# Formamide

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> Markdown URL: https://mediated.wiki/source/Formamide.md
> Source: https://en.wikipedia.org/wiki/Formamide
> Source revision: 1355348730
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{{Short description|CH3NO, simplest amide}}
{{chembox
| Watchedfields = changed
| verifiedrevid = 443825387
| Name = Formamide
| ImageFile = Formamide-2D.png
| ImageClass = skin-invert 
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageName = Structural formula of the formamide molecule
| ImageFileL1_Ref = {{chemboximage|correct|??}}
| ImageFileL1 = Formamide-3D-balls.png
| ImageClassL1 = bg-transparent  
| ImageNameL1 = Ball and stick model of formamide
| ImageFileR1 = Formamide-3D-vdW.png
| ImageClassR1 = bg-transparent  
| ImageNameR1 = Space-filling model of the formamide molecule
| PIN = Formamide<ref name=iupac2013>{{cite book | title =  Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [The Royal Society of Chemistry](/source/Royal_Society_of_Chemistry) | date = 2014 | location = Cambridge | page = 841 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4 | quote = The traditional name ‘formamide’ is retained for HCO-NH<sub>2</sub> and is the preferred IUPAC name.}}</ref>
| SystematicName = Methanamide
| OtherNames = Carbamaldehyde
|Section1={{Chembox Identifiers
| CASNo = 75-12-7
| CASNo_Ref = {{cascite|correct|CAS}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 48431
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 266160
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 693
| EC_number = 200-842-0
| IUPHAR_ligand = 4739
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00488
| PubChem = 713
| InChI = 1/CH3NO/c2-1-3/h1H,(H2,2,3)
| InChIKey = ZHNUHDYFZUAESO-UHFFFAOYAQ
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4781T907ZS
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/CH3NO/c2-1-3/h1H,(H2,2,3)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZHNUHDYFZUAESO-UHFFFAOYSA-N
| SMILES = O=CN
}}
|Section2={{Chembox Properties
|C=1|H=3|N=1|O=1
| Density = 1.133 g/cm<sup>3</sup>
| Appearance = Colorless, oily liquid<ref name=PGCH/>
| MeltingPtC = 2 to 3
| BoilingPtC = 210
| VaporPressure = 0.08 mmHg at 20&nbsp;°C
| Solubility = Miscible
| MagSus = {{val|-2.19|e=-5|u=cm<sup>3</sup>/mol}}
| pKa = 23.5 (in [DMSO](/source/Dimethyl_sulfoxide))<ref>{{cite journal |author1=F. G. Bordwell |author2=J. E. Bartmess |author3=J. A. Hautala | title = Alkyl effects on equilibrium acidities of carbon acids in protic and dipolar aprotic media and the gas phase | year = 1978 | journal = [J. Org. Chem.](/source/J._Org._Chem.) | volume = 43 | issue = 16 | pages = 3095–3101 | doi = 10.1021/jo00410a001}}</ref>
  }}
|Section7={{Chembox Hazards
| FlashPtC = 154
| FlashPt_notes = (closed cup)
| NFPA-F = 1 | NFPA-H = 2 | NFPA-R = 0
| PEL = none<ref name=PGCH>{{PGCH|0295}}</ref>
| IDLH = N.D.<ref name=PGCH/>
| REL = TWA 10 ppm (15 mg/m<sup>3</sup>) [skin]<ref name=PGCH/>
 }}
|Section8={{Chembox Related
| OtherCompounds = [Carbamic acid](/source/Carbamic_acid) <br /> [Dimethylformamide](/source/Dimethylformamide)}}
}}

'''Formamide''' is an [amide](/source/amide) derived from [formic acid](/source/formic_acid). It is a colorless liquid which is miscible with water and has an [ammonia](/source/ammonia)-like odor. It is chemical feedstock for the manufacture of [sulfa drug](/source/sulfa_drug)s and other [pharmaceutical](/source/pharmaceutical)s, [herbicide](/source/herbicide)s and [pesticides](/source/pesticides), and in the manufacture of [hydrocyanic acid](/source/hydrocyanic_acid).  It has been used as a [softener](/source/Fabric_softener) for paper and fiber. It is a [solvent](/source/solvent) for many [ionic compound](/source/ionic_compound)s. It has also been used as a solvent for [resins](/source/resins) and [plasticizers](/source/plasticizers).<ref name= KirkOthmer>{{cite book |last1=Hohn |first1=A.  |editor1-first= Jacqueline I. |editor1-last= Kroschwitz |title=Kirk-Othmer Concise Encyclopedia of Chemical Technology |edition=4th |year=1999 |publisher= John Wiley & Sons, Inc.|location=New York|isbn=978-0471419617|pages=943–944 |chapter=Formamide}}</ref> Some astrobiologists suggest that it may be an alternative to water as the main solvent in other forms of life.<ref>{{cite news | url=https://www.economist.com/science-and-technology/2022/05/25/how-to-improve-the-search-for-aliens | title=How to improve the search for aliens | newspaper=The Economist }}</ref>

'''Formamides''' are compounds of the type RR′NCHO. One important formamide is [dimethylformamide](/source/dimethylformamide), (CH<sub>3</sub>)<sub>2</sub>NCHO.

==Production==
===Historical production===
In the past, formamide was produced by treating [formic acid](/source/formic_acid) with [ammonia](/source/ammonia), which produces [ammonium formate](/source/ammonium_formate), which in turn yields formamide upon heating:<ref>{{cite journal|last1=Lorin|first1=M.|title=Preparation of Formamide by means of Formiates and Oxalates|journal=The Chemical News and Journal of Physical Science|date=1864|volume=IX|page=291|url=https://books.google.com/books?id=7eQEAAAAQAAJ&q=Preparation+of+formamide+by+means+of&pg=RA1-PA291|access-date=14 June 2014}}</ref>
:{{chem2|HCOOH + NH3 → HCOO−[NH4]+}}
:{{chem2|HCOO−[NH4]+ → HCONH2 + [H2O](/source/water)}}

Formamide is also generated by [aminolysis](/source/aminolysis) of [ethyl formate](/source/ethyl_formate):<ref>{{cite journal|last1=Phelps|first1=I. K.|last2=Deming|first2=C. D.|title=The Preparation of Formamide from Ethyl Formate and Ammonium Hydroxide|journal=The Chemical News and Journal of Physical Science|date=1908|volume=97|pages=86–87|url=https://books.google.com/books?id=FhlLAAAAYAAJ&q=The+Preparation+of+Formamide+from+Ethyl+Formate+and+Ammonium+Hydroxide&pg=PA86|access-date=14 June 2014}}</ref>
:{{chem2|HCOOCH2CH3 + NH3 → HCONH2 + [CH3CH2OH](/source/ethanol)}}

===Modern production===
The current industrial process for the manufacture of formamide involves the [carbonylation](/source/carbonylation) of ammonia:<ref name= KirkOthmer />
:[CO](/source/carbon_monoxide) + NH<sub>3</sub> → HCONH<sub>2</sub>

An alternative two-stage process involves the ammonolysis of [methyl formate](/source/methyl_formate), which is formed from carbon monoxide and [methanol](/source/methanol):
:CO + CH<sub>3</sub>OH → HCOOCH<sub>3</sub>
:HCO<sub>2</sub>CH<sub>3</sub> + NH<sub>3</sub> → HCONH<sub>2</sub> + CH<sub>3</sub>OH

==Applications==
Formamide is used in the industrial production of [hydrogen cyanide](/source/hydrogen_cyanide).  It is also used as a solvent for processing various polymers such as [polyacrylonitrile](/source/polyacrylonitrile).<ref name=bipp/>

It is also known that formamide is an excellent swelling agent for [cellulosic](/source/Cellulose) fibres,<ref>{{cite journal | last1=Mantanis | first1=G. I. | last2=Young | first2=R. A. | last3=Rowell | first3=R. M. | author1-link=George Mantanis | author2-link=Raymond A. Young | author3-link=Roger M. Rowell | title=Swelling of compressed cellulose fiber webs in organic liquids | journal=Cellulose | volume=2 | issue=1 | date=1995 | issn=0969-0239 | doi=10.1007/BF00812768 | pages=1–22}}</ref> and is used in some specific wood-related applications.

===Reactions===
Formamide decomposes into carbon monoxide and ammonia when heated above 100&nbsp;°C.  
:HCONH<sub>2</sub> → CO + NH<sub>3</sub>
The reaction is slow below 160&nbsp;°C, but accelerates thereafter.  At very high temperatures, the reaction products shift to [hydrogen cyanide](/source/hydrogen_cyanide) (HCN) and water instead:
:HC(O)NH<sub>2</sub> → HCN + H<sub>2</sub>O
The same effect occurs in the presence of [solid acid](/source/solid_acid) catalysts.<ref name=bipp>{{Ullmann|author=Bipp, H.|author2=Kieczka, H.|title=Formamides|year=2012|doi=10.1002/14356007.a12_001.pub2}}</ref>  Contrariwise, heating potassium formamidate gives [hydrogen gas](/source/hydrogen_gas) and [potassium cyanate](/source/potassium_cyanate).<ref name=ChemRev>{{cite journal|doi=10.1021/cr60261a005|title=The chemistry of formic acid and its simple derivatives|first=Harry W.|last=Gibson|orig-date=January 27, 1969|journal=Chemical Reviews|p=689}}</ref>

===Niche or laboratory applications===
Formamide is a constituent of cryoprotectant [vitrification](/source/Cryopreservation) mixtures used for cryopreservation of tissues and [organ](/source/organ_(anatomy))s.

Formamide is also used as an RNA stabiliser in [gel electrophoresis](/source/gel_electrophoresis) by deionizing RNA. In capillary electrophoresis, it is used for stabilizing (single) strands of denatured DNA.

Another use is to add it in [sol-gel](/source/sol-gel) solutions in order to avoid cracking during [sintering](/source/sintering).

Formamide, in its pure state, has been used as an alternative solvent for the electrostatic [self-assembly](/source/self-assembly) of polymer nanofilms.<ref>{{cite journal |author1=Vimal K. Kamineni |author2=Yuri M. Lvov |author3=Tabbetha A. Dobbins | title = Layer-by-Layer Nanoassembly of Polyelectrolytes Using Formamide as the Working Medium | journal = [Langmuir](/source/Langmuir_(journal)) | volume = 23 | issue = 14 | pages = 7423–7427 | year = 2007 | doi = 10.1021/la700465n | pmid = 17536845}}</ref>

Formamide is used to prepare primary amines directly from ketones via their N-formyl derivatives, using the [Leuckart reaction](/source/Leuckart_reaction).

==Biochemistry==
[[File:Methanogenesis cycle.png|thumb|class=skin-invert-image|left|320px|Cycle for [methanogenesis](/source/methanogenesis), showing two formamide-containing intermediates.<ref name=RT>{{cite journal|author=Thauer, R. K.|title=Biochemistry of Methanogenesis: a Tribute to Marjory Stephenson|journal=Microbiology|year=1998|volume=144|pages=2377–2406|doi=10.1099/00221287-144-9-2377|pmid=9782487|doi-access=free}}</ref>]]
Formamides are intermediates in the [methanogenesis](/source/methanogenesis) cycle.

===Prebiotic chemistry===
{{Main article|Formamide-based prebiotic chemistry}}
Formamide has been proposed as an alternative [solvent](/source/solvent) to water, perhaps with the ability to support life with alternative biochemistries to that currently found on Earth.  It forms by the hydrolysis of hydrogen cyanide. With a large dipole moment, its solvation properties are similar to those of water.<ref>{{cite book |author= Committee On The Limits Of Organic Life In Planetary Systems |title=The Limits of Organic Life in Planetary Systems |url= http://www.nap.edu/catalog.php?record_id=11919 |access-date=2012-08-29  |year=2007 |publisher=The National Academies Press |location= Washington, DC |isbn=978-0-309-66906-1 |page=74}}</ref>

Formamide has been shown to convert to traces of [guanine](/source/guanine) upon heating in the presence of ultraviolet light.<ref>{{cite web | url = https://www.sciencedaily.com/releases/2010/06/100614101957.htm | title = Origin of Life: Adding UV Light Helps Form 'Missing G' of RNA Building Blocks | website = Science Daily | date = June 14, 2010}}</ref>

Several prebiotic chemical reactions producing amino acid derivatives have been shown to take place in formamide.<ref>{{Cite journal |last1=Green |first1=N. J. |last2=Russell |first2=D. A. |last3=Tanner |first3=S. H. |last4=Sutherland |first4=J. D. |year=2023 |title=Prebiotic Synthesis of N-Formylaminonitriles and Derivatives in Formamide |journal=Journal of the American Chemical Society |volume=145 |issue=19 |pages=10533–10541 |doi=10.1021/jacs.2c13306 |pmc=10197134 |pmid=37146260 |doi-access=free|bibcode=2023JAChS.14510533G }}</ref> Similar scenarios implicate [thioformamide](/source/thioformamide).<ref>{{cite journal |last1=Patel |first1=Bhavesh H. |last2=Percivalle |first2=Claudia |last3=Ritson |first3=Dougal J. |last4=Duffy |first4=Colm D. |last5=Sutherland |first5=John D. |title=Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism |journal=Nature Chemistry |date=2015 |volume=7 |issue=4 |pages=301–307 |doi=10.1038/nchem.2202 |pmid=25803468 |bibcode=2015NatCh...7..301P |pmc=4568310 }}</ref>

==Safety==
Contact with skin and eyes is not recommended. With an [LD50](/source/LD50) of grams per kg, formamide is of low acute toxicity. It also has low mutagenicity.<ref name=bipp/>

Formamide is classified as toxic to reproductive health.<ref>{{cite web |url=https://echa.europa.eu/documents/10162/4ff18575-7bcc-4e02-96db-1090a1bdd3a1 |title=Support document for identification of formamide as a substance of very high concern because of its cmr1 properties |publisher=[European Chemicals Agency](/source/European_Chemicals_Agency)}}</ref>

==References==
{{Reflist}}
{{Molecules detected in outer space}}
{{Authority control}}

Category:Formamides
Category:Amide solvents

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Adapted from the Wikipedia article [Formamide](https://en.wikipedia.org/wiki/Formamide) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Formamide?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.