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| | Are individuals in this place getting tricked into buying certain things by repetitive marketing and being told that these things are "cool" because everybody else is buying them? It often seems that method once we are manipulated by big-business with advertisement campaigns, catchphrases, and principles that are inaccurate and often only really stupid. To be honest, folks are falling for this, and it casts serious doubts on our emotional status. The people attempting to push stuff down our throats are playing with our heads, and for probably the most part-they look like winning.<br><br> |
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| | Watchedfields = changed
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| | verifiedrevid = 414415928
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| | Name = Pyridine
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| | ImageFileL1 = Pyridine-2D-full.svg
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| | ImageSizeL1 = 120px
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| | ImageNameL1 = Full structural formula of pyridine
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| | ImageFileR1_Ref = {{chemboximage|correct|??}}
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| | ImageFileR1 = Pyridine_numbers.svg
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| | ImageSizeR1 = 90px
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| | ImageNameR1 = Skeletal formula of pyridine, showing the numbering convention
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| | ImageFileL2 = Pyridine-CRC-MW-3D-balls.png
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| | ImageSizeL2 = 130px
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| | ImageNameL2 = Ball-and-stick diagram of pyridine
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| | ImageFileR2 = Pyridine-CRC-MW-3D-vdW.png
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| | ImageSizeR2 = 120px
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| | ImageNameR2 = Space-filling model of pyridine
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| | ImageFile3 = Pyridine sample.jpg
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| | ImageSize3 = 200px
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| | IUPACName = Pyridine
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| | OtherNames = Azine<br />Azabenzene
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| | Section1 = {{Chembox Identifiers
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| | ChEBI_Ref = {{ebicite|changed|EBI}}
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| | ChEBI = 16227
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| | SMILES = c1ccncc1
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| | UNII_Ref = {{fdacite|correct|FDA}}
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| | UNII = NH9L3PP67S
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| | KEGG_Ref = {{keggcite|correct|kegg}}
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| | KEGG = C00747
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| | InChI = 1/C5H5N/c1-2-4-6-5-3-1/h1-5H
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| | InChIKey = JUJWROOIHBZHMG-UHFFFAOYAY
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| | ChEMBL_Ref = {{ebicite|correct|EBI}}
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| | ChEMBL = 266158
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| | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
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| | StdInChI = 1S/C5H5N/c1-2-4-6-5-3-1/h1-5H
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| | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
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| | StdInChIKey = JUJWROOIHBZHMG-UHFFFAOYSA-N
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| | CASNo_Ref = {{cascite|correct|CAS}}
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| | CASNo = 110-86-1
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| | PubChem = 1049
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| | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
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| | ChemSpiderID = 1020
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| | EINECS = 203-809-9
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| }}
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| | Section2 = {{Chembox Properties
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| | C=5|H=5|N=1
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| | Appearance = colorless liquid
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| | Density = 0.9819 g/mL<ref>[[#Lide|Lide]], p. 3-474</ref>
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| | Solubility = Miscible
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| | MeltingPtC = −41.6
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| | BoilingPtC = 115.2
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| | Viscosity = 0.88 [[Poise|cP]]
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| | Dipole = 2.2 D<ref name=roempp/>
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| | RefractIndex = 1.5093
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| | VaporPressure = 18 mmHg
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| | pKa = 5.25 (for the conjugate acid)<ref>{{cite journal|last1=Linnell|first1=Robert|journal=Journal of Organic Chemistry|volume=25|pages=290|year=1960|doi=10.1021/jo01072a623|issue=2}}</ref><ref>{{cite journal|last1=Pearson|first1=Ralph G.|last2=Williams|first2=Forrest V.|journal=Journal of the American Chemical Society|volume=75|pages=3073|year=1953|doi=10.1021/ja01109a008|issue=13}}</ref>
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| }}
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| | Section7 = {{Chembox Hazards
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| | Reference=<ref>[https://fscimage.fishersci.com/msds/19990.htm Pyridine MSDS]. fishersci.com</ref>
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| | NFPA-H = 3
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| | NFPA-F = 3
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| | NFPA-R = 0
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| | FlashPtC = 21
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| | TLV-TWA = 5 ppm
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| | EUClass = Flammable ('''F''')<br />Harmful ('''Xn''')
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| | RPhrases = {{R20}} {{R21}} {{R22}} {{R34}} {{R36}} {{R38}}
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| | SPhrases =
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| | RSPhrases =}}
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| | Section8 = {{Chembox Related
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| | Function = [[amine]]s
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| | OtherFunctn = [[Picoline]]<br />[[Quinoline]]
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| | OtherCpds = [[Aniline]]<br />[[Pyrimidine]]<br />[[Piperidine]]}}
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| }}
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| '''Pyridine''' is a basic [[heterocyclic compound|heterocyclic]] [[organic compound]] with the [[chemical formula]] [[Carbon|C<sub>5</sub>]][[Hydrogen|H<sub>5</sub>]][[Nitrogen|N]]. It is structurally related to [[benzene]], with one [[methine group]] (=CH-) replaced by a [[nitrogen]] atom. The pyridine ring occurs in many important compounds, including [[azine]]s and the vitamins [[niacin]] and [[pyridoxal]].
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| Pyridine was discovered in 1849 by the Scottish chemist [[Thomas Anderson (chemist)|Thomas Anderson]] as one of the constituents of [[Dippel's oil|bone oil]]. Two years later, Anderson isolated pure pyridine through [[fractional distillation]] of the oil. It is a colorless, highly flammable, weakly alkaline, water-soluble liquid with a distinctive, unpleasant fish-like odor.
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| Pyridine is used as a [[precursor (chemistry)|precursor]] to [[agrochemical]]s and [[pharmaceutical]]s and is also an important [[solvent]] and [[reagent]]. Pyridine is added to [[ethanol]] to make it unsuitable for drinking (see [[denatured alcohol]]). It is used in the ''in vitro'' synthesis of [[DNA]],<ref name="Pyridine Solution in DNA Synthesis">{{cite web|title=Iodine Solution (0.02M in THF/pyridine/H2O 70:20:10)|url=http://www.sigmaaldrich.com/catalog/ProductDetail.do?D7=0&N5=SEARCH_CONCAT_PNO%7CBRAND_KEY&N4=59706%7CFLUKA&N25=0&QS=ON&F=SPEC|publisher=Sigma-Aldrich|accessdate=28 November 2011}}</ref> in the synthesis of [[sulfapyridine]] (a drug against bacterial and viral infections), [[histamine antagonist|antihistaminic]] drugs [[tripelennamine]] and [[mepyramine]], as well as water repellents, [[bactericide]]s, and [[herbicide]]s. Some chemical compounds, although not synthesized from pyridine, contain its ring structure. They include [[B vitamins]] [[niacin]] and [[pyridoxal]], the [[Tuberculosis treatment|anti-tuberculosis]] drug [[isoniazid]], [[nicotine]] and other nitrogen-containing plant products.<ref name=brit>[http://www.britannica.com/EBchecked/topic/484880/pyridine Pyridine]. ''Encyclopædia Britannica'' on-line</ref> Historically, pyridine was produced from [[coal tar]] and as a by-product of the [[coal gasification]]. However, increased demand for pyridine resulted in the development of more economical methods of synthesis from [[acetaldehyde]] and [[ammonia]], and more than 20,000 [[tonne]]s per year are manufactured worldwide.
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| ==Properties==
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| ===Physical properties===
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| [[File:Kristallstruktur Pyridin.png|thumb|Crystal structure of pyridine]]
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| Pyridine is a colorless liquid that boils at 115.2°C and freezes at −41.6°C. Its density, 0.9819 g/cm<sup>3</sup>, is close to that of water, and its [[refractive index]] is 1.5093 at a [[wavelength]] of 589 nm and a temperature of 20°C.<ref name=lide3448>[[#Lide|Lide]], p. 3–448</ref> Addition of up to 40 mol% of water to pyridine gradually lowers its melting point from −41.6°C to −65.0°C.<ref name=str/> The molecular [[electric dipole moment]] is 2.2 [[debye]].<ref name=roempp>{{cite book|work=Thieme Chemistry|title=RÖMPP Online – Version 3.5|publisher=Georg Thieme |place=Stuttgart|year=2009}}</ref> Pyridine is [[diamagnetism|diamagnetic]] and has a [[Magnetic susceptibility|diamagnetic susceptibility]] of −48.7 × 10<sup>−6</sup> cm<sup>3</sup>·mol<sup>−1</sup>.<ref>[[#Lide|Lide]], p. 3–673</ref> The [[standard enthalpy of formation]] is 100.2 kJ·mol<sup>−1</sup> in the liquid phase<ref name=lide528>[[#Lide|Lide]], p. 5-28</ref> and 140.4 kJ·mol<sup>−1</sup> in the gas phase. At 25 °C pyridine has a [[viscosity]]<ref>[[#Lide|Lide]], p. 6-211</ref> of 0.88 mPa/s and [[thermal conductivity]] of 0.166 W·m<sup>−1</sup>·K<sup>−1</sup>.<ref>[[#Lide|Lide]], p. 6–221</ref><ref name="GESTIS"/> The [[enthalpy of vaporization]] is 35.09 kJ·mol<sup>−1</sup> at the [[boiling point]] and normal pressure.<ref name="Majer Svoboda">Majer, V. and Svoboda, V. (1985). ''Enthalpies of Vaporization of Organic Compounds: A Critical Review and Data Compilation'', Blackwell Scientific Publications, Oxford, ISBN 0-632-01529-2</ref> The [[enthalpy of fusion]] is 8.28 kJ·mol<sup>−1</sup> at the [[melting point]].<ref>{{cite journal|last1=Domalski|first1=Eugene S.|last2=Hearing|first2=Elizabeth D.|title=Heat Capacities and Entropies of Organic Compounds in the Condensed Phase|journal=Journal of Physical and Chemical Reference Data|volume=25|pages=1|year=1996|doi=10.1063/1.555985|bibcode = 1996JPCRD..25....1D }}</ref>
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| Pyridine crystallizes in an [[orthorhombic crystal system]] with [[space group]] ''Pna2<sub>1</sub>'' and lattice parameters ''a'' = 1752, ''b'' = 897, ''c'' = 1135 [[picometer|pm]], and 16 [[formula unit]]s per [[unit cell]] (measured at 153 K). For comparison, benzene crystal 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.<ref>{{cite journal|last1=Cox|first1=E.|title=Crystal Structure of Benzene|journal=Reviews of Modern Physics|volume=30|pages=159|year=1958|doi=10.1103/RevModPhys.30.159|bibcode=1958RvMP...30..159C}}</ref> This difference is partly related to the lower symmetry of the individual pyridine molecule (C<sub>2v</sub> vs. D<sub>6h</sub> for benzene). A tri[[hydrate]] (pyridine·3H<sub>2</sub>O) is known; it also crystallizes in an orthorhombic system in the space group ''Pbca'', lattice parameters ''a'' = 1244, ''b'' = 1783, ''c'' = 679 pm and eight formula units per unit cell (measured at 223 K).<ref name=str>{{cite journal|last1=Mootz|first1=D.|title=Crystal structures of pyridine and pyridine trihydrate|journal=The Journal of Chemical Physics|volume=75|pages=1517|year=1981|doi=10.1063/1.442204|issue=3|bibcode = 1981JChPh..75.1517M }}</ref>
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| The [[critical point (thermodynamics)|critical parameters]] of pyridine are pressure 6.70 MPa, temperature 620 K and volume 229 cm<sup>3</sup>·mol<sup>−1</sup>.<ref>[[#Lide|Lide]], p. 6–67</ref> In the temperature range 340–426°C its vapor pressure ''p'' can be described with the [[Antoine equation]]
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| :<math>\log_{10} p = A-\frac{B}{C+T}</math>
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| where ''T'' is temperature, ''A'' = 4.16272, ''B'' = 1371.358 K and ''C'' = -58.496 K.<ref>{{cite journal|last1=McCullough|first1=J. P.|last2=Douslin|first2=D. R.|last3=Messerly|first3=J. F.|last4=Hossenlopp|first4=I. A.|last5=Kincheloe|first5=T. C.|last6=Waddington|first6=Guy|title=Pyridine: Experimental and Calculated Chemical Thermodynamic Properties between 0 and 1500°K.; a Revised Vibrational Assignment|journal=Journal of the American Chemical Society|volume=79|pages=4289|year=1957|doi=10.1021/ja01573a014|issue=16}}</ref>
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| The optical absorption spectrum of pyridine in [[hexane]] contains three bands at the [[wavelength]]s of 195 nm (π → π*transition, [[molar absorptivity]] ε = 7500 L·(mol·cm)<sup>−1</sup>), 251 nm (π → π*transition, ε = 2000 L·(mol·cm)<sup>−1</sup>) and 270 nm (n → π*transition, ε = 450 L·(mol·cm)<sup>−1</sup>).<ref>[[#Joule|Joule]], p. 14</ref> The <sup>1</sup>H [[nuclear magnetic resonance]] (NMR) spectrum of pyridine contains three signals with the integral intensity ratio of 2:1:2 that correspond to the three chemically different protons in the molecule. These signals originate from the α-protons ([[chemical shift]] 8.5 ppm), γ-proton (7.5 ppm) and β-protons (7.1 ppm). The carbon analog of pyridine, benzene, has only one proton signal at 7.27 ppm. The larger chemical shifts of the α- and γ-protons in comparison to benzene result from the lower electron density in the α- and γ-positions, which can be derived from the resonance structures. The situation is rather similar for the <sup>13</sup>C NMR spectra of pyridine and benzene: pyridine shows a triplet at δ (α-C) = 150 ppm, δ (β-C) = 124 ppm and δ (γ-C) = 136 ppm, whereas benzene has a single line at 129 ppm. All shifts are quoted for the solvent-free substances.<ref>[[#Joule|Joule]], p. 16</ref> Pyridine is conventionally detected by the [[gas chromatography]] and [[mass spectrometry]] methods.<ref name=osha/>
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| ===Chemical properties===
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| Pyridine is miscible with water and virtually all organic solvents.<ref name=lide3448/> It is weakly basic, and with [[hydrochloric acid]] it forms a crystalline [[hydrochloride]] salt that melts at 145–147 °C.<ref>[http://www.alfa.com/content/msds/english/L11463.pdf Pyridine hydrochloride MSDS], Alfa Aesar, 26 June 2010</ref> Most chemical properties of pyridine are typical of a [[heteroaromatic]] compound. In [[organic reaction]]s, pyridine behaves both as a tertiary [[amine]], undergoing [[protonation]], [[alkylation]], [[acylation]], and [[N-oxidation]] at the nitrogen atom, and as an [[aromatic compound]], undergoing [[nucleophilic substitution]]s.
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| Because of the electronegative [[nitrogen]] in the pyridine ring, the molecule is relatively electron deficient. It, therefore, enters less readily [[electrophilic aromatic substitution]] reactions, which are characteristic of benzene derivatives. However, unlike benzene and its derivatives, pyridine is more prone to [[nucleophilic substitution]] and [[metalation]] of the ring by strong organometallic bases.<ref name=jou10/><ref name=davies/> The reactivity of pyridine can be distinguished for three chemical groups. With [[electrophile]]s, [[electrophilic substitution]] takes place where pyridine expresses aromatic properties. With [[nucleophile]]s, pyridine reacts via its 2nd and 4th carbon atoms and thus behaves similar to [[imine]]s and [[carbonyl]]s. The reaction with many [[Lewis acid]]s 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 oxide]]s (N-oxides), is also a feature of tertiary amines.<ref>R. Milcent, F. Chau: ''Chimie organique hétérocyclique: Structures fondamentales'', pp. 241–282, EDP Sciences, 2002, ISBN 2-86883-583-X</ref>
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| [[File:1,10-phenanthroline.svg|thumb|120px|1,10-[[phenanthroline]]]]
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| The nitrogen center of pyridine features a basic [[lone pair]] of [[electron]]s. Because this lone pair is not part of the aromatic ring, pyridine is a [[Base (chemistry)|base]], having chemical properties similar to those of [[tertiary amine]]s. The [[pKa]] of the [[conjugate acid]] is 5.25<!-- , i.e. pyridinium is about as strong as [[acetic acid]] I think not, there is a two order of magnitude difference in the K values.-->. Pyridine is [[protonation|protonated]] by [[Chemical reaction|reaction]] with [[acid]]s and forms a positively charged aromatic [[polyatomic ion]] called [[pyridinium]]. The [[bond length]]s and [[bond angle]]s in pyridine and pyridinium are almost identical.<ref>{{cite journal|author = Krygowski, T. M.; Szatyowicz,H. and Zachara, J. E. |journal = [[J. Org. Chem.]]|doi = 10.1021/jo051354h|pmid = 16238319|title = How H-bonding Modifies Molecular Structure and π-Electron Delocalization in the Ring of Pyridine/Pyridinium Derivatives Involved in H-Bond Complexation<sup>†</sup>|year = 2005|volume = 70|issue = 22|pages = 8859–65}}</ref> The pyridinium cation is [[isoelectronic]] with benzene. Pyridinium ''p''-[[toluenesulfonic acid|toluenesulfonate]] (PPTS) is an illustrative pyridinium salt; it is produced by treating pyridine with [[P-Toluenesulfonic acid|''p''-toluenesulfonic acid]].
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| Pyridine can act as [[Lewis base]], donating its pair of electron to a Lewis acid as in the [[sulfur trioxide pyridine complex]].
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| Pyridine itself is a relatively weak ligand in forming [[coordination complex|complexes]] with [[transition metal]] ions. For example, it forms a 1:1 complexes with nickel(II), Ni<sup>2+</sup>, and copper(II), Cu<sup>2+</sup>, with logK<sub>1</sub> values of ca. 1.9 and 2.6, respectively.<ref name=scdb>[http://www.acadsoft.co.uk/scdbase/scdbase.htm IUPAC SC-Database] A comprehensive database of published data on equilibrium constants of metal complexes and ligands</ref> The [[infrared spectrum|infrared spectra]] of pyridine complexes have been discussed in detail.<ref name =nakamoto>{{cite book|last=Nakamoto|first=K.|title=Infrared and Raman spectra of Inorganic and Coordination compounds|edition=5th|series=Part A|year=1997|publisher=Wiley|isbn=0-471-16394-5}}</ref><ref>{{cite book|last=Nakamoto|first=K.|title=Infrared and Raman spectra of Inorganic and Coordination compounds|edition=5th|series=Part B|isbn=0-471-16392-9|page=24}}</ref> Picolinic acid, which is a substituted derivative of pyridine, forms strong complexes due to the [[chelate effect]]; 2,2'-bipyridine and 1,10-phenanthroline, which can also be viewed as substituted derivatives of pyridine, also form strong complexes, such as in [[Ferroin]], which can be used as an [[redox indicator]] in the [[Quantitative analysis (chemistry)|quantitative analysis]] of iron.<ref>{{VogelQuantitative6th|page=418}}</ref>
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| The η<sup>6</sup> coordination mode, as occurs in η<sup>6</sup> benzene complexes, is observed only in [[Steric effects|sterically encumbered]] derivatives that block the nitrogen center.<ref>Elschenbroich, C. ''Organometallchemie'', 6th ed., pp. 524–525, Vieweg+Teubner, 2008, ISBN 3-8351-0167-6</ref>
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| ====Molecular properties====
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| [[File:Pyridine-2D-Skeletal.png|80px|thumb|Pyridine with its free electron pair]]
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| Pyridine has a [[conjugation (organic chemistry)|conjugated]] system of six [[Pi bond|π-electrons]] that are delocalized over the ring. The molecule is planar and, thus, follows the [[Hückel rule|Hückel 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 [[Resonance (chemistry)|resonant stabilization]] than benzene ([[Resonance (chemistry)#Resonance energy|resonance energy]] 117 kJ·mol<sup>−1</sup> in pyridine vs. 150 kJ·mol<sup>−1</sup> in benzene).<ref>[[#Joule|Joule]], p. 7</ref> The electron localization in pyridine is also reflected in the shorter C–N ring bond (137 pm for the C–N bond in pyridine vs. 139 [[picometer|pm]] for C–C bond in benzene),<ref>Elschenbroich, C. ''Organometallchemie'', 6th ed., p. 218, Vieweg+Teubner, 2008, ISBN 3-8351-0167-6</ref> whereas the carbon–carbon bonds in the pyridine ring have the same 139 pm length as in benzene. These bond lengths lie between the values for the single and [[double bond]]s and are typical of aromatic compounds.
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| All the ring atoms in the pyridine molecule are [[orbital hybridisation#sp2 hybrids|sp<sup>2</sup>-hybridized]]. The nitrogen atom "donates" its three hybridized electrons to the ring system, and its extra electron pair lies in the molecule plane, projecting outward, in the plane of the ring. This [[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. However, because of the separation of the lone pair from the aromatic system of the ring affects, the nitrogen atom cannot exhibit a positive [[mesomeric effect]].
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| Many analogues of pyridine are known where N is replaced by other heteroatoms (see Figure). Substitution of one CH in pyridine with a second N gives rise to the "diaza" heterocycles (C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>), with the names [[pyridazine]], [[pyrimidine]], and [[pyrazine]].
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| {|class="wikitable" style="margin: 1em auto 1em auto;"
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| |[[File:Bond lengths of group 15 heterobenzenes and benzene.svg|center|thumb|620px|Bond lengths and angles of benzene, pyridine, [[phosphorine]], [[arsabenzene]], stibabenzene, and bismabenzene ]]
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| |[[File:Pyridine-orbitals.svg|thumb|center|180px|Electron orbitals in pyridine]]
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| |[[File:Pyridine-10.png|620px|thumb|center|Resonance structures of pyridine]]
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| |[[File:Pyridinium-orbitals.svg|180px|center|thumb|Electron orbitals in protonated pyridine]]
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| |}
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| ==History==
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| [[File:ThomasAnderson(1819-1874).jpg|thumb|upright|left|Thomas Anderson]]
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| Impure pyridine was undoubtedly prepared by early alchemists by heating animal bones and other organic matter,<ref name=weiss>Weissberger, A.; Klingberg, A., Barnes, R. A.; Brody, F. and Ruby, P.R. ''Pyridine and its Derivatives'', Volume 1, 1960, Interscience Pub., New York</ref> but the earliest documented reference is attributed to the Scottish scientist [[Thomas Anderson (chemist)|Thomas Anderson]].<ref>Anderson, T. Transactions of Royal Society of Edinburg, 16 (1849) 123</ref><ref name="Von1849">{{cite journal|last1=Von Anderson|first1=Th.|title=Producte der trocknen Destillation thierischer Materien|journal=Annalen der Chemie und Pharmacie|volume=70|pages=32|year=1849|doi=10.1002/jlac.18490700105}}</ref> In 1849, Anderson examined the contents of the oil obtained through high-temperature heating of animal bones.<ref name="Von1849" /> 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.
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| Owing to its flammability, Anderson named the new substance ''pyridine'', after {{lang-gr|[[wikt:πῦρ|πῦρ]]}} (pyr) meaning ''fire''. The suffix ''[[wikt:-idine|idine]]'' was added in compliance with the chemical nomenclature, as in ''[[toluidine]]'', to indicate a carbon cycle containing a nitrogen atom.<ref name=anderson2>{{cite journal|last1=Anderson|first1=Th.|title=Ueber die Producte der trocknen Destillation thierischer Materien|journal=Annalen der Chemie und Pharmacie|volume=80|pages=44|year=1851|doi=10.1002/jlac.18510800104}}</ref>
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| The chemical structure of pyridine was determined decades after its discovery. [[Wilhelm Körner]] (1869)<ref>Körner, W. Giorn. academ. Palermo, vol. 5 (1869)</ref> and [[James Dewar]] (1871)<ref>Dewar, J. Chem. News, 23 (1871) 38</ref> independently suggested that, in analogy between [[quinoline]] and [[naphthalene]], the structure of pyridine is derived from [[benzene]] by substituting one C–H unit with a nitrogen atom.<ref>[[Albert Ladenburg]] [http://www.sciencemadness.org/library/books/lectures_on_the_history_of_the_development_of_chemistry.pdf ''Lectures on the history of the development of chemistry since the time of Lavoisier.''], pp. 283–287</ref><ref>Bansal, Raj K. [http://books.google.com/books?id=RH1l_VQcFDQC&pg=PA216 Heterocyclic Chemistry], (1999) ISBN 81-224-1212-2, p. 216</ref> The suggestion by Körner and Dewar was later confirmed in an experiment where pyridine was reduced to [[piperidine]] with [[sodium]] in ethanol. In 1876, [[William Ramsay]] combined [[acetylene]] and [[hydrogen cyanide]] into pyridine in a [[Red heat|red-hot]] iron-tube furnace. This was the first synthesis of a hetero-aromatic compound.<ref name=osha/><ref>{{cite journal|title=A. Henninger, aus Paris. 12. April 1877|journal=Berichte der deutschen chemischen Gesellschaft|volume=10|pages=727|year=1877|doi=10.1002/cber.187701001202}}</ref>
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| The 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 [[Chichibabin pyridine synthesis|pyridine synthesis reaction]], which was based on inexpensive reagents.<ref name=tschi>{{cite journal
| |
| |author = Tscihtschibabin, A. E.
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| |title = Über Kondensation der Aldehyde mit Ammoniak zu Pyridinebasen
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| |url=http://gallica.bnf.fr/ark:/12148/bpt6k90877m/f132.chemindefer
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| |journal = Journal für Praktische Chemie
| |
| |year = 1924
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| |volume = 107
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| |pages = 122
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| |doi = 10.1002/prac.19241070110}}</ref> This method is still used for the industrial production of pyridine.<ref name=ul/>
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| ==Occurrence==
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| Pyridine is not abundant in nature, except for the leaves and roots of belladonna (''[[Atropa belladonna]]'')<ref>Burdock, G. A. (ed.) ''Fenaroli's Handbook of Flavor Ingredients'', Vol. II, 3rd Edition, CRC Press, Boca Raton, 1995, ISBN 0-8493-2710-5</ref> and in marshmallow (''[[Althaea officinalis]]'').<ref>Täufel, A.; Ternes, W.; Tunger, L. and Zobel, M.: ''Lebensmittel-Lexikon'', 4th ed., p. 450, Behr, 2005, ISBN 3-89947-165-2</ref> Pyridine derivatives, however, are often part of biomolecules such as the eponymous pyridine nucleotides and alkaloids.
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| In daily life, trace amounts of pyridine are components of the [[volatile organic compound]]s that are produced in roasting and [[canning]] processes, e.g. in fried chicken,<ref>{{cite journal|last1=Tang|first1=Jian|last2=Jin|first2=Qi Zhang|last3=Shen|first3=Guo Hui|last4=Ho|first4=Chi Tang|last5=Chang|first5=Stephen S.|title=Isolation and identification of volatile compounds from fried chicken|journal=Journal of Agricultural and Food Chemistry|volume=31|pages=1287|year=1983|doi=10.1021/jf00120a035|issue=6}}</ref> [[sukiyaki]],<ref>{{cite journal|last1=Shibamoto|first1=Takayuki|last2=Kamiya|first2=Yoko|last3=Mihara|first3=Satoru|title=Isolation and identification of volatile compounds in cooked meat: sukiyaki|journal=Journal of Agricultural and Food Chemistry|volume=29|pages=57|year=1981|doi=10.1021/jf00103a015}}</ref> roasted coffee,<ref>{{cite journal|last1=Aeschbacher|first1=HU|last2=Wolleb|first2=U |last3=Löliger|first3=J|last4=Spadone|first4=JC|last5=Liardon|first5=R|title=Contribution of coffee aroma constituents to the mutagenicity of coffee|journal=[[Food and chemical toxicology]] |volume=27|issue=4|pages=227–32|year=1989|pmid=2659457|doi=10.1016/0278-6915(89)90160-9}}</ref> potato chips,<ref>{{cite journal |author= Buttery, Ron G.; Seifert, Richard M.; Guadagni, Dante G. and Ling, Louisa C. |year=1971 |title=Characterization of Volatile Pyrazine and Pyridine Components of Potato Chips |journal=Journal of Agricultural and Food Chemistry |volume=19 |issue=5 | pages= 969–971|location= Washington, DC|publisher=Am Chem Soc |doi= 10.1021/jf60177a020 }}</ref> and fried [[bacon]].<ref>{{cite journal|last1=Ho|first1=Chi Tang|last2=Lee|first2=Ken N.|last3=Jin|first3=Qi Zhang|title=Isolation and identification of volatile flavor compounds in fried bacon|journal=Journal of Agricultural and Food Chemistry|volume=31|pages=336|year=1983|doi=10.1021/jf00116a038|issue=2}}</ref> Traces of pyridine can be found in [[Beaufort (cheese)|Beaufort cheese]],<ref>{{cite journal|last1=Dumont|first1=Jean Pierre|last2=Adda|first2=Jacques|title=Occurrence of sesquiterpene in mountain cheese volatiles|journal=Journal of Agricultural and Food Chemistry|volume=26|pages=364|year=1978|doi=10.1021/jf60216a037|issue=2}}</ref> [[Vaginal lubrication|vaginal secretion]]s,<ref>{{cite book |last1= Labows, Jr. |first1= John N. |editor1-first=Howard R. |editor1-last= Moskowitz |others= Warren, Craig B.,|title= Odor Quality and Chemical Structure |year=1981 |publisher=American Chemical Society |location=Washington, DC|isbn= 9780841206076 |doi= 10.1021/bk-1981-0148.fw001 |pages=195–210 |chapter= Odorants as Chemical Messengers}}</ref> [[black tea]],<ref>{{cite journal|last1=Vitzthum|first1=Otto G.|last2=Werkhoff|first2=Peter.|last3=Hubert|first3=Peter.|title=New volatile constituents of black tea flavored|journal=Journal of Agricultural and Food Chemistry|volume=23|pages=999|year=1975|doi=10.1021/jf60201a032|issue=5}}</ref> saliva of those suffering from [[gingivitis]],<ref>{{cite journal |author= Kostelc, J. G.; Preti, G.; Nelson, P. R.; Brauner, L. and Baehni, P |year=1984 |title= Oral Odors in Early Experimental Gingivitis |journal= J Periodont Res |volume=19 |pages=303–312|doi= 10.1111/j.1600-0765.1984.tb00821.x |issue= 3 |pmid= 6235346}}</ref> and [[Monofloral honey|sunflower honey]].<ref>Täufel, A.; Ternes, W.; Tunger, L. and Zobel, M.: ''Lebensmittel-Lexikon'', 4th ed., p. 226, Behr, 2005, ISBN 3-89947-165-2</ref> The smoke of tobacco<ref>{{cite journal|last1=Curvall|first1=Margareta|last2=Enzell|first2=Curt R.|last3=Pettersson|first3=Bertil|title=An evaluation of the utility of four in vitro short term tests for predicting the cytotoxicity of individual compounds derived from tobacco smoke|journal=Cell Biology and Toxicology|volume=1|issue=1|pages=173–93|year=1984|pmid=6400922|doi=10.1007/BF00125573}}</ref><ref>{{cite journal|last1=Schmeltz|first1=Irwin.|last2=Hoffmann|first2=Dietrich.|title=Nitrogen-containing compounds in tobacco and tobacco smoke|journal=Chemical Reviews|volume=77|pages=295|year=1977|doi=10.1021/cr60307a001|issue=3}}</ref> and [[marijuana]]<ref name=osha/> also contain small amounts of pyridine.
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| ==Nomenclature==
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| The systematic name of pyridine, within the [[Hantzsch–Widman nomenclature]] recommended by the [[IUPAC]], is ''azine''. However, systematic names for simple compounds are used very rarely; instead, heterocyclic nomenclature follows historically established common names. IUPAC discourages the use of ''azine'' in favor of ''pyridine''.<ref>{{cite journal|doi=10.1351/pac198855020409|author=Powell, W. H. |title=Revision of the extended Hantzsch-Widman system of nomenclature for hetero mono-cycles|journal=Pure and Applied Chemistry|year=1983|volume=55|pages=409–416|url=http://www.iupac.org/publications/pac/1983/pdf/5502x0409.pdf|issue=2}}</ref> The numbering of the ring atoms in pyridine starts at the nitrogen (see infobox). An allocation of positions by letter of the [[Greek alphabet]] (α-γ) and the [[Arene substitution patterns|substitution pattern]] nomenclature common for homoaromatic systems (''ortho'', ''meta'', ''para'') are used sometimes. Here α (''ortho''), β (''meta''), and γ (''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, here again the historical name ''pyridyl'' is encouraged by the IUPAC and used instead of the systematic name.<ref>D. Hellwinkel: ''Die systematische Nomenklatur der Organischen Chemie'', 4th ed., p. 45, Springer, Berlin, 1998, ISBN 3-540-63221-2</ref> The [[cation]]ic derivative formed by the addition of an [[electrophile]] to the nitrogen atom is called ''[[pyridinium]]''.
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| <gallery class="centered">
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| File:4-Bromopyridine.svg|4-bromopyridine
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| File:2,2'-Bipyridine.svg|2,2′-bipyridine
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| File:Dipicolinic acid.svg|pyridine-2,6-dicarboxylic acid ([[dipicolinic acid]])
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| File:PyridiniumVerbindungen.svg|General form of the [[pyridinium]] cation
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| </gallery>
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| ==Production==
| |
| Historically, pyridine was extracted from coal tar or obtained as a by-product of coal gasification. The process was labor-consuming and inefficient: [[coal tar]] contains only about 0.1% pyridine,<ref>A. Gossauer: ''Struktur und Reaktivität der Biomoleküle'', 2006, p. 488, Wiley-VCH Weinheim, ISBN 3-906390-29-2</ref> and therefore a multi-stage purification was required, which further reduced the output. Nowadays, most pyridine is produced synthetically using various [[name reaction]]s, and the major ones are discussed below.<ref name=ul>S. Shimizu, N. Watanabe, T. Kataoka, T. Shoji, N. Abe, S. Morishita, H. Ichimura ''Pyridine and Pyridine Derivatives'', in ''Ullmann's Encyclopedia of Industrial Chemistry'', 2005, Wiley-VCH, Weinheim. {{DOI|10.1002/14356007.a22_399}}</ref>
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| ===Chichibabin synthesis===
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| The [[Chichibabin pyridine synthesis]] was reported in 1924 and is still in use in industry.<ref name=tschi/> In its general form, the reaction can be described as a [[condensation reaction]] of [[aldehydes]], [[ketones]], [[α,β-Unsaturated carbonyl compound]]s, or any combination of the above, in [[ammonia]] or [[amine|ammonia derivatives]].<ref name='Frank1949'>{{cite journal
| |
| |author = Frank, R.L.; Seven, R. P.
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| |title = Pyridines. IV. A Study of the Chichibabin Synthesis
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| |journal = Journal of the American Chemical Society
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| |year = 1949
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| |volume = 71
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| |issue = 8
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| |pages = 2629–2635
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| |doi = 10.1021/ja01176a008}}</ref> In particular, unsubstituted pyridine is produced from [[formaldehyde]] and [[acetaldehyde]], which are inexpensive and widely available. First, [[acrolein]] is formed in a [[Knoevenagel condensation]] from the acetaldehyde and formaldehyde. It is then [[condensation reaction|condensed]] with acetaldehyde and ammonia into [[dihydropyridine]], and then oxidized with a solid-state catalyst to pyridine. This process is carried out in a gas phase at 400–450 °C. The product consists of a mixture of pyridine, simple [[methyl group|methylated]] pyridines ([[picoline]]), and [[lutidine]]; its composition depends on the catalyst used and can be adapted to the needs of the manufacturer. The catalyst is usually a transition metal salt such as [[cadmium(II) fluoride]] or [[manganese(II) fluoride]], but [[cobalt]] and [[thallium]] compounds can also be used. The recovered pyridine is separated from by-products in a multistage process.<ref name=ul/>
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| [[File:AcroleinDarstellung.svg|500px|center|thumb|Formation of acrolein from acetaldehyde and formaldehyde]]
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| [[File:Pyridin aus Acrolein.svg|500px|center|thumb|Condensation of pyridine from acrolein and acetaldehyde]]
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| Practical application of the traditional Chichibabin pyridine synthesis are limited by its consistently low yield, typically about 20%. This low yield, together with the high prevalence of byproducts, render unmodified forms of Chichibabin's method unpopular.<ref name = 'Frank1949' />
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| ===Dealkylation of alkylpyridines===
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| Pyridine can be prepared by dealkylation of alkylated pyridines, which are obtained as by-products in the syntheses of other pyridines. The oxidative dealkylation is carried out either using air over [[vanadium(V) oxide]] catalyst,<ref>ICI DE-AS Patent No 1,917,037, (1968)</ref> by vapor-dealkylation on nickel-based catalyst,<ref>Nippon Kayaku, Japanese patent No. 7039545 (1967)</ref><ref>Koei Chemicals, Patent BE 758,201 (1969)</ref> or hydrodealkylation with a silver- or [[platinum]]-based catalyst.<ref>Mensch, F. ''Erdöl Kohle Erdgas Petrochemie'', 1969, ''2'', pp. 67–71</ref> Yields of pyridine up to be 93% can be achieved with the nickel-based catalyst.<ref name=ul/>
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| ===Hantzsch pyridine synthesis===
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| The first major synthesis of pyridine derivatives was described in 1881 by [[Arthur Rudolf Hantzsch]].<ref>{{cite journal|last1=Hantzsch|first1=A.|title=Condensationsprodukte aus Aldehydammoniak und ketonartigen Verbindungen|journal=Berichte der deutschen chemischen Gesellschaft|volume=14|pages=1637|year=1881|doi=10.1002/cber.18810140214|issue=2}}</ref> The [[Hantzsch pyridine synthesis]] typically uses a 2:1:1 mixture of a β-[[keto acid]] (often [[Acetoacetic acid|acetoacetate]]), an [[aldehyde]] (often [[formaldehyde]]), and [[ammonia]] or its salt as the nitrogen donor. First, a double [[Hydration reaction|hydrogenated]] pyridine is obtained, which is then oxidized to the corresponding pyridine derivative. [[Emil Knoevenagel]] showed that unsymmetrically substituted pyridine derivatives can be produced with this process.<ref>{{cite journal|last1=Knoevenagel|first1=E.|last2=Fries|first2=A.|title=Synthesen in der Pyridinreihe. Ueber eine Erweiterung der Hantzsch'schen Dihydropyridinsynthese|journal=Berichte der deutschen chemischen Gesellschaft|volume=31|pages=761|year=1898|doi=10.1002/cber.189803101157}}</ref>
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| [[File:Hantzsch pyridine synthesis.svg|800px|thumb|center|[[Hantzsch pyridine synthesis]] with acetoacetate, formaldehyde and [[ammonium acetate]], and [[iron(III) chloride]] as the catalyst.]]
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| ===Bönnemann cyclization===
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| [[File:BönnemannEn.png|thumb|Bönnemann cyclization]]
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| The trimerization of a part of a [[nitrile]] molecule and two parts of [[acetylene]] into pyridine is called '''Bönnemann cyclization'''. This modification of the [[Walter Reppe|Reppe synthesis]] can be activated either by heat or by [[Photochemistry|light]]. While the thermal activation requires high pressures and temperatures, the photoinduced [[cycloaddition]] proceeds at ambient conditions with CoCp<sub>2</sub>(cod) (Cp = cyclopentadienyl, cod = [[1,5-cyclooctadiene]]) as a catalyst, and can be performed even in water.<ref>Behr, A. (2008) ''Angewandte homogene Katalyse'', p. 722, Wiley-VCH, Weinheim, ISBN 3-527-31666-3</ref> 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.
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| ===Other methods===
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| The '''Kröhnke pyridine synthesis''' involves the condensation of 1,5-di[[ketone]]s with [[ammonium acetate]] in [[acetic acid]] followed by oxidation.<ref>{{cite journal|author=Lowry, M. S.; Hudson, W. R.; Pascal, R. A.; Bernhard, S. |title=Accelerated Luminophore Discovery through Combinatorial Synthesis|journal= J. Am. Chem. Soc. |year=2004|volume= 126|pages=14129–14135|doi=10.1021/ja047156|pmid=15506778|issue=43}}</ref>
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| [[File:Kröhnke Pyridine Synthesis.png|700px|center|Kröhnke Pyridine Synthesis]]
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| {{clear}}
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| The '''Ciamician-Dennstedt rearrangement''' entails the ring-expansion of [[pyrrole]] with [[dichlorocarbene]] to 3-chloropyridine.<ref>[http://www.drugfuture.com/OrganicNameReactions/ONR75.htm Ciamician-Dennstedt Rearrangement], Ciamician, G. L. and Dennstedt, M. Ber. 14, 1153 (1881); Corwin, A. H. Heterocyclic Compounds 1, 309 (1950); Mosher, H. S. Heterocyclic Compounds 475</ref><ref>{{cite journal|doi=10.1021/ja01541a070|author= Skell, P. S. and Sandler R. S. |journal= J. Am. Chem. Soc. |volume=80|pages= 2024 |year=1958|issue=8|title=Reactions of 1,1-Digalocyclopropanes with Electrophilic Reagents. Synthetic Route for Inserting a Carbon Atom Between the Atoms of a Double Bond}}</ref><ref>{{cite journal|doi=10.1039/J39690002249|title=Mechanism of heterocyclic ring expansions. Part III. Reaction of pyrroles with dichlorocarbene|year=1969|last1=Jones|first1=R. L.|last2=Rees|first2=C. W.|journal=Journal of the Chemical Society C: Organic|issue=18|pages=2249}}</ref><ref>{{cite journal|author=Gambacorta, A.; Nicoletti, R.; Cerrini, S.; Fedeli, W. and Gavuzzo, E.|doi=10.1016/S0040-4039(01)94795-1|title=Trapping and structure determination of an intermediate in the reaction between 2-methyl-5-t.butylpyrrole and dichlorocarbene|year=1978|journal=Tetrahedron Letters|volume=19|issue=27|pages=2439}}</ref>
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| [[File:Ciamician-Dennstedt Rearrangement.png|500px|center|Ciamician-Dennstedt Rearrangement]]
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| {{clear}}
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| | |
| In the '''Gattermann-Skita synthesis''',<ref>{{cite journal|title = Eine Synthese von Pyridin-Derivaten|journal = [[Chemische Berichte|Ber.]]|volume = 49|issue = 1|year = 1916|pages = 494–501|author = Gattermann, L. and Skita, A. |doi = 10.1002/cber.19160490155}}</ref> a [[Malonic ester synthesis|malonate ester]] salt reacts with dichloro[[methylamine]].<ref>[http://web.archive.org/web/20060616020955/http://www.pmf.ukim.edu.mk/PMF/Chemistry/reactions/gattermann-skita.htm Gattermann-Skita], Institute of Chemistry, Skopje, Macedonia</ref>
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| [[File:Gattermann-Skita Syntesis.png|500px|center|Gattermann-Skita synthesis]]
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| {{clear}}
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| ===Biosynthesis===
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| Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, [[nicotinic acid]] (vitamin B<sub>3</sub>) occurs in some bacteria, fungi, and mammals. Mammals synthesize nicotinic acid through oxidation of the [[amino acid]] [[tryptophan]], where an intermediate product, [[aniline]], creates a pyridine derivative, [[kynurenine]]. On the contrary, the bacteria ''[[Mycobacterium tuberculosis]]'' and ''[[Escherichia coli]]'' produce nicotinic acid by condensation of [[glyceraldehyde 3-phosphate]] and [[aspartic acid]].<ref>{{cite journal|doi=10.1104/pp.69.3.553|last1=Tarr|pmc=426252|pmid=16662247|first1=J. B.|year=1982|pages=553–6|issue=3|volume=69|last2=Arditti|journal=Plant Physiology|first2=J.|title=Niacin Biosynthesis in Seedlings of Zea mays}}</ref>
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| ==Reactions==
| |
| Many reactions that are characteristic of benzene proceed with pyridine either at more complicated conditions or/and with low yield. Owing to the decreased electron density in the aromatic system, [[electrophilic substitution]]s are suppressed in pyridine and its derivatives in favor of [[Addition reaction|addition]] of nucleophiles at the electron-rich nitrogen atom. The nucleophilic addition at the nitrogen atom leads to a further deactivation of the aromatic properties and hindering of the electrophilic substitution. On the other hand, free-radical and [[nucleophilic aromatic substitution|nucleophilic substitutions]] occur more readily in pyridine than in benzene.<ref name = roempp /><ref name=jou10/>
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| ===Electrophilic substitutions===
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| Many electrophilic substitutions on pyridine either do not proceed or proceed only partially; however, the heteroaromatic character can be activated by electron-donating functionalization. Common [[alkylation]]s and [[acylation]]s, such as [[Friedel–Crafts reaction|Friedel–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.
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| [[File:Pyridine-EAS-2-position-2D-skeletal.png|520px|center|substitution in the 2-position]]
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| [[File:Pyridine-EAS-3-position-2D-skeletal.png|500px|center|substitution in the 3-position]]
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| [[File:Pyridine-EAS-4-position-2D-skeletal.png|430px|center|Substitution in 4-position]]
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| [[File:Pyridine N-oxide.png|thumb|65px|Structure of pyridine-''N'' oxide]]
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| Substitutions to pyridine at the 2- or 4-position result in an energetically unfavorable σ complex. They can be promoted, however, using clever experimental techniques, such as conducting electrophilic substitution on the pyridine-N-oxide followed by deoxygenation of the nitrogen atom. Addition of oxygen reduces electron density on the nitrogen atom and promotes substitution at the 2- and 4-carbons. The oxygen atom can then be removed via several routes, most commonly with compounds of trivalent [[phosphorus]] or divalent [[sulfur]], which are easily oxidized. [[Triphenylphosphine]] is a frequently used reagent, which is oxidized in this reaction to [[triphenylphosphine oxide]]. The following paragraphs describe representative electrophilic substitution reactions of pyridine.<ref name=jou10/>
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| Direct [[nitration]] of pyridine requires harsh conditions and has very low yields. The 3-nitropyridine can be obtained instead by reacting pyridine with [[dinitrogen pentoxide]] in presence of [[sodium]].<ref>[[#Joule|Joule]], p. 129</ref><ref>{{cite journal|last1=Bakke|first1=Jan M.|last2=Hegbom|first2=Ingrid|last3=Verne|first3=Hans Peter|last4=Weidlein|first4=Johann|last5=Schnöckel|first5=Hansgeorg|last6=Paulsen|first6=Gudrun B.|last7=Nielsen|first7=Ruby I.|last8=Olsen|first8=Carl E.|last9=Pedersen|first9=Christian|title=Dinitrogen Pentoxide-Sulfur Dioxide, a New nitrate ion system|journal=Acta Chemica Scandinavica|volume=48|pages=181|year=1994|doi=10.3891/acta.chem.scand.48-0181|last10=Stidsen|first10=Carsten E.}}</ref><ref>{{cite journal|last1=Ono|first1=Noboru|last2=Murashima|first2=Takashi|last3=Nishi|first3=Keiji|last4=Nakamoto|first4=Ken-Ichi|last5=Kato|first5=Atsushi|last6=Tamai|first6=Ryuji|last7=Uno|first7=Hidemitsu|title=Preparation of Novel Heteroisoindoles from nitropyridines and Nitropyridones|journal=Heterocycles|volume=58|pages=301|year=2002|doi=10.3987/COM-02-S(M)22}}</ref> Pyridine derivatives wherein the nitrogen atom is screened sterically and/or electronically can be obtained by nitration with [[nitronium tetrafluoroborate]] (NO<sub>2</sub>BF<sub>4</sub>). In this way, 3-nitropyridine can be obtained via the synthesis of 2,6-dibromopyridine followed by removal of the bromine atoms.<ref>{{cite journal|author=Duffy, Joseph L. and Laali, Kenneth K.|title=Aprotic Nitration (NO<sub>2</sub><sup>+</sup>BF<sub>4</sub><sup>−</sup>) 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}}</ref><ref>[[#Joule|Joule]], p. 126</ref>
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| Direct [[sulfonation]] of pyridine is even more difficult than direct nitration. However, pyridine-3-sulfonic acid can be obtained at acceptable yield by boiling pyridine in an excess of [[sulfuric acid]] at 320°C.<ref>{{cite journal|last1=Gabriel|first1=S.|title=Note on nicotinic acid from pyridine|journal=Berichte der deutschen chemischen Gesellschaft|volume=15|pages=834|year=1882|doi=10.1002/cber.188201501180}}</ref> Reaction with the SO<sub>3</sub> group also facilitates addition of sulfur to the nitrogen atom, especially in the presence of a [[mercury(II) sulfate]] catalyst.<ref name=jou10/><ref>{{cite journal|last1=Möller|first1=Ernst Friedrich|last2=Birkofer|first2=Leonhard|title=Konstitutionsspezifität der Nicotinsäure als Wuchsstoff bei Proteus vulgaris und Streptobacterium plantarum|journal=Berichte der deutschen chemischen Gesellschaft (A and B Series)|volume=75|pages=1108|year=1942|doi=10.1002/cber.19420750912|issue=9}}</ref>
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| In contrast to the nitration and sulfonation, the direct [[bromination]] and [[halogenation|chlorination]] of pyridine proceed well. The reaction of pyridine with molecular [[bromine]] in sulfuric acid at 130°C readily produced 3-bromopyridine. The yield is lower for 3-chloropyridine upon chlorination with molecular [[chlorine]] in the presence of [[aluminium chloride]] at 100°C. Both 2-bromopyridine and 2-chloropyridine can be produced by direct reaction with halogen with a [[palladium(II) chloride]] catalyst.<ref>[[#Joule|Joule]], p. 130</ref>
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| | |
| ===Nucleophilic substitutions===
| |
| In contrast to benzene, pyridine efficiently supports several nucleophilic substitutions, and is regarded as a good [[nucleophile]] ([[donor number]] 33.1). 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 2- or 4-position.<ref name=jou10/><ref name=davies>D. T. Davies ''Aromatic heterocyclic chemistry'', Oxford University Press, 1992, ISBN 0-19-855660-8</ref>
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| [[File:Pyridine-NA-2-position.svg|500px|center|Nucleophilic Substitution in 2-position]]
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| [[File:Pyridine-NA-3-position.svg|500px|center|Nucleophilic Substitution in 3-position]]
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| [[File:Pyridine-NA-4-position.svg|500px|center|Nucleophilic Substitution in 4-position]]
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| Many nucleophilic substitutions occur easier 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 compound]]s. The nucleophilic attack compounds may be [[alkoxide]]s, thiolates, [[amine]]s, and ammonia (at elevated pressures).<ref>[[#Joule|Joule]], p. 133</ref>
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| In 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 [[Amination|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.<ref name=davies/><ref>{{cite journal|last1=Shreve|first1=R. Norris|last2=Riechers|first2=E. H.|last3=Rubenkoenig|first3=Harry|last4=Goodman|first4=A. H.|title=Amination in the Heterocyclic Series by Sodium amide|journal=Industrial & Engineering Chemistry|volume=32|pages=173|year=1940|doi=10.1021/ie50362a008|issue=2}}</ref>
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| Analogous to benzene, nucleophilic substitutions to pyridine can result in the formation of [[pyridyne]] intermediates as hetero[[aryne]]. 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.<ref name=jou10/>
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| ===Radical reactions===
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| Pyridine supports a series of radical reactions, which is used in its [[Dimer (chemistry)|dimerization]] to bipyridines. Radical dimerization of pyridine with elemental [[sodium]] or [[Raney nickel]] selectively yields [[4,4'-bipyridine]],<ref>{{cite journal|last1=Badger|first1=G|last2=Sasse|first2=W|title=Advances in Heterocyclic Chemistry Volume 2|volume=2|pages=179|year=1963|doi=10.1016/S0065-2725(08)60749-7|chapter=The Action of Metal Catalysts on Pyridines|series=Advances in Heterocyclic Chemistry|isbn=9780120206025}}</ref> or [[2,2'-bipyridine]],<ref>{{cite journal|author= Sasse, W. H. F.|title=2,2'-bipyridine|journal=Organic Syntheses|year=1966|volume=46|pages=5–8|url=http://www.orgsyn.org/orgsyn/pdfs/CV5P0102.pdf}}</ref> 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%.<ref name=jou10>[[#Joule|Joule]], pp. 125–141</ref>
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| ===Reactions on the nitrogen atom===
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| [[File:Pyridine-complex.png|thumb|350px|Additions of various [[Lewis acid]]s to pyridine]]
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| [[Lewis acid]]s easily add to the nitrogen atom of pyridine, forming pyridinium salts. The reaction with [[alkylhalide]]s 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]]).
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| ===Hydrogenation and reduction===
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| [[File:Pyridine hydrogenation.png|left|thumb|Reduction of pyridine to piperidine with [[Raney nickel]]]]
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| Hydrogen-saturated piperidine is obtained through reaction with hydrogen gas in the presence of [[Raney nickel]].<ref>{{cite journal|last1=Burrows|first1=George H.|last2=King|first2=Louis A.|title=The Free Energy Change that Accompanies Hydrogenation of pyridines to piperidines|journal=Journal of the American Chemical Society|volume=57|pages=1789|year=1935|doi=10.1021/ja01313a011|issue=10}}</ref> This reaction releases 193.8 kJ·mol<sup>−1</sup> of energy,<ref name="Cox">Cox, J. D. and Pilcher, G. (1970). ''Thermochemistry of Organic and Organometallic Compounds'', Academic Press, New York, p. 1–636, ISBN 0-12-194350-X</ref> which is slightly less than the energy of the hydrogenation of [[benzene]] (205.3 kJ·mol<sup>−1</sup>).<ref name="Cox"/>
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| 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.<ref>{{cite journal|last1=Tanner|first1=Dennis D.|last2=Yang|first2=Chi Ming|title=On the structure and mechanism of formation of the Lansbury reagent, lithium tetrakis (N-dihydropyridyl) aluminate|journal=The Journal of Organic Chemistry|volume=58|pages=1840|year=1993|doi=10.1021/jo00059a041|issue=7}}</ref> Selective synthesis of 1,4-dihydropyridine is achieved in the presence of organometallic complexes of [[magnesium]] and [[zinc]],<ref>{{cite journal|last1=De Koning|first1=A|title=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=Journal of Organometallic Chemistry|volume=199|pages=153|year=1980|doi=10.1016/S0022-328X(00)83849-8|issue=2|last2=Budzelaar|first2=P.H.M.|last3=Boersma|first3=J.|last4=Van Der Kerk|first4=G.J.M.}}</ref> and (Δ3,4)-tetrahydropyridine is obtained by electrochemical reduction of pyridine.<ref>Ferles, M. [[Collection of Czechoslovak Chemical Communications]], 1959, ''24'', pp. 1029–1033</ref>
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| ==Applications==
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| [[File:Bundesarchiv Bild 183-62018-0003, Produktionsverpflichtungen im VEB Berlin-Chemie.jpg|thumb|upright|Use of pyridine in the chemical industry, VEB Berlin-Chemie, 1959.]]
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| Pyridine is an important raw material in of the [[chemical industry]], with the 1989 production of 26,000 tonnes in world-wide.<ref name=ul/> Among major 25 production sites for pyridine eleven are located in Europe (as of 1999).<ref name=osha/> The major producers of pyridine include [[Evonik Industries]], Rütgers Chemicals, [[Imperial Chemical Industries]], and Koei Chemical.<ref name=ul/> The pyridine production has significantly increased in the early 2000s, with an annual production capacity of 30,000 tonnes in mainland China alone.<ref>[http://www.agrochemex.net/en/press/2010/05/11/Pyridine_s_Development_in_China/ Pyridine’s Development in China], AgroChemEx, 11 May 2010</ref> The US-Chinese joint venture [[Vertellus]] is currently the world leader in pyridine production.<ref>[http://www.vertellus.com/company.aspx About Vertellus]. vertellus.com</ref>
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| Pyridine is used as polar, basic, low-reactive solvent, for example in [[Knoevenagel condensation]]s.<ref name=osha/> It is especially suitable for the dehalogenation, where it acts as the base of the [[elimination reaction]] and bonds the resulting hydrogen halide to form a pyridinium salt. In [[esterification]]s and acylations pyridine activates the [[carboxylic acid]] halides or anhydrides. Even more active in these reactions are the pyridine derivatives [[4-dimethylaminopyridine]] (DMAP) and 4-(1-pyrrolidinyl) pyridine. Pyridine is also used as a base in [[condensation reaction]]s.<ref>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}} 2001.</ref>
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| [[File:Chlorocyclopentane elimination.svg|thumb|center|400px|Elimination reaction with pyridine to form pyridinium]]
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| [[Pyridinium chlorochromate]] was developed by [[Elias James Corey]] and William Suggs in 1975 and is used to [[oxidize]] primary [[alcohols]] to [[aldehydes]] and secondary [[alcohols]] to [[ketones]].<ref name = corey>{{cite journal|author = Corey, E.J.; Suggs, W.|title = Pyridinium Chlorochromate. An Efficient Reagent for Oxidation of Primary and Secondary Alcohols to Carbonyl Compounds|journal = [[Tetrahedron Lett.]]|year = 1975|volume = 16|pages = 2647–2650|doi = 10.1016/S0040-4039(00)75204-X|issue = 31}}</ref> It is obtained by adding pyridine to a solution of [[chromic acid]] and concentrated [[hydrochloric acid]]:
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| :C<sub>5</sub>H<sub>5</sub>N + HCl + CrO<sub>3</sub> → [C<sub>5</sub>H<sub>5</sub>NH][CrO<sub>3</sub>Cl]
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| The carcinogenicity of the side-product [[chromyl chloride]] (CrO<sub>2</sub>Cl<sub>2</sub>) urged to look for alternative routes, such as treating [[chromium(VI) oxide]] with pyridinium chloride:<ref>{{cite journal|author = Agarwal, S; Tiwari, H. P.; Sharma, J. P.|title = Pyridinium Chlorochromate: an Improved Method for its Synthesis and use of Anhydrous acetic acid as catalyst for oxidation reactions|journal = [[Tetrahedron (journal)|Tetrahedron]]|year = 1990|volume = 46|pages = 4417–4420|doi = 10.1016/S0040-4020(01)86776-4|issue = 12}}</ref>
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| :[C<sub>5</sub>H<sub>5</sub>NH<sup>+</sup>]Cl<sup>−</sup> + CrO<sub>3</sub> → [C<sub>5</sub>H<sub>5</sub>NH][CrO<sub>3</sub>Cl]
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| The [[Cornforth reagent]] (pyridinium dichromate, PDC),<ref>{{cite journal|author = Cornforth, R.H.; Cornforth, J.W.; Popjak, G.|year = 1962|title = Preparation of R-and S-mevalonolactones|journal = Tetrahedron
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| |volume = 18|pages = 1351–4|doi = 10.1016/S0040-4020(01)99289-0|issue = 12}}</ref> [[pyridinium chlorochromate]] (PCC), the [[Collins reagent]] (complex of [[chromium trioxide|chromium(VI) oxide]] with pyridine in [[dichloromethane]])<ref>{{cite journal|title = Dipyridine-chromium(VI) oxide oxidation of alcohols in dichloromethane| author = Collins, J. C.; Hess, W. W. and Frank, F. J. |journal = [[Tetrahedron Lett.]]|year = 1968|volume = 9|issue = 30|pages = 3363–3366|doi = 10.1016/S0040-4039(00)89494-0}}</ref><ref>{{OrgSynth|author = Collins, J. C. and Hess, W.W. |title = Aldehydes from Primary Alcohols by Oxidation with Chromium Trioxide: Heptanal|collvol = 6|collvolpages = 644|prep = cv6p0644|year = 1988}}</ref> and the Sarret reagent (complex of [[chromium trioxide|chromium(VI) oxide]] with pyridine in pyridine) are similar chromium-based pyridine compounds, which are also used for oxidation, namely conversion of [[primary alcohol|primary]] and secondary alcohols to [[ketone]]s. The Collins and Sarret reagents are both difficult and dangerous to prepare, they are hygroscopic and can inflame during preparation. For this reason, the use of PCC and PDC was preferred. Those reagents were rather popular in the 1970s–1980s, but because of their toxicity and confirmed carcinogenic status, they are rarely used nowadays.<ref name=b1>{{cite book|author = Tojo, G. and Fernandez, M.|title = Oxidation of alcohols to aldehydes and ketones: a guide to current common practice|year = 2006|publisher = Springer|location = New York|isbn = 0-387-23607-4|url=http://books.google.com/books?id=O6USLyDIBOUC&pg=PA86|pages=28, 29, 86}}</ref>
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| [[File:Collins reagent.png|thumb|Oxidation of an alcohol to aldehyde with the [[Collins reagent]].]]
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| [[File:Crabtree.svg|thumb|structure of the [[Crabtree's catalyst]]]]
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| When a pyridine ligand is part of a metal complex, it can be easily replaced by a stronger chelating Lewis base. This property is exploited in catalysis of [[polymerization]]<ref>Bamford, C. H. and Tipper, C. F. H (1980). ''Comprehensive Chemical Kinetics: Non-radical Polymerisation'', Elsevier, Amsterdam, ISBN 0-444-41252-2</ref><ref>Hopper, A. V. (2007). ''Recent Developments in Polymer Research'', Nova Science Publisher, ISBN 1-60021-346-4</ref> and hydrogenation reactions, using, for example, the [[Crabtree's catalyst]].<ref>{{cite journal|last1=Crabtree|first1=Robert|title=Iridium compounds in catalysis|journal=Accounts of Chemical Research|volume=12|pages=331|year=1979|doi=10.1021/ar50141a005|issue=9}}</ref> The pyridine ligand replaced during the reaction is restored after its completion.
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| In the pharmaceutical industry pyridine serves as a building-block for making a variety of drugs, [[insecticide]]s and [[herbicide]]s. It was and is used in large quantities in the production of herbicides [[diquat]] and [[paraquat]], which contain bipyridine fragments. 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 [[fungicide]]s.<ref name=osha/> [[Cetylpyridinium chloride|Cetylpyridinium]] and laurylpyridinium, which can be produced from pyridine with a Zincke reaction, are used as [[antiseptic]] in oral and dental care products.<ref name=roempp/>
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| [[File:Synthesis of paraquat.png|thumb|center|585px|Synthesis of [[paraquat]]<ref>[http://www.inchem.org/documents/ehc/ehc/ehc39.htm Environmental and health criteria for paraquat and diquat], World Health Organization, Geneva, 1984</ref>]]
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| In addition to pyridines, [[piperidine]] derivatives are also important synthetic building-blocks. A common synthesis of piperidine is the reduction of pyridine with a nickel-, [[cobalt]]-, or [[ruthenium]]-based catalyst at elevated temperatures.<ref>Eller, K.; Henkes, E.; Rossbacher, R. and Hoke, H. ''Amines, Aliphatic'', in: ''Ullmann's Encyclopedia of Industrial Chemistry'', 2005, Wiley-VCH Weinheim</ref>
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| Pyridine is used as a solvent in the manufacture of dyes and rubber.<ref>Terry, C. E.; Ryan, R. P. and Leffingwell, S. S. ''Toxicology Desk Reference: The Toxic Exposure & Medical Monitoring Index: The Toxic Exposure and Medical Monitoring Index'', 5th ed., p. 1062, Taylor & Francis, ISBN 1-56032-795-2</ref> It is also used in the textile industry to improve network capacity of cotton.<ref name=roempp/> Pyridine is added to [[ethanol]] to make it unsuitable for drinking.<ref name=roempp/> In low doses, pyridine is added to foods to give them a bitter flavor, and such usage is approved by the US [[Food and Drug Administration]].<ref name=osha/> The detection threshold for pyridine in solutions is about 1–3 m[[Mole (unit)|mole]]·L<sup>−1</sup> (79–237 mg·L<sup>−1</sup>).<ref>Täufel, A.; Ternes, W.; Tunger, L. and Zobel, M. (2005). ''Lebensmittel-Lexikon'', 4th ed., p. 218, Behr, ISBN 3-89947-165-2</ref> As a base, pyridine can be used as the [[Karl Fischer titration|Karl Fischer reagent]], but it is usually replaced by alternatives with a more pleasant odor, such as [[imidazole]].<ref>[http://web.archive.org/web/20110719105206/http://www.ipc.uni-jena.de/downloads/IPC/Lehre/IA_Pharm_12_Karl-Fischer-Titration.pdf Wasserbestimmung mit Karl-Fischer-Titration], Jena University</ref>
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| 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. Pyridine 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 [[adduct]]s of pyridine include pyridine-[[borane]], C<sub>5</sub>H<sub>5</sub>NBH<sub>3</sub> (melting point 10–11 °C), a mild reducing agent with improved stability relative to NaBH<sub>4</sub> in protic solvents and improved solubility in aprotic organic solvents. [[Sulfur trioxide pyridine complex|Pyridine-sulfur trioxide]], C<sub>5</sub>H<sub>5</sub>NSO<sub>3</sub> (melting point 175 °C) is a [[sulfonation]] agent used to convert alcohols to sulfonates, which in turn undergo [[Carbon-oxygen bond|C-O bond]] [[Beta scission|scission]] upon reduction with hydride agents.
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| ==Hazards==
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| Pyridine has a [[flash point]] (the lowest temperature at which it can vaporize to form an ignitable mixture in air) of only 17 °C and is, therefore, highly flammable. Its ignition temperature is 550°C, and mixtures of 1.7–10.6 vol% of pyridine with air are explosive. The thermal modification of pyridine starts above 490°C, resulting in [[bipyridine]] (mainly 2,2'-bipyridine and to a lesser extent 2,3'-bipyridine and 2,4'-bipyridine), [[nitrogen oxide]]s, and [[carbon monoxide]].<ref name="GESTIS">{{GESTIS|ZVG=13850|Name=Pyridine}}</ref> Pyridine easily dissolves in water and harms both animals and plants in aquatic systems.<ref>[http://cfpub.epa.gov/ecotox/ Database of the [[Environmental Protection Agency]] (EPA)]</ref> The permitted [[threshold limit value|maximum allowable concentration]] of pyridine was 15–30 parts per million (ppm, or 15–30 mg·m<sup>−3</sup> in air) in most countries in the 1990s,<ref name=osha/> but was reduced to 5 ppm in the 2000s.<ref>[http://www.alfa.com/content/msds/english/19378.pdf Pyridine MSDS], Alfa Aesar, 3 June 2010</ref> For comparison, indoor air contaminated with tobacco smoke may contain up to 16 µg·m<sup>−3</sup>, and one cigarette contains 21–32 µg of pyridine.<ref name=osha/>
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| ==Health issues==
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| [[File:Pyridin-Metabolisierung.png|400px|thumb|Metabolism of pyridine]]
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| Pyridine is harmful if inhaled, swallowed or absorbed through the skin.<ref name = Aylward>Aylward, G, (2008), "SI Chemical Data 6th Ed.", ISBN 978-0-470-81638-7 (pbk.)</ref> Effects of acute pyridine intoxication include dizziness, headache, [[ataxia|lack of coordination]], nausea, [[saliva]]tion, and loss of appetite. They may progress into abdominal pain, [[pulmonary congestion]] and unconsciousness.<ref name="IARC1"/> One person died after accidental ingestion of half a cup of pyridine.<ref name=osha>[http://monographs.iarc.fr/ENG/Monographs/vol77/mono77-21.pdf Pyridine], IARC Monogrpahs Vol. 77, OSHA, Washington D.C., 1985</ref> The lowest known [[lethal dose]] (LD<sub>Lo</sub>) for the ingestion of pyridine in humans is 500 mg·kg<sup>−1</sup>. In high doses, pyridine has a narcotic effect and its vapor concentrations of above 3600 [[parts per million|ppm]] pose a health risk.<ref name=ul/> The oral [[Median lethal dose|LD<sub>50</sub>]] in rats is 891 mg·kg<sup>−1</sup>. Pyridine is flammable.
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| Evaluations as a possible [[carcinogenic]] agent showed that there is inadequate evidence in humans for the carcinogenicity of pyridine, although there is limited evidence of carcinogenic effects on animals.<ref name="IARC1"/> 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".<ref name="IARC1">{{cite web|last = International Agency for Research on Cancer (IARC)|authorlink = International Agency for Research on Cancer|title = Pyridine Summary & Evaluation|work = IARC Summaries & Evaluations|publisher = IPCS INCHEM|date = 22 August 2000|url = http://www.inchem.org/documents/iarc/vol77/77-16.html|accessdate = 17 January 2007}}</ref>
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| Pyridine might also have minor [[neurotoxin|neurotoxic]], [[genotoxicity|genotoxic]], and [[clastogen]]ic effects.<ref name="GESTIS"/><ref name=osha/><ref name=bonnard/> Exposure to pyridine would normally lead to its inhalation and absorption in the lungs and gastrointestinal tract, where it either remains unchanged or is [[metabolism|metabolized]]. The major products of pyridine metabolism are ''N''-methylpyridiniumhydroxide, which are formed by [[N-methyltransferase (disambiguation)|N-methyltransferase]]s (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.<ref name="GESTIS"/><ref name=bonnard>Bonnard, N.; Brondeau, M. T.; Miraval, S.; Pillière, F.; Protois, J.C. and Schneider, O. [[:commons:File:Pyridine-electronical density.pdf|''Pyridine'']], Fiche Toxicologique, INRS (in French)</ref> Pyridine is readily degraded by bacteria to ammonia and carbon dioxide.<ref>{{cite journal|author = Sims, G.K. and O'Loughlin, E.J.|title = Degradation of pyridines in the environment|journal = CRC Critical Reviews in Environmental Control|year = 1989|volume = 19|issue = 4|pages = 309–340|doi = 10.1080/10643388909388372}}</ref> The unsubstituted pyridine ring degrades more rapidly than [[picoline]], [[lutidine]], [[chloropyridine]], or [[aminopyridine]]s<!-- no disambiguation needed-->,<ref>{{cite journal|doi = 10.1002/etc.5620050601|author = Sims, G. K. and L.E. Sommers|year = 1986|title = Biodegradation of pyridine derivatives in soil suspensions| journal = Environmental Toxicology and Chemistry|volume = 5|pages = 503–509|issue = 6}}</ref> and a number of pyridine degraders have been shown to overproduce [[riboflavin]] in the presence of pyridine.<ref>{{cite journal|author = Sims, G. K. and E.J. O'Loughlin|year = 1992|title = Riboflavin production during growth of Micrococcus luteus on pyridine|journal = [[Applied and Environmental Microbiology]]|volume = 58|issue = 10|pages = 3423–3425|pmc = 183117|pmid = 16348793}}</ref>
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| Minor amounts of pyridine are released into environment from some industrial processes such as steel manufacture,<ref>{{cite journal|last1=Junk|first1=G.A.|last2=Ford|first2=C.S.|title=A review of organic emissions from selected combustion processes|journal=Chemosphere|volume=9|pages=187|year=1980|doi=10.1016/0045-6535(80)90079-X|issue=4}}</ref> processing of [[oil shale]], [[coal gasification]], [[coking]] plants and [[Incineration|incinerators]].<ref name=osha/> The atmosphere at oil shale processing plants can contain pyridine concentrations of up to 13 µg·m<sup>−3</sup>,<ref>{{cite journal|last1=Hawthorne|first1=Steven B.|last2=Sievers|first2=Robert E.|title=Emissions of organic air pollutants from shale oil wastewaters|journal=Environmental Science & Technology|volume=18|pages=483|year=1984|doi=10.1021/es00124a016|issue=6|bibcode = 1984EnST...18..483H }}</ref> and 53 µg·m<sup>−3</sup> levels were measured in the [[groundwater]] in the vicinity of a coal gasification plant.<ref>{{cite journal|last1=Stuermer|first1=Daniel H.|last2=Ng|first2=Douglas J.|last3=Morris|first3=Clarence J.|title=Organic contaminants in groundwater near to underground coal gasification site in northeastern Wyoming|journal=Environmental Science & Technology|volume=16|pages=582|year=1982|doi=10.1021/es00103a009|issue=9|bibcode = 1982EnST...16..582S }}</ref> According to a study by the US [[National Institute for Occupational Safety and Health]], about 43,000 Americans work in contact with pyridine.<ref>National Occupational Exposure Survey 1981–83, Cincinnati, OH, Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occuptional Safety and Health.</ref>
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| ==See also==
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| * 6-membered aromatic rings with one carbon replaced by another group: [[borabenzene]], [[benzene]], [[silabenzene]], [[germabenzene]], [[stannabenzene]], '''pyridine''', [[phosphorine]], [[arsabenzene]], [[pyrylium salt]]
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| * 6-membered rings with two nitrogen atoms: [[diazine]]s
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| * 6-membered rings with three nitrogen atoms: [[triazine]]s
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| * 6-membered rings with four nitrogen atoms: [[tetrazine]]s
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| * 6-membered rings with six nitrogen atoms: [[hexazine]]
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| ==References==
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| {{Reflist|2}}
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| ==Bibliography==
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| *{{cite book|author=Joule, J. A. and Mills, K. |ref=Joule|url=http://books.google.com/books?id=cwe-Ebc64bkC&printsec=frontcover |title=Heterocyclic Chemistry|edition=5th|publisher= Blackwell Publishing|place= Chichester|year= 2010|isbn=1-4051-3300-7}}
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| *{{cite book|editor=Lide, D. R. |ref=Lide|title=Handbook of Chemistry and Physics|edition=90th|publisher= CRC Press|place= Boca Raton|year= 2009|isbn=978-1-4200-9084-0}}
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| {{Commons category|pyridine}}
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| ==External links==
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| *[http://www.chemsynthesis.com/six-membered-ring/pyridines/page-1.html Synthesis and propierties of pyridines] at chemsynthesis.com
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| *[http://www.inchem.org/documents/icsc/icsc/eics0323.htm International Chemical Safety Card 0323]
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| *[http://www.cdc.gov/niosh/npg/npgd0541.html NIOSH Pocket Guide to Chemical Hazards]
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| *[http://www.organic-chemistry.org/synthesis/heterocycles/pyridines.shtm Synthesis of pyridines (overview of recent methods)]
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| {{Functional Groups}}
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| {{Use dmy dates|date=June 2013}}
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| [[Category:Pyridines| ]]
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| [[Category:Amine solvents]]
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| [[Category:Foul-smelling chemicals]]
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| [[Category:Aromatic bases]]
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| {{Link GA|fr}}
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| {{Link FA|de}}
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