Malonic acid (
IUPAC
The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...
systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature.
A semisystematic name or semitrivial ...
: propanedioic acid) is a
dicarboxylic acid with structure CH
2(COOH)
2. The
ion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...
ized form of malonic acid, as well as its
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
s and
salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...
s, are known as malonates. For example,
diethyl malonate
Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds su ...
is malonic acid's
diethyl ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
. The name originates from the
Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
word μᾶλον (''malon'') meaning 'apple'.
History
Malonic acid
is a naturally occurring substance found in many fruits and vegetables.
There is a suggestion that
citrus
''Citrus'' is a genus of flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as oranges, lemons, grapefruits, pomelos, and limes. The genus ''Citrus'' is native to ...
fruits produced in
organic farming
Organic farming, also known as ecological farming or biological farming,Labelling, article 30 o''Regulation (EU) 2018/848 of the European Parliament and of the Council of 30 May 2018 on organic production and labelling of organic products and re ...
contain higher levels of malonic acid than fruits produced in conventional agriculture.
Malonic acid was first prepared in 1858 by the French chemist
Victor Dessaignes via the oxidation of
malic acid
Malic acid is an organic compound with the molecular formula . It is a dicarboxylic acid that is made by all living organisms, contributes to the sour taste of fruits, and is used as a food additive. Malic acid has two stereoisomeric forms ( ...
.
[
]
Structure and preparation
The structure has been determined by X-ray crystallography and extensive property data including for condensed phase thermochemistry are available from the National Institute of Standards and Technology
The National Institute of Standards and Technology (NIST) is an agency of the United States Department of Commerce whose mission is to promote American innovation and industrial competitiveness. NIST's activities are organized into physical s ...
.
A classical preparation of malonic acid starts from chloroacetic acid
Chloroacetic acid, industrially known as monochloroacetic acid (MCA), is the organochlorine compound with the formula ClCH2CO2H. This carboxylic acid is a useful building block in organic synthesis. It is a colorless solid. Related compounds a ...
:
Sodium carbonate generates the sodium salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...
, which is then reacted with sodium cyanide
Sodium cyanide is a poisonous compound with the formula Na C N. It is a white, water-soluble solid. Cyanide has a high affinity for metals, which leads to the high toxicity of this salt. Its main application, in gold mining, also exploits its hi ...
to provide the sodium salt of cyanoacetic acid
Cyanoacetic acid is an organic compound. It is a white, hygroscopic solid. The compound contains two functional groups, a nitrile (−C≡N) and a carboxylic acid. It is a precursor to cyanoacrylates, components of adhesives.Harald Strittmatter, ...
via a nucleophilic substitution
In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...
. 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
Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds su ...
. It has also been produced through fermentation of glucose.
Organic reactions
Malonic acid reacts as a typical carboxylic acid: forming amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
, ester, anhydride
An organic acid anhydride is an acid anhydride that is an organic compound. An acid anhydride is a compound that has two acyl groups bonded to the same oxygen atom. A common type of organic acid anhydride is a carboxylic anhydride, where the pa ...
, and chloride
The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride sa ...
derivatives. Malonic anhydride
Malonic anhydride or oxetane-2,4-dione is an organic compound with chemical formula C3H2O3 or CH2(CO)2O. It can be viewed as the anhydride of malonic acid, or a double ketone of oxetane.
Malonic anhydride was first synthesized in 1988 by ozonolys ...
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
Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor to ...
with urea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important ...
to form barbituric acid
Barbituric acid or malonylurea or 6-hydroxyuracil is an organic compound based on a pyrimidine heterocyclic skeleton. It is an odorless powder soluble in water. Barbituric acid is the parent compound of barbiturate drugs, although barbituric acid i ...
. Malonic acid may also be condensed with acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
to form Meldrum's acid, a versatile intermediate in further transformations. The esters of malonic acid are also used as a −CH2COOH synthon
In retrosynthetic analysis, a synthon is a hypothetical unit within a target molecule that represents a potential starting reagent in the retroactive synthesis of that target molecule. The term was coined in 1967 by E. J. Corey. He noted in 1 ...
in the malonic ester synthesis
The malonic ester synthesis is a chemical reaction where diethyl malonate or another ester of malonic acid is alkylated at the carbon alpha (directly adjacent) to both carbonyl groups, and then converted to a substituted acetic acid. The major ...
.
Additionally, the coenzyme A derivative of malonate, malonyl-CoA, is an important precursor in fatty acid biosynthesis
Fatty is a derogatory term for someone who is obese. It may refer also to:
People
* Mai Fatty, Gambian politician
* Roscoe Arbuckle (1887–1933), American actor and comedian
* Fatty Briody (1858–1903), American Major League Baseball player ...
along with acetyl CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
. Malonyl CoA is formed from acetyl CoA by the action of acetyl-CoA carboxylase, and the malonate is transferred to an acyl carrier protein
The acyl carrier protein (ACP) is a cofactor of both fatty acid and polyketide
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene ...
to be added to a fatty acid chain.
Briggs–Rauscher reaction
Malonic acid is a key component in the Briggs–Rauscher reaction
The Briggs–Rauscher oscillating reaction is one of a small number of known oscillating chemical reactions. It is especially well suited for demonstration purposes because of its visually striking colour changes: the freshly prepared colourless s ...
, the classic example of an oscillating chemical reaction.
Knoevenagel condensation
In Knoevenagel condensation
In organic chemistry, the Knoevenagel condensation () reaction is a type of chemical reaction named after German chemist Emil Knoevenagel. It is a modification of the aldol condensation.
A Knoevenagel condensation is a nucleophilic addition o ...
, malonic acid or its diesters are reacted with the carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...
group of an aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
or ketone, followed by a dehydration reaction
In chemistry, a dehydration reaction is a chemical reaction that involves the loss of water from the reacting molecule or ion. Dehydration reactions are common processes, the reverse of a hydration reaction.
Dehydration reactions in organic ch ...
.
When malonic acid itself is used, it is normally because the desired product is one in which a second step has occurred, with loss of carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
, in the so-called Doebner modification.
Thus, for example, the reaction product of acrolein and malonic acid in pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a ...
is ''trans-2,4-Pentadienoic acid'' with one carboxylic acid group and not two.
Preparation of carbon suboxide
Carbon suboxide
Carbon suboxide, or tricarbon dioxide, is an organic, oxygen-containing chemical compound with formula and structure . Its four cumulative double bonds make it a cumulene. It is one of the stable members of the series of linear oxocarbons , w ...
is prepared by warming a dry mixture of phosphorus pentoxide
Phosphorus pentoxide is a chemical compound with molecular formula P4 O10 (with its common name derived from its empirical formula, P2O5). This white crystalline solid is the anhydride of phosphoric acid. It is a powerful desiccant and dehydra ...
() and malonic acid. It reacts in a similar way to malonic anhydride
Malonic anhydride or oxetane-2,4-dione is an organic compound with chemical formula C3H2O3 or CH2(CO)2O. It can be viewed as the anhydride of malonic acid, or a double ketone of oxetane.
Malonic anhydride was first synthesized in 1988 by ozonolys ...
, forming malonates.
Applications
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. 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.
It is used in a number of manufacturing processes as a high value specialty chemical including the electronics
The field of electronics is a branch of physics and electrical engineering that deals with the emission, behaviour and effects of electrons using electronic devices. Electronics uses active devices to control electron flow by amplification ...
industry, flavors and fragrances industry,[ specialty solvents, polymer crosslinking, and pharmaceutical industry. In 2004, annual global production of malonic acid and related diesters was over 20,000 metric tons. 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.
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.]
Malonic acid is used as a building block chemical to produce numerous valuable compounds, including the flavor and fragrance compounds gamma-nonalactone, cinnamic acid
Cinnamic acid is an organic compound with the formula C6H5-CH=CH- COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxylic acid, it occurs na ...
, and the pharmaceutical compound valproate
Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
.
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. 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.
Eastman Kodak company and others use malonic acid and derivatives as a surgical adhesive.
Pathology
If elevated malonic acid levels are accompanied by elevated methylmalonic acid
Methylmalonic acid (MMA) (conjugate base methylmalonate) is a dicarboxylic acid that is a ''C''-methylated derivative of malonate.
The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalon ...
levels, this may indicate the metabolic disease combined malonic and methylmalonic aciduria
Combined malonic and methylmalonic aciduria (CMAMMA), also called combined malonic and methylmalonic acidemia is an inherited metabolic disease characterized by elevated levels of malonic acid and methylmalonic acid. Some researchers have hypothe ...
(CMAMMA). By calculating the malonic acid to methylmalonic acid ratio in blood plasma, CMAMMA can be distinguished from classic methylmalonic acidemia
Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. It is a classical type of organic acidemia. The result of this condition is the inability to prope ...
.
Biochemistry
Malonic acid is the classic example of a competitive inhibitor
Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected b ...
of the enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
succinate dehydrogenase (complex II), in the respiratory electron transport chain. It binds to the active site of the enzyme without reacting, competing with the usual substrate succinate
Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...
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. Since malonic acid is a natural component of many foods, it is present in mammals including humans.
Related Chemicals
The fluorinated version of malonic acide is difluoromalonic acidbr>
Malonic acid is Acid#Polyprotic_acids, diprotic; that is, it can donate two protons
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mas ...
per molecule. Its first is 2.8 and the second is 5.7. Thus the malonate ion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...
can be or . Malonate or propanedioate compounds include salts
In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...
and ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
s of malonic acid, such as
*Diethyl malonate
Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds su ...
* Dimethyl malonate
*Disodium malonate
Disodium malonate is a sodium salt of malonic acid with the chemical formula C3H2O4Na2. It is a white crystal soluble in water but not in alcohols, esters or benzene. It can be prepared from the reaction of sodium hydroxide and malonic acid
...
* Malonyl-CoA
References
External links
Calculator: Water and solute activities in aqueous malonic acid
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Dicarboxylic acids