Fumaric acid, also known as trans-butenedioic acid, has broad applications in diverse industrial settings due to its exceptional physicochemical characteristics. It is a relatively strong acid that occurs naturally in numerous plants and fruits and is commercially produced through the catalytic isomerization of maleic acid. This white crystalline compound is distinguishable by its fruity aroma and exceptional thermal stability. In recent years, the multi-faceted usage of fumaric acid has gained considerable attention in several industries, ranging from food and beverages to polymers and resins, contributing immensely to the material and economic advancements in the 21st century.
What is Fumaric Acid?
Fumaric acid is an organic compound with the chemical formula HO₂CCH=CHCO₂H. It is classified as a dicarboxylic acid due to its two carboxyl (COOH) functional groups. The compound derives its name from Fumaria officinalis, a flowering plant from which it was first isolated. In its pure form, fumaric acid appears as a white & odorless crystalline powder.
It is non-toxic and has a sour taste. Slight traces of fumaric acid are naturally found in certain fruits and vegetables, including grapes, apples, and mushrooms. It contributes to the tartness and acidity of these foods. It is also commonly used as a food additive in the food and beverage industry. It is an acidulant, pH regulator, and flavor enhancer in various products.
Source: Wikipedia
Fumaric acid’s potential extends from the food and beverage industry to pharmaceuticals, polymer, resin production, and renewable energy production. The widespread usage of fumaric acid is a testament to its versatility and adaptability in various sectors.
How is Fumaric Acid Produced?
Fumaric acid is found naturally in several sources:
| Fumitory (Fumaria officinalis) | This flowering plant is a natural source of fumaric acid. This compound can be isolated from various plant parts, including the leaves and stems. |
| Bolete mushrooms | Fumaric acid can be found specifically in Boletus fomentarius, and has been reported to contain fumaric acid. These mushrooms belong to the fungal family Boletaceae and are sometimes used for medicinal purposes. |
| Lichen | Lichen is a symbiotic organism composed of a fungus and algae or a fungus and cyanobacteria. While the species and genera of lichen that contain fumaric acid may vary, it has been reported as one of the organic acids in some lichen species. |
| Iceland moss (Cetraria islandica) | Iceland moss, a lichen species commonly found in cold regions, is another natural source of fumaric acid. This lichen has a long history of traditional medicinal use and contains various bioactive compounds, including fumaric acid. |
| Fumaric acid can be explicitly found in Boletus fomentarius, and has been reported to contain fumaric acid. These mushrooms belong to the fungal family Boletaceae and are sometimes used for medicinal purposes. | Fumaric acid can be produced in eukaryotic organisms through a metabolic pathway involving succinate in Complex II of the electron transport chain. This process occurs via the enzyme succinate dehydrogenase, also known as Complex II of the respiratory chain. |
Industrial Methods of Production
Chemical Synthesis
The maleic acid-containing wash water is collected as a byproduct of producing maleic anhydride or phthalic anhydride. The maleic acid concentration in the wash water should be at least 30%. The maleic acid is subjected to thermal or catalytic isomerization. In thermal isomerization, the maleic acid is heated to a high temperature, typically above its melting point, to induce the isomerization reaction. Catalytic isomerization involves using a catalyst, such as sulfuric acid or an alkali metal bisulfite, to facilitate the conversion. Maleic acid is converted almost quantitatively into fumaric acid during the isomerization process. Fumaric acid is sparingly soluble in water and precipitates out of solution. The precipitated fumaric acid is separated from the reaction mixture by filtration. The filtrate may contain impurities and unreacted maleic acid, which can be recycled back into the process for further conversion. The collected fumaric acid is washed and dried to obtain the final product.
Fermentation
Fumaric acid can be produced through microbial fermentation using specific strains of fungi like Rhizopus arrhizus. The microorganism is cultivated in a suitable growth medium. The medium typically contains carbon sources like glucose, sucrose, other carbohydrates, and essential nutrients required for microbial growth. The microorganism is inoculated into a fermentation vessel containing the growth medium. The fermentation conditions, such as temperature, pH, oxygen availability, and agitation, are optimized to promote fumaric acid production.
Bioconversion
Fumaric acid can also be produced by bioconversion using genetically modified microorganisms. For example, genetically engineered Escherichia coli (E. coli) strains have been developed to produce fumaric acid from glucose or other sugars. These strains are engineered to express the enzymes necessary for fumaric acid synthesis.
Uses and Applications of Fumaric Acid in Industry
Food and Beverage Industry
Fumaric acid is an acidulant and flavoring agent in the food and beverage industry. It is commonly used to produce carbonated beverages, fruit juices, candies, baked goods, and gelatin desserts.
Pharmaceutical Industry
Fumaric acid is used in the pharmaceutical industry for various purposes. It is essential to produce antihistamines, antimalarials, and analgesics. Fumaric acid esters, such as dimethyl fumarate, have also been used to treat psoriasis, a chronic skin condition. These esters are administered orally or topically to help alleviate symptoms and reduce inflammation associated with psoriasis.
Effervescent Tablets
Fumaric acid is used as the acid component in effervescent tablet formulations. Fumaric acid’s low solubility may limit its use in effervescent tablets, but it can still contribute to the desired effervescence when combined with other ingredients. Fumaric acid has also been studied as a lubricant for effervescent tablets. Lubricants are added to tablet formulations to reduce friction during manufacturing, preventing sticking or adhesion of the tablet material to the equipment.
Chelating Agent
Fumaric acid can act as a chelating agent in pharmaceutical formulations and exhibits synergistic effects when combined with other true antioxidants, which helps prevent oxidation and improve the stability of formulations.
Pelletized Formulations
Fumaric acid has been used to design novel pelletized formulations manufactured by extrusion-spheronization. It aids in spheronization, transforming a powder mixture into spherical pellets. Fumaric acid contributes to the formation of fine pellets with desirable characteristics. It has also been investigated as an alternative filler to lactose in pellet formulations.
Manufacture of Polyester Resins
Fumaric acid is utilized in the production of polyester resins, which are widely used in various industries, including automotive, construction, and packaging. Polyester resins are a class of thermosetting polymers with excellent mechanical properties, chemical resistance, and durability. Fumaric acid is one of the critical raw materials in the synthesis of unsaturated polyester resins. During curing, it reacts with polyhydric alcohols (such as glycols) and styrene monomers to form a crosslinked polymer network.
Mordant for Dyes
Fumaric acid can act as a mordant in the dyeing process. A mordant is a substance that helps fix or bind dyes to fabrics or other materials, improving their colorfastness and adherence. Fumaric acid can form complexes with certain dyes, enhancing their affinity for the substrate and improving the color intensity and stability of the dyed material. It is mainly used as a mordant for textiles’ natural dyes and wool and silk fibers dyeing.
Paper Sizing
Fumaric acid is used in paper manufacturing as a component of paper sizing agents. It helps to improve the surface properties and printability of the paper, making it more resistant to water penetration and enhancing its strength.
Printer Toner
Fumaric acid is used in producing printer toner for laser printers and photocopiers. It contributes to developing a fine, uniform powder that adheres to the paper during printing.
Properties of Fumaric Acid
| Chemical formula | HO2CCH=CHCO2H |
| Molecular weight (g/mol) | 116.07 |
| Appearance | White solid crystalline powder |
| Odor | Odor |
| Boiling point (°C at 1.7 mmHg) | 165 |
| Melting point (°C) | 287 – 305 |
| Refractive index (at 20°C) | 1.488 – 1.526 |
| Density (g/cm³) | 1.635 |
| Vapor Pressure (at 25°C) (mmHg) | 1.54 x 10-4 |
| Solubility | Sparingly soluble in water but exhibits better solubility in organic solvents such as ethanol, methanol, etc. |
| Acidity (pKa) | pka1 = 3.03, pka2 = 4.44 |
| Storage conditions | Fumaric acid should be stored in a cool and dry environment. Avoid exposure to excessive heat or temperature fluctuations, as they can impact the stability of the compound. |
Fumaric Acid Derivatives
Fumaric Acid Esters
Various fumaric acid esters can be synthesized, such as Dimethyl fumarate (DMF) and Monomethyl fumarate (MMF). Dimethyl fumarate is used as an active pharmaceutical ingredient in treating certain skin disorders, such as psoriasis and dermatitis. DMF has immunomodulatory and anti-inflammatory properties.
Monomethyl fumarate is another ester derivative of fumaric acid. It is primarily used as an intermediate in the production of DMF. MMF has also been investigated for its potential therapeutic applications, including its antioxidant and anti-inflammatory properties.
Fumaric Acid Diamides
Fumaric acid diamides, such as N, N’-dimethylfumaramide, and N, N’-diphenylfumaramide, are derivatives studied for their potential as organic catalysts and ligands in metal coordination chemistry.
Fumaric Acid Salts
Fumaric acid can form salts by reacting with various bases. For example, sodium and potassium fumarate are commonly used in the food industry as pH regulators, acidulants, and flavor enhancers.
Safety & Regulatory Considerations
The extensive industrial applications of fumaric acid necessitate a comprehensive understanding of its safety implications and regulatory guidelines to ensure its responsible use.
| FDA Regulations | 21 CFR 172.350 – 72.350 Fumaric acid and salts of fumaric acid. Fumaric acid and its calcium, ferrous, magnesium, potassium, and sodium salts may be safely used in food per the following prescribed conditions(1) fumaric acid contains a minimum of 99.5 percent by weight of fumaric acid, calculated on the anhydrous basis. (2) The calcium, magnesium, potassium, and sodium salts contain a minimum of 99 percent by weight of the respective salt, calculated on an anhydrous basis. Ferrous fumarate has a minimum of 31.3 percent total iron and not more than 2 percent ferric iron. (b) Except ferrous fumarate, fumaric acid, and the named salts are used singly or in combination in food at a level not more than the amount reasonably required to accomplish the intended effect. (c) Ferrous fumarate is used as a source of iron in foods for particular dietary use when the use is consistent with good nutrition practice. |
| Other Regulations | Listed under the code E297 in the European Union’s food additive regulations. |
Safety & Toxicity of Fumaric Acid
Regulatory authorities generally recognize fumaric acid as safe (GRAS) when used per good manufacturing practices. Fumaric acid is also usually considered safe for consumption. However, excessive ingestion may cause gastrointestinal disturbances. Avoid prolonged or repeated skin contact, as fumaric acid may cause irritation or dermatitis in sensitive individuals. Inhalation of fumaric acid dust or vapor should be avoided, as it may cause respiratory irritation. If accidental exposure occurs, remove contaminated clothing and wash affected areas thoroughly with soap and water. Seek medical attention if necessary. Fumaric acid is not flammable but may emit toxic fumes when heated to decomposition. Keep the compound away from ignition sources and potent oxidizing agents. Use suitable extinguishing media, such as carbon dioxide (CO2) or foam, in a fire involving fumaric acid.
Toxicity Information
While fumaric acid is generally considered safe for consumption in average amounts, high doses or long-term use of fumaric acid have been associated with potential nephrotoxicity, meaning it may have adverse effects on the kidneys.
| Acute Toxicity | Fumaric acid is considered to have low acute toxicity. It is not known to cause significant adverse effects when ingested, inhaled, or in contact with the skin in regular use. However, consuming large amounts or exposure to high concentrations may cause gastrointestinal disturbances. |
| Skin Irritation | Fumaric acid may cause skin irritation, particularly in individuals with sensitive skin. Prolonged or repeated contact with fumaric acid powder or solutions may lead to skin redness, itching, or dermatitis. Appropriate protective equipment, such as gloves, should be used when handling fumaric acid to minimize skin contact. |
Identification Numbers
| Chemical Name | Fumaric Acid |
| CAS Number | 110-17-8 |
| EC Number | 203-743-0 |
| DOT Number | UN 926 |
Fun Facts About Fumaric Acid
- Fumaric and maleic acids were discovered in 1817 by Braconnet and independently by Vauquelin during the dry distillation of malic acid.
- In healthy individuals, fumaric acid forms in the skin when exposed to sunlight.
- Fumarate is a product of the citric acid and urea cycle.
- Research studies have shown that adding fumaric acid to the feed of lambs can help reduce methane emissions by up to 70% during digestion.
Additional Resources
- Sciencedirect – Organic and Fatty Acid Production, Microbial
- MDPI – Biofilm Formation and Its Influence on the Survival of Free-Living Helicobacter pylori
- Springer – Biofilm: A Hot Spot for Emerging Infectious Diseases
- Lohbeck K, et al; Ullmann’s Encyclopedia of Industrial Chemistry 7th ed. (2008). NY, NY: John Wiley & Sons; Maleic and Fumaric Acids. Online Posting Date: June 15, 2000.
