Decarboxylation
Encyclopedia
Decarboxylation is a chemical reaction
that releases carbon dioxide
(CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation
, the addition of CO2 to a compound. Enzymes that catalyze decarboxylations are called decarboxylases or, the more formal term, carboxy-lyases
(EC number
4.1.1).
, and volatile products distill from the reactor. Heating is required because the reaction is less favorable at low temperatures. Yields are highly sensitive to conditions. In retrosynthesis, decarboxylation reactions can be considered the opposite of homologation reaction
s, in that the chain length becomes one carbon shorter. Metals, especially copper compounds, are usually required. Such reactions proceed via the intermediacy of metal carboxylate complexes.
Decarboxylation of aryl carboxylates can generate the equivalent of the corresponding aryl anion, which in turn can undergo cross coupling reactions.
Alkylcarboxylic acids and their salts do not always undergo decarboxylation readily. Exceptions are the decarboxylation of beta-keto acid
s, α,β-unsaturated acids, and α-phenyl, α-nitro, and α-cyanoacids. Such reactions are accelerated due to the formation of a zwitterionic tautomer in which the carbonyl is protonated and the carboxyl group is deprotonated. ]. Typically fatty acids do not decarboxylate readily.
, Kolbe electrolysis
and Hunsdiecker reaction
are radical reactions. The Krapcho decarboxylation
is a related decarboxylation of an ester.
to the corresponding hydrocarbon. This is conceptually the same as the more general term "decarboxylation" as defined above except that it specifically requires that the carboxyl group is, as expected, replaced by a proton. The reaction is especially common in conjunction with the malonic ester synthesis
and Knoevenagel condensation
s. The reaction involves the conjugate based of the carboxl group, a carboxylate ion, and an unstaurated receptor of electron density, such as a protonated carbonyl group. Where reactions entail heating the carboxylic acid with concentrated hydrochloric acid
such a direct route is impossible as it would produce protonated carbon dioxide. In these cases, the reaction is likely to occur by initial addition of water and a proton.
decarboxylations of amino acid
s to amine
s are:
Other decarboxylation reactions from the citric acid cycle
include:
.
In beverages stored for long periods, very small amounts of benzene
may form from benzoic acid
by decarboxylation catalyzed by the presence of vitamin C
.
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
that releases carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
(CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation
Carbonation
Carbonation is the process of dissolving carbon dioxide in water. The process usually involves carbon dioxide under high pressure. When the pressure is reduced, the carbon dioxide is released from the solution as small bubbles, which cause the solution to "fizz." This effect is seen in carbonated...
, the addition of CO2 to a compound. Enzymes that catalyze decarboxylations are called decarboxylases or, the more formal term, carboxy-lyases
Carboxy-lyases
Carboxy-lyases, also known as decarboxylases, are carbon–carbon lyases that add or remove a carboxyl group from organic compounds.These enzymes catalyze the decarboxylation of amino acids, beta-keto acids and alpha-keto acids....
(EC number
EC number
The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze....
4.1.1).
In organic chemistry
The term "decarboxylation" literally means removal of the COOH (carboxyl group) and its replacement with a proton. The term simply relates the state of the reactant and product. Decarboxylation is one of the oldest organic reactions, since it often entails simple pyrolysisPyrolysis
Pyrolysis is a thermochemical decomposition of organic material at elevated temperatures without the participation of oxygen. It involves the simultaneous change of chemical composition and physical phase, and is irreversible...
, and volatile products distill from the reactor. Heating is required because the reaction is less favorable at low temperatures. Yields are highly sensitive to conditions. In retrosynthesis, decarboxylation reactions can be considered the opposite of homologation reaction
Homologation reaction
A homologation reaction, also known as homologization, is any chemical reaction that converts the reactant into the next member of the homologous series. A Homologous series is a group of compounds that differ by a constant unit, generally a group. The reactants undergo a homologation when the...
s, in that the chain length becomes one carbon shorter. Metals, especially copper compounds, are usually required. Such reactions proceed via the intermediacy of metal carboxylate complexes.
Decarboxylation of aryl carboxylates can generate the equivalent of the corresponding aryl anion, which in turn can undergo cross coupling reactions.
Alkylcarboxylic acids and their salts do not always undergo decarboxylation readily. Exceptions are the decarboxylation of beta-keto acid
Keto acid
Keto acids are organic compounds that contain a carboxylic acid group and a ketone group. The alpha-keto acids are especially important in biology as they are involved in the Krebs citric acid cycle and in glycolysis...
s, α,β-unsaturated acids, and α-phenyl, α-nitro, and α-cyanoacids. Such reactions are accelerated due to the formation of a zwitterionic tautomer in which the carbonyl is protonated and the carboxyl group is deprotonated. ]. Typically fatty acids do not decarboxylate readily.
Named decarboxylation reactions
Many reactions have been named after early workers in organic chemistry. The Barton decarboxylationBarton decarboxylation
The Barton decarboxylation is a radical reaction in which a carboxylic acid is first converted to a thiohydroxamate ester . The product is then heated in the presence of a radical initiator and a suitable hydrogen donor to complete the reductive decarboxylation of the initial carboxylic acid...
, Kolbe electrolysis
Kolbe electrolysis
Kolbe electrolysis or Kolbe reaction is an organic reaction named after Adolph Wilhelm Hermann Kolbe. The Kolbe reaction is formally a decarboxylative dimerisation and proceeds by a radical reaction mechanism...
and Hunsdiecker reaction
Hunsdiecker reaction
The Hunsdiecker reaction is the organic reaction of silver salts of carboxylic acids with halogens to give organic halides. It is an example of a halogenation reaction...
are radical reactions. The Krapcho decarboxylation
Krapcho decarboxylation
The Krapcho decarboxylation is the chemical reaction of esters with halide anions. The ester must contain an electron-withdrawing group in the beta position, such as β-ketoesters, malonic esters, α-cyanoesters, or α-sulfonylesters. It works best with methyl esters, since it is basically a...
is a related decarboxylation of an ester.
Protodecarboxylation
Protodecarboxylations involve the conversion of a carboxylic acidCarboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
to the corresponding hydrocarbon. This is conceptually the same as the more general term "decarboxylation" as defined above except that it specifically requires that the carboxyl group is, as expected, replaced by a proton. The reaction is especially common in conjunction with the malonic ester synthesis
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 to both carbonyl groups, and then converted to a substituted acetic acid. The major drawback of malonic ester synthesis is that the alkylation stage can also...
and Knoevenagel condensation
Knoevenagel condensation
The Knoevenagel condensation reaction is an organic reaction named after Emil Knoevenagel. It is a modification of the Aldol condensation.A Knoevenagel condensation is a nucleophilic addition of an active hydrogen compound to a carbonyl group followed by a dehydration reaction in which a molecule...
s. The reaction involves the conjugate based of the carboxl group, a carboxylate ion, and an unstaurated receptor of electron density, such as a protonated carbonyl group. Where reactions entail heating the carboxylic acid with concentrated hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
such a direct route is impossible as it would produce protonated carbon dioxide. In these cases, the reaction is likely to occur by initial addition of water and a proton.
Common biochemical examples
Common biosyntheticBiosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
decarboxylations of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s to amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
s are:
- tryptophanTryptophanTryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
to tryptamineTryptamineTryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived... - phenylalaninePhenylalaninePhenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
to phenylethylamine - tyrosineTyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
to tyramineTyramineTyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent... - histidineHistidineHistidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
to histamineHistamineHistamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by... - serineSerineSerine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
to ethanolamineEthanolamineEthanolamine, also called 2-aminoethanol or monoethanolamine , is an organic chemical compound that is both a primary amine and a primary alcohol . Like other amines, monoethanolamine acts as a weak base... - glutamic acidGlutamic acidGlutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
to GABAGabâGabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions... - lysineLysineLysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
to cadaverineCadaverineCadaverine is a foul-smelling compound produced by protein hydrolysis during putrefaction of animal tissue. Cadaverine is a toxic diamine with the formula NH25NH2, which is similar to putrescine... - arginineArginineArginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
to agmatineAgmatineAgmatine is the decarboxylation product of the amino acid arginine and is an intermediate in polyamine biosynthesis. It is discussed as a putative neurotransmitter. It is synthesized in the brain, stored in synaptic vesicles, accumulated by uptake, released by membrane depolarization, and... - ornithineOrnithineOrnithine is an amino acid that plays a role in the urea cycle.-Role in urea cycle:L-Ornithine is one of the products of the action of the enzyme arginase on L-arginine, creating urea. Therefore, ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen....
to putrescinePutrescinePutrescine is a foul-smelling organic chemical compound NH24NH2 that is related to cadaverine; both are produced by the breakdown of amino acids in living and dead organisms and both are toxic in large doses... - melatoninMelatoninMelatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
to 5-methoxytryptamine5-Methoxytryptamine5-Methoxytryptamine , also known as mexamine, is a tryptamine derivative closely related to the neurotransmitters serotonin and melatonin. 5-MT has been shown to occur naturally in the body in low levels. It is biosynthesized via the deacetylation of melatonin in the pineal gland.5-MT acts as a... - 5-HTP to serotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
- L-DOPA to dopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
Other decarboxylation reactions from the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
include:
- pyruvate to acetyl-CoA
- oxalosuccinateOxalosuccinic acidOxalosuccinic acid is a substrate of the citric acid cycle. It is acted upon by isocitrate dehydrogenase. Salts and esters of oxalosuccinic acid are known as oxalosuccinates....
to α-ketoglutarate - α-ketoglutarate to succinyl-CoA.
Case studies
Upon heating, Δ9-Tetrahydrocannabinolic acid decarboxylates to give the psychoactive compound Δ9-TetrahydrocannabinolTetrahydrocannabinol
Tetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ1-THC , or dronabinol, is the main chemical psychoactive substance found in the cannabis plant. It was first isolated in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed...
.
In beverages stored for long periods, very small amounts of benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
may form from benzoic acid
Benzoic acid
Benzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...
by decarboxylation catalyzed by the presence of vitamin C
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
.