Pyridine

Pyridine
IUPAC name
Pyridine
Other names
Azabenzene
Azine
py
Identifiers
CAS number 110-86-1 YesY
PubChem 1049
ChemSpider 1020
EC number 203-809-9
Properties
Molecular formula C5H5N
Molar mass 79.1 g mol−1
Appearance colourless liquid
Density 0.9819 g/cm3, liquid
Melting point

-41.6 °C, 232 K, -43 °F
Boiling point

115.2 °C, 388 K, 239 °F
Solubility in water Miscible
Vapor pressure 18 mmHg
Refractive index (nD) 1.5093
Viscosity 0.88 cP
Hazards[1]
EU classification Flammable (F)
Harmful (Xn)
R-phrases R20 R21 R22 R34 R36 R38
NFPA 704
NFPA 704.svg
3
3
0
Flash point 21 °C
Threshold Limit Value 5 ppm (TWA)
Related compounds
Related amines Picoline
Quinoline
Related compounds Aniline
Pyrimidine
Piperidine
 YesY (what is this?)  (verify)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Pyridine is a heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one CH group replaced by a nitrogen atom. It is used as a precursor to agrochemicals and pharmaceuticals and is also an important solvent and reagent. It is a colorless liquid with a distinctive, unpleasant fish-like odor. The pyridine ring occurs in many important compounds, including the vitamins nicotinamides and pyridoxal.

Contents

Preparation and occurrence

Pyridine was originally industrially produced by extraction from coal tar. It is currently synthesized from formaldehyde, ammonia, and acetaldehyde:

CH2O + NH3 + 2 CH3CHO → C5H5N + 3 H2O + 2 H2

This process (Chichibabin pyridine synthesis) involves the intermediacy of acrolein. An estimated 26,000 tons were produced worldwide in 1989. Condensations of ammonia sources and related unsaturated carbon sources affords alkyl- and aryl-substituted pyridines, e.g. monomethyl compounds (picolines), dimethyl compounds (lutidines), and trimethyl derivatives (collidines).[2] Pyridine occurs in numerous plants, although this was mostly recorded just by smell. Goris and Larsonneau[3] did show definite evidence of its presence in belladonna leaves, while Kuhn and Schäfer[4] of its presence in the roots of the same plant.

For specialized applications, the synthesis of the pyridine skeleton is well developed.[5] The Hantzsch pyridine synthesis, for example, is a multicomponent reaction involving formaldehyde, a keto-ester and a nitrogen donor. The Kröhnke pyridine synthesis involves the condensation of 1,5-diketones with ammonium acetate in acetic acid followed by oxidation. The Ciamician-Dennstedt Rearrangement entails the ring-expansion of pyrrole with dichlorocarbene to 3-chloropyridine.[6] In the Gattermann-Skita synthesis,[7] a malonate ester salt reacts with dichloromethylamine.[8]

Reactions

As a base

In organic reactions pyridine behaves both as a tertiary amine, undergoing protonation, alkylation, acylation, and N-oxidation at nitrogen, and as an aromatic compound, undergoing nucleophilic substitutions.

The nitrogen atom on pyridine features a basic lone pair of electrons. Because this lone pair is not delocalized into the aromatic pi-system, pyridine is basic with chemical properties similar to tertiary amines. The pKa of the conjugate acid is 5.21. Pyridine is protonated by reaction with acids and forms a positively charged aromatic polyatomic ion called pyridinium. The bond lengths and bond angles in pyridine and the pyridinium ion are almost identical.[9] In addition, the pyridinium cation is isoelectronic with benzene. Pyridinium p-toluenesulfonate (PPTS) is an illustrative pyridinium salt; it is formed by treating pyridine with p-toluenesulfonic acid.

As an N-nucleophile and ligand

Pyridine is a good nucleophile with a donor number of 33.1. It is easily attacked by alkylating agents to give N-alkylpyridinium salts. One example is cetylpyridinium chloride, a cationic surfactant that is a widely used disinfection and antiseptic agent. Pyridinium salts can be obtained in the Zincke reaction. Useful adducts of pyridine include Pyridine-borane, C5H5NBH3 (m.p. 10–11 °C), a mild reducing agent with improved stability relative to NaBH4 in protic solvents and improved solubility in aprotic organic solvents. Pyridine-sulfur trioxide, C5H5NSO3 (mp 175 °C) is a sulfonation agent used to convert alcohols to sulfonates, which in turn undergo C-O bond scission upon reduction with hydride agents.

Pyridine is widely used as a ligand in coordination chemistry. Also important are its chelating derivatives 2,2'-bipyridine, consisting of two pyridine molecules joined by a single bond, and terpyridine, a molecule of three pyridine rings linked together.

Nucleophilic reactions at the ring

Nucleophilic aromatic substitution occurs at C-2 and at C-4. For example in the Chichibabin reaction, pyridine reacts with sodium amide to give 2-aminopyridine. In the Emmert reaction, pyridine reacts with a ketone in presence of aluminium or magnesium and mercuric chloride to give the carbinol also at C2.[10][11]

Applications

Role in chemical synthesis

Pyridine is an important solvent and reagent in organic synthesis.[12] It is used as a solvent in Knoevenagel condensations. It is the precursor to myriad insecticides, herbicides, pharmaceuticals, food flavorings, dyes, rubber chemicals, adhesives, paints, explosives and disinfectants. Examples include paraquat[2]

Pyridine as a solvent

Pyridine is a widely used polar but aprotic solvent. It is miscible with a broad range of solvents including hexane and water. Deuterated pyridine, called pyridine-d5, is a common solvent for1H NMR spectroscopy.

Specialised uses

As a denaturant

Pyridine is also used as a denaturant for antifreeze mixtures, for ethyl alcohol, for fungicides, and as a dyeing aid for textiles.[13]

Role in analytical chemistry

Pyridine, along with barbituric acid, is commonly used in colorimetric determinations of cyanide in aqueous matrices. Pyridine reacts with cyanogen chloride (formed in an earlier step by reaction of the cyanide anion with chloramine-T) to form a conjugated species that couples two molecules of barbituric acid, forming a red-colored dye. Color intensity is directly proportional to cyanide concentration. Pyridine was originally used as the base in the Karl Fischer titration, but has since been largely replaced by imidazole, which is more basic, allowing for a more stable equivalence point and a faster reaction rate. Imidazole also has the advantage of being odorless.

Safety and environmental aspects

Pyridine is harmful if inhaled, swallowed or absorbed through the skin.[14] Effects of an acute pyridine intoxication include dizziness, headache, nausea and loss of appetite. Further symptoms include abdominal pain and pulmonary congestion.[15] Currently its evaluations as a possible carcinogenic agent showed there is inadequate evidence in humans for the carcinogenicity of pyridine, albeit there is limited evidence of carcinogenic effects on animals.[15] Available data indicate that "exposure to pyridine in drinking-water led to reduction of sperm motility at all dose levels in mice and increased estrous cycle length at the highest dose level in rats".[15] The LD50 in rats (oral) is 891 mg kg−1. Pyridine is flammable. Pyridine is readily degraded by bacteria to ammonia and carbon dioxide.[16] The unsubstituted pyridine ring degrades more rapidly than picoline, lutidine, chloropyridine, or aminopyridine[17], and a number of pyridine degraders have been shown to overproduce riboflavin in the presence of pyridine.[18]

Other 6-membered aromatic rings

With one carbon replaced by another group, these molecules include borabenzene, silabenzene, germanabenzene, stannabenzene, phosphorine, arsabenzene and pyrylium salt.

References

  1. ↑ https://fscimage.fishersci.com/msds/19990.htm
  2. ↑ 2.0 2.1 Shinkichi Shimizu, Nanao Watanabe, Toshiaki Kataoka, Takayuki Shoji, Nobuyuki Abe, Sinji Morishita, Hisao Ichimura "Pyridine and Pyridine Derivatives" in "Ullmann's Encyclopedia of Industrial Chemistry" 2007, Wiley-VCH, Weinheim. doi:10.1002/14356007.a22_399
  3. ↑ Bull. Sci. Pharmacol., 1921, 28, 497-499.
  4. ↑ Deut. Apoth. Zeit., 1938, 53, 405, 424.
  5. ↑ Gilchrist, T.L. (1997). Heterocyclic Chemistry ISBN 0470204818
  6. ↑ Ciamician-Dennstedt Rearrangement @ drugfuture.com Link
  7. ↑ Eine Synthese von Pyridin-Derivaten Berichte der deutschen chemischen Gesellschaft Volume 49, Issue 1, Date: Januar-Juni 1916, Pages: 494-501 L. Gattermann, A. Skita doi:10.1002/cber.19160490155
  8. ↑ Gattermann-Skita @ Institute of Chemistry, Skopje, Macedonia http://www.pmf.ukim.edu.mk/PMF/Chemistry/reactions/gattermann-skita.htm
  9. ↑ T. M. Krygowski, H. Szatyowicz, and J. E. Zachara (2005). "How H-bonding Modifies Molecular Structure and π-Electron Delocalization in the Ring of Pyridine/Pyridinium Derivatives Involved in H-Bond Complexation†". J. Org. Chem. 70 (22): 8859. doi:10.1021/jo051354h. PMID 16238319. .
  10. ↑ Charles H. Tilford, Robert S. Shelton, and M. G. van Campen (1948). "Histamine Antagonists. Basically Substituted Pyridine Derivatives". J. Am. Chem. Soc. 70: 4001. doi:10.1021/ja01192a010. 
  11. ↑ Bruno Emmert, Erich Asendorf (1939). "Eine Synthese von -Pyridyl-dialkyl-carbinolen". Berichte der deutschen chemischen Gesellschaft 72: 1188. doi:10.1002/cber.19390720610. 
  12. ↑ Sherman, A. R. “Pyridine” in e-EROS (Encyclopedia of Reagents for Organic Synthesis) (Ed: L. Paquette) 2004, J. Wiley & Sons, New York. doi:10.1002/047084289X.rp280 Article Online Posting Date: April 15, 2001.
  13. ↑ "PRODUCTION, IMPORT, USE, AND DISPOSAL". Centers for Disease Control and Prevention. http://www.atsdr.cdc.gov/toxprofiles/tp52-c4.pdf. Retrieved 2008-12-28. 
  14. ↑ Aylward, G, (2008), "SI Chemical Data 6th Ed.", ISBN 978 0 470 81638 7 (pbk.)"
  15. ↑ 15.0 15.1 15.2 International Agency for Research on Cancer (IARC) (2000-08-22). "Pyridine Summary & Evaluation". IARC Summaries & Evaluations. IPCS INCHEM. http://www.inchem.org/documents/iarc/vol77/77-16.html. Retrieved 2007-01-17. 
  16. ↑ Sims, G.K. and O'Loughlin, E.J. (1989). "Degradation of pyridines in the environment". CRC Critical Reviews in Environmental Control 19 (4): 309–340. doi:10.1080/10643388909388372. 
  17. ↑ Sims, G. K. and L.E. Sommers. 1986. Biodegradation of pyridine derivatives in soil suspensions. Environmental Toxicology and Chemistry. 5:503-509.
  18. ↑ Sims, G. K. and E.J. O'Loughlin. 1992. Riboflavin production during growth of Micrococcus luteus on pyridine. Applied and Environmental Microbiology 58(10):3423-3425.

External links

Functional groups

Alcohol · Aldehyde · Alkane · Alkene · Alkyne · Amide · Amine · Azo compound · Benzene derivative · Carboxylic acid · Cyanate · Disulfide · Ester · Ether · Haloalkane · Hydrazone · Imine · Isocyanate · Isonitrile · Isothiocyanate · Ketone · Organophosphorus · Oxime · Nitrile · Nitro compound · Nitroso compound · Peroxide · Phosphonous and Phosphonic acid · Pyridine derivative · Sulfone · Sulfonic acid · Sulfoxide · Thiocyanate · Thioester · Thioether · Thiol · Urea
See also Chemical classification