{{short description|Heterocyclic aromatic organic compound}}{{Distinguish|Pyrimidine|Pyridyne}}{{Use dmy dates|date=September 2020}}{{chembox|Verifiedfields = changed|Watchedfields = changed|verifiedrevid = 414415928|Name = Pyridine|ImageFileL1 = Pyridine-2D-full.svg|ImageNameL1 = Full structural formula of pyridine

correct|??}}|ImageFileR1 = Pyridine numbers.svg|ImageNameR1 = Skeletal formula of pyridine, showing the numbering convention|ImageFileL2 = Pyridine-CRC-MW-3D-balls.png|ImageNameL2 = Ball-and-stick diagram of pyridine|ImageFileR2 = Pyridine-CRC-MW-3D-vdW.png|ImageNameR2 = Space-filling model of pyridine|ImageFile3 = Pyridine sample.jpg

ROYAL SOCIETY OF CHEMISTRY>THE ROYAL SOCIETY OF CHEMISTRY

LOCATION = CAMBRIDGE

DOI = 10.1039/9781849733069-FP001

ISBN = 978-0-85404-182-4, |SystematicName = Azabenzene|OtherNames = AzineAzinine|Section1 = {{Chembox Identifiers

changed|EBI}}|ChEBI = 16227|SMILES = c1ccncc1

correct|FDA}}|UNII = NH9L3PP67S

correct|kegg}}|KEGG = C00747|InChI = 1/C5H5N/c1-2-4-6-5-3-1/h1-5H|InChIKey = JUJWROOIHBZHMG-UHFFFAOYAY

correct|EBI}}|ChEMBL = 266158

correct|chemspider}}|StdInChI = 1S/C5H5N/c1-2-4-6-5-3-1/h1-5H

correct|chemspider}}|StdInChIKey = JUJWROOIHBZHMG-UHFFFAOYSA-N

correct|CAS}}|CASNo = 110-86-1|PubChem = 1049

correct|chemspider}}|ChemSpiderID = 1020|EINECS = 203-809-9}}|Section2 = {{Chembox Properties

#Haynes>Haynes, p. 3.474 |BoilingPtC = 115.2|BoilingPt_ref =

Poise (unit)>cP (25 Â°C)Haynes, p. 6.246

#Haynes>Haynes, p. 6.258

#Haynes>Haynes, p. 9.65|RefractIndex = 1.5095 (20 Â°C)|VaporPressure = 16 mmHg (20 Â°C)

#Haynes>Haynes, p. 5.95|ConjugateAcid = Pyridinium

#Haynes>Haynes, p. 3.579

#Haynes>Haynes, p. 5.176}}|Section3 = {{Chembox Thermochemistry|DeltaHf = 100.2 kJ/mol|HeatCapacity = 132.7 J/(molÂ·K)|DeltaHc = âˆ’2.782{{nbsp}}MJ/mol

#Haynes>Haynes, pp. 5.34, 5.67 }}|Section4 = {{Chembox Hazards|MainHazards= Low to moderate hazardPyridine: main hazards, precautions and toxicity

WEBSITE=FISHERSCI.COM

ACCESS-DATE=2 FEBRUARY 2010

ARCHIVE-URL=HTTPS://WEB.ARCHIVE.ORG/WEB/20100611053419/HTTP://FSCIMAGE.FISHERSCI.COM/MSDS/19990.HTM, live, |NFPA-H = 2|NFPA-F = 3|NFPA-R = 0|FlashPtC = 20

#Haynes>Haynes, p. 15.19|AutoignitionPtC = 482|AutoignitionPt_ref=|TLV-TWA = 5 ppm|GHSPictograms = {{GHS02}}{{GHS07}}|GHSSignalWord = Danger

225

312

315|319}}

210

301+312

304+340+312|305+351+338}}

0541}}|ExploLimits = 1.8â€“12.4%|IDLH = 1000 ppm |REL = TWA 5 ppm (15 mg/m3)

110861|Pyridine}}|LD50 = 891 mg/kg (rat, oral)1500 mg/kg (mouse, oral)1580 mg/kg (rat, oral)}}|Section5 = {{Chembox Related|OtherFunction_label = amines|OtherFunction = Picoline Quinoline|OtherCompounds = Aniline Pyrimidine Piperidine}}}}Pyridine is a basic heterocyclic organic compound with the chemical formula {{chem2|C5H5N|auto=1}}. It is structurally related to benzene, with one methine group {{chem2|(dCHs)}} replaced by a nitrogen atom {{chem2|(dNs)}}. It is a highly flammable, weakly alkaline, water-miscible liquid with a distinctive, unpleasant fish-like smell. Pyridine is colorless, but older or impure samples can appear yellow. due to the formation of extended, unsaturated polymeric chains, which show significant electrical conductivity.{{page needed|date=March 2024}}JOURNAL, Vaganova, Evgenia, Eliaz, Dror, Shimanovich, Ulyana, Leitus, Gregory, Aqad, Emad, Lokshin, Vladimir, Khodorkovsky, Vladimir, January 2021, Light-Induced Reactions within Poly(4-vinyl pyridine)/Pyridine Gels: The 1,6-Polyazaacetylene Oligomers Formation, Molecules, en, 26, 22, 6925, 10.3390/molecules26226925, 34834017, 8621047, 1420-3049, free, The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Historically, pyridine was produced from coal tar. As of 2016, it is synthesized on the scale of about 20,000 tons per year worldwide.

Properties

(File:PyridineXray.svg|thumb|142px|left|Internal bond angles and bond distances (pm) for pyridine.)

Physical properties

(File:Kristallstruktur Pyridin.png|thumb|left|Crystal structure of pyridine)Pyridine is diamagnetic. Its critical parameters are: pressure 5.63 MPa, temperature 619 K and volume 248 cm3Â·molâˆ’1.Haynes, p. 6.80 In the temperature range 340â€“426 Â°C its vapor pressure p can be described with the Antoine equation

log_{10} p = A-frac{B}{C+T}

where T is temperature, A = 4.16272, B = 1371.358 K and C = âˆ’58.496 K.JOURNAL, McCullough, J. P., Douslin, D. R., Messerly, J. F., Hossenlopp, I. A., Kincheloe, T. C., Waddington, Guy, Pyridine: Experimental and Calculated Chemical Thermodynamic Properties between 0 and 1500 K.; a Revised Vibrational Assignment, Journal of the American Chemical Society, 79, 4289, 1957, 10.1021/ja01573a014, 16,

Structure

Pyridine ring forms a {{chem2|C5N}} hexagon. Slight variations of the {{chem2|CsC}} and {{chem2|CsN}} distances as well as the bond angles are observed.

Crystallography

Pyridine crystallizes in an orthorhombic crystal system with space group Pna21 and lattice parameters a = 1752 pm, b = 897 pm, c = 1135 pm, and 16 formula units per unit cell (measured at 153 K). For comparison, crystalline benzene is also orthorhombic, with space group Pbca, a = 729.2 pm, b = 947.1 pm, c = 674.2 pm (at 78 K), but the number of molecules per cell is only 4.JOURNAL, Cox, E., Crystal Structure of Benzene, Reviews of Modern Physics, 30, 1, 159â€“162, 1958, 10.1103/RevModPhys.30.159, 1958RvMP...30..159C, This difference is partly related to the lower symmetry of the individual pyridine molecule (C2v vs D6h for benzene). A trihydrate (pyridineÂ·3H2O) is known; it also crystallizes in an orthorhombic system in the space group Pbca, lattice parameters a = 1244 pm, b = 1783 pm, c = 679 pm and eight formula units per unit cell (measured at 223 K).JOURNAL, Mootz, D., Crystal structures of pyridine and pyridine trihydrate, The Journal of Chemical Physics, 75, 1517â€“1522, 1981, 10.1063/1.442204, 3, 1981JChPh..75.1517M,

Spectroscopy

The optical absorption spectrum of pyridine in hexane consists of bands at the wavelengths of 195, 251, and 270 nm. With respective extinction coefficients (Îµ) of 7500, 2000, and 450 LÂ·molâˆ’1Â·cmâˆ’1, these bands are assigned to Ï€ â†’ Ï€*, Ï€ â†’ Ï€*, and n â†’ Ï€* transitions.The 1H nuclear magnetic resonance (NMR) spectrum shows signals for Î±-(Î´ 8.5), Î³-(Î´7.5) and Î²-protons (Î´7). By contrast, the proton signal for benzene is found at Î´7.27. The larger chemical shifts of the Î±- and Î³-protons in comparison to benzene result from the lower electron density in the Î±- and Î³-positions, which can be derived from the resonance structures. The situation is rather similar for the 13C NMR spectra of pyridine and benzene: pyridine shows a triplet at Î´(Î±-C) = 150 ppm, Î´(Î²-C) = 124 ppm and Î´(Î³-C) = 136 ppm, whereas benzene has a single line at 129 ppm. All shifts are quoted for the solvent-free substances.Joule, p. 16 Pyridine is conventionally detected by the gas chromatography and mass spectrometry methods.BOOK,weblink Pyridine, IARC Monographs 77, OSHA, Washington DC, 1985, 7 January 2011, 4 March 2016,weblink" title="web.archive.org/web/20160304083832weblink">weblink live,

Bonding

(File:Pyridine-2D-Skeletal.png|upright=.5|thumb|left|Pyridine with its free electron pair)Pyridine has a conjugated system of six Ï€ electrons that are delocalized over the ring. The molecule is planar and, thus, follows the HÃ¼ckel criteria for aromatic systems. In contrast to benzene, the electron density is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. For this reason, pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJÂ·molâˆ’1 in pyridine vs. 150 kJÂ·molâˆ’1 in benzene).Joule, p. 7The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the Ï€-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the Ïƒ bonds. As a result, the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack.BOOK, Sundberg, Francis A. Carey; Richard J., Advanced Organic Chemistry : Part A: Structure and Mechanisms, 2007, Springer US, Berlin, 978-0-387-68346-1, 5., 794, However, because of the separation of the lone pair from the aromatic ring system, the nitrogen atom cannot exhibit a positive mesomeric effect.Many analogues of pyridine are known where N is replaced by other heteroatoms from the same column of the Periodic Table of Elements (see figure below). Substitution of one Câ€“H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.

History

File:ThomasAnderson(1819-1874).jpg|thumb|upright|Thomas Anderson ]]Impure pyridine was undoubtedly prepared by early alchemists by heating animal bones and other organic matter,BOOK, Weissberger, A., Klingberg, A., Barnes, R. A., Brody, F., Ruby, P.R., Pyridine and its Derivatives, 1, 1960, Interscience, New York, but the earliest documented reference is attributed to the Scottish scientist Thomas Anderson.JOURNAL, Anderson, Thomas, On the constitution and properties of picoline, a new organic base from coal-tar, Transactions of the Royal Societies of Edinburgh University, 1849, 16, 2, 123â€“136,weblink 10.1017/S0080456800024984, 100301190, 24 September 2018, 24 May 2020,weblink live, JOURNAL, Anderson, T., Producte der trocknen Destillation thierischer Materien, Products of the dry distillation of animal matter, Annalen der Chemie und Pharmacie, 70, 32â€“38, 1849, de,weblink 10.1002/jlac.18490700105, 24 September 2018, 24 May 2020,weblink live, In 1849, Anderson examined the contents of the oil obtained through high-temperature heating of animal bones. Among other substances, he separated from the oil a colorless liquid with unpleasant odor, from which he isolated pure pyridine two years later. He described it as highly soluble in water, readily soluble in concentrated acids and salts upon heating, and only slightly soluble in oils.Owing to its flammability, Anderson named the new substance pyridine, after (pyr) meaning fire. The suffix (wikt:-idine|idine) was added in compliance with the chemical nomenclature, as in toluidine, to indicate a cyclic compound containing a nitrogen atom.JOURNAL, Anderson, Thomas, On the products of the destructive distillation of animal substances. Part II., Transactions of the Royal Society of Edinburgh, 1851, 20, 2, 247â€“260,weblink 10.1017/S0080456800033160, 102143621, 24 September 2018, 24 May 2020,weblink live, From p. 253: "Pyridine. The first of these bases, to which I give the name of pyridine, â€¦ "JOURNAL, Anderson, T., Ueber die Producte der trocknen Destillation thierischer Materien, On the products of dry distillation of animal matter, Annalen der Chemie und Pharmacie, 80, 44â€“65, 1851, de,weblink 10.1002/jlac.18510800104, 24 September 2018, 24 May 2020,weblink live, The chemical structure of pyridine was determined decades after its discovery. Wilhelm KÃ¶rner (1869)JOURNAL, Koerner, W., SynthÃ¨se d'une base isomÃ¨re Ã la toluidine, Giornale di Scienze Naturali ed Economiche (Journal of Natural Science and Economics (Palermo, Italy)), 1869, 5, 111â€“114,weblink Synthesis of a base [that is] isomeric to toluidine, fr, and James Dewar (1871)JOURNAL, Dewar, James, On the oxidation products of picoline, Chemical News, 27 January 1871, 23, 38â€“41,weblink$c193335;view=1up;seq=46, 27 September 2018, 24 May 2020,weblink$c193335;view=1up;seq=46, live, JOURNAL, Koerner, Dewar and the Structure of Pyridine, Alan J., Rocke, Bulletin for the History of Chemistry, 2, 1988, 4,weblink 5 May 2016, 24 September 2018,weblink" title="web.archive.org/web/20180924105914weblink">weblink live, {{open access}} suggested that, in analogy between quinoline and naphthalene, the structure of pyridine is derived from benzene by substituting one Câ€“H unit with a nitrogen atom.BOOK, Albert Ladenburg, Ladenburg, Albert,weblink Lectures on the history of the development of chemistry since the time of Lavoisier, 283â€“287, 7 January 2011, 20 September 2018,weblink" title="web.archive.org/web/20180920134805weblink">weblink live, {{open access}}BOOK, Bansal, Raj K.,weblink Heterocyclic Chemistry, 1999, 81-224-1212-2, 216, New Age International, The suggestion by KÃ¶rner and Dewar was later confirmed in an experiment where pyridine was reduced to piperidine with sodium in ethanol.JOURNAL, Ladenburg, A., Synthese des Piperidins, Berichte der Deutschen Chemischen Gesellschaft, 1884, 17, 156,weblink Synthesis of piperidine, de, 10.1002/cber.18840170143, 15 October 2018, 24 May 2020,weblink live, JOURNAL, Ladenburg, A., Synthese des Piperidins und seiner Homologen, Berichte der Deutschen Chemischen Gesellschaft, 1884, 17, 388â€“391,weblink Synthesis of piperidine and its homologues, de, 10.1002/cber.188401701110, 15 October 2018, 24 May 2020,weblink live, In 1876, William Ramsay combined acetylene and hydrogen cyanide into pyridine in a red-hot iron-tube furnace.JOURNAL, Ramsay, William, On picoline and its derivatives, Philosophical Magazine, 1876, 2, 269â€“281,weblink 5th series, 11, 10.1080/14786447608639105, 24 September 2018, 24 May 2020,weblink live, This was the first synthesis of a heteroaromatic compound.JOURNAL, A. Henninger, aus Paris. 12. April 1877, Berichte der Deutschen Chemischen Gesellschaft, 10, 727â€“737, 1877, 10.1002/cber.187701001202, Correspondence, The first major synthesis of pyridine derivatives was described in 1881 by Arthur Rudolf Hantzsch.JOURNAL, Hantzsch, A., Condensationsprodukte aus Aldehydammoniak und ketonartigen Verbindungen, Condensation products from aldehyde ammonia and ketone-type compounds, Berichte der Deutschen Chemischen Gesellschaft, 14, 1637â€“1638, 1881, 10.1002/cber.18810140214, 2,weblink 6 September 2019, 22 January 2021,weblink live, The Hantzsch pyridine synthesis typically uses a 2:1:1 mixture of a Î²-keto acid (often acetoacetate), an aldehyde (often formaldehyde), and ammonia or its salt as the nitrogen donor. First, a double hydrogenated pyridine is obtained, which is then oxidized to the corresponding pyridine derivative. Emil Knoevenagel showed that asymmetrically substituted pyridine derivatives can be produced with this process.JOURNAL, Knoevenagel, E., Fries, A., Synthesen in der Pyridinreihe. Ueber eine Erweiterung der Hantzsch'schen Dihydropyridinsynthese, Syntheses in the pyridine series. On an extension of the Hantzsch dihydropyridine synthesis, Berichte der Deutschen Chemischen Gesellschaft, 31, 761â€“767, 1898, 10.1002/cber.189803101157,weblink 29 June 2019, 15 January 2020,weblink live, File:Hantzsch pyridine synthesis.svg|800px|thumb|center|Hantzsch pyridine synthesis with acetoacetate, formaldehyde and ammonium acetate, and iron(III) chloride iron(III) chlorideThe contemporary methods of pyridine production had a low yield, and the increasing demand for the new compound urged to search for more efficient routes. A breakthrough came in 1924 when the Russian chemist Aleksei Chichibabin invented a pyridine synthesis reaction, which was based on inexpensive reagents.JOURNAL, Chichibabin, A. E., On condensation of aldehydes with ammonia to make pyridines, Ãœber Kondensation der Aldehyde mit Ammoniak zu Pyridinebasen,weblink Journal fÃ¼r Praktische Chemie, 1924, 107, 122, 10.1002/prac.19241070110, 7 January 2011, 20 September 2018,weblink live, This method is still used for the industrial production of pyridine.

Occurrence

Pyridine is not abundant in nature, except for the leaves and roots of belladonna (Atropa belladonna)BOOK, Burdock, G. A., Fenaroli's Handbook of Flavor Ingredients, 2, 3rd, CRC Press, Boca Raton, 1995, 0-8493-2710-5, and in marshmallow (Althaea officinalis).BOOK, TÃ¤ufel, A., Ternes, W., Tunger, L., Zobel, M., Lebensmittel-Lexikon, 4th, 450, Behr, 2005, 3-89947-165-2, Pyridine derivatives, however, are often part of biomolecules such as alkaloids.In daily life, trace amounts of pyridine are components of the volatile organic compounds that are produced in roasting and canning processes, e.g. in fried chicken,JOURNAL, Tang, Jian, Jin, Qi Zhang, Shen, Guo Hui, Ho, Chi Tang, Chang, Stephen S., Isolation and identification of volatile compounds from fried chicken, Journal of Agricultural and Food Chemistry, 31, 1287, 1983, 10.1021/jf00120a035, 6, sukiyaki,JOURNAL, Shibamoto, Takayuki, Kamiya, Yoko, Mihara, Satoru, Isolation and identification of volatile compounds in cooked meat: sukiyaki, Journal of Agricultural and Food Chemistry, 29, 57â€“63, 1981, 10.1021/jf00103a015, roasted coffee,JOURNAL, Aeschbacher, HU, Wolleb, U, LÃ¶liger, J, Spadone, JC, Liardon, R, Contribution of coffee aroma constituents to the mutagenicity of coffee, Food and Chemical Toxicology, 27, 4, 227â€“232, 1989, 2659457, 10.1016/0278-6915(89)90160-9, free, potato chips,JOURNAL, Buttery, Ron G., Seifert, Richard M., Guadagni, Dante G., Ling, Louisa C., 1971, Characterization of Volatile Pyrazine and Pyridine Components of Potato Chips, Journal of Agricultural and Food Chemistry, 19, 5, 969â€“971, Washington, DC, ACS, 10.1021/jf60177a020, and fried bacon.JOURNAL, Ho, Chi Tang, Lee, Ken N., Jin, Qi Zhang, Isolation and identification of volatile flavor compounds in fried bacon, Journal of Agricultural and Food Chemistry, 31, 336, 1983, 10.1021/jf00116a038, 2, Traces of pyridine can be found in Beaufort cheese,JOURNAL, Dumont, Jean Pierre, Adda, Jacques, Occurrence of sesquiterpene in mountain cheese volatiles, Journal of Agricultural and Food Chemistry, 26, 364, 1978, 10.1021/jf60216a037, 2, vaginal secretions,BOOK, Labows, John N. Jr., Howard R., Moskowitz, Warren, Craig B., Odor Quality and Chemical Structure, 1981, American Chemical Society, Washington, DC, 9780841206076, 10.1021/bk-1981-0148.fw001, 195â€“210, Odorants as Chemical Messengers, black tea,JOURNAL, Vitzthum, Otto G., Werkhoff, Peter, Hubert, Peter, New volatile constituents of black tea flavor, Journal of Agricultural and Food Chemistry, 23, 999, 1975, 10.1021/jf60201a032, 5, saliva of those suffering from gingivitis,JOURNAL, Kostelc, J. G., Preti, G., Nelson, P. R., Brauner, L., Baehni, P., 1984, Oral Odors in Early Experimental Gingivitis, Journal of Periodontal Research, 19, 303â€“312, 10.1111/j.1600-0765.1984.tb00821.x, 3, 6235346, and sunflower honey.BOOK, TÃ¤ufel, A., Ternes, W., Tunger, L., Zobel, M., Lebensmittel-Lexikon, 4th, 226, Behr, 2005, 3-89947-165-2, File:4-Bromopyridine.svg|4-bromopyridineFile:2,2'-Bipyridine.svg|2,2'-bipyridineFile:Dipicolinic acid.svg|pyridine-2,6-dicarboxylic acid (dipicolinic acid)File:PyridiniumVerbindungen.svg|General form of the pyridinium cation

Production

Historically, pyridine was extracted from coal tar or obtained as a byproduct of coal gasification. The process is labor-consuming and inefficient: coal tar contains only about 0.1% pyridine,BOOK, A., Gossauer, Struktur und ReaktivitÃ¤t der BiomolekÃ¼le, 2006, 488, Wiley-VCH, Weinheim, 3-906390-29-2, and therefore a multi-stage purification was required, which further reduced the output. Nowadays, most pyridines are synthesized from ammonia, aldehydes, and nitriles, a few combinations of which are suited for pyridine itself. Various name reactions are also known, but they are not practiced on scale.{{Ullmann|first1=S. |last1=Shimizu |first2=N. |last2=Watanabe |first3=T. |last3=Kataoka |first4=T. |last4=Shoji |first5=N. |last5=Abe |first6=S. |last6=Morishita |first7=H. |last7=Ichimura |title=Pyridine and Pyridine Derivatives |doi=10.1002/14356007.a22_399}}In 1989, 26,000 tonnes of pyridine was produced worldwide. Other major derivatives are 2-, 3-, 4-methylpyridines and 5-ethyl-2-methylpyridine. The combined scale of these alkylpyridines matches that of pyridine itself. Among the largest 25 production sites for pyridine, eleven are located in Europe (as of 1999). The major producers of pyridine include Evonik Industries, RÃ¼tgers Chemicals, Jubilant Life Sciences, Imperial Chemical Industries, and Koei Chemical. Pyridine production significantly increased in the early 2000s, with an annual production capacity of 30,000 tonnes in mainland China alone.WEB,weblink Pyridine's Development in China, AgroChemEx, 11 May 2010, 7 January 2011,weblink" title="web.archive.org/web/20180920134906weblink">weblink 20 September 2018, dead, The USâ€“Chinese joint venture Vertellus is currently the world leader in pyridine production.WEB,weblink About Vertellus, vertellus.com, 7 January 2011,weblink" title="archive.today/20120918012717weblink">weblink 18 September 2012, dead,

Chichibabin synthesis

The Chichibabin pyridine synthesis was reported in 1924 and the basic approach underpins several industrial routes. In its general form, the reaction involves the condensation reaction of aldehydes, ketones, Î±,Î²-unsaturated carbonyl compounds, or any combination of the above, in ammonia or ammonia derivatives. Application of the Chichibabin pyridine synthesis suffer from low yields, often about 30%,FRANK>FIRST1= R. L.

FIRST2= R. P., Pyridines. IV. A Study of the Chichibabin Synthesis, Journal of the American Chemical Society, 1949, 71, 8, 2629â€“2635

formaldehyde and acetaldehyde. First, acrolein is formed in a Knoevenagel condensation from the acetaldehyde and formaldehyde. The acrolein then condensation reaction>condenses with acetaldehyde and ammonia to give dihydropyridine, which is oxidized to pyridine. This process is carried out in a gas phase at 400â€“450 Â°C. Typical catalysts are modified forms of alumina and silica. The reaction has been tailored to produce various methylpyridines.(File:AcroleinDarstellung.svg|500px|center|thumb|Formation of acrolein from acetaldehyde and formaldehyde)(File:Pyridin aus Acrolein.svg|500px|center|thumb|Condensation of pyridine from acrolein and acetaldehyde)

Dealkylation and decarboxylation of substituted pyridines

Pyridine can be prepared by dealkylation of alkylated pyridines, which are obtained as byproducts in the syntheses of other pyridines. The oxidative dealkylation is carried out either using air over vanadium(V) oxide catalyst,PATENT, patent, DE, 1917037, 1968, Verfahren zur Herstellung von Pyridin und Methylpyridinen, Swift, Graham, by vapor-dealkylation on nickel-based catalyst,PATENT, patent, Nippon Kayaku, JP, 7039545, 1967, Electrically-assisted bicycle, driving system thereof, and manufacturing method, PATENT, patent, BE, 758201, 1969, Procede de preparation de bases pyridiques, Koei Chemical, or hydrodealkylation with a silver- or platinum-based catalyst.JOURNAL, Hydrodealkylierung von Pyridinbasen bei Normaldruck, Mensch, F., 1969, ErdÃ¶l Kohle Erdgas Petrochemie, 2, 67â€“71, Yields of pyridine up to be 93% can be achieved with the nickel-based catalyst. Pyridine can also be produced by the decarboxylation of nicotinic acid with copper chromite.JOURNAL, A method for the Degradation of Radioactive Nicotinic Acid, Biochemical Journal, 102, 1, 87â€“93, Scott, T. A., 10.1042/bj1020087, 1270213, 1967, 6030305,

BÃ¶nnemann cyclization

(File:BÃ¶nnemannEn.png|thumb|BÃ¶nnemann cyclization)The trimerization of a part of a nitrile molecule and two parts of acetylene into pyridine is called BÃ¶nnemann cyclization. This modification of the Reppe synthesis can be activated either by heat or by light. While the thermal activation requires high pressures and temperatures, the photoinduced cycloaddition proceeds at ambient conditions with CoCp2(cod) (Cp = cyclopentadienyl, cod = 1,5-cyclooctadiene) as a catalyst, and can be performed even in water.BOOK, Behr, A., 2008, Angewandte homogene Katalyse, 722, Wiley-VCH, Weinheim, 978-3-527-31666-3, A series of pyridine derivatives can be produced in this way. When using acetonitrile as the nitrile, 2-methylpyridine is obtained, which can be dealkylated to pyridine.

Other methods

The KrÃ¶hnke pyridine synthesis provides a fairly general method for generating substituted pyridines using pyridine itself as a reagent which does not become incorporated into the final product. The reaction of pyridine with bromomethyl ketones gives the related pyridinium salt, wherein the methylene group is highly acidic. This species undergoes a Michael-like addition to Î±,Î²-unsaturated carbonyls in the presence of ammonium acetate to undergo ring closure and formation of the targeted substituted pyridine as well as pyridinium bromide.JOURNAL, Fritz, Kroehnke, The Specific Synthesis of Pyridines and Oligopyridines, Synthesis, 1976, 1976, 1, 1â€“24, 10.1055/s-1976-23941, 95238046, .(File:Kroehnke Pyridine Figure 1.png|600px|Figure 1|center){{clear}}The Ciamicianâ€“Dennstedt rearrangementJOURNAL, Ciamician, G. L., Dennstedt, M., 1881, Ueber die Einwirkung des Chloroforms auf die Kaliumverbindung Pyrrols,weblink Berichte der Deutschen Chemischen Gesellschaft, en, 14, 1, 1153â€“1163, 10.1002/cber.188101401240, 0365-9496, entails the ring-expansion of pyrrole with dichlorocarbene to 3-chloropyridine.JOURNAL, 10.1021/ja01541a070, Skell, P. S., Sandler, R. S., Journal of the American Chemical Society, 80, 2024, 1958, 8, Reactions of 1,1-Dihalocyclopropanes with Electrophilic Reagents. Synthetic Route for Inserting a Carbon Atom Between the Atoms of a Double Bond, JOURNAL, 10.1039/J39690002249, Mechanism of heterocyclic ring expansions. Part III. Reaction of pyrroles with dichlorocarbene, 1969, Jones, R. L., Rees, C. W., Journal of the Chemical Society C: Organic, 18, 2249, JOURNAL, Gambacorta, A., Nicoletti, R., Cerrini, S., Fedeli, W., Gavuzzo, E., 10.1016/S0040-4039(01)94795-1, Trapping and structure determination of an intermediate in the reaction between 2-methyl-5-t-butylpyrrole and dichlorocarbene, 1978, Tetrahedron Letters, 19, 27, 2439, (File:Ciamician-Dennstedt Rearrangement.png|500px|center|Ciamicianâ€“Dennstedt Rearrangement){{clear}}In the Gattermannâ€“Skita synthesis,JOURNAL, Eine Synthese von Pyridin-Derivaten, A synthesis of pyridine derivatives, Chemische Berichte, 49, 1, 1916, 494â€“501, Gattermann, L., Skita, A., 10.1002/cber.19160490155,weblink 29 June 2019, 25 September 2020,weblink live, a malonate ester salt reacts with dichloromethylamine.WEB,weblink" title="web.archive.org/web/20060616020955weblink">weblinkweblink Gattermannâ€“Skita, Institute of Chemistry, Skopje, 2006-06-16, (File:Gattermann-Skita Syntesis.png|500px|center|Gattermannâ€“Skita synthesis){{clear}}Other methods include the Boger pyridine synthesis and Dielsâ€“Alder reaction of an alkene and an oxazole.JOURNAL, Karpeiskii, Y., Florent'ev V. L., 1969, Condensation of Oxazoles with Dienophiles â€” a New Method for the Synthesis of Pyridine Bases, Russian Chemical Reviews, 38, 7, 540â€“546, 10.1070/RC1969v038n07ABEH001760, 1969RuCRv..38..540K, 250852496,

Biosynthesis

Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals. Mammals synthesize nicotinic acid through oxidation of the amino acid tryptophan, where an intermediate product, the aniline derivative kynurenine, creates a pyridine derivative, quinolinate and then nicotinic acid. On the contrary, the bacteria Mycobacterium tuberculosis and Escherichia coli produce nicotinic acid by condensation of glyceraldehyde 3-phosphate and aspartic acid.JOURNAL, 10.1104/pp.69.3.553, Tarr, 426252, 16662247, J. B., 1982, 553â€“556, 3, 69, Arditti, Plant Physiology, J., Niacin Biosynthesis in Seedlings of Zea mays,

Reactions

Because of the electronegative nitrogen in the pyridine ring, pyridine enters less readily into electrophilic aromatic substitution reactions than benzene derivatives.BOOK, Sundberg, Francis A. Carey; Richard J., Advanced Organic Chemistry : Part A: Structure and Mechanisms, 2007, Springer US, Berlin, 978-0-387-68346-1, 5., 794, Instead, in terms of its reactivity, pyridine resembles nitrobenzene.JOURNAL, Adrien Albert and the Rationalization of Heterocyclic chemistry, E., Campaigne, J. Chem. Educ., 1986, 63, 10, 860, 10.1021/ed063p860, 1986JChEd..63..860C, Correspondingly pyridine is more prone to nucleophilic substitution, as evidenced by the ease of metalation by strong organometallic bases. The reactivity of pyridine can be distinguished for three chemical groups. With electrophiles, electrophilic substitution takes place where pyridine expresses aromatic properties. With nucleophiles, pyridine reacts at positions 2 and 4 and thus behaves similar to imines and carbonyls. The reaction with many Lewis acids results in the addition to the nitrogen atom of pyridine, which is similar to the reactivity of tertiary amines. The ability of pyridine and its derivatives to oxidize, forming amine oxides (N-oxides), is also a feature of tertiary amines.BOOK, R., Milcent, F., Chau, Chimie organique hÃ©tÃ©rocyclique: Structures fondamentales, 241â€“282, EDP Sciences, 2002, 2-86883-583-X, The nitrogen center of pyridine features a basic lone pair of electrons. This lone pair does not overlap with the aromatic Ï€-system ring, consequently pyridine is basic, having chemical properties similar to those of tertiary amines. Protonation gives pyridinium, C5H5NH+.The pKa of the conjugate acid (the pyridinium cation) is 5.25. The structures of pyridine and pyridinium are almost identical.JOURNAL, Krygowski, T. M., Szatyowicz, H., Zachara, J. E., J. Org. Chem., 10.1021/jo051354h, 16238319, How H-bonding Modifies Molecular Structure and Ï€-Electron Delocalization in the Ring of Pyridine/Pyridinium Derivatives Involved in H-Bond Complexation, 2005, 70, 22, 8859â€“8865, The pyridinium cation is isoelectronic with benzene. Pyridinium p-toluenesulfonate (PPTS) is an illustrative pyridinium salt; it is produced by treating pyridine with p-toluenesulfonic acid. In addition to protonation, pyridine undergoes N-centred alkylation, acylation, and N-oxidation. Pyridine and poly(4-vinyl) pyridine have been shown to form conducting molecular wires with remarkable polyenimine structure on UV irradiation, a process which accounts for at least some of the visible light absorption by aged pyridine samples. These wires have been theoretically predicted to be both highly efficient electron donors and acceptors, and yet are resistant to air oxidation.JOURNAL, Vaganova, Evgenia, Eliaz, Dror, Shimanovich, Ulyana, Leitus, Gregory, Aqad, Emad, Lokshin, Vladimir, Khodorkovsky, Vladimir, January 2021, Light-Induced Reactions within Poly(4-vinyl pyridine)/Pyridine Gels: The 1,6-Polyazaacetylene Oligomers Formation, Molecules, en, 26, 22, 6925, 10.3390/molecules26226925, 34834017, 8621047, 1420-3049, free,

Electrophilic substitutions

Owing to the decreased electron density in the aromatic system, electrophilic substitutions are suppressed in pyridine and its derivatives. Friedelâ€“Crafts alkylation or acylation, usually fail for pyridine because they lead only to the addition at the nitrogen atom. Substitutions usually occur at the 3-position, which is the most electron-rich carbon atom in the ring and is, therefore, more susceptible to an electrophilic addition.(File:Pyridine-EAS-2-position-2D-skeletal.png|520px|center|substitution in the 2-position)(File:Pyridine-EAS-3-position-2D-skeletal.png|500px|center|substitution in the 3-position)(File:Pyridine-EAS-4-position-2D-skeletal.png|430px|center|Substitution in 4-position)Direct nitration of pyridine is sluggish.JOURNAL, Bakke, Jan M., Hegbom, Ingrid, Dinitrogen Pentoxide-Sulfur Dioxide, a New nitrate ion system, Acta Chemica Scandinavica, 48, 181â€“182, 1994, 10.3891/acta.chem.scand.48-0181, Stidsen, Carsten E., free, JOURNAL, Ono, Noboru, Murashima, Takashi, Nishi, Keiji, Nakamoto, Ken-Ichi, Kato, Atsushi, Tamai, Ryuji, Uno, Hidemitsu, Preparation of Novel Heteroisoindoles from nitropyridines and Nitropyridones, Heterocycles, 58, 301, 2002, 10.3987/COM-02-S(M)22, 17 February 2024, Pyridine derivatives wherein the nitrogen atom is screened sterically and/or electronically can be obtained by nitration with nitronium tetrafluoroborate (NO2BF4). In this way, 3-nitropyridine can be obtained via the synthesis of 2,6-dibromopyridine followed by nitration and debromination.JOURNAL, Duffy, Joseph L., Laali, Kenneth K., Aprotic Nitration ({{chem, NO, 2, +, BF, 4, âˆ’, ) of 2-Halo- and 2,6-Dihalopyridines and Transfer-Nitration Chemistry of Their N-Nitropyridinium Cations|journal=The Journal of Organic Chemistry|volume=56|pages=3006|year=1991|doi=10.1021/jo00009a015|issue=9}}Joule, p. 126Sulfonation of pyridine is even more difficult than nitration. However, pyridine-3-sulfonic acid can be obtained. Reaction with the SO3 group also facilitates addition of sulfur to the nitrogen atom, especially in the presence of a mercury(II) sulfate catalyst.JOURNAL, MÃ¶ller, Ernst Friedrich, Birkofer, Leonhard, KonstitutionsspezifitÃ¤t der NicotinsÃ¤ure als Wuchsstoff bei Proteus vulgaris und Streptobacterium plantarum, Constitutional specificity of nicotinic acid as a growth factor in Proteus vulgaris and Streptobacterium plantarum, Berichte der Deutschen Chemischen Gesellschaft (A and B Series), 75, 1108, 1942, 10.1002/cber.19420750912, 9, In contrast to the sluggish nitrations and sulfonations, the bromination and chlorination of pyridine proceed well.(File:simple chlorination.png|500px|center)

Pyridine N-oxide

(File:Pyridine N-oxide.png|thumb|upright=.4|Structure of pyridine N-oxide)Oxidation of pyridine occurs at nitrogen to give pyridine N-oxide. The oxidation can be achieved with peracids:JOURNAL, H. S., Mosher, L., Turner, A., Carlsmith, Pyridine-N-oxide, Org. Synth., 1953, 33, 79, 10.15227/orgsyn.033.0079,

C5H5N + RCO3H → C5H5NO + RCO2H

Some electrophilic substitutions on the pyridine are usefully effected using pyridine N-oxide followed by deoxygenation. Addition of oxygen suppresses further reactions at nitrogen atom and promotes substitution at the 2- and 4-carbons. The oxygen atom can then be removed, e.g., using zinc dust.JOURNAL, Synthesis of 2-aryl Pyridines By Palladium-catalyzed Direct Arylation of Pyridine N-oxides, Campeau, Louis-Charles, Fagnou, Keith, Org. Synth., 2011, 88, 22, 10.15227/orgsyn.088.0022, free,

Nucleophilic substitutions

In contrast to benzene ring, pyridine efficiently supports several nucleophilic substitutions. The reason for this is relatively lower electron density of the carbon atoms of the ring. These reactions include substitutions with elimination of a hydride ion and elimination-additions with formation of an intermediate aryne configuration, and usually proceed at the 2- or 4-position.BOOK, D. T., Davies, Aromatic Heterocyclic Chemistry, Oxford University Press, 1992, 0-19-855660-8, (File:Pyridine-NA-2-position.svg|500px|center|Nucleophilic substitution in 2-position)(File:Pyridine-NA-3-position.svg|500px|center|Nucleophilic substitution in 3-position)(File:Pyridine-NA-4-position.svg|500px|center|Nucleophilic substitution in 4-position)Many nucleophilic substitutions occur more easily not with bare pyridine but with pyridine modified with bromine, chlorine, fluorine, or sulfonic acid fragments that then become a leaving group. So fluorine is the best leaving group for the substitution with organolithium compounds. The nucleophilic attack compounds may be alkoxides, thiolates, amines, and ammonia (at elevated pressures).Joule, p. 133In general, the hydride ion is a poor leaving group and occurs only in a few heterocyclic reactions. They include the Chichibabin reaction, which yields pyridine derivatives aminated at the 2-position. Here, sodium amide is used as the nucleophile yielding 2-aminopyridine. The hydride ion released in this reaction combines with a proton of an available amino group, forming a hydrogen molecule.JOURNAL, Shreve, R. Norris, Riechers, E. H., Rubenkoenig, Harry, Goodman, A. H., Amination in the Heterocyclic Series by Sodium amide, Industrial & Engineering Chemistry, 32, 173, 1940, 10.1021/ie50362a008, 2, Analogous to benzene, nucleophilic substitutions to pyridine can result in the formation of pyridyne intermediates as heteroaryne. For this purpose, pyridine derivatives can be eliminated with good leaving groups using strong bases such as sodium and potassium tert-butoxide. The subsequent addition of a nucleophile to the triple bond has low selectivity, and the result is a mixture of the two possible adducts.

Radical reactions

Pyridine supports a series of radical reactions, which is used in its dimerization to bipyridines. Radical dimerization of pyridine with elemental sodium or Raney nickel selectively yields 4,4'-bipyridine,BOOK, Badger, G, Sasse, W, The Action of Metal Catalysts on Pyridines, 2, 179â€“202, 1963, 10.1016/S0065-2725(08)60749-7, Advances in Heterocyclic Chemistry Volume 2, 14279523, 9780120206025, or 2,2'-bipyridine,JOURNAL, Sasse, W. H. F., 2,2'-bipyridine, Organic Syntheses, 1966, 46, 5â€“8,weblink 10.1002/0471264180.os046.02, 0471264229, dead,weblink" title="web.archive.org/web/20120121055946weblink">weblink 21 January 2012, dmy-all, which are important precursor reagents in the chemical industry. One of the name reactions involving free radicals is the Minisci reaction. It can produce 2-tert-butylpyridine upon reacting pyridine with pivalic acid, silver nitrate and ammonium in sulfuric acid with a yield of 97%.Joule, pp. 125â€“141

Reactions on the nitrogen atom

File:Pyridine-complex.svg|thumb|upright=1.5|Additions of various Lewis acid Lewis acid Lewis acids easily add to the nitrogen atom of pyridine, forming pyridinium salts. The reaction with alkyl halides leads to alkylation of the nitrogen atom. This creates a positive charge in the ring that increases the reactivity of pyridine to both oxidation and reduction. The Zincke reaction is used for the selective introduction of radicals in pyridinium compounds (it has no relation to the chemical element zinc).

Hydrogenation and reduction

File:Pyridine hydrogenation.png|left|thumb|Reduction of pyridine to piperidine with Raney nickel Raney nickel Piperidine is produced by hydrogenation of pyridine with a nickel-, cobalt-, or ruthenium-based catalyst at elevated temperatures.{{Ullmann|last1=Eller |first1=K. |last2=Henkes |first2=E. |last3=Rossbacher |first3=R. |last4=Hoke |first4=H. |title=Amines, aliphatic}} The hydrogenation of pyridine to piperidine releases 193.8 kJÂ·molâˆ’1,BOOK, Cox, J. D., Pilcher, G., 1970, Thermochemistry of Organic and Organometallic Compounds, Academic Press, New York, 1â€“636, 0-12-194350-X, which is slightly less than the energy of the hydrogenation of benzene (205.3 kJÂ·molâˆ’1).Partially hydrogenated derivatives are obtained under milder conditions. For example, reduction with lithium aluminium hydride yields a mixture of 1,4-dihydropyridine, 1,2-dihydropyridine, and 2,5-dihydropyridine.JOURNAL, Tanner, Dennis D., Yang, Chi Ming, On the structure and mechanism of formation of the Lansbury reagent, lithium tetrakis(N-dihydropyridyl) aluminate, The Journal of Organic Chemistry, 58, 1840, 1993, 10.1021/jo00059a041, 7, Selective synthesis of 1,4-dihydropyridine is achieved in the presence of organometallic complexes of magnesium and zinc,JOURNAL, De Koning, A., Specific and selective reduction of aromatic nitrogen heterocycles with the bis-pyridine complexes of bis(1,4-dihydro-1-pyridyl)zinc and bis(1,4-dihydro-1-pyridyl)magnesium, Journal of Organometallic Chemistry, 199, 153, 1980, 10.1016/S0022-328X(00)83849-8, 2, Budzelaar, P. H. M., Boersma, J., Van Der Kerk, G. J. M., and (Î”3,4)-tetrahydropyridine is obtained by electrochemical reduction of pyridine.JOURNAL, Ferles, M., Studies in the pyridine series. II. Ladenburg and electrolytic reductions of pyridine bases, Collection of Czechoslovak Chemical Communications, Institute of Organic Chemistry & Biochemistry, 24, 4, 1959, 10.1135/cccc19591029, 1029â€“1035, Birch reduction converts pyridine to dihydropyridines.JOURNAL, 10.1021/ol0065930, Partial Reduction of Electron-Deficient Pyridines, 2000, Donohoe, Timothy J., McRiner, Andrew J., Sheldrake, Peter, Organic Letters, 2, 24, 3861â€“3863, 11101438,

Lewis basicity and coordination compounds

Pyridine is a Lewis base, donating its pair of electrons to a Lewis acid. Its Lewis base properties are discussed in the ECW model. Its relative donor strength toward a series of acids, versus other Lewis bases, can be illustrated by C-B plots.Laurence, C. and Gal, J-F. (2010) Lewis Basicity and Affinity Scales, Data and Measurement. Wiley. pp. 50â€“51. {{ISBN|978-0-470-74957-9}}JOURNAL, Cramer, R. E., Bopp, T. T., 1977, Graphical display of the enthalpies of adduct formation for Lewis acids and bases, Journal of Chemical Education, 54, 612â€“613, 10.1021/ed054p612, The plots shown in this paper used older parameters. Improved E&C parameters are listed in ECW model. One example is the sulfur trioxide pyridine complex (melting point 175 Â°C), which is a sulfation agent used to convert alcohols to sulfate esters. Pyridine-borane ({{chem2|C5H5NBH3}}, melting point 10â€“11 Â°C) is a mild reducing agent.File:Crabtree.svg|thumb|structure of the Crabtree's catalyst Crabtree's catalyst Transition metal pyridine complexes are numerous.BOOK, Nakamoto, K., Infrared and Raman spectra of Inorganic and Coordination compounds, 5th, Part A, 1997, Wiley, 0-471-16394-5, BOOK, Nakamoto, K., Infrared and Raman spectra of Inorganic and Coordination compounds, 5th, Part B, 0-471-16392-9, 24, 31 July 1997, Typical octahedral complexes have the stoichiometry {{chem2|MCl2(py)4}} and {{chem2|MCl3(py)3}}. Octahedral homoleptic complexes of the type {{chem2|M(py)6(+)}} are rare or tend to dissociate pyridine. Numerous square planar complexes are known, such as Crabtree's catalyst.JOURNAL, Crabtree, Robert, Iridium compounds in catalysis, Accounts of Chemical Research, 12, 331â€“337, 1979, 10.1021/ar50141a005, 9, The pyridine ligand replaced during the reaction is restored after its completion.The Î·6 coordination mode, as occurs in Î·6 benzene complexes, is observed only in sterically encumbered derivatives that block the nitrogen center.BOOK, Elschenbroich, C., Organometallchemie, 6th, 524â€“525, Vieweg & Teubner, 2008, 978-3-8351-0167-8,

Applications

Pesticides and pharmaceuticals

The main use of pyridine is as a precursor to the herbicides paraquat and diquat. The first synthesis step of insecticide chlorpyrifos consists of the chlorination of pyridine. Pyridine is also the starting compound for the preparation of pyrithione-based fungicides. Cetylpyridinium and laurylpyridinium, which can be produced from pyridine with a Zincke reaction, are used as antiseptic in oral and dental care products.BOOK, Thieme Chemistry, RÃ–MPP Online â€“ Version 3.5, Georg Thieme, Stuttgart, 2009, Pyridine is easily attacked by alkylating agents to give N-alkylpyridinium salts. One example is cetylpyridinium chloride.File:Synthesis of paraquat.png|thumb|center|585px|Synthesis of paraquat paraquatIt is also used in the textile industry to improve network capacity of cotton.

Laboratory use

Pyridine is used as a polar, basic, low-reactive solvent, for example in Knoevenagel condensations.BOOK, Carey, 2007, Advanced Organic Chemistry: Part B: Reactions and Synthesis, 5th, Springer, New York, Carey, Francis A., Sundberg, Richard J., 978-0387683546, 147, It is especially suitable for the dehalogenation, where it acts as the base for the elimination reaction. In esterifications and acylations, pyridine activates the carboxylic acid chlorides and anhydrides. Even more active in these reactions are the derivatives 4-dimethylaminopyridine (DMAP) and 4-(1-pyrrolidinyl) pyridine. Pyridine is also used as a base in some condensation reactions.ENCYCLOPEDIA, Sherman, A. R., e-EROS (Encyclopedia of Reagents for Organic Synthesis), L., Paquette, 2004, J. Wiley & Sons, New York, 10.1002/047084289X.rp280, Pyridine, Encyclopedia of Reagents for Organic Synthesis, 0471936235, (File:Chlorocyclopentane elimination.svg|thumb|center|400px|Elimination reaction with pyridine to form pyridinium)

Reagents

File:Alcohol oxidation with Collins reagent.svg|thumb|Oxidation of an alcohol to aldehyde with the Collins reagent Collins reagentAs a base, pyridine can be used as the Karl Fischer reagent, but it is usually replaced by alternatives with a more pleasant odor, such as imidazole.WEB,weblink Wasserbestimmung mit Karl-Fischer-Titration, Water analysis with the Karl Fischer titration, Jena University, dead,weblink" title="web.archive.org/web/20110719105206weblink">weblink 19 July 2011, dmy-all, Pyridinium chlorochromate, pyridinium dichromate, and the Collins reagent (the complex of chromium(VI) oxide) are used for the oxidation of alcohols.BOOK, Tojo, G., Fernandez, M., Oxidation of alcohols to aldehydes and ketones: a guide to current common practice, 2006, Springer, New York, 0-387-23607-4,weblink 28, 29, 86,

Hazards

Pyridine is a toxic, flammable liquid with a strong and unpleasant fishy odour. Its odour threshold of 0.04 to 20 ppm is close to its threshold limit of 5 ppm for adverse effects,WEB,weblink Pyridine MSDS, Alfa Aesar, 3 June 2010, 3 April 2015,weblink" title="web.archive.org/web/20150403012740weblink">weblink dead, thus most (but not all) adults will be able to tell when it is present at harmful levels. Pyridine easily dissolves in water and harms both animals and plants in aquatic systems.WEB,weblink Database of the (EPA), U.S. Environmental Protection Agency, 7 January 2011, 18 September 2011,weblink" title="web.archive.org/web/20110918110610weblink">weblink live,

Fire

Pyridine has a flash point of 20 Â°C and is therefore highly flammable. Combustion produces toxic fumes which can include bipyridines, nitrogen oxides, and carbon monoxide.{{GESTIS|ZVG=13850|Name=Pyridine}}

Short-term exposure

Pyridine can cause chemical burns on contact with the skin and its fumes may be irritating to the eyes or upon inhalation.BOOK, Aylward, G, 2008, SI Chemical Data, Wiley, 6th, 978-0-470-81638-7, Pyridine depresses the nervous system giving symptoms similar to intoxication with vapor concentrations of above 3600 ppm posing a greater health risk. The effects may have a delayed onset of several hours and include dizziness, headache, lack of coordination, nausea, salivation, and loss of appetite. They may progress into abdominal pain, pulmonary congestion and unconsciousness.WEB, International Agency for Research on Cancer (IARC), International Agency for Research on Cancer, Pyridine Summary & Evaluation, IARC Summaries & Evaluations, IPCS INCHEM, 22 August 2000,weblink 17 January 2007, 2 October 2018,weblink" title="web.archive.org/web/20181002182604weblink">weblink live, The lowest known lethal dose (LDLo) for the ingestion of pyridine in humans is 500 mgÂ·kgâˆ’1.

Long-term exposure

Prolonged exposure to pyridine may result in liver, heart and kidney damage. Evaluations as a possible carcinogenic agent showed that there is inadequate evidence in humans for the carcinogenicity of pyridine, although there is sufficient evidence in experimental animals. Therefore, IARC considers pyridine as possibly carcinogenic to humans (Group 2B).BOOK, IARC Working Group on the Evaluation of Carcinogenic Risks to Humans,weblink Some chemicals that cause tumours of the urinary tract in rodents, 2019, International Agency for Research on Cancer, 173â€“198, 978-92-832-0186-1, Lyon, France, 1086392170, 2 June 2021, 6 May 2021,weblink live,

Occurrence

Trace amounts of up to 16 ÂµgÂ·mâˆ’3 have been detected in tobacco smoke. Minor amounts of pyridine are released into environment from some industrial processes such as steel manufacture,JOURNAL, Junk, G. A., Ford, C. S., A review of organic emissions from selected combustion processes, Chemosphere, 9, 187, 1980, 10.1016/0045-6535(80)90079-X, 4, 1980Chmsp...9..187J, 5295035, processing of oil shale, coal gasification, coking plants and incinerators. The atmosphere at oil shale processing plants can contain pyridine concentrations of up to 13 ÂµgÂ·mâˆ’3,JOURNAL, Hawthorne, Steven B., Sievers, Robert E., Emissions of organic air pollutants from shale oil wastewaters, Environmental Science & Technology, 18, 483â€“90, 1984, 10.1021/es00124a016, 6, 22247953, 1984EnST...18..483H, and 53 ÂµgÂ·mâˆ’3 levels were measured in the groundwater in the vicinity of a coal gasification plant.JOURNAL, Stuermer, Daniel H., Ng, Douglas J., Morris, Clarence J., Organic contaminants in groundwater near to underground coal gasification site in northeastern Wyoming, Environmental Science & Technology, 16, 582â€“7, 1982, 10.1021/es00103a009, 9, 22284199, 1982EnST...16..582S, According to a study by the US National Institute for Occupational Safety and Health, about 43,000 Americans work in contact with pyridine.BOOK, National Occupational Exposure Survey 1981â€“83, Cincinnati, OH, Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occuptional Safety and Health,

In foods

Pyridine has historically been added to foods to give them a bitter flavour, although this practise is now banned in the U.S.{{Federal Register|83|50490}}NEWS,weblink FDA Removes 7 Synthetic Flavoring Substances from Food Additives List, 5 October 2018, 8 October 2018, 7 October 2018,weblink live, It may still be added to ethanol to make it unsuitable for drinking.

Metabolism

(File:Pyridin-Metabolisierung.png|thumb|upright=1.5|Metabolism of pyridine)Exposure to pyridine would normally lead to its inhalation and absorption in the lungs and gastrointestinal tract, where it either remains unchanged or is metabolized. The major products of pyridine metabolism are N-methylpyridiniumhydroxide, which are formed by N-methyltransferases (e.g., pyridine N-methyltransferase), as well as pyridine N-oxide, and 2-, 3-, and 4-hydroxypyridine, which are generated by the action of monooxygenase. In humans, pyridine is metabolized only into N-methylpyridiniumhydroxide.WEB, Bonnard, N., Brondeau, M. T., Miraval, S., PilliÃ¨re, F., Protois, J. C., Schneider, O., Pyridine, Fiche Toxicologique, INRS, 2011, fr,weblink 2 June 2021, 2 June 2021,weblink live,

Environmental fate

Pyridine is readily degraded by bacteria to ammonia and carbon dioxide.JOURNAL, Sims, G. K., O'Loughlin, E. J., Degradation of pyridines in the environment, CRC Critical Reviews in Environmental Control, 1989, 19, 4, 309â€“340, 10.1080/10643388909388372, The unsubstituted pyridine ring degrades more rapidly than picoline, lutidine, chloropyridine, or aminopyridines,JOURNAL, 10.1002/etc.5620050601, Sims, G. K., L.E., Sommers, 1986, Biodegradation of pyridine derivatives in soil suspensions, Environmental Toxicology and Chemistry, 5, 503â€“509, 6, and a number of pyridine degraders have been shown to overproduce riboflavin in the presence of pyridine.JOURNAL, Sims, G. K., E.J., O'Loughlin, 1992, Riboflavin production during growth of Micrococcus luteus on pyridine, Applied and Environmental Microbiology, 58, 10, 3423â€“3425, 10.1128/AEM.58.10.3423-3425.1992, 183117, 16348793, 1992ApEnM..58.3423S, Ionizable N-heterocyclic compounds, including pyridine, interact with environmental surfaces (such as soils and sediments) via multiple pH-dependent mechanisms, including partitioning to soil organic matter, cation exchange, and surface complexation.JOURNAL, Bi, E., Schmidt, T. C., Haderlein, S. B., 2006, Sorption of heterocyclic organic compounds to reference soils: column studies for process identification, Environ Sci Technol, 40, 19, 5962â€“5970, 10.1021/es060470e, 17051786, 2006EnST...40.5962B, Such adsorption to surfaces reduces bioavailability of pyridines for microbial degraders and other organisms, thus slowing degradation rates and reducing ecotoxicity.JOURNAL, O'Loughlin, E. J, Traina, S. J., Sims, G. K., 2000, Effects of sorption on the biodegradation of 2-methylpyridine in aqueous suspensions of reference clay minerals, Environmental Toxicology and Chemistry, 19, 9, 2168â€“2174, 10.1002/etc.5620190904, 98654832,

Nomenclature

The systematic name of pyridine, within the Hantzschâ€“Widman nomenclature recommended by the IUPAC, is {{chem name|azinine}}. However, systematic names for simple compounds are used very rarely; instead, heterocyclic nomenclature follows historically established common names. IUPAC discourages the use of {{chem name|azinine/azine}} in favor of pyridine.JOURNAL, 10.1351/pac198855020409, Powell, W. H., Revision of the extended Hantzsch-Widman system of nomenclature for hetero mono-cycles, Pure and Applied Chemistry, 1983, 55, 409â€“416,weblink 2, 4686578, 7 January 2011, 20 September 2018,weblink" title="web.archive.org/web/20180920135014weblink">weblink live, The numbering of the ring atoms in pyridine starts at the nitrogen (see infobox). An allocation of positions by letter of the Greek alphabet (Î±-Î³) and the substitution pattern nomenclature common for homoaromatic systems (ortho, meta, para) are used sometimes. Here Î± (ortho), Î² (meta), and Î³ (para) refer to the 2, 3, and 4 position, respectively. The systematic name for the pyridine derivatives is pyridinyl, wherein the position of the substituted atom is preceded by a number. However, the historical name pyridyl is encouraged by the IUPAC and used instead of the systematic name.BOOK, D., Hellwinkel, Die systematische Nomenklatur der Organischen Chemie, 4th, 45, Springer, Berlin, 1998, 3-540-63221-2, The cationic derivative formed by the addition of an electrophile to the nitrogen atom is called pyridinium.

References

Bibliography

BOOK, Sundberg, Francis A. Carey; Richard J., Advanced Organic Chemistry : Part A: Structure and Mechanisms, 2007, Springer US, Berlin, 978-0-387-68346-1, 5.,
BOOK, Haynes, Haynes, William M., 2016, CRC Handbook of Chemistry and Physics, 97th, CRC Press, 9781498754293,
BOOK, Joule, J. A., Mills, K., Joule,weblink Heterocyclic Chemistry, 5th, Blackwell Publishing, Chichester, 2010, 978-1-4051-3300-5,

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pyridine

Properties

Physical properties

Structure

Crystallography

Spectroscopy

Bonding

History

Occurrence

Production

Chichibabin synthesis

Dealkylation and decarboxylation of substituted pyridines

BÃ¶nnemann cyclization

Other methods

Biosynthesis

Reactions

Electrophilic substitutions

Pyridine N-oxide

Nucleophilic substitutions

Radical reactions

Reactions on the nitrogen atom

Hydrogenation and reduction

Lewis basicity and coordination compounds

Applications

Pesticides and pharmaceuticals

Laboratory use

Reagents

Hazards

Fire

Short-term exposure

Long-term exposure

Occurrence

In foods

Metabolism

Environmental fate

Nomenclature

See also

References

Bibliography

External links