Fumaric acid

Structural formula
General
Surname	Fumaric acid
other names	trans -butenedioic acid; trans -ethylene dicarboxylic acid; ( E ) -butenic acid ( IUPAC ); FUMARIC ACID ( INCI ) ; E 279 ;
Molecular formula	C 4 H 4 O 4
Brief description	white, odorless crystals
External identifiers / databases
EC number	203-743-0
ECHA InfoCard	100.003.404
PubChem	444972
DrugBank	DB01677
Wikidata	Q139857
Drug information
ATC code	D05 AX01
properties
Molar mass	116.07 g mol −1
Physical state	firmly
density	1.64 g cm −3 (20 ° C)
Melting point	287 ° C (closed capillary)
Sublimation point	200 ° C
Vapor pressure	<0.1 Pa (20 ° C)
pK s value	pK s 1 = 3.0; 3.02; pK s 2 = 4.5; 4.38;
solubility	poor in water (4.9 g l −1 at 20 ° C)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling from Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary Caution
H and P phrases	H: 319
	P: 280-305 + 351 + 338-337 + 313
Toxicological data	9300 mg kg −1 ( LD 50 , rat , oral ) ; 212 mg l −1 ( EC 50 , crustaceans , 48 h , median value) ;
Thermodynamic properties
ΔH f 0	−811.7 kJ / mol
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fumaric acid is the common name of a naturally occurring organic chemical substance. It is an unsaturated dicarboxylic acid with the IUPAC name trans -butenedioic acid , also called trans -ethylene dicarboxylic acid. Their salts are called fumarates . The isomeric cis form is called maleic acid .

history

In 1937 Albert Szent-Györgyi received the Nobel Prize for Medicine for his biochemical work, including on fumaric acid.

Occurrence and manufacture

Fumaric acid is found in large quantities in various plants, fungi and lichens. It got its name from common earth smoke (Fumaria officinalis) , which contains large amounts of acid.

Common earth smoke ( Fumaria officinalis )

Fumaric acid is produced synthetically from maleic acid by isomerization . This is done by heating to over 150 ° C, by UV radiation or catalytically in an aqueous solution.

It arises in all organisms (e.g. in several genera of the Mucorales ) on different biochemical metabolic pathways:

as an intermediate in the citric acid cycle through oxidation of succinic acid in the presence of the enzyme succinate dehydrogenase (an oxidoreductase )

in the urea cycle by splitting arginine succinic acid

in the biosynthesis of purine nucleotides (from aspartate )

in nucleotide metabolism in the representation of adenosine monophosphate from inosine monophosphate

by hydrolytic breakdown of amino acids such as phenylalanine and tyrosine

by deamination of aspartic acid

properties

Fumaric acid does not have a melting point under normal pressure, but sublimes from around 200 ° C. At room temperature it forms white, almost odorless, flammable crystals. The aqueous solution is strongly acidic: 1 liter of water with 4.9 g of fumaric acid dissolved in it has a pH value of 2.1. The biprotonic acid has a pK _{s ₁} of 3.0 and a pK _{s ₂} of 4.5. The compound dissolves only slightly in water. At 15.5 ° C, only 0.428 g of fumaric acid dissolves in 100 g of water; at 100 ° C, the solubility increases to 9.97 g per 100 g of water. The flash point of fumaric acid is 273 ° C, the decomposition temperature is> 350 ° C and the ignition temperature is 375 ° C.

use

Fumaric acid is approved as a food additive E 297 and is used as an acidulant . In synthetic chemistry it is used for the production of polyester . In biotechnology, ammonia is stereoselectively attached to the carbon-carbon double bond, and enzyme-catalyzed L - aspartic acid is formed . Many pharmaceutically active substances - especially those containing amino groups - are administered as salts of fumaric acid. Fumaric acid esters such as dimethyl fumarate and monoethyl fumarate are used to treat psoriasis and, since March 2013, relapsing-remitting multiple sclerosis .

In pig rearing, fumaric acid is used as a feed additive for piglets to prevent coli-related infections by keeping the pH value in the intestine sufficiently low.

It has been proven that fumaric acid as a feed additive in lambs can reduce their methane production by up to 70%.

Fumaric acid is also used in cosmetic products. It is used there as a buffer substance and stabilizes the pH value of the cosmetic.

Web links

Commons : Fumaric Acid - Collection of Pictures, Videos and Audio Files

Individual evidence

↑ Entry on FUMARIC ACID in the CosIng database of the EU Commission, accessed on December 28, 2019.
↑ Entry on E 279: undefined in the European database on food additives, accessed on August 6, 2020.
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Entry on fumaric acid in the GESTIS substance database of the IFA , accessed on December 16, 2019(JavaScript required) .
↑ ^a ^b ^c A. Reichert: Potentiometric titrations in theory and practice. ( Memento from April 1, 2007 in the Internet Archive )
↑ ^a ^b chem.wisc.edu: pKa Data , Compiled by R. Williams (PDF, 78 kB).
↑ Entry on Fumaric acid in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Standard Thermodynamic Properties of Chemical Substances, pp. 5-25.
↑ K. Lohbeck, H. Haferkorn, W. Fuhrmann, N. Fedke: Maleic and Fumaric Acids. In: Ullmann's Encyclopedia of Industrial Chemistry. Wiley-VCH Verlag, Weinheim 2012. doi : 10.1002 / 14356007.a16_053 .
↑ German Multiple Sclerosis Society: Green light for fumaric acid and teriflunomide for the treatment of relapsing multiple sclerosis. ( Memento from May 25, 2013 in the Internet Archive ) March 23, 2013.
↑ Scientists look to cut cow flatulence m.phys.org, March 21, 2008, accessed November 30, 2019
↑ Marina Bährle-Rapp: Aleurites moluccana . In: Springer Lexicon Cosmetics and Body Care . 4th edition. Springer, 2012, ISBN 978-3-642-24688-3 , pp. 221 ( limited preview in Google Book search).

[CosIng-1] Entry on FUMARIC ACID in the CosIng database of the EU Commission, accessed on December 28, 2019.

[E-Nummer279-2] Entry on E 279: undefined in the European database on food additives, accessed on August 6, 2020.

[GESTIS-3] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Entry on fumaric acid in the GESTIS substance database of the IFA , accessed on December 16, 2019(JavaScript required) .

[Reichert-4] A. Reichert: Potentiometric titrations in theory and practice. ( Memento from April 1, 2007 in the Internet Archive )

[Williams-5] .wisc.edu: pKa Data , Compiled by R. Williams (PDF, 78 kB).

[CLP_100.003.404-6] Entry on Fumaric acid in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .

[CRC90_5_25-7] David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Standard Thermodynamic Properties of Chemical Substances, pp. 5-25.

[Ullmann-8] K. Lohbeck, H. Haferkorn, W. Fuhrmann, N. Fedke: Maleic and Fumaric Acids. In: Ullmann's Encyclopedia of Industrial Chemistry. Wiley-VCH Verlag, Weinheim 2012. doi : 10.1002 / 14356007.a16_053 .

[9] German Multiple Sclerosis Society: Green light for fumaric acid and teriflunomide for the treatment of relapsing multiple sclerosis. ( Memento from May 25, 2013 in the Internet Archive ) March 23, 2013.

[10] Scientists look to cut cow flatulence m.phys.org, March 21, 2008, accessed November 30, 2019

[Springer-11] Marina Bährle-Rapp: Aleurites moluccana . In: Springer Lexicon Cosmetics and Body Care . 4th edition. Springer, 2012, ISBN 978-3-642-24688-3 , pp. 221 ( limited preview in Google Book search).