{{Short description|Organic compound}} {{Use dmy dates|date=January 2026}} {{chembox | Watchedfields = changed | verifiedrevid = 443828437 | Name = Fumaric acid | ImageFile = Fumarsäure.svg | ImageClass = skin-invert | ImageSize = | ImageName = Skeletal formula of fumaric acid | ImageFile1 = Fumaric-acid-3D-balls.png | ImageClass1 = bg-transparent | ImageSize1 = | ImageName1 = Ball-and-stick model of the fumaric acid molecule | PIN = (2''E'')-But-2-enedioic acid<!-- Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013 (Blue Book) --> | OtherNames = {{ubl | Fumaric acid | ''trans''-1,2-Ethylenedicarboxylic acid | 2-Butenedioic acid | ''trans''-Butenedioic acid | Allomaleic acid | Boletic acid | Donitic acid | Lichenic acid }} | Section1 = {{Chembox Identifiers | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB04299 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 18012 | SMILES = C(=C/C(=O)O)\C(=O)O | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 10197150 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 503160 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 88XHZ13131 | Gmelin = 49855 | Beilstein = 605763 | PubChem = 444972 | RTECS = LS9625000 | UNNumber = 9126 | InChI = 1/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+ | InChIKey = VZCYOOQTPOCHFL-OWOJBTEDBF | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+ | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VZCYOOQTPOCHFL-OWOJBTEDSA-N | CASNo_Ref = {{cascite|correct|CAS}} | CASNo = 110-17-8 | EINECS = 203-743-0 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C00122 }} | Section2 = {{Chembox Properties | C=4 | H=4 | O=4 | Dipole = non zero | Appearance = White solid | Density = 1.635{{nbsp}}g/cm<sup>3</sup> | Solubility = 6.3{{nbsp}}g/L at 25{{nbsp}}°C<ref>{{GESTIS|ZVG=33440}}</ref> | SolubleOther = | Solvent = Ethanol | MeltingPtC = 287 | MeltingPt_notes = (decomposes)<ref> {{cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/fumaric_acid|title=Fumaric acid | last=Pubchem | website=pubchem.ncbi.nlm.nih.gov }}</ref> | pKa = {{nowrap|p''k''<sub>a1</sub> {{=}} 3.03}}, {{nowrap|p''k''<sub>a2</sub> {{=}} 4.44}} (15{{nbsp}}°C, cis isomer) | MagSus = −49.11·10<sup>−6</sup>{{nbsp}}cm<sup>3</sup>/mol }} | Section7 = {{Chembox Hazards | NFPA-H = 2 | NFPA-F = 1 | NFPA-R = 0 | NFPA-S = | AutoignitionPtC = 375 | GHSPictograms = {{GHS07}} | GHSSignalWord = Warning | HPhrases = {{H-phrases|319}} | PPhrases = {{P-phrases|264|280|305+351+338|313}} }} | Section6 = {{Chembox Pharmacology | ATCCode_prefix = D05 | ATCCode_suffix = AX01 }} | Section8 = {{Chembox Related | OtherFunction_label = carboxylic acids | OtherFunction = {{ubl | Maleic acid | Succinic acid | Crotonic acid }} | OtherCompounds = {{ubl | Fumaryl chloride | Fumaronitrile | Dimethyl fumarate | Ammonium fumarate | Iron(II) fumarate }} }} }}

'''Fumaric acid''' or '''''trans''-butenedioic acid''' is an organic compound with the formula HO<sub>2</sub>CCH=CHCO<sub>2</sub>H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297.<ref name=Ullmann>{{cite book|doi=10.1002/14356007.a16_053|chapter=Maleic and Fumaric Acids|title=Ullmann's Encyclopedia of Industrial Chemistry|year=2000|last1=Lohbeck|first1=Kurt|last2=Haferkorn|first2=Herbert|last3=Fuhrmann|first3=Werner|last4=Fedtke|first4=Norbert|isbn=3-527-30673-0}} </ref> The salts and esters are known as '''fumarates'''. Fumarate can also refer to the {{chem|C|4|H|2|O|4|2−}} ion (in solution). Fumaric acid is the ''trans'' isomer of butenedioic acid, while maleic acid is the ''cis'' isomer.

==Biosynthesis and occurrence== It is produced in eukaryotic organisms from succinate in complex 2 of the electron transport chain via the enzyme succinate dehydrogenase.

Fumaric acid is found in fumitory (''Fumaria officinalis''), bolete mushrooms (specifically ''Boletus fomentarius var. pseudo-igniarius''), lichen, and Iceland moss.

Fumarate is an intermediate in the citric acid cycle used by cells to produce energy in the form of adenosine triphosphate (ATP) from food. It is formed by the oxidation of succinate by the enzyme succinate dehydrogenase. Fumarate is then converted by the enzyme fumarase to malate.

Human skin naturally produces fumaric acid when exposed to sunlight.<ref>[https://books.google.com/books?id=tWJLUWT06BEC&dq=Human+skin+fumaric+acid&pg=PA159 Active Ingredients Used in Cosmetics: Safety Survey], Council of Europe. Committee of Experts on Cosmetic Products</ref><ref>{{Cite news|url=http://healthyeating.sfgate.com/fumaric-acid-foods-12220.html|archive-url=https://web.archive.org/web/20141004041648/http://healthyeating.sfgate.com/fumaric-acid-foods-12220.html|url-status=dead|archive-date=4 October 2014|title=Fumaric Acid Foods|access-date=22 April 2018|language=en}}</ref>

Fumarate is also a product of the urea cycle.

{{TCACycle_WP78|highlight=Fumaric_acid}}

==Uses==

===Food=== Fumaric acid has been used as a food acidulant since 1946. It is approved for use as a food additive in the EU,<ref>UK Food Standards Agency: {{cite web |url=http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |title=Current EU approved additives and their E Numbers |access-date=27 October 2011}}</ref> USA<ref>US Food and Drug Administration: {{cite web |url=https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm#ftnT |archive-url=https://web.archive.org/web/20100108135705/http://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm#ftnT |url-status=dead |archive-date=8 January 2010 |title=Listing of Food Additives Status Part II |website=Food and Drug Administration |access-date=27 October 2011}}</ref> and Australia and New Zealand.<ref>Australia New Zealand Food Standards Code{{cite web |url=http://www.comlaw.gov.au/Details/F2011C00827 |title=Standard 1.2.4 - Labelling of ingredients |date=8 September 2011 |access-date=27 October 2011}}</ref> As a food additive, it is used as an acidity regulator and can be denoted by the E number E297. It is generally used in beverages and baking powders for which requirements are placed on purity. Fumaric acid is used in the making of wheat tortillas as a food preservative and as the acid in leavening.<ref>{{Cite news|url=https://thechemco.com/chemical/fumaric-acid/|title=Fumaric Acid - The Chemical Company|work=The Chemical Company|access-date=22 April 2018|language=en-US}}</ref> It is generally used as a substitute for tartaric acid and occasionally in place of citric acid, at a rate of 1&nbsp;g of fumaric acid to every ~1.5&nbsp;g of citric acid, in order to add sourness, similarly to the way malic acid is used. As well as being a component of some artificial vinegar flavors, such as "Salt and Vinegar" flavored potato chips,<ref>{{cite web|url=http://www.seriouseats.com/2012/09/the-best-salt-and-vinegar-chips-tasting-brands-most-acidic.html|title=The Science Behind Salt and Vinegar Chips|first=Serious|last=Eats|website=www.seriouseats.com}}</ref> it is also used as a coagulant in stove-top pudding mixes.

The European Commission Scientific Committee on Animal Nutrition, part of DG Health, found in 2014 that fumaric acid is "practically non-toxic" but high doses are probably nephrotoxic after long-term use.<ref name=ecscfa>{{cite web |author=European Commission |url=http://ec.europa.eu/food/fs/sc/scan/out112_en.pdf |title=European Commission Report of the Scientific Committee on Animal Nutrition on the Safety of Fumaric Acid |date=22 January 2003 |access-date=7 March 2014}}</ref>

===Medicine=== Fumaric acid was developed as a medicine to treat the autoimmune condition psoriasis in the 1950s in Germany as a tablet containing 3 esters, primarily dimethyl fumarate, and marketed as Fumaderm by Biogen Idec in Europe. Biogen would later go on to develop the main ester, dimethyl fumarate, as a treatment for multiple sclerosis.

In patients with relapsing-remitting multiple sclerosis, the ester dimethyl fumarate (BG-12, Biogen) significantly reduced relapse and disability progression in a phase 3 trial. It activates the Nrf2 antioxidant response pathway, the primary cellular defense against the cytotoxic effects of oxidative stress.<ref name="Gold">{{cite journal| title = Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis| journal = N Engl J Med | date = 20 September 2012|author1=Gold R. |author2=Kappos L. |author3=Arnold D.L. | s2cid = 6614191 | volume =367| issue =12| pages =1098–1107| doi =10.1056/NEJMoa1114287| pmid =22992073| display-authors=etal| doi-access =free| hdl =2078.1/124401| hdl-access =free}}</ref>

===Other uses=== Fumaric acid is used in the manufacture of polyester resins and polyhydric alcohols and as a mordant for dyes.

Fumaric acid can be used to make 6-methylcoumarin.<ref>{{cite journal | last1=Thompson | first1=T. J. | last2=Edee | first2=R. Herbert | title=Preparation of 6-Methylcoumarin and ITS Derivatives | journal=Journal of the American Chemical Society | volume=47 | issue=10 | date=1925 | issn=0002-7863 | doi=10.1021/ja01687a019 | pages=2556–2559 | bibcode=1925JAChS..47.2556T }}</ref>

When fumaric acid is added to their feed, lambs produce up to 70% less methane during digestion.<ref>{{Cite news | url = https://m.phys.org/news/2008-03-scientists-cow-flatulence.html | title = Scientists look to cut cow flatulence | date = 21 March 2008 | publisher = phys.org }}</ref> ==Synthesis== Fumaric acid is produced based on catalytic isomerisation of maleic acid in aqueous solutions at low p''H''. It precipitates from the reaction solution. Maleic acid is accessible in large volumes as a hydrolysis product of maleic anhydride, produced by catalytic oxidation of benzene or butane.<ref name=Ullmann/> ===Historic and laboratory routes=== Fumaric acid was first prepared from succinic acid.<ref>Volhard, J. "Darstellung von Maleïnsäureanhydrid" Justus Liebig's Annalen der Chemie 1892, volume 268, page 255-6. {{doi|10.1002/jlac.18922680108}}</ref> A traditional synthesis involves oxidation of furfural (from the processing of maize) using chlorate in the presence of a vanadium-based catalyst.<ref>{{cite journal|doi=10.15227/orgsyn.011.0046 |title=Fumaric Acid |journal=Organic Syntheses |date=1931 |volume=11 |page=46|author=Nicholas A. Milas }}</ref>

==Reactions== The chemical properties of fumaric acid can be anticipated from its component functional groups. This weak acid forms a diester, it undergoes bromination across the double bond,<ref>{{cite journal |doi=10.15227/orgsyn.018.0017 |title=α,β-Dibromosuccinic Acid |journal=Organic Syntheses |date=1938 |volume=18 |page=17|author=Herbert S. Rhinesmith }}</ref> and it is a good dienophile. <!--Fumaric acid does not combust in a bomb calorimeter under conditions where maleic acid deflagrates smoothly. For teaching experiments designed to measure the difference in energy between the cis- and trans- isomers, a measured quantity of carbon can be ground with the subject compound and the enthalpy of combustion computed by difference.-->

==Safety== The oral {{LD50}} is 10 g/kg.<ref name=Ullmann/>

==See also== *Citric acid cycle (TCA cycle) *Fumarate reductase *Photosynthesis *Maleic acid, the ''cis'' isomer of fumaric acid *Succinic acid

==References== <references/>

==External links== *[http://www.inchem.org/documents/icsc/icsc/eics1173.htm International Chemical Safety Card 1173]

{{citric acid cycle}} {{Urea cycle}} {{Antipsoriatics}} {{Amino acid metabolism intermediates}}

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Category:Dicarboxylic acids Category:Food additives Category:Food acidity regulators Category:Fumarates Category:Urea cycle Category:Citric acid cycle compounds Category:Nephrotoxins Category:E-number additives Category:Alkene derivatives Category:Metabolic intermediates Category:Biomolecules Category:Carboxylic acid-based monomers