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Malonic acid is a dicarboxylic acid with structure CH2(COOH)2. The ionized form of malonic acid, as well as its esters and salts, are known as malonates. For example, diethyl malonate is malonic acid's diethyl ester. The name originates from the Greek word μᾶλον (malon) meaning 'apple'.
HistoryEdit
Malonic acid<ref name=EB1911>Template:Cite EB1911</ref> is a naturally occurring substance found in many fruits and vegetables.<ref name="gsc">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> There is a suggestion that citrus fruits produced in organic farming contain higher levels of malonic acid than fruits produced in conventional agriculture.<ref>Template:Cite journal</ref>
Malonic acid was first prepared in 1858 by the French chemist Victor Dessaignes via the oxidation of malic acid.<ref name=EB1911/><ref>Template:Cite journal</ref>
Hermann Kolbe and Hugo Müller independently discovered how to synthesize malonic acid from propionic acid, and decided to publish their results back-to-back in the Chemical Society journal in 1864.<ref name=":0">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> This led to priority dispute with Hans Hübner and Maxwell Simpson who had independently published preliminary results on related reactions.<ref name=":0" />
Structure and preparationEdit
The structure has been determined by X-ray crystallography<ref>Template:Cite journal</ref> and extensive property data including for condensed phase thermochemistry are available from the National Institute of Standards and Technology.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A classical preparation of malonic acid starts from chloroacetic acid:<ref>Template:OrgSynth</ref>
Sodium carbonate generates the sodium salt, which is then reacted with sodium cyanide to provide the sodium salt of cyanoacetic acid via a nucleophilic substitution. The nitrile group can be hydrolyzed with sodium hydroxide to sodium malonate, and acidification affords malonic acid. Industrially, however, malonic acid is produced by hydrolysis of dimethyl malonate or diethyl malonate.<ref>Template:Cite patent</ref> It has also been produced through fermentation of glucose.<ref>Template:Cite patent</ref>
ReactionsEdit
Malonic acid reacts as a typical carboxylic acid forming amide, ester, and chloride derivatives.<ref>Template:Cite book</ref> Malonic anhydride can be used as an intermediate to mono-ester or amide derivatives, while malonyl chloride is most useful to obtain diesters or diamides. In a well-known reaction, malonic acid condenses with urea to form barbituric acid. Malonic acid may also be condensed with acetone to form Meldrum's acid, a versatile intermediate in further transformations. The esters of malonic acid are also used as a −CH2COOH synthon in the malonic ester synthesis.
Briggs–Rauscher reactionEdit
Malonic acid is a key component in the Briggs–Rauscher reaction, the classic example of an oscillating chemical reaction.<ref>Template:Cite journal</ref>
Knoevenagel condensationEdit
Malonic acid is used to prepare a,b-unsaturated carboxylic acids by condensation and decarboxylation. Cinnamic acids are prepared in this way:
In this, the so-called Knoevenagel condensation, malonic acid condenses with the carbonyl group of an aldehyde or ketone, followed by a decarboxylation.
When malonic acid is condensed in hot pyridine, the condensation is accompanied by decarboxylation, the so-called Doebner modification.<ref>Template:OrgSynth</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Preparation of carbon suboxideEdit
Malonic acid does not readily form an anhydride, dehydration gives carbon suboxide instead:
The transformation is achieved by warming a dry mixture of phosphorus pentoxide (Template:Chem2) and malonic acid.<ref>Template:Cite journal</ref> It reacts in a similar way to malonic anhydride, forming malonates.<ref>Template:Cite journal</ref>
ApplicationsEdit
Malonic acid is a precursor to specialty polyesters. It can be converted into 1,3-propanediol for use in polyesters and polymers (whose usefulness is unclear though). It can also be a component in alkyd resins, which are used in a number of coatings applications for protecting against damage caused by UV light, oxidation, and corrosion. One application of malonic acid is in the coatings industry as a crosslinker for low-temperature cure powder coatings, which are becoming increasingly valuable for heat sensitive substrates and a desire to speed up the coatings process.<ref>Template:Cite book</ref> The global coatings market for automobiles was estimated to be $18.59 billion in 2014 with projected combined annual growth rate of 5.1% through 2022.<ref>Template:Cite report</ref>
It is used in a number of manufacturing processes as a high value specialty chemical including the electronics industry, flavors and fragrances industry,<ref name=gsc/> specialty solvents, polymer crosslinking, and pharmaceutical industry. In 2004, annual global production of malonic acid and related diesters was over 20,000 metric tons.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Potential growth of these markets could result from advances in industrial biotechnology that seeks to displace petroleum-based chemicals in industrial applications.
In 2004, malonic acid was listed by the US Department of Energy as one of the top 30 chemicals to be produced from biomass.<ref>Template:Cite report</ref>
In food and drug applications, malonic acid can be used to control acidity, either as an excipient in pharmaceutical formulation or natural preservative additive for foods.<ref name=gsc />
Malonic acid is used as a building block chemical to produce numerous valuable compounds,<ref>Hildbrand, S.; Pollak, P. Malonic Acid & Derivatives. March 15, 2001. Ullmann's Encyclopedia of Industrial Chemistry</ref> including the flavor and fragrance compounds gamma-nonalactone, cinnamic acid, and the pharmaceutical compound valproate.
Malonic acid (up to 37.5% w/w) has been used to cross-link corn and potato starches to produce a biodegradable thermoplastic; the process is performed in water using non-toxic catalysts.<ref>Template:Cite patent</ref><ref name="pmid22944425">Template:Cite journal</ref> Starch-based polymers comprised 38% of the global biodegradable polymers market in 2014 with food packaging, foam packaging, and compost bags as the largest end-use segments.<ref>Template:Cite report</ref>
Eastman Kodak company and others use malonic acid and derivatives as a surgical adhesive.<ref>Template:Cite patent</ref>
PathologyEdit
If elevated malonic acid levels are accompanied by elevated methylmalonic acid levels, this may indicate the metabolic disease combined malonic and methylmalonic aciduria (CMAMMA). By calculating the malonic acid to methylmalonic acid ratio in blood plasma, CMAMMA can be distinguished from classic methylmalonic acidemia.<ref>Template:Cite journal</ref>
BiochemistryEdit
Malonic acid is the precursor in mitochondrial fatty acid synthesis (mtFASII), in which it is converted to malonyl-CoA by acyl-CoA synthetase family member 3 (ACSF3).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Additionally, the coenzyme A derivative of malonate, malonyl-CoA, is an important precursor in cytosolic fatty acid biosynthesis along with acetyl CoA. Malonyl CoA is formed there from acetyl CoA by the action of acetyl-CoA carboxylase, and the malonate is transferred to an acyl carrier protein to be added to a fatty acid chain.
Malonic acid is the classic example of a competitive inhibitor of the enzyme succinate dehydrogenase (complex II), in the respiratory electron transport chain.<ref name="pardee_potter">Template:Cite journal</ref> It binds to the active site of the enzyme without reacting, competing with the usual substrate succinate but lacking the −CH2CH2− group required for dehydrogenation. This observation was used to deduce the structure of the active site in succinate dehydrogenase. Inhibition of this enzyme decreases cellular respiration.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Since malonic acid is a natural component of many foods, it is present in mammals including humans.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Salts and estersEdit
Malonic acid is diprotic; that is, it can donate two protons per molecule. Its first <math chem>pK_a</math> is 2.8 and the second is 5.7.<ref name=Williams /> Thus the malonate ion can be Template:Chem2 or Template:Chem2. Malonate or propanedioate compounds include salts and esters of malonic acid, such as