Maleic acid

Maleic acid
Names
	Preferred IUPAC name (2Z)-But-2-enedioic acid
	Other names (Z)-Butenedioic acid; cis-Butenedioic acid; Malenic acid; Maleinic acid; Toxilic acid
Identifiers
CAS Number	110-16-7 ;
3D model (JSmol)	Interactive image;
3DMet	B00280;
Beilstein Reference	605762
ChEBI	CHEBI:18300 ;
ChEMBL	ChEMBL539648 ;
ChemSpider	392248 ;
DrugBank	DB04299;
ECHA InfoCard	100.003.403
EC Number	203-742-5;
Gmelin Reference	49854
KEGG	C01384 ;
PubChem CID	444266;
RTECS number	OM9625000;
UNII	91XW058U2C ;
CompTox Dashboard (EPA)	DTXSID8021517 ;
	InChI InChI=1S/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1- Key: VZCYOOQTPOCHFL-UPHRSURJSA-N ; InChI=1/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1- Key: VZCYOOQTPOCHFL-UPHRSURJBG;
	SMILES O=C(O)\C=C/C(=O)O;
Properties
Chemical formula	C4H4O4
Molar mass	116.072 g·mol−1
Appearance	White solid
Density	1.59 g/cm3
Melting point	135 °C (275 °F; 408 K) (decomposes)
Solubility in water	478.8 g/L at 20 C
Acidity (pKa)	pka1 = 1.90; pka2 = 6.07
Magnetic susceptibility (χ)	-49.71·10−6 cm3/mol
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302, H315, H317, H319, H335
Precautionary statements	P261, P264, P270, P271, P272, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P403+P233, P405, P501
NFPA 704 (fire diamond)	3 0 0
Safety data sheet (SDS)	MSDS from J. T. Baker
Related compounds
Related carboxylic acids	fumaric acid; succinic acid; crotonic acid
Related compounds	maleic anhydride; maleimide
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Maleic acid or cis-butenedioic acid is an organic compound that is a dicarboxylic acid, a molecule with two carboxyl groups. Its chemical formula is HO₂CCH=CHCO₂H. Maleic acid is the cis isomer of butenedioic acid, whereas fumaric acid is the trans isomer. Maleic acid is mainly used as a precursor to fumaric acid, and relative to its parent maleic anhydride, which has many applications.^[4]

Physical properties

Maleic acid has a heat of combustion of -1,355 kJ/mol.,^[5] 22.7 kJ/mol higher than that of fumaric acid. Maleic acid is more soluble in water than fumaric acid. The melting point of maleic acid (135 °C) is also much lower than that of fumaric acid (287 °C). As confirmed by X-ray crystallography, maleic acid is planar. Two normal hydrogen bonds are observed, one intramolecular and one intermolecular. Crystallographic analysis shows that the intramolecular hydrogen bond is little affected in the monopotassium salt.^[6]

Production and industrial applications

In industry, maleic acid is derived by hydrolysis of maleic anhydride, the latter being produced by oxidation of benzene or butane.^[4]

Maleic acid is an industrial raw material for the production of glyoxylic acid by ozonolysis.^[7]

Maleic acid may be used to form acid addition salts with drugs to make them more stable, such as indacaterol maleate.

Maleic acid is also used as an adhesion promoter for different substrates, such as nylon and zinc coated metals e.g galvanized steel, in methyl methacrylate based adhesives.

Isomerization to fumaric acid

The major industrial use of maleic acid is its conversion to fumaric acid. This conversion, an isomerization, is catalysed by a variety of reagents, such as mineral acids and thiourea. Again, the large difference in water solubility makes fumaric acid purification easy.

The isomerization is a popular topic in schools. Maleic acid and fumaric acid do not spontaneously interconvert because rotation around a carbon carbon double bond is not energetically favourable. However, conversion of the cis isomer into the trans isomer is possible by photolysis in the presence of a small amount of bromine.^[8] Light converts elemental bromine into a bromine radical, which attacks the alkene in a radical addition reaction to a bromo-alkane radical; and now single bond rotation is possible. The bromine radicals recombine and fumaric acid is formed. In another method (used as a classroom demonstration), maleic acid is transformed into fumaric acid through the process of heating the maleic acid in hydrochloric acid solution. Reversible addition (of H⁺) leads to free rotation about the central C-C bond and formation of the more stable and less soluble fumaric acid.

Some bacteria produce the enzyme maleate isomerase, which is used by bacteria in nicotinate metabolism. This enzyme catalyses isomerization between fumarate and maleate.

Other reactions

Although not practised commercially, maleic acid can be converted into maleic anhydride by dehydration, to malic acid by hydration, and to succinic acid by hydrogenation (ethanol / palladium on carbon).^[9] It reacts with thionyl chloride or phosphorus pentachloride to give the maleic acid chloride (it is not possible to isolate the mono acid chloride). Maleic acid, being electrophilic, participates as a dienophile in many Diels-Alder reactions.

Maleates

The maleate ion is the ionized form of maleic acid. The maleate ion is useful in biochemistry as an inhibitor of transaminase reactions. Maleic acid esters are also called maleates, for instance dimethyl maleate.

Use in pharmaceutical drugs

Many drugs that contain amines are provided as the maleate acid salt, e.g. carfenazine, chlorpheniramine, pyrilamine, methylergonovine, and thiethylperazine.^[10]

References

^ Budavari, Susan, ed. (1996), The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (12th ed.), Merck, ISBN 0911910123
^ ^a ^b Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health
^ CRC Handbook of Chemistry and Physics, 73rd ed.; CRC Press: Boca Raton, Florida., 1993
^ ^a ^b Lohbeck, Kurt; Haferkorn, Herbert; Fuhrmann, Werner; Fedtke, Norbert (2000). "Maleic and Fumaric Acids". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a16_053. ISBN 9783527303854.
^ Maleic Anhydride, Maleic Acid, and Fumaric Acid Archived 2013-11-02 at the Wayback Machine, Huntsman Petrochemical Corporation
^ M. N. G James, G. J. B Williams (1974). "A Refinement of the Crystal Structure of Maleic Acid". Acta Crystallographica. B30 (5) (5): 1249–1275. Bibcode:1974AcCrB..30.1249J. doi:10.1107/S0567740874004626.
^ DSM glyoxylic acid production Archived 2005-11-30 at the Wayback Machine
^ Light isomerization experiment Archived 2005-11-27 at the Wayback Machine (from the University of Regensburg, with video)
^ Kwesi Amoa (2007). "Catalytic Hydrogenation of Maleic Acid at Moderate Pressures A Laboratory Demonstration". Journal of Chemical Education. 84 (12): 1948. Bibcode:2007JChEd..84.1948A. doi:10.1021/ed084p1948.
^ "NCATS Inxight Drugs — Fumaric acid". drugs.ncats.io. Retrieved 2023-11-10.

External links

[Merck-1] Budavari, Susan, ed. (1996), The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (12th ed.), Merck, ISBN 0911910123

[GESTIS-2] Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health

[3] CRC Handbook of Chemistry and Physics, 73rd ed.; CRC Press: Boca Raton, Florida., 1993

[Ullmann-4] Lohbeck, Kurt; Haferkorn, Herbert; Fuhrmann, Werner; Fedtke, Norbert (2000). "Maleic and Fumaric Acids". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a16_053. ISBN 9783527303854.

[5] Maleic Anhydride, Maleic Acid, and Fumaric Acid Archived 2013-11-02 at the Wayback Machine, Huntsman Petrochemical Corporation

[6] M. N. G James, G. J. B Williams (1974). "A Refinement of the Crystal Structure of Maleic Acid". Acta Crystallographica. B30 (5) (5): 1249–1275. Bibcode:1974AcCrB..30.1249J. doi:10.1107/S0567740874004626.

[7] DSM glyoxylic acid production Archived 2005-11-30 at the Wayback Machine

[8] Light isomerization experiment Archived 2005-11-27 at the Wayback Machine (from the University of Regensburg, with video)

[9] Kwesi Amoa (2007). "Catalytic Hydrogenation of Maleic Acid at Moderate Pressures A Laboratory Demonstration". Journal of Chemical Education. 84 (12): 1948. Bibcode:2007JChEd..84.1948A. doi:10.1021/ed084p1948.

[10] "NCATS Inxight Drugs — Fumaric acid". drugs.ncats.io. Retrieved 2023-11-10.

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