless solid is a commodity chemical, used principally as a precursor to the polyester PET, used to make clothing and plastic bottles. Several billion kilograms are produced annually...
(PTA) in the production of polyesters and other current polymers containing an aromatic moiety. Avantium has announced plans to produce 40 ton/year of FDCA monomer at a pilot plant in the second half of 2011.
Synthesis of FDCA
Methods for the synthesis of the FDCA may be divided into four groups:- Dehydration of hexose derivatives
- Oxidation of 2,5-disubstituted furans
- Catalytic conversions of various furan derivatives
- Biological conversion of HMF
Dehydration of hexose derivatives
First group is based on the acid-promoted triple dehydration of aldaricAldaric acid
Aldaric acids are a group of sugar acids, where the terminal hydroxyl groups of the sugars have been replaced by terminal carboxylic acids, and are characterised by the formula HOOC-n-COOH....
(mucic
Mucic acid
Mucic acid, C6H10O8 or HOOC-4-COOH, is obtained by nitric acid oxidation of galactose or galactose-containing compounds like lactose, dulcite, quercite, and most varieties of gum....
) acids. This reaction requires severe conditions (highly concentrated acids, temp > 120 °C, React time > 20h) and all the methods were non-selective with yields < 50%. The process has also been patented by the French company Agro Industrie Recherches et Developements.
Oxidation of 2,5-disubstitured furans
The second class of synthesis routes include the oxidation reactions of various 2,5-disubstituted furans utilizing a variety of inorganic oxidants. Several routes to FDCA via oxidation of hydroxymethylfurfuralHydroxymethylfurfural
Hydroxymethylfurfural , also 5-furfural, is an organic compound derived from dehydration of certain sugars. This yellow low-melting solid is highly water-soluble. The molecule consists of a furan ring, containing both aldehyde and alcohol functional groups...
(HMF) with air over different catalysts have been reported. Oxidation of HMF under strongly alkaline conditions over noble metal catalysts gives almost quantitative formation of FDCA. HMF and methoxymethylfurfural
Methoxymethylfurfural
Methoxymethylfurfural , also 5-methoxymethylfuran-2-carbaldehyde, is an organic compound derived from dehydration of sugars and subsequent etherification with methanol. This colourless liquid is soluble in a wide range of solvents including lower alcohols. The molecule is a derivative of furan,...
(MMF) oxidation was also studied with a series of conventional metal bromide catalysts (Co, Mn, Br) used for the oxidation of para-xylene to terephthalic acid
Terephthalic acid
Terephthalic acid is the organic compound with formula C6H42. This colourless solid is a commodity chemical, used principally as a precursor to the polyester PET, used to make clothing and plastic bottles. Several billion kilograms are produced annually...
. Also, the direct, one pot dehydration and oxidation of fructose to FDCA via intermediate HMF has been investigated with good selectivities, unfortunately this system does not work in water.
Catalytic conversions of various furan derivatives
The third class includes reactions describing the synthesis of FDCA from furfural. Furfural can be oxidized to 2-furoic acid with nitric acidNitric acid
Nitric acid , also known as aqua fortis and spirit of nitre, is a highly corrosive and toxic strong acid.Colorless when pure, older samples tend to acquire a yellow cast due to the accumulation of oxides of nitrogen. If the solution contains more than 86% nitric acid, it is referred to as fuming...
and the latter was subsequently converted to its methyl ester. The ester was then converted via chloromethylation at position 5 to give 5-chloromethylfuroate. The latter was oxidized with nitric acid to form dimethyl 2,5-furandicarboxylate, which, after the alkaline hydrolysis gave FDCA in 50% yield. Andrisano reported that potassium 2-furoate, when heated up to 300 ºC in a nitrogen atmosphere, underwent decarboxylation to furan with simultaneous carboxylation at position 5 to di-potassium 2,5-furandicarboxylate.
Biological conversion of HMF
Recently, the enzyme furfural/HMF oxidoreductase was isolated from the bacterium CupriavidusCupriavidus
Cupriavidus is a genus of bacteria that includes the former genus Wautersia. The cells are short rod-shaped. Furthermore, they are motile by peritrichous flagella, obligat aerobic and chemoorganotroph.-External links:*...
basilensis HMF14. This enzyme is able to convert HMF to FDCA using molecular oxygen. A Pseudomonas putida
Pseudomonas putida
Pseudomonas putida is a gram-negative rod-shaped saprotrophic soil bacterium. Based on 16S rRNA analysis, P. putida has been placed in the P. putida group, to which it lends its name....
strain that was genetically engineered to express this enzyme can completely and selectively convert HMF to FDCA. This biocatalysis
Biocatalysis
Biocatalysis is the use of natural catalysts, such as protein enzymes, to perform chemical transformations on organic compounds. Both enzymes that have been more or less isolated and enzymes still residing inside living cells are employed for this task....
is performed in water, at ambient temperature and pressure, without toxic or polluting chemicals, making it very environmentally friendly.
History
In 1876 Fitting and Heinzelman synthesised FDCA from mucic acid using concentrated hydrobromic acid. The first review by Henry Hill was already published in 1901.Properties and conversions
FDCA is a very stable compound. Its physical properties, such as insolubility in most of common solvents and a very high melting point (it melts at 342 ºC) seem to indicate intermolecular hydrogen bonding. Despite its chemical stability, FDCA undergoes reactions typical for carboxylic acids, such as halogen substitution to give carboxylic dihalides, the di-ester formation and the formation of amides. All these reactions were elaborated at the end of 19th and in the beginning of 20th century. Newer methods have been described by Janda et al., who introduced the synthesis of 2,5-furandicarboxylic dichloride, by the reaction of FDCA with thionyl chloride The synthesis of diethyl ester and dimethyl ester as well as the amidation as well as several other modifications have been reported. The versatility of FDCA is also seen in the number of derivatives available via relatively simple chemical transformations. Selective reduction can lead to partially hydrogenated products, such as 2,5 dihydroxymethylfuran, and fully hydrogenated materials, such as 2,5 bis(hydroxymethyl)tetrahydrofuran (Figure 2).Applications
The most important group of FDCA conversions is undoubtedly the polymerization. The potential applications of furan based building blocks for polymerPolymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
applications has been extensively reviewed by Gandini. Examples of polyesters, polyamides and polyurethanes have been described in literature. The company Avantium claims to have developed a cost effective route to produce FDCA and the derived polyesters via so-called YXY Building Blocks
YXY Building Blocks
YXY is a brand name for furan based building blocks developed by the high throughput company . Furanics have been referred to as “Sleeping Giants” because of their enormous market potential, as evidenced by the research of DuPont and DSM in this area and its position in the US Department of Energy...
. FDCA has also been applied in pharmacology. It was demonstrated that its diethyl ester had a strong anaesthetic action similar to cocaine. Dicalcium 2,5-furandicarboxylate was shown to inhibit the growth of Baccillus megatorium. Screening studies on FDCA-derived anilides showed their important anti-bacterial action. The diacid itself is a strong complexing agent, chelating such ions as: Ca2+, Cu2+ and Pb2+, it is utilized in medicine to remove kidney stones. Interestingly, HMF is metabolized via FDCA in mammals including humans. A very diluted solution of FDCA in tetrahydrofuran is utilized for preparing artificial veins for transplantation. At the beginning of this chapter, it was mentioned that FDCA is a chemically stable compound. This property has been well benefited in industry – FDCA as most of polycarboxylic acids can be an ingredient of fire foams. Such foams help to extinguish fires in a short time caused by polar and non-polar solvents.
Technical barriers
The primary technical barrier in the production and use of FDCA is the development of an effective and selective dehydration process from sugars. The control of sugar dehydration could be a very powerful technology, leading to a wide range of additional, inexpensive building blocks, but it is not yet well understood. Currently, dehydration processes using hydroxymethylfurfuralHydroxymethylfurfural
Hydroxymethylfurfural , also 5-furfural, is an organic compound derived from dehydration of certain sugars. This yellow low-melting solid is highly water-soluble. The molecule consists of a furan ring, containing both aldehyde and alcohol functional groups...
(HMF) as intermediate are generally nonselective, unless, immediately upon their formation, the unstable intermediate products can be transformed into more stable materials such as methoxymethylfurfural
Methoxymethylfurfural
Methoxymethylfurfural , also 5-methoxymethylfuran-2-carbaldehyde, is an organic compound derived from dehydration of sugars and subsequent etherification with methanol. This colourless liquid is soluble in a wide range of solvents including lower alcohols. The molecule is a derivative of furan,...
(MMF). Necessary R&D will include development of selective dehydration systems and catalysts. FDCA formation will require development of cost effective and industrially viable oxidation technology that can operate in concert with the necessary dehydration processes.