Carbamate
Encyclopedia
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
s derived from carbamic acid
Carbamic acid
Carbamic acid is a compound that is unstable under normal circumstances. It is technically the simplest amino acid, though its instability allows glycine to assume this title. Its importance is due more to its relevance in identifying the names of larger compounds...
(NH2COOH). A carbamate group, carbamate ester, and carbamic acids are functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
s that are inter-related structurally and often are interconverted chemically. Carbamate esters are also called urethanes.
Synthesis
Carbamic acids are derived from amines:- R2NH + CO2 → R2NCO2H
Carbamic acid is about as acidic as acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
. Ionization of a proton gives the carbamate anion, the conjugate base of carbamic acid:
- R2NCO2H → R2NCO2- + H+
Carbamates also arise via hydrolysis of chloroformamides:
- R2NC(O)Cl + H2O → R2NCO2H + HCl
Carbamates may be formed from the Curtius Rearrangement
Curtius rearrangement
The Curtius rearrangement , as first defined by Theodor Curtius, is a chemical reaction that involves the rearrangement of an acyl azide to an isocyanate. Several reviews have been published....
, where isocyanate
Isocyanate
Isocyanate is the functional group of elements –N=C=O , not to be confused with the cyanate functional group which is arranged as –O–C≡N or with isocyanide, R-N≡C. Any organic compound which contains an isocyanate group may also be referred to in brief as an isocyanate. An isocyanate may have more...
s formed are reacted with an alcohol.
- RNCO + R'OH → RNHCO2R'
Applications and occurrence
Although most of this article concerns organic carbamates, the inorganic salt ammonium carbamate is produced on a large scale as an intermediate in the production of the commodity chemical ureaUrea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
from ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
and carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
.
Carbamates in biochemistry
N-terminal amino groups of valine residues in the α- and β-chains of deoxyhemoglobin exist as carbamates. They help to stabilize the protein, when it becomes deoxyhemoglobin and increases the likelihood of the release of remaining oxygenOxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
molecules bound to the protein. The influence of these carbamates on the affinity of hemoglobin for O2 is called the Bohr effect
Bohr effect
Bohr effect is a property of hemoglobin first described in 1904 by the Danish physiologist Christian Bohr , which states that an increasing concentration of protons and/or carbon dioxide will reduce the oxygen affinity of hemoglobin...
.
The ε-amino groups of the lysine residues in urease
Urease
Urease is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia. The reaction occurs as follows:In 1926, James Sumner showed that urease is a protein. Urease is found in bacteria, yeast, and several higher plants. The structure of urease was first solved by P.A...
and phosphotriesterase also feature carbamate. The carbamate derived from aminoimidazole is an intermediate in the biosynthesis of inosine
Inosine
Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring via a β-N9-glycosidic bond....
. Carbamoyl phosphate is generated from carboxyphosphate
rather than CO2.
CO2 capture by ribulose 1,5-bisphosphate carboxylase
Perhaps the most important carbamate is the one involved in the capture of CO2 by plants since this process is relevant to global warmingGlobal warming
Global warming refers to the rising average temperature of Earth's atmosphere and oceans and its projected continuation. In the last 100 years, Earth's average surface temperature increased by about with about two thirds of the increase occurring over just the last three decades...
. The enzyme Ribulose 1,5-bisphosphate carboxylase/oxygenase
RuBisCO
Ribulose-1,5-bisphosphate carboxylase oxygenase, commonly known by the shorter name RuBisCO, is an enzyme involved in the first major step of carbon fixation, a process by which atmospheric carbon dioxide is converted by plants to energy-rich molecules such as glucose. RuBisCo is an abbreviation...
fixes a molecule of carbon dioxide as a carbamate at the start of the Calvin cycle
Calvin cycle
The Calvin cycle or Calvin–Benson-Bassham cycle or reductive pentose phosphate cycle or C3 cycle or CBB cycle is a series of biochemical redox reactions that take place in the stroma of chloroplasts in photosynthetic organisms...
). At the active site of the enzyme, a Mg2+ ion is bound to glutamate
Glutamic acid
Glutamic 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...
and aspartate
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...
residues as well as a lysine
Lysine
Lysine 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....
carbamate. The carbamate is formed when an uncharged lysine side-chain near the ion reacts with a carbon dioxide molecule from the air (not the substrate carbon dioxide molecule), which then renders it charged, and, therefore, able to bind the Mg2+ ion.
Carbamate insecticides
The so-called carbamate insecticideInsecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
s feature the carbamate ester functional group. Included in this group are aldicarb
Aldicarb
Aldicarb is a carbamate insecticide which is the active substance in the pesticide Temik. It is effective against thrips, aphids, spider mites, lygus, fleahoppers, and leafminers, but is primarily used as a nematicide. Aldicarb is a cholinesterase inhibitor which prevents the breakdown of...
, carbofuran
Carbofuran
Carbofuran is one of the most toxic carbamate pesticides. It is marketed under the trade names Furadan, by FMC Corporation and Curater, among several others. It is used to control insects in a wide variety of field crops, including potatoes, corn and soybeans...
(Furadan), carbaryl
Carbaryl
Carbaryl is a chemical in the carbamate family used chiefly as an insecticide. It is a white crystalline solid commonly sold under the brand name Sevin, a trademark of the Bayer Company. Union Carbide discovered carbaryl and introduced it commercially in 1958...
(Sevin), ethienocarb, and fenobucarb. These insecticides kill insects by reversibly inactivating the enzyme acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
. The organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...
pesticides also inhibit this enzyme, although irreversibly, and cause a more severe form of cholinergic poisoning.
Fenoxycarb
Fenoxycarb
Fenoxycarb is a carbamate insect growth regulator. It has a low toxicity for bees, birds, and humans, but is toxic to fish. The oral LD50 for rats is greater than 16,800 mg/kg....
has a carbamate group but acts as a juvenile hormone mimic
Insect growth regulator
An insect growth regulator is a substance that inhibits the life cycle of an insect. IGRs are typically used to control populations of harmful pests, such as cockroaches or fleas.- Advantages :...
, rather than inactivating acetylcholinesterase.
The insect repellent
Insect repellent
An insect repellent is a substance applied to skin, clothing, or other surfaces which discourages insects from landing or climbing on that surface. There are also insect repellent products available based on sound production, particularly ultrasound...
icaridin
Icaridin
Icaridin, also known as picaridine, KBR 3023, under the INCI name hydroxyethyl isobutyl piperidine carboxylate, and the trade names Bayrepel and Saltidin, is an insect repellent...
is a substituted carbamate.
Polyurethanes
PolyurethanePolyurethane
A polyurethane is any polymer composed of a chain of organic units joined by carbamate links. Polyurethane polymers are formed through step-growth polymerization, by reacting a monomer with another monomer in the presence of a catalyst.Polyurethanes are...
s contain multiple carbamate groups as part of their structure. The "urethane" in the name "polyurethane" refers to these carbamate groups; ethyl carbamate
Ethyl carbamate
Ethyl carbamate is a chemical compound with the molecular formula C3H7NO2 first prepared in the nineteenth century. Structurally, it is an ester of carbamic acid...
(common name "urethane") is neither a component of polyurethanes, nor is used in their manufacture. Polyurethane polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
s have a wide range of properties and are commercially available as foams, elastomers, and solids. Typically, polyurethane polymers are made by combining diisocyanates, e.g. toluene diisocyanate
Toluene diisocyanate
Toluene diisocyanate is an aromatic diisocyanate. It is produced for reaction with polyols to form polyurethanes. It exists in two isomers, 2,4-TDI and 2,6-TDI . 2,4-TDI is produced in the pure state, but TDI is often marketed as 80/20 and 65/35 mixtures of the 2,4 and 2,6 isomers respectively...
, and diol
Diol
A diol or glycol is a chemical compound containing two hydroxyl groups A geminal diol has two hydroxyl groups bonded to the same atom...
s, e.g. bisphenol-A, where the carbamate groups are formed by reaction of the alcohols with the isocyanate
Isocyanate
Isocyanate is the functional group of elements –N=C=O , not to be confused with the cyanate functional group which is arranged as –O–C≡N or with isocyanide, R-N≡C. Any organic compound which contains an isocyanate group may also be referred to in brief as an isocyanate. An isocyanate may have more...
s:
- RN=C=O + R'OH → RNHC(O)OR'
Preservatives and cosmetics
Iodopropynyl butylcarbamateIodopropynyl butylcarbamate
Iodopropynyl butylcarbamate is a water-based preservative agent originally used in the wood and paint industries, now also used in some cosmetics and personal care formulations. IPBC is a member of the carbamate family of insecticides....
is a wood and paint preservative and used in cosmetics.
In human medicine
UrethaneUrethane
Urethane can refer to*Carbamates, compounds with the functional group RONHR'*Ethyl carbamate, the colloquial name of which is urethane*Polyurethane in colloquial usage...
or ethyl carbamate
Ethyl carbamate
Ethyl carbamate is a chemical compound with the molecular formula C3H7NO2 first prepared in the nineteenth century. Structurally, it is an ester of carbamic acid...
was once produced commercially in the United States as an antineoplastic agent and for other medicinal purposes. It was found to be toxic and largely ineffective. It is occasionally used as a veterinary medicine.
In addition, some carbamates are used in human pharmacotherapy
Pharmacotherapy
Pharmacotherapy is the treatment of disease through the administration of drugs. As such, it is considered part of the larger category of therapy....
, for example, the cholinesterase
Cholinesterase
In biochemistry, cholinesterase is a family of enzymes that catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.-Types:...
inhibitors neostigmine
Neostigmine
Neostigmine is a parasympathomimetic that acts as a reversible acetylcholinesterase inhibitor.- Synthesis :Neostigmine was first synthesized by Aeschlimann and Reinert in 1931....
and rivastigmine
Rivastigmine
Rivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which...
, whose chemical structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
is based on the natural alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
physostigmine
Physostigmine
Physostigmine is a parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean....
. Other examples are meprobamate
Meprobamate
Meprobamate is a carbamate derivative which is used as an anxiolytic drug...
and its derivatives like carisoprodol
Carisoprodol
Carisoprodol is a centrally-acting skeletal muscle relaxant. Carisoprodol is slightly soluble in water and freely soluble in alcohol, chloroform and acetone. The drug's solubility is practically independent of pH. Carisoprodol is manufactured and marketed in the United States by Meda Pharmaceuticals...
, felbamate
Felbamate
Felbamate is an anticonvulsant drug used in the treatment of epilepsy. It is used to treat partial seizures in adults and partial and generalized seizures associated with Lennox-Gastaut syndrome in children...
, and tybamate
Tybamate
Tybamate is an anxiolytic. It is a prodrug for meprobamate in the same way as the better known drug carisoprodol. It has liver enzyme inducing effects similar to those of phenobarbital but much weaker....
, a class of anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
and muscle relaxant
Muscle relaxant
A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...
drugs widely used in the 60s before the rise of benzodiazepines, and still used nowadays in some cases.
The protease inhibitor
Protease inhibitor
Protease inhibitor can refer to:* Protease inhibitor : a class of medication that inhibits viral protease* Protease inhibitor : molecules that inhibit proteases...
darunavir
Darunavir
Darunavir is a drug used to treat HIV infection. It is in the protease inhibitor class. Prezista is an OARAC recommended treatment option for treatment-naïve and treatment-experienced adults and adolescents. Developed by pharmaceutical company Tibotec, darunavir is named after Arun K...
for HIV treatment also contains a carbamate functional group.
Sulfur analogues
There are two oxygen atoms in a carbamate (1), ROC(=O)NR2, and either or both of them can be conceptually replaced by sulfurSulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
. Analogues of carbamates with only one of the oxygens replaced by sulfur are called thiocarbamate
Thiocarbamate
Thiocarbamates are a family of organosulfur compounds. There are two isomeric forms of thiocarbamate esters: O-thiocarbamates, ROCNR2, and S-thiocarbamates, RSCNR2...
s (2 and 3). Carbamates with both oxygens replaced by sulfur are called dithiocarbamate
Dithiocarbamate
A dithiocarbamate is a functional group in organic chemistry. It is the analog of a carbamate in which both oxygen atoms are replaced by sulfur atoms. Sodium diethyldithiocarbamate is a common ligand in inorganic chemistry....
s (4), RSC(=S)NR2.
There are two different structurally isomeric types of thiocarbamate:
- O-thiocarbamates (2), ROC(=S)NR2, where the carbonylCarbonylIn 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....
group (C=O) is replaced with a thiocarbonyl group (C=S) - S-thiocarbamates (3), RSC(=O)NR2, where the R–O– group is replaced with an R–S– group
O-thiocarbamates can isomerise
Isomerisation
In chemistry isomerisation is the process by which one molecule is transformed into another molecule which has exactly the same atoms, but the atoms are rearranged e.g. A-B-C → B-A-C . In some molecules and under some conditions, isomerisation occurs spontaneously...
to S-thiocarbamates, for example in the Newman-Kwart rearrangement
Newman-Kwart rearrangement
The Newman–Kwart rearrangement is a type of rearrangement reaction in which the aryl group of an O-aryl thiocarbamate, ArOCNMe2, migrates from the oxygen atom to the sulfur atom, forming an S-aryl thiocarbamate, ArSCNMe2...
.