View source for Chemistry:Carbamate

{{Short description|1=Chemical group (>N–C(=O)–O–)}}
[[File:Carbamate-group-2D.png|thumb|Chemical structure of carbamates]]

In [[Chemistry:Organic chemistry|organic chemistry]], a '''carbamate''' is a category of [[Chemistry:Organic compound|organic compound]]s with the general [[Chemistry:Chemical formula|formula]] {{chem2|R2NC(O)OR}} and [[Chemistry:Chemical structure|structure]] {{chem2|>N\sC(\dO)\sO\s}}, which are formally [[Chemistry:Derivative|derived]] from [[Chemistry:Carbamic acid|carbamic acid]] ({{chem2|NH2COOH}}).  The term includes organic compounds (e.g., the [[Chemistry:Ester|ester]] [[Chemistry:Ethyl carbamate|ethyl carbamate]]), formally obtained by replacing one or more of the [[Chemistry:Hydrogen|hydrogen]] atoms by other organic [[Chemistry:Functional group|functional group]]s; as well as [[Chemistry:Salt|salts]] with the carbamate anion {{chem2|H2NCOO-}} (e.g. [[Chemistry:Ammonium carbamate|ammonium carbamate]]).<ref name= Jäger>{{Ullmann|doi=10.1002/14356007.a05_051|title=Carbamates and Carbamoyl Chlorides |year=2000 |last1=Jäger |first1=Peter |last2=Rentzea |first2=Costin N. |last3=Kieczka |first3=Heinz |isbn=3-527-30673-0 }}</ref>

Polymers whose repeat units are joined by carbamate like groups {{chem2|\sNH\sC(\dO)\sO\s}} are an important family of [[Chemistry:Plastic|plastic]]s, the [[Chemistry:Polyurethane|polyurethane]]s. See Etymology for clarification.

==Properties==
While carbamic acids are unstable, many carbamate esters and [[Chemistry:Salt|salts]] are stable and well known.<ref>{{Cite journal |last1=Ghosh |first1=Arun K. |last2=Brindisi |first2=Margherita |date=2015-04-09 |title=Organic Carbamates in Drug Design and Medicinal Chemistry |journal=Journal of Medicinal Chemistry|language=en |volume=58 |issue=7 |pages=2895–2940 |doi=10.1021/jm501371s |issn=0022-2623 |pmc=4393377 |pmid=25565044}}</ref>

===Equilibrium with carbonate and bicarbonate===
In water solutions, the carbamate anion slowly equilibrates with the [[Chemistry:Ammonium|ammonium]] {{chem|NH|4|+}} cation and the [[Chemistry:Carbonate|carbonate]] {{chem|CO|3|2-}} or [[Chemistry:Bicarbonate|bicarbonate]] {{chem|HCO|3|-}} anions:<ref name=burr1912>{{cite journal | last1 = Burrows | first1 = George H. | last2 = Lewis | first2 = Gilbert N. | year = 1912 | title = The equilibrium between ammonium carbonate and ammonium carbamate in aqueous solution at 25° | url = https://zenodo.org/record/2430153| journal =[[Organization:Journal of the American Chemical Society|Journal of the American Chemical Society]]| volume = 34 | issue = 8| pages = 993–995 | doi = 10.1021/ja02209a003}}</ref><ref name = clark>{{cite journal | author1 = Clark, K. G. | author2 = Gaddy, V. L. | author3 = Rist, C. E. | year = 1933 | title = Equilibria in the Ammonium Carbamate-Urea-Water System | journal =Ind. Eng. Chem.| volume = 25 | issue = 10 | pages = 1092–1096 | doi = 10.1021/ie50286a008}}</ref><ref name=mani2006>{{cite journal | last1=Mani | first1=Fabrizio | last2=Peruzzini | first2=Maurizio | last3=Stoppioni | first3=Piero | title=CO2 absorption by aqueous {{chem|N|H|3}} solutions: speciation of ammonium carbamate, bicarbonate and carbonate by a {{chem|13|C}} NMR study | journal=Green Chemistry| publisher=[[Organization:Royal Society of Chemistry|Royal Society of Chemistry]] | volume=8 | issue=11 | year=2006 | issn=1463-9262 | doi=10.1039/b602051h | page=995}}</ref>
: {{chem2|H2NCO2-  +  2 H2O <-> NH4+  +  HCO3- +  OH-}}
: {{chem2|H2NCO2-  +   H2O <->  NH4+  +  CO3(2-)}}

Calcium carbamate is soluble in water, whereas [[Chemistry:Calcium carbonate|calcium carbonate]] is not.  Adding a [[Chemistry:Calcium|calcium]] salt to an ammonium carbamate/carbonate solution will precipitate some calcium carbonate immediately, and then slowly precipitate more as the carbamate hydrolyzes.<ref name=burr1912/>

==Synthesis==
===Carbamate salts===
The salt [[Chemistry:Ammonium carbamate|ammonium carbamate]] is generated by treatment of [[Chemistry:Ammonia|ammonia]] with [[Chemistry:Carbon dioxide|carbon dioxide]]:<ref name="Brooks1946">{{cite book | author1 = Brooks, L. A. | author2 = Audrieta, L. F. | author3 = Bluestone, H. | author4 = Jofinsox, W. C. | title = Inorganic Syntheses | chapter = Ammonium Carbamate | year = 1946 | volume = 2 | pages = 85–86 | doi = 10.1002/9780470132333.ch23| isbn = 978-0-470-13233-3 }}</ref>
:2 NH<sub>3</sub>  +  CO<sub>2</sub>   →    NH<sub>4</sub>[H<sub>2</sub>NCO<sub>2</sub>]

===Carbamate esters===
Carbamate esters also arise via alcoholysis of [[Chemistry:Carbamoyl chloride|carbamoyl chloride]]s:<ref name= Jäger/>
:R<sub>2</sub>NC(O)Cl + R'OH → R<sub>2</sub>NCO<sub>2</sub>R' + HCl
Alternatively, carbamates can be formed from [[Chemistry:Chloroformate|chloroformate]]s and [[Chemistry:Amine|amine]]s:<ref name="Chaturvedi2011">{{cite journal | last=Chaturvedi | first=Devdutt | title=Recent Developments on the Carbamation of Amines | journal=[[Chemistry:Current Organic Chemistry|Current Organic Chemistry]]| publisher=Bentham Science Publishers Ltd.| volume=15 | issue=10 | date=1 May 2011 | issn=1385-2728 | doi=10.2174/138527211795378173 | pages=1593–1624}}</ref>
:R'OC(O)Cl + R<sub>2</sub>NH → R<sub>2</sub>NCO<sub>2</sub>R' + HCl
Carbamates may be formed from the [[Chemistry:Curtius rearrangement|Curtius rearrangement]], where [[Chemistry:Isocyanate|isocyanate]]s formed are reacted with an alcohol.<ref name="Chaturvedi2011"/>
:RCON<sub>3</sub> → RNCO + N<sub>2</sub>
:RNCO + R′OH → RNHCO<sub>2</sub>R′

==Natural occurrence==
Within nature carbon dioxide can bind with neutral amine groups to form a carbamate, this post-translational modification is known as carbamylation. This modification is known to occur on several important proteins; see examples below.<ref>{{Cite journal|last1=Linthwaite|first1=Victoria L.|last2=Janus|first2=Joanna M.|last3=Brown|first3=Adrian P.|last4=Wong-Pascua|first4=David|last5=O'Donoghue|first5=AnnMarie C.|last6=Porter|first6=Andrew|last7=Treumann|first7=Achim|last8=Hodgson|first8=David R. W.|last9=Cann|first9=Martin J.|date=2018-08-06|title=The identification of carbon dioxide mediated protein post-translational modifications|journal=Nature Communications|language=en|volume=9|issue=1|page=3092|doi=10.1038/s41467-018-05475-z|pmid=30082797|pmc=6078960|bibcode=2018NatCo...9.3092L|issn=2041-1723}}</ref>

===Hemoglobin===
The N-terminal amino groups of [[Chemistry:Valine|valine]] residues in the α- and β-chains of [[Biology:Hemoglobin|deoxyhemoglobin]] exist as carbamates. They help to stabilise the protein when it becomes deoxyhemoglobin, and increases the likelihood of the release of remaining [[Chemistry:Oxygen|oxygen]] molecules bound to the protein. This stabilizing effect should not be confused with the [[Medicine:Bohr effect|Bohr effect]] (an indirect effect caused by carbon dioxide).<ref>{{Cite journal|last1=Ferguson|first1=J. K. W.|last2=Roughton|first2=F. J. W.|date=1934-12-14|title=The direct chemical estimation of carbamino compounds of CO2 with hæmoglobin|journal=The Journal of Physiology|volume=83|issue=1|pages=68–86|doi=10.1113/jphysiol.1934.sp003212|issn=0022-3751|pmc=1394306|pmid=16994615}}</ref>

===Urease and phosphotriesterase===
The ε-amino groups of the [[Chemistry:Lysine|lysine]] residues in [[Biology:Urease|urease]] and phosphotriesterase also feature carbamate. The carbamate derived from aminoimidazole is an intermediate in the biosynthesis of [[Chemistry:Inosine|inosine]]. Carbamoyl phosphate is generated from carboxyphosphate
rather than CO<sub>2</sub>.<ref>{{cite journal|last1=Bartoschek|first1=S.|last2=Vorholt|first2=J. A.|last3=Thauer|first3=R. K.|last4=Geierstanger|first4=B. H.|last5=Griesinger|first5=C.|title=''N''-Carboxymethanofuran (carbamate) formation from methanofuran and CO<sub>2</sub> in methanogenic archaea: Thermodynamics and kinetics of the spontaneous reaction|journal=Eur. J. Biochem.|date=2001|volume=267|issue=11|pages=3130–3138|doi=10.1046/j.1432-1327.2000.01331.x|pmid=10824097|doi-access=free}}</ref>

===CO<sub>2</sub> capture by ribulose 1,5-bisphosphate carboxylase===
Perhaps the most prevalent carbamate is the one involved in the capture of [[Chemistry:Carbon dioxide|CO<sub>2</sub>]] by plants.  This process is necessary for their growth. The enzyme [[Biology:RuBisCO|ribulose 1,5-bisphosphate carboxylase/oxygenase]] (RuBisCO) fixes a molecule of carbon dioxide as phosphoglycerate in the [[Biology:Calvin cycle|Calvin cycle]]. At the active site of the enzyme, a [[Chemistry:Magnesium|Mg<sup>2+</sup>]] ion is bound to [[Chemistry:Glutamic acid|glutamate]] and [[Chemistry:Aspartic acid|aspartate]] residues as well as a lysine carbamate. The carbamate is formed when an uncharged lysine [[Chemistry:Side chain|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 Mg<sup>2+</sup> ion.<ref>{{Cite journal|title=Crystal Structure of the Ternary Complex of ribulose-1,5-bisphosphate Carboxylase, Mg(II), and Activator CO2 at 2.3-A Resolution|last1=T|first1=Lundqvist|last2=G|first2=Schneider|journal=Biochemistry|date=1991-01-29|volume=30|issue=4|pages=904–8|doi=10.1021/bi00218a004|language=en|pmid=1899197}}</ref>
[[File:RuBisCO regulation.svg|350px|center|thumb|Carbamate formation is a critical step in the formation of biomass from atmospheric carbon dioxide.]]

==Applications==
===Synthesis of urea===
Although not usually isolated as such, the salt [[Chemistry:Ammonium carbamate|ammonium carbamate]] is produced on a large scale as an intermediate in the production of the commodity chemical [[Chemistry:Urea|urea]] from [[Chemistry:Ammonia|ammonia]] and [[Chemistry:Carbon dioxide|carbon dioxide]].<ref name= Jäger/>

===Polyurethane plastics===
{{main|Chemistry:Polyurethane}}
[[Chemistry:Polyurethane|Polyurethane]]s contain multiple carbamate groups as part of their structure. The "urethane" in the name "polyurethane" refers to these carbamate groups; the term "urethane links" describe how carbamates polymerize.<sup>[Requires Citation]</sup> In contrast, the substance commonly called "urethane", [[Chemistry:Ethyl carbamate|ethyl carbamate]], is neither a component of polyurethanes, nor is it used in their manufacture.<sup>[Requires Citation]</sup> Urethanes are usually formed by reaction of an [[Chemistry:Alcohol|alcohol]] with an [[Chemistry:Isocyanate|isocyanate]].<sup>[Requires Citation]</sup> Commonly, urethanes made by a non-isocyanate route are called carbamates.<sup>[Requires Citation]</sup>

Polyurethane [[Chemistry:Polymer|polymer]]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. [[Chemistry:Toluene diisocyanate|toluene diisocyanate]], and [[Chemistry:Diol|diol]]s, where the carbamate groups are formed by reaction of the alcohols with the [[Chemistry:Isocyanate|isocyanate]]s:<ref>{{Ullmann |doi=10.1002/14356007.a21_665.pub3 |title=Polyurethanes |year=2005 |last1=Adam |first1=Norbert |last2=Avar |first2=Geza |last3=Blankenheim |first3=Herbert |last4=Friederichs |first4=Wolfgang |last5=Giersig |first5=Manfred |last6=Weigand |first6=Eckehard |last7=Halfmann |first7=Michael |last8=Wittbecker |first8=Friedrich-Wilhelm |last9=Larimer |first9=Donald-Richard |last10=Maier |first10=Udo |last11=Meyer-Ahrens |first11=Sven |last12=Noble |first12=Karl-Ludwig |last13=Wussow |first13=Hans-Georg |isbn=978-3-527-30673-2 }}</ref>
:RN=C=O + R′OH → RNHC(O)OR′

===Carbamate insecticides===
[[File:Carbaryl-2D-skeletal.png|thumb|100 px|The carbamate insecticide [[Chemistry:Carbaryl|Carbaryl]].]]
The so-called carbamate [[Biology:Insecticide|insecticide]]s feature the carbamate ester functional group. Included in this group are [[Chemistry:Aldicarb|aldicarb]] (Temik), [[Chemistry:Carbofuran|carbofuran]] (Furadan), [[Chemistry:Carbaryl|carbaryl]] (Sevin), ethienocarb, [[Chemistry:Fenobucarb|fenobucarb]], [[Chemistry:Oxamyl|oxamyl]], and [[Chemistry:Methomyl|methomyl]]. These insecticides kill insects by reversibly inactivating the enzyme [[Biology:Acetylcholinesterase|acetylcholinesterase]] (AChE inhibition)<ref>{{cite journal |pmc=1567830|year=1990|last1=Fukuto|first1=T. R.|title=Mechanism of action of organophosphorus and carbamate insecticides|journal=Environmental Health Perspectives |volume=87|pages=245–254|doi=10.1289/ehp.9087245|pmid=2176588}}</ref> (IRAC [[Chemistry:Mode of action|mode of action]] 1a).<ref name="IRAC-MoAs-9.4" /> The [[Chemistry:Organophosphate|organophosphate]] pesticides also inhibit this enzyme, although irreversibly, and cause a more severe form of cholinergic poisoning<ref name=Ullmann>{{Ullmann|first=Robert L.|last=Metcalf|title=Insect Control|doi=10.1002/14356007.a14_263}}</ref> (the similar IRAC MoA 1b).<ref name="IRAC-MoAs-9.4" />

[[Chemistry:Fenoxycarb|Fenoxycarb]] has a carbamate group but acts as a [[Chemistry:Insect growth regulator|juvenile hormone mimic]], rather than inactivating acetylcholinesterase.<ref>{{cite web|url=http://pmep.cce.cornell.edu/profiles/extoxnet/dienochlor-glyphosate/fenoxycarb-ext.html|publisher=[[Organization:Cornell University|Cornell University]]|title=Pesticide Information Project: Fenoxycarb|access-date=15 June 2019}}</ref>

The insect repellent [[Chemistry:Icaridin|icaridin]] is a substituted carbamate.<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/Icaridin|title=PubChem Compound Summary for CID 125098, Icaridin|author=((National Center for Biotechnology Information))|website=Pubchem|access-date=2024-01-08}}</ref>

Besides their common use as arthropodocides/insecticides, they are also nematicidal.<ref name="Updates" /> One such is [[Chemistry:Oxamyl|Oxamyl]].<ref name="Updates" />

Sales have declined dramatically over recent decades.<ref name="Updates">{{cite journal|year=2020|publisher=[[Company:Elsevier|Elsevier]]|last1=Sparks|first1=Thomas|last2=Crossthwaite|first2=Andrew|last3=Nauen|first3=Ralf|last4=Banba|first4=Shinichi|last5=Cordova|first5=Daniel|last6=Earley|first6=Fergus|last7=Ebbinghaus-Kintscher|first7=Ulrich|last8=Fujioka|first8=Shinsuke|last9=Hirao|first9=Ayako|last10=Karmon|first10=Danny|last11=Kennedy|first11=Robert|last12=Nakao|first12=Toshifumi|last13=Popham|first13=Holly|last14=Salgado|first14=Vincent|last15=Watson|first15=Gerald|last16=Wedel|first16=Barbara|last17=Wessels|first17=Frank|volume=167|page=104587|journal=Pesticide Biochemistry and Physiology|issn=0048-3575|doi=10.1016/j.pestbp.2020.104587|title=Insecticides, biologics and nematicides: Updates to IRAC's mode of action classification - a tool for resistance management|pmid=32527435 |doi-access=free}}</ref>

==Resistance==
Among mutations in [[Biology:Esterase|esterase]]s, carbamate resistance most commonly involves [[Biology:Acetylcholinesterase|acetylcholinesterase]] (AChE) desensitization, while organophosphate resistance most commonly is [[Biology:Carboxylesterase|carboxylesterase]] metabolization.<ref name="Comparing">{{cite journal|year=2005|publisher=Elsevier BV|last1=Oakeshott|first1=John|last2=Devonshire|first2=Alan|last3=Claudianos|first3=Charles|last4=Sutherland|first4=Tara|last5=Horne|first5=Irene|last6=Campbell|first6=Peter|last7=Ollis|first7=David|last8=Russell|first8=Robyn|pages=269–275|volume=157-158|journal=Chemico-Biological Interactions|issn=0009-2797|s2cid=32597626|pmid=16289012|doi=10.1016/j.cbi.2005.10.041|title=Comparing the organophosphorus and carbamate insecticide resistance mutations in cholin- and carboxyl-esterases}}</ref>

===Carbamate nerve agents===
While the carbamate acetylcholinesterase inhibitors are commonly referred to as "carbamate insecticides" due to their generally high selectivity for insect acetylcholinesterase enzymes over the mammalian versions, the most potent compounds such as [[Chemistry:Aldicarb|aldicarb]] and [[Chemistry:Carbofuran|carbofuran]] are still capable of inhibiting mammalian acetylcholinesterase enzymes at low enough concentrations that they pose a significant risk of poisoning to humans, especially when used in large amounts for agricultural applications. Other carbamate based acetylcholinesterase inhibitors are known with even higher toxicity to humans, and some such as [[Chemistry:T-1123|T-1123]] and [[Chemistry:EA-3990|EA-3990]] were investigated for potential military use as [[Biology:Nerve agent|nerve agent]]s. However, since all compounds of this type have a [[Chemistry:Quaternary ammonium cation|quaternary ammonium group]] with a permanent positive charge, they have poor [[Biology:Blood–brain barrier|blood–brain barrier]] penetration, and also are only stable as crystalline salts or aqueous solutions, and so were not considered to have suitable properties for weaponisation.<ref name="Handbook_of_Toxicology_of_Chemical_Warfare_Agents">{{cite book | url=https://books.google.com/books?id=MXKDBAAAQBAJ&pg=PA338 | title=Handbook of Toxicology of Chemical Warfare Agents | publisher=Academic Press | editor=Gupta, Ramesh C   | year=2015 | location=Cambridge, Massachusetts, United States | pages=338–339 | isbn=978-0-12-800494-4}}</ref><ref>{{cite book | last=Ellison | first=D | title=Handbook of chemical and biological warfare agents | publisher=CRC Press | publication-place=Boca Raton | year=2008 | isbn=978-0-8493-1434-6 | oclc=82473582 }}</ref>

===Preservatives and cosmetics===
[[Chemistry:Iodopropynyl butylcarbamate|Iodopropynyl butylcarbamate]] is a wood and paint preservative and used in cosmetics.<ref name="Badreshia2002">{{cite journal|last=Badreshia|first=S.|year=2002|title=Iodopropynyl butylcarbamate|journal=Am. J. Contact Dermat.|volume=13|issue=2|pages=77–79|issn=1046-199X|doi=10.1053/ajcd.2002.30728|pmid=12022126}}</ref>

===Chemical research===
Some of the most common amine protecting groups, such as [[Chemistry:Tert-Butyloxycarbonyl protecting group|BOC]],<ref>{{cite book | doi = 10.1002/9783527631827.ch1 | chapter = Protection Reactions | editor = Andrew B. Hughes | author1 = Vommina V. Sureshbabu | author2 = Narasimhamurthy Narendra | volume = 4 | series = Amino Acids, Peptides and Proteins in Organic Chemistry | title = Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis | publisher = Wiley-VCH | chapter-url = https://books.google.com/books?id=uZK2i-FkeAUC&pg=PP18 | isbn = 9783527641574 | pages = XVIII – LXXXIV| year = 2011 }}</ref> [[Biology:Fluorenylmethyloxycarbonyl protecting group|FMOC]],<ref>{{cite book |doi=10.1016/s0076-6879(97)89043-x |chapter=&#91;4&#93; Standard Fmoc protocols |title=Solid-Phase Peptide Synthesis |series=Methods in Enzymology |date=1997 |last1=Wellings |first1=Donald A. |last2=Atherton |first2=Eric |volume=289 |pages=44–67 |pmid=9353717 |isbn=9780121821906 }}</ref> [[Chemistry:Benzyl chloroformate|benzyl chloroformate]]<ref>{{Cite book|url=https://org.chem.uoa.gr/istoriki_exelixi_toy_ergastirioy_organikis_chimeias_historical_development_of_organic_chemistry_laboratory/afieroma_ston_leonida_zerba_dedication_to_prof_leonidas_zervas/i_symboli_toy_l_zerba_stin_epistimi_tis_chimeias_contribution_of_l_zervas_in_the_science_of_chemistry/|title=The Chemistry of Polypeptides|publisher=Plenum Press|year=1973|isbn=978-1-4613-4571-8|editor-last=Katsoyannis|editor-first=P. G.|location=New York|doi=10.1007/978-1-4613-4571-8|s2cid=35144893|access-date=2021-04-01|archive-date=2022-10-13|archive-url=https://web.archive.org/web/20221013010830/https://org.chem.uoa.gr/istoriki_exelixi_toy_ergastirioy_organikis_chimeias_historical_development_of_organic_chemistry_laboratory/afieroma_ston_leonida_zerba_dedication_to_prof_leonidas_zervas/i_symboli_toy_l_zerba_stin_epistimi_tis_chimeias_contribution_of_l_zervas_in_the_science_of_chemistry/|url-status=dead}}</ref> and [[Chemistry:2,2,2-Trichloroethoxycarbonyl chloride|trichloroethyl chloroformate]]<ref>{{Cite journal|last=Marullo|first=N. P.|last2=Wagener|first2=E. H.|date=1969-01-01|title=Structural organic chemistry by nmr. III. Isomerization of compounds containing the carbon-nitrogen double bond|journal=Tetrahedron Letters|volume=10|issue=30|pages=2555–2558|doi=10.1016/S0040-4039(01)88566-X}}</ref> are carbamates.

===Medicine===
====Ethyl carbamate====
Urethane ([[Chemistry:Ethyl carbamate|ethyl carbamate]]) was once produced commercially in the United States as a [[Medicine:Chemotherapy|chemotherapy]] agent and for other medicinal purposes. It was found to be toxic and largely ineffective.<ref>{{cite journal |pmid= 5933438 |last1= Holland |first1= J. R. |last2= Hosley |first2= H. |last3= Scharlau |first3= C. |last4= Carbone |first4= P. P. |last5= Frei |first5= E. III |last6= Brindley |first6= C. O. |last7= Hall |first7= T. C. |last8= Shnider |first8= B. I. |last9= Gold |first9= G. L. |last10= Lasagna |first10= L. |last11= Owens |first11= A. H. Jr |last12= Miller |first12= S. P. |title= A controlled trial of urethane treatment in multiple myeloma |journal=Blood|volume= 27 |issue= 3 |pages= 328–42 |date= 1 March 1966 |doi= 10.1182/blood.V27.3.328.328 |issn= 0006-4971 |doi-access= free }}</ref> It is occasionally used in veterinary medicine in combination with other drugs to produce [[Medicine:Anesthesia|anesthesia]].<ref>{{cite web|publisher=Virginia Commonwealth University |author=((The Chemical/Biological Safety Section (CBSS) of the Office of Environmental Health and Safety)) |url=http://www.vcu.edu/oehs/chemical/biosafe/urethane.pdf|title= Working with Urethane |archive-url=https://web.archive.org/web/20130511205145/http://www.vcu.edu/oehs/chemical/biosafe/urethane.pdf |archive-date=2013-05-11 }}</ref>

====Carbamate drugs====
In addition, some carbamates are used in human [[Medicine:Pharmacotherapy|pharmacotherapy]], for example, the [[Biology:Acetylcholinesterase inhibitor|acetylcholinesterase inhibitor]]s [[Chemistry:Neostigmine|neostigmine]] and [[Chemistry:Rivastigmine|rivastigmine]], whose [[Chemistry:Chemical structure|chemical structure]] is based on the natural [[Chemistry:Alkaloid|alkaloid]] [[Chemistry:Physostigmine|physostigmine]]. Other examples are [[Chemistry:Meprobamate|meprobamate]] and its derivatives like [[Chemistry:Carisoprodol|carisoprodol]], [[Chemistry:Felbamate|felbamate]], [[Chemistry:Mebutamate|mebutamate]], [[Chemistry:Phenprobamate|phenprobamate]], and [[Chemistry:Tybamate|tybamate]], a class of [[Chemistry:Anxiolytic|anxiolytic]] and [[Chemistry:Muscle relaxant|muscle relaxant]] drugs widely used in the 1960s before the rise of benzodiazepines, and still used nowadays in some cases. [[Chemistry:Carbachol|Carbachol]] is primarily used for various ophthalmic purposes.<ref>Carbachol {{Drugs.com|MTM|carbachol}}. Accessed 27 April 2021.</ref>

The [[Biology:Protease inhibitor (pharmacology)|protease inhibitor]] [[Chemistry:Darunavir|darunavir]] for HIV treatment also contains a carbamate functional group.<ref>{{DrugBank|DB01264}}. Accessed 27 April 2021.</ref>

[[Chemistry:List of aminorex analogues|Ephedroxane]], an [[Chemistry:Aminorex|aminorex]] analogue used as a [[Chemistry:Stimulant|stimulant]], also falls into the carbamate category.<ref>{{cite journal | vauthors = Hikino H, Ogata K, Kasahara Y, Konno C | title = Pharmacology of ephedroxanes | journal = Journal of Ethnopharmacology | volume = 13 | issue = 2 | pages = 175–191 | date = May 1985 | doi = 10.1016/0378-8741(85)90005-4 | pmid = 4021515 }}</ref>

==Toxicity==
Besides inhibiting human acetylcholinesterase<ref>{{cite journal | pmc=3648782 | pmid=24179466 | doi=10.2174/1570159X11311030006 | volume=11 | title=Acetylcholinesterase inhibitors: pharmacology and toxicology | year=2013 | journal=Curr Neuropharmacol| pages=315–35 | last1 = Colović | first1 = MB | last2 = Krstić | first2 = DZ | last3 = Lazarević-Pašti | first3 = TD | last4 = Bondžić | first4 = AM | last5 = Vasić | first5 = VM| issue=3 }}</ref> (although to a lesser degree than the insect enzyme), carbamate insecticides also target human melatonin receptors.<ref>{{cite journal | pmc=5318275 | pmid=28027439 | doi=10.1021/acs.chemrestox.6b00301 | volume=30 | title=Carbamate Insecticides Target Human Melatonin Receptors | year=2017 | journal=Chem Res Toxicol| pages=574–582 | last1 = Popovska-Gorevski | first1 = M | last2 = Dubocovich | first2 = ML | last3 = Rajnarayanan | first3 = RV| issue=2 }}</ref> The human health effects of carbamates are well documented in the list of known endocrine disruptor compounds.<ref name=":0">{{Cite journal |last1=Marais |first1=Simone |last2=Diase |first2=Elsa |last3=Pereira |first3=Maria de Lourdes |date=2012 |title=Carbamates: Human Exposure and Health Effects |url=https://www.researchgate.net/publication/232936639 |journal=The Impact of Pesticides|volume=21 |page=38 |via=Research Gate}}</ref> Clinical effects of carbamate exposure can vary from slightly toxic to highly toxic depending on a variety of factors including such as dose and route of exposure with ingestion and inhalation resulting in the most rapid clinical effects.<ref name=":0" /> These clinical manifestations of carbamate intoxication are muscarinic signs, nicotinic signs, and in rare cases central nervous system signs.<ref name=":0" />

==Sulfur analogues==
There are two oxygen atoms in a carbamate ('''1'''), ROC(=O)NR<sub>2</sub>, and either or both of them can be conceptually replaced by [[Chemistry:Sulfur|sulfur]]. [[Chemistry:Structural analog|Analogues]] of carbamates with only one of the oxygens replaced by sulfur are called [[Chemistry:Thiocarbamate|thiocarbamate]]s ('''2''' and '''3'''). Carbamates with both oxygens replaced by sulfur are called [[Chemistry:Dithiocarbamate|dithiocarbamate]]s ('''4'''), RSC(=S)NR<sub>2</sub>.<ref>{{cite encyclopedia|title=Dithiocarbamic Acid and Derivatives|encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry|author=Rüdiger Schubart|year=2000|doi=10.1002/14356007.a09_001|publisher=Wiley-VCH|isbn=3-527-30673-0|place=Weinheim}}</ref>

There are two different [[Chemistry:Structural isomer|structurally isomeric]] types of thiocarbamate:
*''O''-thiocarbamates ('''2'''), ROC(=S)NR<sub>2</sub>, where the carbonyl group (C=O) is replaced with a thiocarbonyl group (C=S)<ref name="synth rev a">{{cite journal |last1=Walter |first1=W. |last2=Bode |first2=K.-D. |title=Syntheses of Thiocarbamates |journal=Angewandte Chemie International Edition in English |date=April 1967 |volume=6 |issue=4 |pages=281–293 |doi=10.1002/anie.196702811}}</ref>
*''S''-thiocarbamates ('''3'''), RSC(=O)NR<sub>2</sub>, where the R–O– group is replaced with an R–S– group<ref name="synth rev a" />

''O''-thiocarbamates can isomerise to ''S''-thiocarbamates, for example in the [[Chemistry:Newman–Kwart rearrangement|Newman–Kwart rearrangement]].<ref>{{cite journal |title=Thiophenols from Phenols: [[Chemistry:2-Naphthalenethiol|2-Naphthalenethiol]] |last1=Newman |first1=Melvin S. |last2=Hetzel |first2=Frederick W. |journal=Org. Synth. |year=1971 |volume=51 |page=139 |doi=10.15227/orgsyn.051.0139}}</ref>
[[File:Carbamates-thiocarbamates-dithiocarbamates-general-2D.png|700px]]

== Etymology ==
The etymology of the words "urethane" and "carbamate" are highly similar but not the same. The word "urethane" was first coined in 1833 by French chemist Jean-Baptiste Dumas.<ref>{{Cite book |title=A dictionary of chemistry |date=2008 |publisher=Oxford University Press |others=John Daintith |isbn=978-1-61583-965-0 |edition=6th |location=New York |oclc=713875281}}</ref><ref name=":1">{{Cite journal |last=Dumas |first=Jean |date=1833 |title=Recherches de chimie organique |url=https://books.google.com/books?id=xEFRnP2_OmQC&q=j.+Dumas%2C+%27Recherches+de+chimie+organique%27&pg=PA499 |journal=Annales de Chimie et de Physique|series=2nd series |volume=56 |pages=496–556}}</ref> Dumas states "Urethane. The new ether, brought into contact with liquid and concentrated ammonia, exerts on this substance a reaction so strong that the mixture boils, and sometimes even produces a sort of explosion. If the ammonia is in excess, all the ether disappears. It forms ammonium hydrochlorate and a new substance endowed with interesting properties."<ref name=":1" /> Dumas appears to be naming this compound urethane. However, later Dumas states "While waiting for opinion to settle on the nature of this body, I propose to designate by the names of urethane and oxamethane the two materials which I have just studied, and <em>which I regard as types of a new family, among nitrogenous substances</em>. These names which, in my eyes, do not prejudge anything in the question of alcohol and ethers, will at least have the advantage of satisfying chemists who still refuse to accept our theory."<ref name=":1" /> The word urethane is derived from the words "urea" and "ether" with the suffix "-ane" as a generic chemical suffix, making it specific for the R2NC(=O)OR' (R' not = H) bonding structure.<ref>{{Cite web |title=urethane {{!}} Etymology, origin and meaning of urethane by etymonline |url=https://www.etymonline.com/word/urethane |access-date=2023-03-29 |website=www.etymonline.com |language=en}}</ref>

The use of the word "carbamate" appears to come later only being traced back to at least 1849, in a description of Dumas's work by Henry Medlock.<ref name=":2">{{Cite journal |last=Medlock |first=Henry |date=1849 |title=XXIX.—Researches on the amyl series |journal=Q. J. Chem. Soc.|volume=1 |issue=4 |pages=368–379 |doi=10.1039/qj8490100368 |issn=1743-6893|url=https://zenodo.org/record/2080479 }}</ref> Medlock states "It is well known that the action of ammonia on chloro-carbonate (phosgene) of ethyl gives rise to the formation of the substance which Dumas, the discoverer, called urethane, and which we are now in the habit of considering as the ether of carbamic acid."<ref name=":2" /> This suggests that instead of continuing with the urethane family naming convention Dumas coined, they altered the naming convention to ethyl ether of carbamic acid. Carbamate is derived from the words "carbamide", otherwise known as urea, and "-ate" a suffix which indicates the salt or ester of an acid.<ref>{{Cite web |title=Definition of CARBAMATE |url=https://www.merriam-webster.com/dictionary/carbamate |access-date=2023-03-29 |website=www.merriam-webster.com |language=en}}</ref><ref>{{Cite journal |last=Divers |first=Edward |date=1870-01-01 |title=XXVII.—On the precipitation of solutions of ammonium carbonate, sodium carbonate, and ammonium carbamate by calcium chloride |url=https://pubs.rsc.org/en/content/articlelanding/1870/js/js8702300359 |journal=[[Organization:Journal of the Chemical Society|Journal of the Chemical Society]]|language=en |volume=23 |pages=359–364 |doi=10.1039/JS8702300359 |issn=0368-1769}}</ref>

Both words have roots deriving from urea. Carbamate is less-specific because the -ate suffix is ambiguous for either the salt or ester of a carbamic acid. However, the -ate suffix is also more specific because it suggests carbamates must be derived from the acid of carbamate, or carbamic acids''.'' Although, a urethane has the same chemical structure as a carbamate ester moiety, a urethane not derived from a carbamic acid is not a carbamate ester. In other words, any synthesis of the R2NC(=O)OR' (R' not = H) moiety that ''does not derive from carbamic acids'' is not a carbamate ester but instead a urethane. Furthermore, carbamate esters are urethanes but not all urethanes are carbamate esters. This further suggests that polyurethanes are not simply polycarbamate-esters because polyurethanes are not typically synthesized using carbamic acids.

IUPAC states  "The esters are often called urethanes or urethans, a usage that is strictly correct only for the ethyl esters."<ref>{{Cite book |chapter=Carbamates (C00803) |title=Goldbook |url=https://goldbook.iupac.org/terms/view/C00803 |access-date=2023-03-29 |publisher=IUPAC|doi=10.1351/goldbook.C00803 }}</ref> But also states, "An alternative term for the compounds R2NC(=O)OR' (R' not = H), esters of carbamic acids, R,NC(=O)OH, in strict use limited to the ethyl esters, but widely used in the general sense".<ref>{{Cite journal |last1=Moss |first1=G. P. |last2=Smith |first2=P. a. S. |last3=Tavernier |first3=D. |date=1995-01-01 |title=Glossary of class names of organic compounds and reactivity intermediates based on structure (IUPAC Recommendations 1995) |journal=[[Chemistry:Pure and Applied Chemistry|Pure and Applied Chemistry]]|language=de |volume=67 |issue=8–9 |pages=1307–1375 |doi=10.1351/pac199567081307 |s2cid=95004254 |issn=1365-3075|doi-access=free }}</ref> IUPAC provides these statements without citation.

==See also==
*[[Chemistry:Methyl carbamate|Methyl carbamate]]
*[[Chemistry:Ethyl carbamate|Ethyl carbamate]]
*[[Chemistry:Polyurethane|Polyurethane]]
*[[Biology:Cholinesterase inhibitor|Cholinesterase inhibitor]]

==References==
{{Reflist|30em|refs=

<ref name="IRAC-MoAs-9.4">{{cite web|url=http://irac-online.org/documents/moa-classification/|title=IRAC Mode of Action Classification Scheme Version 9.4|publisher=[[Organization:Insecticide Resistance Action Committee|Insecticide Resistance Action Committee]]|type=pdf|date=March 2020}}</ref>

}}

{{Functional groups}}

[[Category:Functional groups]]
[[Category:Carbamates| ]]

{{Sourceattribution|Carbamate}}