formamide
{{Short description|CH3NO, simplest amide}}
{{chembox
| Watchedfields = changed
| verifiedrevid = 443825387
| Name = Formamide
| ImageFile = Formamide-2D.png
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageName = Structural formula of the formamide molecule
| ImageFileL1_Ref = {{chemboximage|correct|??}}
| ImageFileL1 = Formamide-3D-balls.png
| ImageNameL1 = Ball and stick model of formamide
| ImageFileR1 = Formamide-3D-vdW.png
| ImageNameR1 = Space-filling model of the formamide molecule
| PIN = Formamide{{cite book | title = Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = The 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-NH2 and is the preferred IUPAC name.}}
| SystematicName = Methanamide
| OtherNames = Carbamaldehyde
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4739
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 693
| PubChem = 713
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00488
| InChI = 1/CH3NO/c2-1-3/h1H,(H2,2,3)
| InChIKey = ZHNUHDYFZUAESO-UHFFFAOYAQ
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 266160
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/CH3NO/c2-1-3/h1H,(H2,2,3)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZHNUHDYFZUAESO-UHFFFAOYSA-N
| CASNo = 75-12-7
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4781T907ZS
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 48431
| SMILES = O=CN
}}
|Section2={{Chembox Properties
| Formula = CH3NO
| MolarMass = 45.04 g/mol
| Density = 1.133 g/cm3
| Appearance = Colorless, oily liquid
| MeltingPtC = 2 to 3
| BoilingPtC = 210
| VaporPressure = 0.08 mmHg at 20 °C
| Solubility = Miscible
| MagSus = {{val|-2.19|e=-5|u=cm3/mol}}
| pKa = 23.5 (in DMSO){{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. | volume = 43 | issue = 16 | pages = 3095–3101 | doi = 10.1021/jo00410a001}}
}}
|Section7={{Chembox Hazards
| FlashPtC = 154
| FlashPt_notes = (closed cup)
| NFPA-F = 1 | NFPA-H = 2 | NFPA-R = 0
| PEL = none{{PGCH|0295}}
| REL = TWA 10 ppm (15 mg/m3) [skin]
}}
|Section8={{Chembox Related
| OtherCompounds = Carbamic acid
Dimethylformamide}}
}}
Formamide is an amide derived from formic acid. It is a colorless liquid which is miscible with water and has an ammonia-like odor. It is chemical feedstock for the manufacture of sulfa drugs and other pharmaceuticals, herbicides and pesticides, and in the manufacture of hydrocyanic acid. It has been used as a softener for paper and fiber. It is a solvent for many ionic compounds. It has also been used as a solvent for resins and plasticizers.{{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}} Some astrobiologists suggest that it may be an alternative to water as the main solvent in other forms of life.{{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 }}
Formamides are compounds of the type RR′NCHO. One important formamide is dimethylformamide, (CH3)2NCHO.
Production
=Historical production=
In the past, formamide was produced by treating formic acid with ammonia, which produces ammonium formate, which in turn yields formamide upon heating:{{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}}
: HCOOH + NH3 → {{chem|HCOO|−|NH|4|+}}
: {{chem|HCOO|−|NH|4|+}} → HCONH2 + H2O
Formamide is also generated by aminolysis of ethyl formate:{{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}}
:HCOOCH2CH3 + NH3 → HCONH2 + CH3CH2OH
=Modern production=
The current industrial process for the manufacture of formamide involves the carbonylation of ammonia:
:CO + NH3 → HCONH2
An alternative two-stage process involves the ammonolysis of methyl formate, which is formed from carbon monoxide and methanol:
:CO + CH3OH → HCOOCH3
:HCO2CH3 + NH3 → HCONH2 + CH3OH
Applications
Formamide is used in the industrial production of hydrogen cyanide. It is also used as a solvent for processing various polymers such as polyacrylonitrile.
=Reactions=
Formamide decomposes into carbon monoxide and ammonia when heated above 100 °C.
:HCONH2 → CO + NH3
The reaction is slow below 160 °C, but accelerates thereafter. At very high temperatures, the reaction products shift to hydrogen cyanide (HCN) and water instead:
:HC(O)NH2 → HCN + H2O
The same effect occurs in the presence of solid acid catalysts.{{Ullmann|author=Bipp, H.|author2=Kieczka, H.|title=Formamides|year=2012|doi=10.1002/14356007.a12_001.pub2}}
=Niche or laboratory applications=
Formamide is a constituent of cryoprotectant vitrification mixtures used for cryopreservation of tissues and organs.
Formamide is also used as an RNA stabiliser in 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 solutions in order to avoid cracking during sintering.
Formamide, in its pure state, has been used as an alternative solvent for the electrostatic self-assembly of polymer nanofilms.{{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 | volume = 23 | issue = 14 | pages = 7423–7427 | year = 2007 | doi = 10.1021/la700465n | pmid = 17536845}}
Formamide is used to prepare primary amines directly from ketones via their N-formyl derivatives, using the Leuckart reaction.
Biochemistry
File:Methanogenesis cycle.png, showing two formamide-containing intermediates.{{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}}]]
Formamides are intermediates in the methanogenesis cycle.
=Prebiotic chemistry=
{{Main article|Formamide-based prebiotic chemistry}}
Formamide has been proposed as an alternative 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.{{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}}
Formamide has been shown to convert to traces of guanine upon heating in the presence of ultraviolet light.{{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}}
Several prebiotic chemical reactions producing amino acid derivatives have been shown to take place in formamide.{{Cite journal |last=Green |first=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}}
Safety
Contact with skin and eyes is not recommended. With an LD50 of grams per kg, formamide is of low acute toxicity. It also has low mutagenicity.
Formamide is classified as toxic to reproductive health.{{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}}