Formamide

Summary

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.[4] Some astrobiologists suggest that it may be an alternative to water as the main solvent in other forms of life.[5]

Formamide
Structural formula of the formamide molecule
Ball and stick model of formamide
Ball and stick model of formamide
Space-filling model of the formamide molecule
Space-filling model of the formamide molecule
Names
Preferred IUPAC name
Formamide[1]
Systematic IUPAC name
Methanamide
Other names
Carbamaldehyde
Identifiers
  • 75-12-7 checkY
3D model (JSmol)
  • Interactive image
ChEBI
  • CHEBI:48431 checkY
ChEMBL
  • ChEMBL266160 checkY
ChemSpider
  • 693 checkY
ECHA InfoCard 100.000.766 Edit this at Wikidata
  • 4739
KEGG
  • C00488 checkY
  • 713
UNII
  • 4781T907ZS checkY
  • DTXSID8025337 Edit this at Wikidata
  • InChI=1S/CH3NO/c2-1-3/h1H,(H2,2,3) checkY
    Key: ZHNUHDYFZUAESO-UHFFFAOYSA-N checkY
  • InChI=1/CH3NO/c2-1-3/h1H,(H2,2,3)
    Key: ZHNUHDYFZUAESO-UHFFFAOYAQ
  • O=CN
Properties
CH3NO
Molar mass 45.04 g/mol
Appearance Colorless, oily liquid[2]
Density 1.133 g/cm3
Melting point 2 to 3 °C (36 to 37 °F; 275 to 276 K)
Boiling point 210 °C (410 °F; 483 K)
Miscible
Vapor pressure 0.08 mmHg at 20 °C
Acidity (pKa) 23.5 (in DMSO)[3]
−2.19×10−5 cm3/mol
Hazards
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Flash point 154 °C (309 °F; 427 K) (closed cup)
NIOSH (US health exposure limits):
PEL (Permissible)
none[2]
REL (Recommended)
TWA 10 ppm (15 mg/m3) [skin][2]
IDLH (Immediate danger)
N.D.[2]
Related compounds
Related compounds
Carbamic acid
Dimethylformamide
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)
Infobox references

Formamides are compounds of the type RR′NCHO. One important formamide is dimethylformamide, (CH3)2NCHO.

Production edit

Historical production edit

In the past, formamide was produced by treating formic acid with ammonia, which produces ammonium formate, which in turn yields formamide upon heating:[6]

HCOOH + NH3HCOO
NH+
4
HCOO
NH+
4
→ HCONH2 + H2O

Formamide is also generated by aminolysis of ethyl formate:[7]

HCOOCH2CH3 + NH3 → HCONH2 + CH3CH2OH

Modern production edit

The current industrial process for the manufacture of formamide involves the carbonylation of ammonia:[4]

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 edit

Formamide is used in the industrial production of hydrogen cyanide. It is also used as a solvent for processing various polymers such as polyacrylonitrile.[8]

Reactions edit

Formamide decomposes into carbon monoxide and ammonia at 180 °C.

HCONH2 → CO + NH3

Traces of hydrogen cyanide (HCN) and water are also observed.

In the presence of solid acid catalysts, formamide dehydrates to HCN:[8]

HC(O)NH2 → HCN + H2O

Niche or laboratory applications edit

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.[9]

Formamide is used to prepare primary amines directly from ketones via their N-formyl derivatives, using the Leuckart reaction.

Biochemistry edit

 
Cycle for methanogenesis, showing two formamide-containing intermediates.[10]

Formamides are intermediates in the methanogenesis cycle.

Prebiotic chemistry edit

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.[11]

Formamide has been shown to convert to traces of guanine upon heating in the presence of ultraviolet light.[12]

Several prebiotic chemical reactions producing amino acid derivatives have been shown to take place in formamide. [13]

Safety edit

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.[8]

Formamide is classified as toxic to reproductive health.[14]

References edit

  1. ^ Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 841. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4. The traditional name 'formamide' is retained for HCO-NH2 and is the preferred IUPAC name.
  2. ^ a b c d NIOSH Pocket Guide to Chemical Hazards. "#0295". National Institute for Occupational Safety and Health (NIOSH).
  3. ^ F. G. Bordwell; J. E. Bartmess; J. A. Hautala (1978). "Alkyl effects on equilibrium acidities of carbon acids in protic and dipolar aprotic media and the gas phase". J. Org. Chem. 43 (16): 3095–3101. doi:10.1021/jo00410a001.
  4. ^ a b Hohn, A. (1999). "Formamide". In Kroschwitz, Jacqueline I. (ed.). Kirk-Othmer Concise Encyclopedia of Chemical Technology (4th ed.). New York: John Wiley & Sons, Inc. pp. 943–944. ISBN 978-0471419617.
  5. ^ "How to improve the search for aliens". The Economist.
  6. ^ Lorin, M. (1864). "Preparation of Formamide by means of Formiates and Oxalates". The Chemical News and Journal of Physical Science. IX: 291. Retrieved 14 June 2014.
  7. ^ Phelps, I. K.; Deming, C. D. (1908). "The Preparation of Formamide from Ethyl Formate and Ammonium Hydroxide". The Chemical News and Journal of Physical Science. 97: 86–87. Retrieved 14 June 2014.
  8. ^ a b c Bipp, H.; Kieczka, H. (2012). "Formamides". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a12_001.pub2. ISBN 978-3527306732.
  9. ^ Vimal K. Kamineni; Yuri M. Lvov; Tabbetha A. Dobbins (2007). "Layer-by-Layer Nanoassembly of Polyelectrolytes Using Formamide as the Working Medium". Langmuir. 23 (14): 7423–7427. doi:10.1021/la700465n. PMID 17536845.
  10. ^ Thauer, R. K. (1998). "Biochemistry of Methanogenesis: a Tribute to Marjory Stephenson". Microbiology. 144: 2377–2406. doi:10.1099/00221287-144-9-2377. PMID 9782487.
  11. ^ Committee On The Limits Of Organic Life In Planetary Systems (2007). The Limits of Organic Life in Planetary Systems. Washington, DC: The National Academies Press. p. 74. ISBN 978-0-309-66906-1. Retrieved 2012-08-29.
  12. ^ "Origin of Life: Adding UV Light Helps Form 'Missing G' of RNA Building Blocks". Science Daily. June 14, 2010.
  13. ^ Green, N. J., Russell, D. A., Tanner, S. H., Sutherland, J. D. (2023). "Prebiotic Synthesis of N-Formylaminonitriles and Derivatives in Formamide". Journal of the American Chemical Society. 145 (19): 10533–10541. doi:10.1021/jacs.2c13306. PMC 10197134. PMID 37146260.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ "Support document for identification of formamide as a substance of very high concern because of its cmr1 properties". European Chemicals Agency.