3-Methylpyridine Explained

3-Methylpyridine or 3-picoline, is an organic compound with formula 3-CH3C5H4N. It is one of three positional isomers of methylpyridine, whose structures vary according to where the methyl group is attached around the pyridine ring. This colorless liquid is a precursor to pyridine derivatives that have applications in the pharmaceutical and agricultural industries. Like pyridine, 3-methylpyridine is a colorless liquid with a strong odor and is classified as a weak base.

Synthesis

3-Methylpyridine is produced industrially by the reaction of acrolein, with ammonia. These ingredients are combined as gases which flows over an oxide-based heterogeneous catalyst. The reaction is multistep, culminating in cyclisation.

2 CH2CHCHO + NH3 → CH3C5H4N + 2H2OThis process also affords substantial amounts of pyridine, which arises by demethylation of the 3-methylpyridine. A route that gives better control of the product starts with acrolein, propionaldehyde, and ammonia:

CH2CHCHO + CH3CH2CHO + NH3 → 3-CH3C5H4N + 2 H2O + H2It may also be obtained as a co-product of pyridine synthesis from acetaldehyde, formaldehyde, and ammonia via Chichibabin pyridine synthesis. Approximately 9,000,000 kilograms were produced worldwide in 1989. It has also been prepared by dehydrogenation of 3-methylpiperidine, derived from hydrogenation of 2-Methylglutaronitrile.[1]

Uses

3-Picoline is a useful precursor to agrochemicals, such as chlorpyrifos. Chlorpyrifos is produced from 3,5,6-trichloro-2-pyridinol, which is generated from 3-picoline by way of cyanopyridine. This conversion involves the ammoxidation of 3-methylpyridine:

CH3C5H4N + 1.5O2 + NH3 → NCC5H4N + 3H2O

3-Cyanopyridine is also a precursor to 3-pyridinecarboxamide,[2] [3] [4] which is a precursor to pyridinecarbaldehydes:

3-NCC5H3N + [H] + catalyst → 3-HC(O)C5H4N Pyridinecarbaldehydes are used to make antidotes for poisoning by organophosphate acetylcholinesterase inhibitors.

Environmental behavior

Pyridine derivatives (including 3-methylpyridine) are environmental contaminants, generally associated with processing fossil fuels, such as oil shale or coal.[5] They are also found in the soluble fractions of crude oil spills. They have also been detected at legacy wood treatment sites. The high water solubility of 3-methyl pyridine increases the potential for the compound to contaminate water sources. 3-methyl pyridine is biodegradable, although it degrades more slowly and volatilize more readily from water samples than either 2-methyl- or 4-methyl-pyridine.,[6] [7]

3-Methylpyridine is the main precursor to niacin, one of the B vitamins. Approximately 10,000 tons of niacin are produced annually worldwide.[8]

See also

Toxicity

Like most alkylpyridines, the LD50 of 2-methylpyridine is modest, being 400 mg/kg (oral, rat).[8]

Notes and References

  1. Eric F. V. Scriven. Ramiah Murugan. Pyridine and Pyridine Derivatives. Kirk-Othmer Encyclopedia of Chemical Technology. 2005. XLI. 10.1002/0471238961.1625180919031809.a01.pub2. 0471238961.
  2. Nitrile Hydratase-Catalyzed Production of Nicotinamide from 3-Cyanopyridine in Rhodococcus rhodochrous J1. Toru. Nagasawa. Caluwadewa Deepal. Mathew. Jacques. Mauger. Hideaki. Yamada. Appl. Environ. Microbiol.. 1988. 54. 7. 1766–1769. 10.1128/AEM.54.7.1766-1769.1988. 16347686. 202743. 1988ApEnM..54.1766N .
  3. Book: White Biotechnology. Roland. Ulber. Dieter. Sell. Building Blocks. 105. Advances in Biochemical Engineering / Biotechnology. 9783540456957. 10.1007/10_033. 133–173. https://books.google.com/books?id=_tXoG93OWHgC&pg=PA141. Springer Science & Business Media. 2007. 17408083. Hilterhaus. L.. Liese. A..
  4. Book: Biocatalysis in Organic Synthesis 1. Science of Synthesis. Georg Thieme Verlag. 2015. Enzymatic Synthesis of Amides. J. W.. Schmidberger. L. J.. Hepworth. A. P.. Green. S. L.. Flitsch. 329–372. 9783131766113. Kurt. Faber. Wolf-Dieter. Fessner. Nicholas J.. Turner. https://books.google.com/books?id=8h_wBgAAQBAJ&pg=PA362.
  5. Sims . Gerald K. . O'Loughlin . Edward J. . Crawford . Ronald L. . January 1989 . Degradation of pyridines in the environment . Critical Reviews in Environmental Control . en . 19 . 4 . 309–340 . 10.1080/10643388909388372 . 1989CRvEC..19..309S . 1040-838X.
  6. Sims . Gerald K. . Sommers . Lee E. . June 1986 . Biodegradation of pyridine derivatives in soil suspensions . Environmental Toxicology and Chemistry . en . 5 . 6 . 503–509 . 10.1002/etc.5620050601 . 0730-7268.
  7. Sims . Gerald K. . Sommers . Lee E. . October 1985 . Degradation of Pyridine Derivatives in Soil . Journal of Environmental Quality . en . 14 . 4 . 580–584 . 10.2134/jeq1985.00472425001400040022x . 1985JEnvQ..14..580S . 0047-2425.
  8. Manfred Eggersdorfer. Vitamins. Ullmann's Encyclopedia of Industrial Chemistry. 2000. 10.1002/14356007.a27_443. 3527306730. etal.