Formamide Explained

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.[1] Some astrobiologists suggest that it may be an alternative to water as the main solvent in other forms of life.[2]

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:[3]

HCOOH + NH3

→ HCONH2 + H2O

Formamide is also generated by aminolysis of ethyl formate:[4]

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 + NH3The 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 + H2OThe same effect occurs in the presence of solid acid catalysts.

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.[5]

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

Biochemistry

Formamides are intermediates in the methanogenesis cycle.

Prebiotic chemistry

See main article: article and Hypothetical types of biochemistry. 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.[6]

Formamide has been shown to convert to traces of guanine upon heating in the presence of ultraviolet light.[7]

Several prebiotic chemical reactions producing amino acid derivatives have been shown to take place in formamide.[8]

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.[9]

Notes and References

  1. Book: Hohn . A. . Jacqueline I. . Kroschwitz . Kirk-Othmer Concise Encyclopedia of Chemical Technology . 4th . 1999 . John Wiley & Sons, Inc.. New York. 978-0471419617. 943–944 . Formamide.
  2. News: How to improve the search for aliens . The Economist .
  3. Lorin. M.. Preparation of Formamide by means of Formiates and Oxalates. The Chemical News and Journal of Physical Science. 1864. IX. 291. 14 June 2014.
  4. Phelps. I. K.. Deming. C. D.. The Preparation of Formamide from Ethyl Formate and Ammonium Hydroxide. The Chemical News and Journal of Physical Science. 1908. 97. 86–87. 14 June 2014.
  5. Vimal K. Kamineni . Yuri M. Lvov . Tabbetha A. Dobbins . Layer-by-Layer Nanoassembly of Polyelectrolytes Using Formamide as the Working Medium . . 23 . 14 . 7423–7427 . 2007 . 10.1021/la700465n . 17536845.
  6. Book: Committee On The Limits Of Organic Life In Planetary Systems . The Limits of Organic Life in Planetary Systems . 2012-08-29 . 2007 . The National Academies Press . Washington, DC . 978-0-309-66906-1 . 74.
  7. Web site: Origin of Life: Adding UV Light Helps Form 'Missing G' of RNA Building Blocks . Science Daily . June 14, 2010.
  8. 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 . 10.1021/jacs.2c13306 . 10197134 . 37146260 . free.
  9. Web site: Support document for identification of formamide as a substance of very high concern because of its cmr1 properties . European Chemicals Agency.