PROPANEDIOIC ACID (MALONIC ACID)

Propanedioic Acid (Malonic Acid) is a dicarboxylic acid with structure CH2(COOH)2.
The ionized form of Propanedioic Acid (Malonic Acid), as well as its esters and salts, are known as malonates.

IUPAC name: Propanedioic acid
CAS Number: 141-82-2
EC Number: 205-503-0
Chemical formula: C6H14O2

Other names: malonic acid, propanedioic acid, 141-82-2, Dicarboxymethane, Carboxyacetic acid, Methanedicarboxylic acid, malonate, Kyselina malonova, USAF EK-695, 1,3-Propanedioic acid, Dicarboxylate, Malonicacid, Dicarboxylic acid, NSC 8124, UNII-9KX7ZMG0MK, 9KX7ZMG0MK, AI3-15375, H2malo, EINECS 205-503-0, MFCD00002707, BRN 1751370, Methanedicarbonic acid, CHEBI:30794, Thallium malonate, HOOC-CH2-COOH, NSC-8124, Propane-1,3-dioic acid, alpha,omega-Dicarboxylic acid, DTXSID7021659, HSDB 8437, NSC8124, 4-02-00-01874, 1,3-Propanoic acid, PROPANEDIOLIC ACID, METAHNEDICARBOXYLIC ACID, 2fah, MLI, 1o4m, Malonate dicarboxylic acid, SCHEMBL336, WLN: QV1VQ, CH2(COOH)2, CHEMBL7942, DTXCID401659, SCHEMBL1471092, BDBM14673, AMY11201, BCP05571, STR00614, Tox21_200534, AC825, LMFA01170041, s3029, AKOS000119034, CS-W019962, DB0215, NCGC00248681-01, NCGC00258088-01, BP-11453, CAS-141-82-2, SY001875, FT-0628127, FT-0628128, FT-0690260, FT-0693474, M0028, EN300-18457, C00383, C02028, C04025, Q421972, J-521669, Z57965450, F1908-0177

History
Propanedioic Acid (Malonic Acid) is a naturally occurring substance found in many fruits and vegetables.
There is a suggestion that citrus fruits produced in organic farming contain higher levels of Propanedioic Acid (Malonic Acid) than fruits produced in conventional agriculture.

Propanedioic Acid (Malonic Acid) was first prepared in 1858 by the French chemist Victor Dessaignes via the oxidation of malic acid.

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.
A classical preparation of Propanedioic Acid (Malonic Acid) starts from chloroacetic acid.

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 Propanedioic Acid (Malonic Acid).

Industrially, however, Propanedioic Acid (Malonic Acid) is produced by hydrolysis of dimethyl malonate or diethyl malonate.
Propanedioic Acid (Malonic Acid) has also been produced through fermentation of glucose.

Propanedioic Acid (Malonic Acid) reacts as a typical carboxylic acid: forming amide, ester, anhydride, and chloride derivatives.
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, Propanedioic Acid (Malonic Acid) condenses with urea to form barbituric acid.

Propanedioic Acid (Malonic Acid) may also be condensed with acetone to form Meldrum's acid, a versatile intermediate in further transformations.
The esters of Propanedioic Acid (Malonic Acid) are also used as a −CH2COOH synthon in the malonic ester synthesis.

Mitochondrial fatty acid synthesis
Propanedioic Acid (Malonic Acid) is the starting substrate of mitochondrial fatty acid synthesis (mtFASII), in which it is converted to malonyl-CoA by malonyl-CoA synthetase (ACSF3).

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.

Briggs–Rauscher reaction
Propanedioic Acid (Malonic Acid) is a key component in the Briggs–Rauscher reaction, the classic example of an oscillating chemical reaction.

Knoevenagel condensation
In Knoevenagel condensation, Propanedioic Acid (Malonic Acid) or its diesters are reacted with the carbonyl group of an aldehyde or ketone, followed by a dehydration reaction.

When Propanedioic Acid (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, in the so-called Doebner modification.

Thus, for example, the reaction product of acrolein and Propanedioic Acid (Malonic Acid) in pyridine is trans-2,4-Pentadienoic acid with one carboxylic acid group and not two.

Preparation of carbon suboxide
Carbon suboxide is prepared by warming a dry mixture of phosphorus pentoxide (P4O10) and Propanedioic Acid (Malonic Acid).
It reacts in a similar way to malonic anhydride, forming malonates.

Applications
Propanedioic Acid (Malonic Acid) is a precursor to specialty polyesters.
Propanedioic Acid (Malonic Acid) can be converted into 1,3-propanediol for use in polyesters and polymers (whose usefulness is unclear though).
Propanedioic Acid (Malonic Acid) 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 Propanedioic Acid (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.

Propanedioic Acid (Malonic Acid) is used in a number of manufacturing processes as a high value specialty chemical including the electronics industry, flavors and fragrances industry, specialty solvents, polymer crosslinking, and pharmaceutical industry.

In 2004, annual global production of Propanedioic Acid (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, Propanedioic Acid (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, Propanedioic Acid (Malonic Acid) can be used to control acidity, either as an excipient in pharmaceutical formulation or natural preservative additive for foods.

Propanedioic Acid (Malonic Acid) is used as a building block chemical to produce numerous valuable compounds, including the flavor and fragrance compounds gamma-nonalactone, cinnamic acid, and the pharmaceutical compound valproate.

Propanedioic Acid (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 Propanedioic Acid (Malonic Acid) and derivatives as a surgical adhesive.

Pathology
If elevated Propanedioic Acid (Malonic Acid) levels are accompanied by elevated methylPropanedioic Acid (Malonic Acid) levels, this may indicate the metabolic disease combined malonic and methylPropanedioic Acid (Malonic Acid)uria (CMAMMA).
By calculating the Propanedioic Acid (Malonic Acid) to methylPropanedioic Acid (Malonic Acid) ratio in blood plasma, CMAMMA can be distinguished from classic methylPropanedioic Acid (Malonic Acid)emia.

Biochemistry
Propanedioic Acid (Malonic Acid) is the classic example of a competitive inhibitor of the enzyme succinate dehydrogenase (complex II), in the respiratory electron transport chain.
Propanedioic Acid (Malonic Acid) 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.
Since Propanedioic Acid (Malonic Acid) is a natural component of many foods, it is present in mammals including humans.

Molar mass: 104.061 g·mol−1
Density: 1.619 g/cm3
Melting point: 135 to 137 °C
Boiling point: decomposes

Solubility in water: 763 g/L
Acidity (pKa): pKa1 = 2.83, pKa2 = 5.69
XLogP3: -0.8
Hydrogen Bond Donor Count: 2

Hydrogen Bond Acceptor Count: 4
Rotatable Bond Count: 2
Exact Mass: 104.01095860 g/mol
Monoisotopic Mass: 104.01095860 g/mol

Topological Polar Surface Area: 74.6Å²
Heavy Atom Count: 7
Formal Charge: 0
Complexity: 83.1

Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0

Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Consumer Uses
Propanedioic Acid (Malonic Acid) is used in the following products: adhesives and sealants, inks and toners, pH regulators and water treatment products, washing & cleaning products, coating products, fillers, putties, plasters, modelling clay, polishes and waxes and cosmetics and personal care products.
Other release to the environment of Propanedioic Acid (Malonic Acid) is likely to occur from: indoor use as reactive substance.

Article service life
Release to the environment of Propanedioic Acid (Malonic Acid) can occur from industrial use: of articles where the substances are not intended to be released and where the conditions of use do not promote release and industrial abrasion processing with low release rate (e.g. cutting of textile, cutting, machining or grinding of metal).

Other release to the environment of Propanedioic Acid (Malonic Acid) is likely to occur from: outdoor use in long-life materials with low release rate (e.g. metal, wooden and plastic construction and building materials) and indoor use in long-life materials with low release rate (e.g. flooring, furniture, toys, construction materials, curtains, foot-wear, leather products, paper and cardboard products, electronic equipment).

Widespread uses by professional workers
Propanedioic Acid (Malonic Acid) is used in the following products: coating products, metal surface treatment products, non-metal-surface treatment products, polymers and laboratory chemicals.

Propanedioic Acid (Malonic Acid) is used for the manufacture of: plastic products, fabricated metal products, electrical, electronic and optical equipment and machinery and vehicles.

Other release to the environment of Propanedioic Acid (Malonic Acid) is likely to occur from: indoor use (e.g. machine wash liquids/detergents, automotive care products, paints and coating or adhesives, fragrances and air fresheners).

Formulation and re-packing
Propanedioic Acid (Malonic Acid) is used in the following products: laboratory chemicals, coating products, metal surface treatment products, non-metal-surface treatment products, pharmaceuticals and polymers.
Release to the environment of Propanedioic Acid (Malonic Acid) can occur from industrial use: formulation of mixtures.

Uses at industrial sites
Propanedioic Acid (Malonic Acid) is used in the following products: pH regulators and water treatment products, pharmaceuticals, laboratory chemicals, polymers, non-metal-surface treatment products, coating products and metal surface treatment products.

Propanedioic Acid (Malonic Acid) is used for the manufacture of: chemicals, plastic products, fabricated metal products, electrical, electronic and optical equipment and machinery and vehicles.

Release to the environment of Propanedioic Acid (Malonic Acid) can occur from industrial use: as an intermediate step in further manufacturing of another substance (use of intermediates), as processing aid, in the production of articles and as processing aid.

Propanedioic Acid (Malonic Acid) is an alpha,omega-dicarboxylic acid in which the two carboxy groups are separated by a single methylene group.
Propanedioic Acid (Malonic Acid) has a role as a human metabolite.
Propanedioic Acid (Malonic Acid) is a conjugate acid of a malonate(1-).

Propanedioic Acid (Malonic Acid), formally propanedioic acid, is the second-smallest aliphatic dicarboxylic acid.
Propanedioic Acid (Malonic Acid) should not be confused with malic or maleic acid, both of which also contain two carboxyls.
Propanedioic Acid (Malonic Acid) is a white crystalline solid with a decomposition point of ≈135 °C.
Propanedioic Acid (Malonic Acid) is highly soluble in water and oxygenated solvents.

Propanedioic Acid (Malonic Acid) has numerous commercial uses:
Propanedioic Acid (Malonic Acid) is a precursor to specialty polyesters; Propanedioic Acid (Malonic Acid) is used in the manufacture of barbiturates, coatings, and biodegradable containers; and Propanedioic Acid (Malonic Acid) is even a component of surgical adhesives.

Uses
Propanedioic Acid (Malonic Acid) is used as a precursor in polymers and polyester.
Propanedioic Acid (Malonic Acid) is used in flavours as well as the fragrance industry.
Propanedioic Acid (Malonic Acid) is used to control the acidity.
Propanedioic Acid (Malonic Acid) is used in pharmaceutical products.
Propanedioic Acid (Malonic Acid) is used as a cross-linking agent between potato starch and cornstarch to enhance its mechanical properties.

Propanedioic Acid (Malonic Acid) is used in the preparation of barbituric salt.
Propanedioic Acid (Malonic Acid) is used in electroplating.
Propanedioic Acid (Malonic Acid) is used to produce vitamin B1, vitamin B6, vitamin B2, and amino acids.
Propanedioic Acid (Malonic Acid) is used in chemical synthesis as a building block.

Propanedioic Acid (Malonic Acid), also known as malonate or H2MALO, belongs to the class of organic compounds known as dicarboxylic acids and derivatives.
These are organic compounds containing exactly two carboxylic acid groups.
Propanedioic Acid (Malonic Acid) is a very hydrophobic molecule, practically insoluble (in water), and relatively neutral.

Propanedioic Acid (Malonic Acid) exists in all living species, ranging from bacteria to humans.
Within humans, Propanedioic Acid (Malonic Acid) participates in a number of enzymatic reactions.
In particular, Propanedioic Acid (Malonic Acid) and acetic acid can be converted into acetoacetic acid; which is mediated by the enzyme fatty acid synthase.

Propanedioic Acid (Malonic Acid) is a dicarboxylic acid with the chemical formula C3H4O4. Dicarboxylic acids are organic compounds containing two carboxylic acid functional groups.
Dicarboxylic acids generally show the same chemical behaviour and reactivity as monocarboxylic acids.

Propanedioic Acid (Malonic Acid) is a substance found in some fruits that occurs naturally.
Fruits generated in organic farming contain greater concentrations of Propanedioic Acid (Malonic Acid) in citrus compared to fruits generated in conventional farming.

Propanedioic Acid (Malonic Acid) is the archetypal instance of a competitive inhibitor: it functions in the respiratory electron transport chain against succinate dehydrogenase.
Propanedioic Acid (Malonic Acid) is correlated with deficiency of malonyl-CoA decarboxylase, an inborn metabolism mistake.

Within humans, Propanedioic Acid (Malonic Acid) participates in a number of enzymatic reactions.
In particular, Propanedioic Acid (Malonic Acid) and acetic acid can be converted into acetoacetic acid; which is mediated by the enzyme fatty acid synthase.
Beta ketoacyl synthase domain.

In addition, Propanedioic Acid (Malonic Acid) and coenzyme A can be biosynthesized from malonyl-CoA through its interaction with the enzyme fatty acid synthase. malonyl/acetyl transferase domain.
An Propanedioic Acid (Malonic Acid) in which the two carboxy groups are separated by a single methylene group.

In humans, Propanedioic Acid (Malonic Acid) is involved in fatty acid biosynthesis.
Outside of the human body, Propanedioic Acid (Malonic Acid) has been detected, but not quantified in, several different foods, such as red beetroots, corns, scarlet beans, common beets, and cow milks.

This could make Propanedioic Acid (Malonic Acid) a potential biomarker for the consumption of these foods.
Propanedioic Acid (Malonic Acid), with regard to humans, has been found to be associated with several diseases such as eosinophilic esophagitis, combined malonic and methylPropanedioic Acid (Malonic Acid)uria, and early preeclampsia; Propanedioic Acid (Malonic Acid) has also been linked to the inborn metabolic disorder malonyl-coa decarboxylase deficiency.

Propanedioic Acid (Malonic Acid) is highly soluble in water and oxygenated solvents.
Propanedioic Acid (Malonic Acid) has numerous commercial uses: Propanedioic Acid (Malonic Acid) is a precursor to specialty polyesters; it is used in the manufacture of barbiturates, coatings, and biodegradable containers; and it is even a component of surgical adhesives.

French chemist Victor Dessaignes reported the first synthesis of Propanedioic Acid (Malonic Acid) in 1858; he made it by oxidatively decomposing four-carbon malic acid with potassium dichromate.
Since then, it has been synthesized commercially starting from chloroacetic acid, diethyl malonate, and even sodium acetate.

Propanedioic Acid (Malonic Acid) is a dicarboxylic acid belonging to the family of carboxylic acids.
A dicarboxylic acid contains two carboxylic acid functional groups.
Usually, a dicarboxylic acid exhibits the same chemical behavior as monocarboxylic acids.

This naturally occurs in certain fruits.
Propanedioic Acid (Malonic Acid) is a useful organic compound with various benefits.
Propanedioic Acid (Malonic Acid) should not be confused with malic or maleic acid.

Propanedioic Acid (Malonic Acid) is an organic compound naturally found in some fruits.
Fruits produced in organic farming have greater concentrations of Propanedioic Acid (Malonic Acid) than those generated from conventional farming practices.
Propanedioic Acid (Malonic Acid) is often found in some citrus fruits and vegetables.
Propanedioic Acid (Malonic Acid) is a component of food items, it is present in animals, including humans.

The ionized form of Propanedioic Acid (Malonic Acid) is malonate, along with its salts and esters.
Propanedioic Acid (Malonic Acid) occurs as a white crystal or crystalline powder in nature.