Methylamine Explained

Methylamine is an organic compound with a formula of . This colorless gas is a derivative of ammonia, but with one hydrogen atom being replaced by a methyl group. It is the simplest primary amine.

Methylamine is sold as a solution in methanol, ethanol, tetrahydrofuran, or water, or as the anhydrous gas in pressurized metal containers. Industrially, methylamine is transported in its anhydrous form in pressurized railcars and tank trailers. It has a strong odor similar to rotten fish. Methylamine is used as a building block for the synthesis of numerous other commercially available compounds.

Industrial production

Methylamine has been produced industrially since the 1920s (originally by Commercial Solvents Corporation for dehairing of animal skins). This was made possible by and his wife Eugenia who discovered amination of alcohols, including methanol, on alumina or kaolin catalyst after WWI, filed two patent applications in 1919[1] and published an article in 1921.[2]

It is now prepared commercially by the reaction of ammonia with methanol in the presence of an aluminosilicate catalyst. Dimethylamine and trimethylamine are co-produced; the reaction kinetics and reactant ratios determine the ratio of the three products. The product most favored by the reaction kinetics is trimethylamine.[3]

In this way, an estimated 115,000 tons were produced in 2005.

Laboratory methods

Methylamine was first prepared in 1849 by Charles-Adolphe Wurtz via the hydrolysis of methyl isocyanate and related compounds.[4] [5] An example of this process includes the use of the Hofmann rearrangement, to yield methylamine from acetamide and bromine.[6] [7]

In the laboratory, methylamine hydrochloride is readily prepared by various other methods. One method entails treating formaldehyde with ammonium chloride.

The colorless hydrochloride salt can be converted to an amine by the addition of a strong base, such as sodium hydroxide (NaOH):

Another method entails reducing nitromethane with zinc and hydrochloric acid.[8]

Another method of methylamine production is spontaneous decarboxylation of glycine with a strong base in water.[9]

Reactivity and applications

Methylamine is a good nucleophile as it is an unhindered amine.[10] As an amine it is considered a weak base. Its use in organic chemistry is pervasive. Some reactions involving simple reagents include: with phosgene to methyl isocyanate, with carbon disulfide and sodium hydroxide to the sodium methyldithiocarbamate, with chloroform and base to methyl isocyanide and with ethylene oxide to methylethanolamines. Liquid methylamine has solvent properties analogous to those of liquid ammonia.[11]

Representative commercially significant chemicals produced from methylamine include the pharmaceuticals ephedrine and theophylline, the pesticides carbofuran, carbaryl, and metham sodium, and the solvents N-methylformamide and N-methylpyrrolidone. The preparation of some surfactants and photographic developers require methylamine as a building block.[4]

Biological chemistry

Methylamine arises as a result of putrefaction and is a substrate for methanogenesis.[12]

Additionally, methylamine is produced during PADI4-dependent arginine demethylation.[13]

Safety

The LD50 (mouse, s.c.) is 2.5 g/kg.[14]

The Occupational Safety and Health Administration (OSHA) and National Institute for Occupational Safety and Health (NIOSH) have set occupational exposure limits at 10 ppm or 12 mg/m3 over an eight-hour time-weighted average.[15]

Regulation

In the United States, methylamine is controlled as a List 1 precursor chemical by the Drug Enforcement Administration[16] due to its use in the illicit production of methamphetamine.[17]

In popular culture

Fictional characters Walter White and Jesse Pinkman use aqueous methylamine as part of a process to synthesize methamphetamine in the AMC series Breaking Bad.[18] [19]

See also

Notes and References

  1. ,, https://uprp.gov.pl/sites/default/files/2019-12/KWARTALNIK_100_lat_wydanie_specjalne.pdf
  2. Book: Not Available . Chemical Abstracts (1922) Vol.16, No.18 . 1922.
  3. Corbin D.R. . Schwarz S. . Sonnichsen G.C. . Methylamines synthesis: A review. Catalysis Today. 1997. 37. 24. 71–102. 10.1016/S0920-5861(97)00003-5 .
  4. Karsten Eller, Erhard Henkes, Roland Rossbacher, Hartmut Höke "Amines, Aliphatic" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.
  5. Charles-Adolphe Wurtz (1849) "Sur une série d'alcalis organiques homologues avec l'ammoniaque" (On a series of homologous organic alkalis containing ammonia), Comptes rendus …, 28 : 223-226. Note: Wurtz's empirical formula for methylamine is incorrect because chemists in that era used an incorrect atomic mass for carbon (6 instead of 12).
  6. Book: Mann . F. G. . Saunders . B. C.. Practical Organic Chemistry. 4th. 1960. Longman. London. 9780582444072. 128.
  7. Book: Cohen, Julius. Practical Organic Chemistry. 2nd. 1900. Macmillan and Co., Limited. London. 72.
  8. Book: Gatterman, Ludwig . Wieland, Heinrich . amp . Laboratory Methods of Organic Chemistry. 1937. R & R Clark, Limited. Edinburgh, UK. 157–158.
  9. Callahan . Brian P. . Wolfenden . Richard . 2003-07-31 . Migration of Methyl Groups between Aliphatic Amines in Water  [<i>J. Am. Chem. Soc</i>. <b>2003</b>, <i>125</i>, 310-311]. ]. Journal of the American Chemical Society . 125 . 34 . 10481–10481 . 10.1021/ja033448j . 0002-7863.
  10. Book: Linker Strategies in Solid-Phase Organic Synthesis . 13 October 2009 . Peter Scott . 80 . John Wiley & Sons . 9780470749050 . ...an unhindered amine such as methylamine.
  11. 10.1021/ja952634p. The Lithium−Sodium−Methylamine System: Does a Low-Melting Sodide Become a Liquid Metal?. Journal of the American Chemical Society. 118. 8. 1997. 1996. Debacker. Marc G.. Mkadmi. El Bachir. Sauvage. François X.. Lelieur. Jean-Pierre. Wagner. Michael J.. Concepcion. Rosario. Kim. Jineun. McMills. Lauren E. H.. Dye. James L..
  12. 10.1099/00221287-144-9-2377. Biochemistry of methanogenesis: A tribute to Marjory Stephenson:1998 Marjory Stephenson Prize Lecture. Microbiology. 144. 9. 2377–406. 1998. Thauer. R. K.. 9782487. free.
  13. Ng. SS. Yue. WW. Oppermann. U. Klose. RJ. Dynamic protein methylation in chromatin biology.. Cellular and Molecular Life Sciences. February 2009. 66. 3. 407–22. 18923809. 10.1007/s00018-008-8303-z. 2794343.
  14. The Merck Index, 10th Ed. (1983), p.864, Rahway: Merck & Co.
  15. https://www.cdc.gov/niosh/npg/npgd0398.html CDC - NIOSH Pocket Guide to Chemical Hazards
  16. https://www.deadiversion.usdoj.gov/21cfr/cfr/1310/1310_02.htm Title 21 Code of Federal Regulations
  17. 10.1520/JFS12235J. The Clandestine Drug Laboratory Situation in the United States. Journal of Forensic Sciences. 28. 18–31. 1983. Frank. R. S.. 1. 6680736.
  18. Web site: . Here’s what ‘Breaking Bad’ gets right, and wrong, about the meth business . 15 August 2013 . Matthews . Dylan . 3 February 2023 . https://web.archive.org/web/20230203140004/https://www.washingtonpost.com/news/wonk/wp/2013/08/15/heres-what-breaking-bad-gets-right-and-wrong-about-the-meth-business/.
  19. Web site: Chemistry Views . . The Chemistry of Breaking Bad . Harnisch . Falk . Salthammer . Tunga . https://web.archive.org/web/20240208125657/https://www.chemistryviews.org/details/ezine/5416791/The_Chemistry_of_Breaking_Bad/ . 8 February 2024 .