{"history":[],"article":{"id":"5fa515fa-ab0c-46b2-b80a-ab8251988292","title":"Pyridine","slug":"pyridine","content":":::summary\n:::\n\n# \n**Pyridine** is a [basic](https://bliptext.com/articles/basic-chemistry) [heterocyclic](https://bliptext.com/articles/heterocyclic-compound) [organic compound](https://bliptext.com/articles/organic-compound) with the [chemical formula](https://bliptext.com/articles/chemical-formula) C5H5N.\nIt is structurally related to [benzene](https://bliptext.com/articles/benzene), with one [methine group](https://bliptext.com/articles/methine-group) (\\dCH\\s) replaced by a [nitrogen](https://bliptext.com/articles/nitrogen) atom (\\dN\\s).\nIt is a highly flammable, weakly [alkaline](https://bliptext.com/articles/alkali), water-miscible liquid with a distinctive, unpleasant fish-like smell.\nPyridine is colorless, but older or impure samples can appear yellow, due to the formation of extended, unsaturated [polymeric](https://bliptext.com/articles/polymer) chains, which show significant [electrical conductivity](https://bliptext.com/articles/electrical-conductivity).\nThe pyridine ring occurs in many important compounds, including [agrochemicals](https://bliptext.com/articles/agrochemical), [pharmaceuticals](https://bliptext.com/articles/pharmaceutical), and [vitamins](https://bliptext.com/articles/vitamin).\nHistorically, pyridine was produced from [coal tar](https://bliptext.com/articles/coal-tar).\nAs of 2016, it is synthesized on the scale of about 20,000 tons per year worldwide.\n\n# Properties\n# [Internal bond angles and bond distances (pm) for pyridine. | upload.wikimedia.org/wikipedia/commons/9/9d/PyridineXray.svg]\n\n## Physical properties\nPyridine is [diamagnetic](https://bliptext.com/articles/diamagnetism).\nIts [critical parameters](https://bliptext.com/articles/critical-point-thermodynamics) are: pressure 5.63 MPa, temperature 619 K and volume 248 cm3/mol.\nIn the temperature range 340–426 °C its vapor pressure p can be described with the [Antoine equation](https://bliptext.com/articles/antoine-equation)\nwhere T is temperature, A = 4.16272, B = 1371.358 K and C = −58.496 K.\n# [Crystal structure of pyridine | upload.wikimedia.org/wikipedia/commons/6/62/Kristallstruktur///Pyridin.png]\n\n## Structure\nPyridine ring forms a C5N hexagon.\nSlight variations of the C\\sC and C\\sN distances as well as the bond angles are observed.\n\n## Crystallography\nPyridine crystallizes in an [orthorhombic crystal system](https://bliptext.com/articles/orthorhombic-crystal-system) with [space group](https://bliptext.com/articles/space-group) Pna21 and [lattice parameters](https://bliptext.com/articles/lattice-parameters) a = 1752 [pm](https://bliptext.com/articles/picometer), b = 897 [pm](https://bliptext.com/articles/picometer), c = 1135 [pm](https://bliptext.com/articles/picometer), and 16 [formula units](https://bliptext.com/articles/formula-unit) per [unit cell](https://bliptext.com/articles/unit-cell) (measured at 153 K).\nFor comparison, crystalline [benzene](https://bliptext.com/articles/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.\nThis difference is partly related to the lower [symmetry](https://bliptext.com/articles/molecular-symmetry) of the individual pyridine molecule (C2v vs D6h for benzene).\nA tri[hydrate](https://bliptext.com/articles/hydrate) (pyridine·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).\n\n## Spectroscopy\nThe optical [absorption spectrum](https://bliptext.com/articles/absorption-spectrum) of pyridine in [hexane](https://bliptext.com/articles/hexane) consists of bands at the [wavelengths](https://bliptext.com/articles/wavelength) of 195, 251, and 270 nm.\nWith respective extinction coefficients (ε) of 7500, 2000, and 450 L·mol−1·cm−1, these bands are assigned to π → π*, π → π*, and n → π* transitions.\nThe compound displays very low [fluorescence](https://bliptext.com/articles/fluorescence).\nThe 1H [nuclear magnetic resonance](https://bliptext.com/articles/nuclear-magnetic-resonance) (NMR) spectrum shows signals for α-([δ](https://bliptext.com/articles/chemical-shift) 8.5), γ-([δ](https://bliptext.com/articles/chemical-shift)7.5) and β-protons ([δ](https://bliptext.com/articles/chemical-shift)7).\nBy contrast, the proton signal for benzene is found at δ7.27.\nThe 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.\nThe situation is rather similar for the [13C NMR](https://bliptext.com/articles/13c-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.\nAll shifts are quoted for the solvent-free substances.\nPyridine is conventionally detected by the [gas chromatography](https://bliptext.com/articles/gas-chromatography) and [mass spectrometry](https://bliptext.com/articles/mass-spectrometry) methods.\n\n## Bonding\nPyridine has a [conjugated](https://bliptext.com/articles/conjugation-organic-chemistry) system of six [π electrons](https://bliptext.com/articles/pi-bond) that are delocalized over the ring.\nThe molecule is planar and, thus, follows the [Hückel criteria](https://bliptext.com/articles/h-ckel-rule) for aromatic systems.\nIn contrast to benzene, the [electron density](https://bliptext.com/articles/electron-density) is not evenly distributed over the ring, reflecting the negative [inductive effect](https://bliptext.com/articles/inductive-effect) of the nitrogen atom.\nFor this reason, pyridine has a dipole moment and a weaker [resonant stabilization](https://bliptext.com/articles/resonance-chemistry) than benzene ([resonance energy](https://bliptext.com/articles/resonance-chemistry) 117 kJ/mol in pyridine vs. 150 kJ/mol in benzene).\nThe ring atoms in the pyridine molecule are [sp2-hybridized](https://bliptext.com/articles/orbital-hybridisation).\nThe nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital.\nThe [lone pair](https://bliptext.com/articles/lone-pair) is in an sp2 orbital, projecting outward from the ring in the same plane as the [σ bonds](https://bliptext.com/articles/bond).\nAs 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.\nHowever, because of the separation of the lone pair from the aromatic ring system, the nitrogen atom cannot exhibit a positive [mesomeric effect](https://bliptext.com/articles/mesomeric-effect).\nMany analogues of pyridine are known where N is replaced by other heteroatoms from the same column of the [Periodic Table of Elements](https://bliptext.com/articles/periodic-table-of-elements) (see figure below).\nSubstitution of one C–H in pyridine with a second N gives rise to the [diazine](https://bliptext.com/articles/diazine) heterocycles (C4H4N2), with the names [pyridazine](https://bliptext.com/articles/pyridazine), [pyrimidine](https://bliptext.com/articles/pyrimidine), and [pyrazine](https://bliptext.com/articles/pyrazine).\n

\n# [Pyridine with its free electron pair | upload.wikimedia.org/wikipedia/commons/d/d9/Pyridine-2D-Skeletal.png]\n# [Bond lengths and angles of benzene, pyridine, phosphorine, arsabenzene, stibabenzene, and bismabenzene | upload.wikimedia.org/wikipedia/commons/0/0c/Bond///lengths///of///group///15///heterobenzenes///and///benzene.svg]\n# [Atomic orbitals in pyridine | upload.wikimedia.org/wikipedia/commons/2/27/Pyridine-orbitals.svg]\n# [Resonance structures of pyridine | upload.wikimedia.org/wikipedia/commons/e/e9/Pyridine-10.png]\n# [Atomic orbitals in protonated pyridine | upload.wikimedia.org/wikipedia/commons/7/77/Pyridinium-orbitals.svg]\n\n# History\nImpure pyridine was undoubtedly prepared by early [alchemists](https://bliptext.com/articles/alchemy) by heating animal bones and other organic matter, but the earliest documented reference is attributed to the Scottish scientist [Thomas Anderson](https://bliptext.com/articles/thomas-anderson-chemist).\nIn 1849, Anderson examined the contents of the [oil obtained through high-temperature heating of animal bones](https://bliptext.com/articles/dippel-s-oil).\nAmong other substances, he separated from the oil a colorless liquid with unpleasant odor, from which he isolated pure pyridine two years later.\nHe described it as highly soluble in water, readily soluble in concentrated acids and salts upon heating, and only slightly soluble in oils.\nOwing to its flammability, Anderson named the new substance pyridine, after (pyr) meaning fire.\nThe suffix [idine](https://bliptext.com/articles/idine) was added in compliance with the chemical nomenclature, as in tolu[idine](https://bliptext.com/articles/idine), to indicate a [cyclic compound](https://bliptext.com/articles/cyclic-compound) containing a nitrogen atom.\nThe chemical structure of pyridine was determined decades after its discovery.\n[Wilhelm Körner](https://bliptext.com/articles/wilhelm-k-rner) (1869) and [James Dewar](https://bliptext.com/articles/james-dewar) (1871) suggested that, in analogy between [quinoline](https://bliptext.com/articles/quinoline) and [naphthalene](https://bliptext.com/articles/naphthalene), the structure of pyridine is derived from [benzene](https://bliptext.com/articles/benzene) by substituting one C–H unit with a nitrogen atom.\nThe suggestion by Körner and Dewar was later confirmed in an experiment where pyridine was reduced to [piperidine](https://bliptext.com/articles/piperidine) with [sodium](https://bliptext.com/articles/sodium) in [ethanol](https://bliptext.com/articles/ethanol).\nIn 1876, [William Ramsay](https://bliptext.com/articles/william-ramsay) combined [acetylene](https://bliptext.com/articles/acetylene) and [hydrogen cyanide](https://bliptext.com/articles/hydrogen-cyanide) into pyridine in a [red-hot](https://bliptext.com/articles/red-heat) iron-tube furnace.\nThis was the first synthesis of a heteroaromatic compound.\nThe first major synthesis of pyridine derivatives was described in 1881 by [Arthur Rudolf Hantzsch](https://bliptext.com/articles/arthur-rudolf-hantzsch).\nThe [Hantzsch pyridine synthesis](https://bliptext.com/articles/hantzsch-pyridine-synthesis) typically uses a 2:1:1 mixture of a β-[keto acid](https://bliptext.com/articles/keto-acid) (often [acetoacetate](https://bliptext.com/articles/acetoacetic-acid)), an [aldehyde](https://bliptext.com/articles/aldehyde) (often form[aldehyde](https://bliptext.com/articles/aldehyde)), and [ammonia](https://bliptext.com/articles/ammonia) or its salt as the nitrogen donor.\nFirst, a double [hydrogenated](https://bliptext.com/articles/hydration-reaction) pyridine is obtained, which is then oxidized to the corresponding pyridine derivative.\n[Emil Knoevenagel](https://bliptext.com/articles/emil-knoevenagel) showed that asymmetrically substituted pyridine derivatives can be produced with this process.\nThe contemporary methods of pyridine production had a low yield, and the increasing demand for the new compound urged to search for more efficient routes.\nA breakthrough came in 1924 when the Russian chemist [Aleksei Chichibabin](https://bliptext.com/articles/aleksei-chichibabin) invented a [pyridine synthesis reaction](https://bliptext.com/articles/chichibabin-pyridine-synthesis), which was based on inexpensive reagents.\nThis method is still used for the industrial production of pyridine.\n# [Thomas Anderson | upload.wikimedia.org/wikipedia/commons/c/c0/ThomasAnderson%281819-1874%29.jpg]\n# [Hantzsch pyridine synthesis with acetoacetate, formaldehyde and ammonium acetate, and iron(III) chloride as the oxidizer. | upload.wikimedia.org/wikipedia/commons/5/5b/Hantzsch///pyridine///synthesis.svg]\n\n# Occurrence\nPyridine is not abundant in nature, except for the leaves and roots of belladonna ([Atropa belladonna](https://bliptext.com/articles/atropa-belladonna)) and in marshmallow ([Althaea officinalis](https://bliptext.com/articles/althaea-officinalis)).\nPyridine derivatives, however, are often part of biomolecules such as [alkaloids](https://bliptext.com/articles/alkaloid).\nIn daily life, trace amounts of pyridine are components of the [volatile organic compounds](https://bliptext.com/articles/volatile-organic-compound) that are produced in roasting and [canning](https://bliptext.com/articles/canning) processes, e.g. in fried chicken, [sukiyaki](https://bliptext.com/articles/sukiyaki), roasted coffee, potato chips, and fried [bacon](https://bliptext.com/articles/bacon).\nTraces of pyridine can be found in [Beaufort cheese](https://bliptext.com/articles/beaufort-cheese), [vaginal secretions](https://bliptext.com/articles/vaginal-lubrication), [black tea](https://bliptext.com/articles/black-tea), saliva of those suffering from [gingivitis](https://bliptext.com/articles/gingivitis), and [sunflower honey](https://bliptext.com/articles/monofloral-honey).\n\n# Production\nHistorically, pyridine was extracted from [coal tar](https://bliptext.com/articles/coal-tar) or obtained as a byproduct of coal [gasification](https://bliptext.com/articles/gasification).\nThe process is labor-consuming and inefficient: [coal tar](https://bliptext.com/articles/coal-tar) contains only about 0.1% pyridine, and therefore a multi-stage purification was required, which further reduced the output.\nNowadays, most pyridines are synthesized from ammonia, aldehydes, and nitriles, a few combinations of which are suited for pyridine itself.\nVarious [name reactions](https://bliptext.com/articles/name-reaction) are also known, but they are not practiced on scale.\nIn 1989, 26,000 tonnes of pyridine was produced worldwide.\nOther major derivatives are [2-](https://bliptext.com/articles/2-methylpyridine), [3-](https://bliptext.com/articles/3-methylpyridine), [4-methylpyridines](https://bliptext.com/articles/4-methylpyridine) and 5-ethyl-[2-](https://bliptext.com/articles/2-methylpyridine)methylpyridine.\nThe combined scale of these alkylpyridines matches that of pyridine itself.\nAmong the largest 25 production sites for pyridine, eleven are located in Europe (as of 1999).\nThe major producers of pyridine include [Evonik Industries](https://bliptext.com/articles/evonik-industries), Rütgers Chemicals, Jubilant Life Sciences, [Imperial Chemical Industries](https://bliptext.com/articles/imperial-chemical-industries), and Koei Chemical.\nPyridine production significantly increased in the early 2000s, with an annual production capacity of 30,000 tonnes in mainland China alone.\nThe US–Chinese joint venture Vertellus is currently the world leader in pyridine production.\n\n## Chichibabin synthesis\nThe [Chichibabin pyridine synthesis](https://bliptext.com/articles/chichibabin-pyridine-synthesis) was reported in 1924 and the basic approach underpins several industrial routes.\nIn its general form, the reaction involves the [condensation reaction](https://bliptext.com/articles/condensation-reaction) of [aldehydes](https://bliptext.com/articles/aldehydes), [ketones](https://bliptext.com/articles/ketones), [α,β-unsaturated carbonyl compounds](https://bliptext.com/articles/unsaturated-carbonyl-compound), or any combination of the above, in [ammonia](https://bliptext.com/articles/ammonia) or [ammonia](https://bliptext.com/articles/ammonia) derivatives.\nApplication of the Chichibabin pyridine synthesis suffer from low yields, often about 30%, however the precursors are inexpensive.\nIn particular, unsubstituted pyridine is produced from [formaldehyde](https://bliptext.com/articles/formaldehyde) and [acetaldehyde](https://bliptext.com/articles/acetaldehyde).\nFirst, [acrolein](https://bliptext.com/articles/acrolein) is formed in a [Knoevenagel condensation](https://bliptext.com/articles/knoevenagel-condensation) from the acetaldehyde and formaldehyde.\nThe acrolein then [condenses](https://bliptext.com/articles/condensation-reaction) with acetaldehyde and ammonia to give [dihydropyridine](https://bliptext.com/articles/dihydropyridine), which is oxidized to pyridine.\nThis process is carried out in a gas phase at 400–450 °C.\nTypical catalysts are modified forms of [alumina](https://bliptext.com/articles/alumina) and [silica](https://bliptext.com/articles/silica).\nThe reaction has been tailored to produce various [methylpyridines](https://bliptext.com/articles/methylpyridine).\n# [Formation of acrolein from acetaldehyde and formaldehyde | upload.wikimedia.org/wikipedia/commons/7/7a/AcroleinDarstellung.svg]\n# [Condensation of pyridine from acrolein and acetaldehyde | upload.wikimedia.org/wikipedia/commons/7/73/Pyridin///aus///Acrolein.svg]\n\n## Dealkylation and decarboxylation of substituted pyridines\nPyridine can be prepared by dealkylation of alkylated pyridines, which are obtained as byproducts in the syntheses of other pyridines.\nThe oxidative dealkylation is carried out either using air over [vanadium(V) oxide](https://bliptext.com/articles/vanadium-v-oxide) catalyst, by vapor-dealkylation on [nickel](https://bliptext.com/articles/nickel)-based catalyst, or hydrodealkylation with a [silver](https://bliptext.com/articles/silver)- or [platinum](https://bliptext.com/articles/platinum)-based catalyst.\nYields of pyridine up to be 93% can be achieved with the nickel-based catalyst.\nPyridine can also be produced by the [decarboxylation](https://bliptext.com/articles/decarboxylation) of [nicotinic acid](https://bliptext.com/articles/nicotinic-acid) with [copper chromite](https://bliptext.com/articles/copper-chromite).\n\n## Bönnemann cyclization\nThe [trimerization](https://bliptext.com/articles/trimerization) of a part of a [nitrile](https://bliptext.com/articles/nitrile) molecule and two parts of [acetylene](https://bliptext.com/articles/acetylene) into pyridine is called **Bönnemann cyclization**.\nThis modification of the [Reppe synthesis](https://bliptext.com/articles/walter-reppe) can be activated either by heat or by [light](https://bliptext.com/articles/photochemistry).\nWhile the [thermal activation](https://bliptext.com/articles/thermal-activation) requires high pressures and temperatures, the photoinduced [cycloaddition](https://bliptext.com/articles/cycloaddition) proceeds at ambient conditions with CoCp2(cod) (Cp = cyclopentadienyl, cod = [1,5-cyclooctadiene](https://bliptext.com/articles/1-5-cyclooctadiene)) as a catalyst, and can be performed even in water.\nA series of pyridine derivatives can be produced in this way.\nWhen using [acetonitrile](https://bliptext.com/articles/acetonitrile) as the nitrile, 2-methylpyridine is obtained, which can be dealkylated to pyridine.\n# [Bönnemann cyclization | upload.wikimedia.org/wikipedia/commons/8/87/B%C3%B6nnemannEn.png]\n\n## Other methods\nThe [Kröhnke pyridine synthesis](https://bliptext.com/articles/kr-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.\nThe reaction of pyridine with bromomethyl ketones gives the related [pyridinium](https://bliptext.com/articles/pyridinium) salt, wherein the [methylene group](https://bliptext.com/articles/methylene-group) is highly acidic.\nThis species undergoes a [Michael-like addition](https://bliptext.com/articles/michael-addition) to [α,β-unsaturated carbonyls](https://bliptext.com/articles/unsaturated-carbonyl-compound) in the presence of [ammonium acetate](https://bliptext.com/articles/ammonium-acetate) to undergo ring closure and formation of the targeted substituted pyridine as well as pyridinium bromide.\nThe Ciamician–Dennstedt rearrangement entails the ring-expansion of [pyrrole](https://bliptext.com/articles/pyrrole) with [dichlorocarbene](https://bliptext.com/articles/dichlorocarbene) to [3-chloropyridine](https://bliptext.com/articles/3-chloropyridine).\nIn the Gattermann–Skita synthesis, a [malonate ester](https://bliptext.com/articles/malonic-ester-synthesis) salt reacts with dichloro[methylamine](https://bliptext.com/articles/methylamine).\nOther methods include the [Boger pyridine synthesis](https://bliptext.com/articles/boger-pyridine-synthesis) and [Diels–Alder reaction](https://bliptext.com/articles/diels-alder-reaction) of an [alkene](https://bliptext.com/articles/alkene) and an [oxazole](https://bliptext.com/articles/oxazole).\n# [Figure 1 | upload.wikimedia.org/wikipedia/commons/7/79/Kroehnke///Pyridine///Figure///1.png]\n# [Ciamician–Dennstedt Rearrangement | upload.wikimedia.org/wikipedia/commons/5/56/Ciamician-Dennstedt///Rearrangement.png]\n# [Gattermann–Skita synthesis | upload.wikimedia.org/wikipedia/commons/e/e1/Gattermann-Skita///Syntesis.png]\n\n## Biosynthesis\nSeveral pyridine derivatives play important roles in biological systems.\nWhile its biosynthesis is not fully understood, [nicotinic acid](https://bliptext.com/articles/nicotinic-acid) (vitamin B3) occurs in some [bacteria](https://bliptext.com/articles/bacteria), [fungi](https://bliptext.com/articles/fungi), and [mammals](https://bliptext.com/articles/mammal).\nMammals synthesize nicotinic acid through oxidation of the [amino acid](https://bliptext.com/articles/amino-acid) [tryptophan](https://bliptext.com/articles/tryptophan), where an intermediate product, the [aniline](https://bliptext.com/articles/aniline) derivative [kynurenine](https://bliptext.com/articles/kynurenine), creates a pyridine derivative, [quinolinate](https://bliptext.com/articles/quinolinate) and then nicotinic acid.\nOn the contrary, the bacteria [Mycobacterium tuberculosis](https://bliptext.com/articles/mycobacterium-tuberculosis) and [Escherichia coli](https://bliptext.com/articles/escherichia-coli) produce nicotinic acid by condensation of [glyceraldehyde 3-phosphate](https://bliptext.com/articles/glyceraldehyde-3-phosphate) and [aspartic acid](https://bliptext.com/articles/aspartic-acid).\n\n# Reactions\nBecause of the [electronegative](https://bliptext.com/articles/electronegativity) [nitrogen](https://bliptext.com/articles/nitrogen) in the pyridine ring, pyridine enters less readily into [electrophilic aromatic substitution](https://bliptext.com/articles/electrophilic-aromatic-substitution) reactions than benzene derivatives.\nInstead, in terms of its reactivity, pyridine resembles [nitrobenzene](https://bliptext.com/articles/nitrobenzene).\nCorrespondingly pyridine is more prone to [nucleophilic substitution](https://bliptext.com/articles/nucleophilic-substitution), as evidenced by the ease of [metalation](https://bliptext.com/articles/metalation) by strong [organometallic](https://bliptext.com/articles/organometallic-chemistry) bases.\nThe reactivity of pyridine can be distinguished for three chemical groups.\nWith [electrophiles](https://bliptext.com/articles/electrophile), [electrophilic substitution](https://bliptext.com/articles/electrophilic-substitution) takes place where pyridine expresses aromatic properties.\nWith [nucleophiles](https://bliptext.com/articles/nucleophile), pyridine reacts at positions 2 and 4 and thus behaves similar to [imines](https://bliptext.com/articles/imine) and [carbonyls](https://bliptext.com/articles/carbonyl).\nThe reaction with many [Lewis acids](https://bliptext.com/articles/lewis-acid) results in the addition to the nitrogen atom of pyridine, which is similar to the reactivity of tertiary amines.\nThe ability of pyridine and its derivatives to oxidize, forming [amine oxides](https://bliptext.com/articles/amine-oxide) (N-oxides), is also a feature of tertiary amines.\nThe nitrogen center of pyridine features a basic [lone pair](https://bliptext.com/articles/lone-pair) of [electrons](https://bliptext.com/articles/electron).\nThis lone pair does not overlap with the aromatic π-system ring, consequently pyridine is [basic](https://bliptext.com/articles/base-chemistry), having chemical properties similar to those of [tertiary amines](https://bliptext.com/articles/tertiary-amine).\n[Protonation](https://bliptext.com/articles/protonation) gives [pyridinium](https://bliptext.com/articles/pyridinium), C5H5NH+.The pKa of the [conjugate acid](https://bliptext.com/articles/conjugate-acid) (the [pyridinium](https://bliptext.com/articles/pyridinium) cation) is 5.25.\nThe structures of pyridine and pyridinium are almost identical.\nThe pyridinium cation is [isoelectronic](https://bliptext.com/articles/isoelectronic) with benzene.\nPyridinium p-[toluenesulfonate](https://bliptext.com/articles/toluenesulfonic-acid) (PPTS) is an illustrative pyridinium salt; it is produced by treating pyridine with p-toluenesulfonic acid.\nIn addition to [protonation](https://bliptext.com/articles/protonation), pyridine undergoes N-centred [alkylation](https://bliptext.com/articles/alkylation), [acylation](https://bliptext.com/articles/acylation), and N-oxidation.\nPyridine and poly(4-vinyl) pyridine have been shown to form conducting [molecular wires](https://bliptext.com/articles/molecular-wire) with remarkable polyenimine structure on [UV irradiation](https://bliptext.com/articles/uv-irradiation), a process which accounts for at least some of the visible light absorption by aged pyridine samples.\nThese wires have been theoretically predicted to be both highly efficient electron donors and acceptors, and yet are resistant to air oxidation.\n\n## Electrophilic substitutions\nOwing to the decreased electron density in the aromatic system, [electrophilic substitutions](https://bliptext.com/articles/electrophilic-substitution) are suppressed in pyridine and its derivatives.\n[Friedel–Crafts alkylation or acylation](https://bliptext.com/articles/friedel-crafts-reaction), usually fail for pyridine because they lead only to the addition at the nitrogen atom.\nSubstitutions 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.\nDirect [nitration](https://bliptext.com/articles/nitration) of pyridine is sluggish.\nPyridine derivatives wherein the nitrogen atom is screened sterically and/or electronically can be obtained by nitration with [nitronium tetrafluoroborate](https://bliptext.com/articles/nitronium-tetrafluoroborate) (NO2BF4).\nIn this way, 3-nitropyridine can be obtained via the synthesis of 2,6-dibromopyridine followed by nitration and debromination.\n[Sulfonation](https://bliptext.com/articles/sulfonation) of pyridine is even more difficult than nitration.\nHowever, pyridine-3-sulfonic acid can be obtained.\nReaction with the SO3 group also facilitates addition of sulfur to the nitrogen atom, especially in the presence of a [mercury(II) sulfate](https://bliptext.com/articles/mercury-ii-sulfate) catalyst.\nIn contrast to the sluggish nitrations and sulfonations, the [bromination](https://bliptext.com/articles/bromination) and [chlorination](https://bliptext.com/articles/chlorination-reaction) of pyridine proceed well.\n# [substitution in the 2-position | upload.wikimedia.org/wikipedia/commons/5/50/Pyridine-EAS-2-position-2D-skeletal.png]\n# [substitution in the 3-position | upload.wikimedia.org/wikipedia/commons/e/e5/Pyridine-EAS-3-position-2D-skeletal.png]\n# [Substitution in 4-position | upload.wikimedia.org/wikipedia/commons/0/0a/Pyridine-EAS-4-position-2D-skeletal.png]\n# [500px | upload.wikimedia.org/wikipedia/commons/0/09/simple///chlorination.png]\n\n### Pyridine N-oxide\nOxidation of pyridine occurs at nitrogen to give pyridine N-oxide.\nThe oxidation can be achieved with [peracids](https://bliptext.com/articles/peracid):\nSome electrophilic substitutions on the pyridine are usefully effected using pyridine N-oxide followed by deoxygenation.\nAddition of oxygen suppresses further reactions at nitrogen atom and promotes substitution at the 2- and 4-carbons.\nThe oxygen atom can then be removed, e.g., using zinc dust.\n# [Structure of pyridine N-oxide | upload.wikimedia.org/wikipedia/commons/6/65/Pyridine///N-oxide.png]\n\n## Nucleophilic substitutions\nIn contrast to benzene ring, pyridine efficiently supports several nucleophilic substitutions.\nThe reason for this is relatively lower electron density of the carbon atoms of the ring.\nThese reactions include substitutions with elimination of a [hydride](https://bliptext.com/articles/hydride) ion and elimination-additions with formation of an intermediate [aryne](https://bliptext.com/articles/aryne) configuration, and usually proceed at the 2- or 4-position.\nMany 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.\nSo fluorine is the best leaving group for the substitution with [organolithium compounds](https://bliptext.com/articles/organolithium-compound).\nThe nucleophilic attack compounds may be [alkoxides](https://bliptext.com/articles/alkoxide), thiolates, [amines](https://bliptext.com/articles/amine), and ammonia (at elevated pressures).\nIn general, the hydride ion is a poor leaving group and occurs only in a few heterocyclic reactions.\nThey include the [Chichibabin reaction](https://bliptext.com/articles/chichibabin-reaction), which yields pyridine derivatives [aminated](https://bliptext.com/articles/amination) at the 2-position.\nHere, [sodium amide](https://bliptext.com/articles/sodium-amide) is used as the nucleophile yielding 2-aminopyridine.\nThe hydride ion released in this reaction combines with a proton of an available amino group, forming a hydrogen molecule.\nAnalogous to benzene, nucleophilic substitutions to pyridine can result in the formation of [pyridyne](https://bliptext.com/articles/pyridyne) intermediates as hetero[aryne](https://bliptext.com/articles/aryne).\nFor this purpose, pyridine derivatives can be eliminated with good leaving groups using strong bases such as sodium and [potassium tert-butoxide](https://bliptext.com/articles/potassium-tert-butoxide).\nThe subsequent addition of a nucleophile to the [triple bond](https://bliptext.com/articles/triple-bond) has low selectivity, and the result is a mixture of the two possible adducts.\n# [Nucleophilic substitution in 2-position | upload.wikimedia.org/wikipedia/commons/d/d8/Pyridine-NA-2-position.svg]\n# [Nucleophilic substitution in 3-position | upload.wikimedia.org/wikipedia/commons/6/6e/Pyridine-NA-3-position.svg]\n# [Nucleophilic substitution in 4-position | upload.wikimedia.org/wikipedia/commons/a/a2/Pyridine-NA-4-position.svg]\n\n## Radical reactions\nPyridine supports a series of radical reactions, which is used in its [dimerization](https://bliptext.com/articles/dimer-chemistry) to bipyridines.\nRadical dimerization of pyridine with elemental [sodium](https://bliptext.com/articles/sodium) or [Raney nickel](https://bliptext.com/articles/raney-nickel) selectively yields [4,4'-bipyridine](https://bliptext.com/articles/4-4-bipyridine), or [2,2'-bipyridine](https://bliptext.com/articles/2-2-bipyridine), which are important precursor reagents in the chemical industry.\nOne of the [name reactions](https://bliptext.com/articles/name-reactions) involving free radicals is the [Minisci reaction](https://bliptext.com/articles/minisci-reaction).\nIt can produce 2-tert-butylpyridine upon reacting pyridine with [pivalic acid](https://bliptext.com/articles/pivalic-acid), [silver nitrate](https://bliptext.com/articles/silver-nitrate) and [ammonium](https://bliptext.com/articles/ammonium) in [sulfuric acid](https://bliptext.com/articles/sulfuric-acid) with a yield of 97%.\n\n## Reactions on the nitrogen atom\n[Lewis acids](https://bliptext.com/articles/lewis-acid) easily add to the nitrogen atom of pyridine, forming pyridinium salts.\nThe reaction with [alkyl halides](https://bliptext.com/articles/alkyl-halide) leads to [alkylation](https://bliptext.com/articles/alkylation) of the nitrogen atom.\nThis creates a positive charge in the ring that increases the reactivity of pyridine to both oxidation and reduction.\nThe [Zincke reaction](https://bliptext.com/articles/[zinc](https://bliptext.com/articles/zinc)ke-reaction) is used for the selective introduction of radicals in pyridinium compounds (it has no relation to the chemical element [zinc](https://bliptext.com/articles/zinc)).\n# [Additions of various Lewis acids to pyridine | upload.wikimedia.org/wikipedia/commons/3/37/Pyridine-complex.svg]\n\n## Hydrogenation and reduction\n[Piperidine](https://bliptext.com/articles/piperidine) is produced by [hydrogenation](https://bliptext.com/articles/hydrogenation) of pyridine with a [nickel](https://bliptext.com/articles/nickel)-, [cobalt](https://bliptext.com/articles/cobalt)-, or [ruthenium](https://bliptext.com/articles/ruthenium)-based catalyst at elevated temperatures.\nThe hydrogenation of pyridine to piperidine releases 193.8 kJ/mol, which is slightly less than the energy of the hydrogenation of [benzene](https://bliptext.com/articles/benzene) (205.3 kJ/mol).\nPartially hydrogenated derivatives are obtained under milder conditions.\nFor example, reduction with [lithium aluminium hydride](https://bliptext.com/articles/lithium-aluminium-hydride) yields a mixture of 1,4-dihydropyridine, 1,2-dihydropyridine, and 2,5-dihydropyridine.\nSelective synthesis of 1,4-dihydropyridine is achieved in the presence of organometallic complexes of [magnesium](https://bliptext.com/articles/magnesium) and [zinc](https://bliptext.com/articles/zinc), and (Δ3,4)-tetrahydropyridine is obtained by electrochemical reduction of pyridine.\n[Birch reduction](https://bliptext.com/articles/birch-reduction) converts pyridine to dihydropyridines.\n# [Reduction of pyridine to piperidine with Raney nickel | upload.wikimedia.org/wikipedia/commons/2/20/Pyridine///hydrogenation.png]\n\n## Lewis basicity and coordination compounds\nPyridine is a [Lewis base](https://bliptext.com/articles/lewis-base), donating its pair of electrons to a Lewis acid.\nIts Lewis base properties are discussed in the [ECW model](https://bliptext.com/articles/ecw-model).\nIts relative donor strength toward a series of acids, versus other Lewis bases, can be illustrated by [C-B plots](https://bliptext.com/articles/ecw-model).\nOne example is the [sulfur trioxide pyridine complex](https://bliptext.com/articles/sulfur-trioxide-pyridine-complex) (melting point 175 °C), which is a [sulfation](https://bliptext.com/articles/sulfation) agent used to convert alcohols to [sulfate esters](https://bliptext.com/articles/sulfate-ester).\nPyridine-[borane](https://bliptext.com/articles/borane) (C5H5NBH3, melting point 10–11 °C) is a mild reducing agent.\n[Transition metal pyridine complexes](https://bliptext.com/articles/transition-metal-pyridine-complexes) are numerous.\nTypical octahedral complexes have the stoichiometry MCl2(py)4 and MCl3(py)3.\nOctahedral homoleptic complexes of the type M(py)6(+) are rare or tend to dissociate pyridine.\nNumerous square planar complexes are known, such as [Crabtree's catalyst](https://bliptext.com/articles/crabtree-s-catalyst).\nThe pyridine ligand replaced during the reaction is restored after its completion.\nThe η6 coordination mode, as occurs in η6 benzene complexes, is observed only in [sterically encumbered](https://bliptext.com/articles/steric-effects) derivatives that block the nitrogen center.\n# [structure of the Crabtree's catalyst | upload.wikimedia.org/wikipedia/commons/6/60/Crabtree.svg]\n\n# Applications\n\n## Pesticides and pharmaceuticals\nThe main use of pyridine is as a precursor to the herbicides [paraquat](https://bliptext.com/articles/paraquat) and [diquat](https://bliptext.com/articles/diquat).\nThe first synthesis step of insecticide [chlorpyrifos](https://bliptext.com/articles/chlorpyrifos) consists of the chlorination of pyridine.\nPyridine is also the starting compound for the preparation of [pyrithione](https://bliptext.com/articles/pyrithione)-based [fungicides](https://bliptext.com/articles/fungicide).\n[Cetylpyridinium](https://bliptext.com/articles/cetylpyridinium-chloride) and laurylpyridinium, which can be produced from pyridine with a [Zincke reaction](https://bliptext.com/articles/zincke-reaction), are used as [antiseptic](https://bliptext.com/articles/antiseptic) in oral and dental care products.\nPyridine is easily attacked by alkylating agents to give N-alkylpyridinium salts.\nOne example is [cetylpyridinium chloride](https://bliptext.com/articles/cetylpyridinium-chloride).\nIt is also used in the textile industry to improve network capacity of cotton.\n# [Synthesis of paraquat | upload.wikimedia.org/wikipedia/commons/c/ca/Synthesis///of///paraquat.png]\n\n## Laboratory use\nPyridine is used as a polar, basic, low-reactive solvent, for example in [Knoevenagel condensations](https://bliptext.com/articles/knoevenagel-condensation).\nIt is especially suitable for the dehalogenation, where it acts as the base for the [elimination reaction](https://bliptext.com/articles/elimination-reaction).\nIn [esterifications](https://bliptext.com/articles/esterification) and acylations, pyridine activates the carboxylic [acid chlorides](https://bliptext.com/articles/acid-chloride) and anhydrides.\nEven more active in these reactions are the derivatives [4-dimethylaminopyridine](https://bliptext.com/articles/4-dimethylaminopyridine) (DMAP) and 4-(1-pyrrolidinyl) pyridine.\nPyridine is also used as a base in some [condensation reactions](https://bliptext.com/articles/condensation-reaction).\n# [Elimination reaction with pyridine to form pyridinium | upload.wikimedia.org/wikipedia/commons/c/c0/Chlorocyclopentane///elimination.svg]\n\n## Reagents\nAs a base, pyridine can be used as the [Karl Fischer reagent](https://bliptext.com/articles/karl-fischer-titration), but it is usually replaced by alternatives with a more pleasant odor, such as [imidazole](https://bliptext.com/articles/imidazole).\n[Pyridinium chlorochromate](https://bliptext.com/articles/pyridinium-chlorochromate), [pyridinium dichromate](https://bliptext.com/articles/cornforth-reagent), and the [Collins reagent](https://bliptext.com/articles/collins-reagent) (the complex of [chromium(VI) oxide](https://bliptext.com/articles/chromium-trioxide)) are used for the oxidation of alcohols.\n# [Oxidation of an alcohol to aldehyde with the Collins reagent | upload.wikimedia.org/wikipedia/commons/3/38/Alcohol///oxidation///with///Collins///reagent.svg]\n\n# Hazards\nPyridine is a toxic, flammable liquid with a strong and unpleasant fishy odour.\nIts [odour threshold](https://bliptext.com/articles/odour-threshold) of 0.04 to 20 ppm is close to its [threshold limit](https://bliptext.com/articles/threshold-limit-value) of 5 ppm for adverse effects, thus most (but not all) adults will be able to tell when it is present at harmful levels.\nPyridine easily dissolves in water and harms both animals and plants in aquatic systems.\n\n## Fire\nPyridine has a [flash point](https://bliptext.com/articles/flash-point) of 20 °C and is therefore highly flammable.\nCombustion produces toxic fumes which can include [bipyridines](https://bliptext.com/articles/bipyridine), [nitrogen oxides](https://bliptext.com/articles/nitrogen-oxide), and [carbon monoxide](https://bliptext.com/articles/carbon-monoxide).\n\n## Short-term exposure\nPyridine can cause chemical burns on contact with the skin and its fumes may be irritating to the eyes or upon inhalation.\nPyridine depresses the [nervous system](https://bliptext.com/articles/nervous-system) giving symptoms similar to intoxication with vapor concentrations of above 3600 [ppm](https://bliptext.com/articles/parts-per-million) posing a greater health risk.\nThe effects may have a delayed onset of several hours and include dizziness, headache, [lack of coordination](https://bliptext.com/articles/ataxia), nausea, [salivation](https://bliptext.com/articles/saliva), and loss of appetite.\nThey may progress into abdominal pain, [pulmonary congestion](https://bliptext.com/articles/pulmonary-congestion) and unconsciousness.\nThe lowest known [lethal dose](https://bliptext.com/articles/lethal-dose) (LDLo) for the ingestion of pyridine in humans is 500 mg/kg.\n\n## Long-term exposure\nProlonged exposure to pyridine may result in liver, heart and kidney damage.\nEvaluations as a possible [carcinogenic](https://bliptext.com/articles/carcinogenic) agent showed that there is inadequate evidence in humans for the [carcinogenic](https://bliptext.com/articles/carcinogenic)ity of pyridine, although there is sufficient evidence in experimental animals.\nTherefore, [IARC](https://bliptext.com/articles/international-agency-for-research-on-cancer) considers pyridine as possibly carcinogenic to humans (Group 2B).\n\n# Occurrence\nTrace amounts of up to 16 μg/m3 have been detected in tobacco smoke.\nMinor amounts of pyridine are released into environment from some industrial processes such as steel manufacture, processing of [oil shale](https://bliptext.com/articles/oil-shale), [coal gasification](https://bliptext.com/articles/coal-gasification), [coking](https://bliptext.com/articles/coking) plants and [incinerators](https://bliptext.com/articles/incineration).\nThe atmosphere at oil shale processing plants can contain pyridine concentrations of up to 13 μg/m3, and 53 μg/m3 levels were measured in the [groundwater](https://bliptext.com/articles/groundwater) in the vicinity of a coal gasification plant.\nAccording to a study by the US [National Institute for Occupational Safety and Health](https://bliptext.com/articles/national-institute-for-occupational-safety-and-health), about 43,000 Americans work in contact with pyridine.\n\n## In foods\nPyridine has historically been added to foods to give them a bitter flavour, although this practise is now banned in the U.S. It may still be added to [ethanol](https://bliptext.com/articles/ethanol) to make it unsuitable for drinking.\n\n# Metabolism\nExposure to pyridine would normally lead to its inhalation and absorption in the lungs and gastrointestinal tract, where it either remains unchanged or is [metabolized](https://bliptext.com/articles/metabolism).\nThe 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](https://bliptext.com/articles/monooxygenase).\nIn humans, pyridine is metabolized only into N-methylpyridiniumhydroxide.\n# [Metabolism of pyridine | upload.wikimedia.org/wikipedia/commons/7/7f/Pyridin-Metabolisierung.png]\n\n# Environmental fate\nPyridine is readily degraded by bacteria to ammonia and carbon dioxide.\nThe unsubstituted pyridine ring degrades more rapidly than [picoline](https://bliptext.com/articles/picoline), [lutidine](https://bliptext.com/articles/lutidine), [chloropyridine](https://bliptext.com/articles/chloropyridine), or [aminopyridines](https://bliptext.com/articles/aminopyridine), and a number of pyridine degraders have been shown to overproduce [riboflavin](https://bliptext.com/articles/riboflavin) in the presence of pyridine.\nIonizable 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](https://bliptext.com/articles/soil-organic-matter), [cation exchange](https://bliptext.com/articles/cation-exchange), and surface complexation.\nSuch [adsorption](https://bliptext.com/articles/adsorption) to surfaces reduces bioavailability of pyridines for microbial degraders and other organisms, thus slowing degradation rates and reducing [ecotoxicity](https://bliptext.com/articles/ecotoxicity).\n\n# Nomenclature\nThe systematic name of pyridine, within the [Hantzsch–Widman nomenclature](https://bliptext.com/articles/hantzsch-widman-nomenclature) recommended by the [IUPAC](https://bliptext.com/articles/iupac), is .\nHowever, systematic names for simple compounds are used very rarely; instead, heterocyclic nomenclature follows historically established common names.\nIUPAC discourages the use of in favor of pyridine.\nThe numbering of the ring atoms in pyridine starts at the nitrogen (see infobox).\nAn allocation of positions by letter of the [Greek alphabet](https://bliptext.com/articles/greek-alphabet) (α-γ) and the [substitution pattern](https://bliptext.com/articles/arene-substitution-patterns) nomenclature common for homoaromatic systems (ortho, meta, para) are used sometimes.\nHere α (ortho), β (meta), and γ (para) refer to the 2, 3, and 4 position, respectively.\nThe systematic name for the pyridine derivatives is pyridinyl, wherein the position of the substituted atom is preceded by a number.\nHowever, the historical name pyridyl is encouraged by the IUPAC and used instead of the systematic name.\nThe [cationic](https://bliptext.com/articles/cation) derivative formed by the addition of an [electrophile](https://bliptext.com/articles/electrophile) to the nitrogen atom is called [pyridinium](https://bliptext.com/articles/pyridinium).","current_revision":null,"created_by":"kACnuQmH5k9Nr5VNVEpVeg7XpvUmMctD","created_at":"2025-01-25T17:22:15.372Z","updated_at":"2025-01-25T17:22:15.372Z","search_vector":"'pyridin':1","search_content":" \n \n\n# \n**Pyridine** is a [basic](https://bliptext.com/articles/basic-chemistry) [heterocyclic](https://bliptext.com/articles/heterocyclic-compound) [organic compound](https://bliptext.com/articles/organic-compound) with the [chemical formula](https://bliptext.com/articles/chemical-formula) C5H5N.\nIt is structurally related to [benzene](https://bliptext.com/articles/benzene), with one [methine group](https://bliptext.com/articles/methine-group) (\\dCH\\s) replaced by a [nitrogen](https://bliptext.com/articles/nitrogen) atom (\\dN\\s).\nIt is a highly flammable, weakly [alkaline](https://bliptext.com/articles/alkali), water-miscible liquid with a distinctive, unpleasant fish-like smell.\nPyridine is colorless, but older or impure samples can appear yellow, due to the formation of extended, unsaturated [polymeric](https://bliptext.com/articles/polymer) chains, which show significant [electrical conductivity](https://bliptext.com/articles/electrical-conductivity).\nThe pyridine ring occurs in many important compounds, including [agrochemicals](https://bliptext.com/articles/agrochemical), [pharmaceuticals](https://bliptext.com/articles/pharmaceutical), and [vitamins](https://bliptext.com/articles/vitamin).\nHistorically, pyridine was produced from [coal tar](https://bliptext.com/articles/coal-tar).\nAs of 2016, it is synthesized on the scale of about 20,000 tons per year worldwide.\n\n# Properties\n# [Internal bond angles and bond distances (pm) for pyridine. | upload.wikimedia.org/wikipedia/commons/9/9d/PyridineXray.svg]\n\n## Physical properties\nPyridine is [diamagnetic](https://bliptext.com/articles/diamagnetism).\nIts [critical parameters](https://bliptext.com/articles/critical-point-thermodynamics) are: pressure 5.63 MPa, temperature 619 K and volume 248 cm3/mol.\nIn the temperature range 340–426 °C its vapor pressure p can be described with the [Antoine equation](https://bliptext.com/articles/antoine-equation)\nwhere T is temperature, A = 4.16272, B = 1371.358 K and C = −58.496 K.\n# [Crystal structure of pyridine | upload.wikimedia.org/wikipedia/commons/6/62/Kristallstruktur///Pyridin.png]\n\n## Structure\nPyridine ring forms a C5N hexagon.\nSlight variations of the C\\sC and C\\sN distances as well as the bond angles are observed.\n\n## Crystallography\nPyridine crystallizes in an [orthorhombic crystal system](https://bliptext.com/articles/orthorhombic-crystal-system) with [space group](https://bliptext.com/articles/space-group) Pna21 and [lattice parameters](https://bliptext.com/articles/lattice-parameters) a = 1752 [pm](https://bliptext.com/articles/picometer), b = 897 [pm](https://bliptext.com/articles/picometer), c = 1135 [pm](https://bliptext.com/articles/picometer), and 16 [formula units](https://bliptext.com/articles/formula-unit) per [unit cell](https://bliptext.com/articles/unit-cell) (measured at 153 K).\nFor comparison, crystalline [benzene](https://bliptext.com/articles/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.\nThis difference is partly related to the lower [symmetry](https://bliptext.com/articles/molecular-symmetry) of the individual pyridine molecule (C2v vs D6h for benzene).\nA tri[hydrate](https://bliptext.com/articles/hydrate) (pyridine·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).\n\n## Spectroscopy\nThe optical [absorption spectrum](https://bliptext.com/articles/absorption-spectrum) of pyridine in [hexane](https://bliptext.com/articles/hexane) consists of bands at the [wavelengths](https://bliptext.com/articles/wavelength) of 195, 251, and 270 nm.\nWith respective extinction coefficients (ε) of 7500, 2000, and 450 L·mol−1·cm−1, these bands are assigned to π → π*, π → π*, and n → π* transitions.\nThe compound displays very low [fluorescence](https://bliptext.com/articles/fluorescence).\nThe 1H [nuclear magnetic resonance](https://bliptext.com/articles/nuclear-magnetic-resonance) (NMR) spectrum shows signals for α-([δ](https://bliptext.com/articles/chemical-shift) 8.5), γ-([δ](https://bliptext.com/articles/chemical-shift)7.5) and β-protons ([δ](https://bliptext.com/articles/chemical-shift)7).\nBy contrast, the proton signal for benzene is found at δ7.27.\nThe 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.\nThe situation is rather similar for the [13C NMR](https://bliptext.com/articles/13c-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.\nAll shifts are quoted for the solvent-free substances.\nPyridine is conventionally detected by the [gas chromatography](https://bliptext.com/articles/gas-chromatography) and [mass spectrometry](https://bliptext.com/articles/mass-spectrometry) methods.\n\n## Bonding\nPyridine has a [conjugated](https://bliptext.com/articles/conjugation-organic-chemistry) system of six [π electrons](https://bliptext.com/articles/pi-bond) that are delocalized over the ring.\nThe molecule is planar and, thus, follows the [Hückel criteria](https://bliptext.com/articles/h-ckel-rule) for aromatic systems.\nIn contrast to benzene, the [electron density](https://bliptext.com/articles/electron-density) is not evenly distributed over the ring, reflecting the negative [inductive effect](https://bliptext.com/articles/inductive-effect) of the nitrogen atom.\nFor this reason, pyridine has a dipole moment and a weaker [resonant stabilization](https://bliptext.com/articles/resonance-chemistry) than benzene ([resonance energy](https://bliptext.com/articles/resonance-chemistry) 117 kJ/mol in pyridine vs. 150 kJ/mol in benzene).\nThe ring atoms in the pyridine molecule are [sp2-hybridized](https://bliptext.com/articles/orbital-hybridisation).\nThe nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital.\nThe [lone pair](https://bliptext.com/articles/lone-pair) is in an sp2 orbital, projecting outward from the ring in the same plane as the [σ bonds](https://bliptext.com/articles/bond).\nAs 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.\nHowever, because of the separation of the lone pair from the aromatic ring system, the nitrogen atom cannot exhibit a positive [mesomeric effect](https://bliptext.com/articles/mesomeric-effect).\nMany analogues of pyridine are known where N is replaced by other heteroatoms from the same column of the [Periodic Table of Elements](https://bliptext.com/articles/periodic-table-of-elements) (see figure below).\nSubstitution of one C–H in pyridine with a second N gives rise to the [diazine](https://bliptext.com/articles/diazine) heterocycles (C4H4N2), with the names [pyridazine](https://bliptext.com/articles/pyridazine), [pyrimidine](https://bliptext.com/articles/pyrimidine), and [pyrazine](https://bliptext.com/articles/pyrazine).\n \n \n \n \n \n \n# [Pyridine with its free electron pair | upload.wikimedia.org/wikipedia/commons/d/d9/Pyridine-2D-Skeletal.png]\n# [Bond lengths and angles of benzene, pyridine, phosphorine, arsabenzene, stibabenzene, and bismabenzene | upload.wikimedia.org/wikipedia/commons/0/0c/Bond///lengths///of///group///15///heterobenzenes///and///benzene.svg]\n# [Atomic orbitals in pyridine | upload.wikimedia.org/wikipedia/commons/2/27/Pyridine-orbitals.svg]\n# [Resonance structures of pyridine | upload.wikimedia.org/wikipedia/commons/e/e9/Pyridine-10.png]\n# [Atomic orbitals in protonated pyridine | upload.wikimedia.org/wikipedia/commons/7/77/Pyridinium-orbitals.svg]\n\n# History\nImpure pyridine was undoubtedly prepared by early [alchemists](https://bliptext.com/articles/alchemy) by heating animal bones and other organic matter, but the earliest documented reference is attributed to the Scottish scientist [Thomas Anderson](https://bliptext.com/articles/thomas-anderson-chemist).\nIn 1849, Anderson examined the contents of the [oil obtained through high-temperature heating of animal bones](https://bliptext.com/articles/dippel-s-oil).\nAmong other substances, he separated from the oil a colorless liquid with unpleasant odor, from which he isolated pure pyridine two years later.\nHe described it as highly soluble in water, readily soluble in concentrated acids and salts upon heating, and only slightly soluble in oils.\nOwing to its flammability, Anderson named the new substance pyridine, after (pyr) meaning fire.\nThe suffix [idine](https://bliptext.com/articles/idine) was added in compliance with the chemical nomenclature, as in tolu[idine](https://bliptext.com/articles/idine), to indicate a [cyclic compound](https://bliptext.com/articles/cyclic-compound) containing a nitrogen atom.\nThe chemical structure of pyridine was determined decades after its discovery.\n[Wilhelm Körner](https://bliptext.com/articles/wilhelm-k-rner) (1869) and [James Dewar](https://bliptext.com/articles/james-dewar) (1871) suggested that, in analogy between [quinoline](https://bliptext.com/articles/quinoline) and [naphthalene](https://bliptext.com/articles/naphthalene), the structure of pyridine is derived from [benzene](https://bliptext.com/articles/benzene) by substituting one C–H unit with a nitrogen atom.\nThe suggestion by Körner and Dewar was later confirmed in an experiment where pyridine was reduced to [piperidine](https://bliptext.com/articles/piperidine) with [sodium](https://bliptext.com/articles/sodium) in [ethanol](https://bliptext.com/articles/ethanol).\nIn 1876, [William Ramsay](https://bliptext.com/articles/william-ramsay) combined [acetylene](https://bliptext.com/articles/acetylene) and [hydrogen cyanide](https://bliptext.com/articles/hydrogen-cyanide) into pyridine in a [red-hot](https://bliptext.com/articles/red-heat) iron-tube furnace.\nThis was the first synthesis of a heteroaromatic compound.\nThe first major synthesis of pyridine derivatives was described in 1881 by [Arthur Rudolf Hantzsch](https://bliptext.com/articles/arthur-rudolf-hantzsch).\nThe [Hantzsch pyridine synthesis](https://bliptext.com/articles/hantzsch-pyridine-synthesis) typically uses a 2:1:1 mixture of a β-[keto acid](https://bliptext.com/articles/keto-acid) (often [acetoacetate](https://bliptext.com/articles/acetoacetic-acid)), an [aldehyde](https://bliptext.com/articles/aldehyde) (often form[aldehyde](https://bliptext.com/articles/aldehyde)), and [ammonia](https://bliptext.com/articles/ammonia) or its salt as the nitrogen donor.\nFirst, a double [hydrogenated](https://bliptext.com/articles/hydration-reaction) pyridine is obtained, which is then oxidized to the corresponding pyridine derivative.\n[Emil Knoevenagel](https://bliptext.com/articles/emil-knoevenagel) showed that asymmetrically substituted pyridine derivatives can be produced with this process.\nThe contemporary methods of pyridine production had a low yield, and the increasing demand for the new compound urged to search for more efficient routes.\nA breakthrough came in 1924 when the Russian chemist [Aleksei Chichibabin](https://bliptext.com/articles/aleksei-chichibabin) invented a [pyridine synthesis reaction](https://bliptext.com/articles/chichibabin-pyridine-synthesis), which was based on inexpensive reagents.\nThis method is still used for the industrial production of pyridine.\n# [Thomas Anderson | upload.wikimedia.org/wikipedia/commons/c/c0/ThomasAnderson%281819-1874%29.jpg]\n# [Hantzsch pyridine synthesis with acetoacetate, formaldehyde and ammonium acetate, and iron(III) chloride as the oxidizer. | upload.wikimedia.org/wikipedia/commons/5/5b/Hantzsch///pyridine///synthesis.svg]\n\n# Occurrence\nPyridine is not abundant in nature, except for the leaves and roots of belladonna ([Atropa belladonna](https://bliptext.com/articles/atropa-belladonna)) and in marshmallow ([Althaea officinalis](https://bliptext.com/articles/althaea-officinalis)).\nPyridine derivatives, however, are often part of biomolecules such as [alkaloids](https://bliptext.com/articles/alkaloid).\nIn daily life, trace amounts of pyridine are components of the [volatile organic compounds](https://bliptext.com/articles/volatile-organic-compound) that are produced in roasting and [canning](https://bliptext.com/articles/canning) processes, e.g. in fried chicken, [sukiyaki](https://bliptext.com/articles/sukiyaki), roasted coffee, potato chips, and fried [bacon](https://bliptext.com/articles/bacon).\nTraces of pyridine can be found in [Beaufort cheese](https://bliptext.com/articles/beaufort-cheese), [vaginal secretions](https://bliptext.com/articles/vaginal-lubrication), [black tea](https://bliptext.com/articles/black-tea), saliva of those suffering from [gingivitis](https://bliptext.com/articles/gingivitis), and [sunflower honey](https://bliptext.com/articles/monofloral-honey).\n\n# Production\nHistorically, pyridine was extracted from [coal tar](https://bliptext.com/articles/coal-tar) or obtained as a byproduct of coal [gasification](https://bliptext.com/articles/gasification).\nThe process is labor-consuming and inefficient: [coal tar](https://bliptext.com/articles/coal-tar) contains only about 0.1% pyridine, and therefore a multi-stage purification was required, which further reduced the output.\nNowadays, most pyridines are synthesized from ammonia, aldehydes, and nitriles, a few combinations of which are suited for pyridine itself.\nVarious [name reactions](https://bliptext.com/articles/name-reaction) are also known, but they are not practiced on scale.\nIn 1989, 26,000 tonnes of pyridine was produced worldwide.\nOther major derivatives are [2-](https://bliptext.com/articles/2-methylpyridine), [3-](https://bliptext.com/articles/3-methylpyridine), [4-methylpyridines](https://bliptext.com/articles/4-methylpyridine) and 5-ethyl-[2-](https://bliptext.com/articles/2-methylpyridine)methylpyridine.\nThe combined scale of these alkylpyridines matches that of pyridine itself.\nAmong the largest 25 production sites for pyridine, eleven are located in Europe (as of 1999).\nThe major producers of pyridine include [Evonik Industries](https://bliptext.com/articles/evonik-industries), Rütgers Chemicals, Jubilant Life Sciences, [Imperial Chemical Industries](https://bliptext.com/articles/imperial-chemical-industries), and Koei Chemical.\nPyridine production significantly increased in the early 2000s, with an annual production capacity of 30,000 tonnes in mainland China alone.\nThe US–Chinese joint venture Vertellus is currently the world leader in pyridine production.\n\n## Chichibabin synthesis\nThe [Chichibabin pyridine synthesis](https://bliptext.com/articles/chichibabin-pyridine-synthesis) was reported in 1924 and the basic approach underpins several industrial routes.\nIn its general form, the reaction involves the [condensation reaction](https://bliptext.com/articles/condensation-reaction) of [aldehydes](https://bliptext.com/articles/aldehydes), [ketones](https://bliptext.com/articles/ketones), [α,β-unsaturated carbonyl compounds](https://bliptext.com/articles/unsaturated-carbonyl-compound), or any combination of the above, in [ammonia](https://bliptext.com/articles/ammonia) or [ammonia](https://bliptext.com/articles/ammonia) derivatives.\nApplication of the Chichibabin pyridine synthesis suffer from low yields, often about 30%, however the precursors are inexpensive.\nIn particular, unsubstituted pyridine is produced from [formaldehyde](https://bliptext.com/articles/formaldehyde) and [acetaldehyde](https://bliptext.com/articles/acetaldehyde).\nFirst, [acrolein](https://bliptext.com/articles/acrolein) is formed in a [Knoevenagel condensation](https://bliptext.com/articles/knoevenagel-condensation) from the acetaldehyde and formaldehyde.\nThe acrolein then [condenses](https://bliptext.com/articles/condensation-reaction) with acetaldehyde and ammonia to give [dihydropyridine](https://bliptext.com/articles/dihydropyridine), which is oxidized to pyridine.\nThis process is carried out in a gas phase at 400–450 °C.\nTypical catalysts are modified forms of [alumina](https://bliptext.com/articles/alumina) and [silica](https://bliptext.com/articles/silica).\nThe reaction has been tailored to produce various [methylpyridines](https://bliptext.com/articles/methylpyridine).\n# [Formation of acrolein from acetaldehyde and formaldehyde | upload.wikimedia.org/wikipedia/commons/7/7a/AcroleinDarstellung.svg]\n# [Condensation of pyridine from acrolein and acetaldehyde | upload.wikimedia.org/wikipedia/commons/7/73/Pyridin///aus///Acrolein.svg]\n\n## Dealkylation and decarboxylation of substituted pyridines\nPyridine can be prepared by dealkylation of alkylated pyridines, which are obtained as byproducts in the syntheses of other pyridines.\nThe oxidative dealkylation is carried out either using air over [vanadium(V) oxide](https://bliptext.com/articles/vanadium-v-oxide) catalyst, by vapor-dealkylation on [nickel](https://bliptext.com/articles/nickel)-based catalyst, or hydrodealkylation with a [silver](https://bliptext.com/articles/silver)- or [platinum](https://bliptext.com/articles/platinum)-based catalyst.\nYields of pyridine up to be 93% can be achieved with the nickel-based catalyst.\nPyridine can also be produced by the [decarboxylation](https://bliptext.com/articles/decarboxylation) of [nicotinic acid](https://bliptext.com/articles/nicotinic-acid) with [copper chromite](https://bliptext.com/articles/copper-chromite).\n\n## Bönnemann cyclization\nThe [trimerization](https://bliptext.com/articles/trimerization) of a part of a [nitrile](https://bliptext.com/articles/nitrile) molecule and two parts of [acetylene](https://bliptext.com/articles/acetylene) into pyridine is called **Bönnemann cyclization**.\nThis modification of the [Reppe synthesis](https://bliptext.com/articles/walter-reppe) can be activated either by heat or by [light](https://bliptext.com/articles/photochemistry).\nWhile the [thermal activation](https://bliptext.com/articles/thermal-activation) requires high pressures and temperatures, the photoinduced [cycloaddition](https://bliptext.com/articles/cycloaddition) proceeds at ambient conditions with CoCp2(cod) (Cp = cyclopentadienyl, cod = [1,5-cyclooctadiene](https://bliptext.com/articles/1-5-cyclooctadiene)) as a catalyst, and can be performed even in water.\nA series of pyridine derivatives can be produced in this way.\nWhen using [acetonitrile](https://bliptext.com/articles/acetonitrile) as the nitrile, 2-methylpyridine is obtained, which can be dealkylated to pyridine.\n# [Bönnemann cyclization | upload.wikimedia.org/wikipedia/commons/8/87/B%C3%B6nnemannEn.png]\n\n## Other methods\nThe [Kröhnke pyridine synthesis](https://bliptext.com/articles/kr-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.\nThe reaction of pyridine with bromomethyl ketones gives the related [pyridinium](https://bliptext.com/articles/pyridinium) salt, wherein the [methylene group](https://bliptext.com/articles/methylene-group) is highly acidic.\nThis species undergoes a [Michael-like addition](https://bliptext.com/articles/michael-addition) to [α,β-unsaturated carbonyls](https://bliptext.com/articles/unsaturated-carbonyl-compound) in the presence of [ammonium acetate](https://bliptext.com/articles/ammonium-acetate) to undergo ring closure and formation of the targeted substituted pyridine as well as pyridinium bromide.\nThe Ciamician–Dennstedt rearrangement entails the ring-expansion of [pyrrole](https://bliptext.com/articles/pyrrole) with [dichlorocarbene](https://bliptext.com/articles/dichlorocarbene) to [3-chloropyridine](https://bliptext.com/articles/3-chloropyridine).\nIn the Gattermann–Skita synthesis, a [malonate ester](https://bliptext.com/articles/malonic-ester-synthesis) salt reacts with dichloro[methylamine](https://bliptext.com/articles/methylamine).\nOther methods include the [Boger pyridine synthesis](https://bliptext.com/articles/boger-pyridine-synthesis) and [Diels–Alder reaction](https://bliptext.com/articles/diels-alder-reaction) of an [alkene](https://bliptext.com/articles/alkene) and an [oxazole](https://bliptext.com/articles/oxazole).\n# [Figure 1 | upload.wikimedia.org/wikipedia/commons/7/79/Kroehnke///Pyridine///Figure///1.png]\n# [Ciamician–Dennstedt Rearrangement | upload.wikimedia.org/wikipedia/commons/5/56/Ciamician-Dennstedt///Rearrangement.png]\n# [Gattermann–Skita synthesis | upload.wikimedia.org/wikipedia/commons/e/e1/Gattermann-Skita///Syntesis.png]\n\n## Biosynthesis\nSeveral pyridine derivatives play important roles in biological systems.\nWhile its biosynthesis is not fully understood, [nicotinic acid](https://bliptext.com/articles/nicotinic-acid) (vitamin B3) occurs in some [bacteria](https://bliptext.com/articles/bacteria), [fungi](https://bliptext.com/articles/fungi), and [mammals](https://bliptext.com/articles/mammal).\nMammals synthesize nicotinic acid through oxidation of the [amino acid](https://bliptext.com/articles/amino-acid) [tryptophan](https://bliptext.com/articles/tryptophan), where an intermediate product, the [aniline](https://bliptext.com/articles/aniline) derivative [kynurenine](https://bliptext.com/articles/kynurenine), creates a pyridine derivative, [quinolinate](https://bliptext.com/articles/quinolinate) and then nicotinic acid.\nOn the contrary, the bacteria [Mycobacterium tuberculosis](https://bliptext.com/articles/mycobacterium-tuberculosis) and [Escherichia coli](https://bliptext.com/articles/escherichia-coli) produce nicotinic acid by condensation of [glyceraldehyde 3-phosphate](https://bliptext.com/articles/glyceraldehyde-3-phosphate) and [aspartic acid](https://bliptext.com/articles/aspartic-acid).\n\n# Reactions\nBecause of the [electronegative](https://bliptext.com/articles/electronegativity) [nitrogen](https://bliptext.com/articles/nitrogen) in the pyridine ring, pyridine enters less readily into [electrophilic aromatic substitution](https://bliptext.com/articles/electrophilic-aromatic-substitution) reactions than benzene derivatives.\nInstead, in terms of its reactivity, pyridine resembles [nitrobenzene](https://bliptext.com/articles/nitrobenzene).\nCorrespondingly pyridine is more prone to [nucleophilic substitution](https://bliptext.com/articles/nucleophilic-substitution), as evidenced by the ease of [metalation](https://bliptext.com/articles/metalation) by strong [organometallic](https://bliptext.com/articles/organometallic-chemistry) bases.\nThe reactivity of pyridine can be distinguished for three chemical groups.\nWith [electrophiles](https://bliptext.com/articles/electrophile), [electrophilic substitution](https://bliptext.com/articles/electrophilic-substitution) takes place where pyridine expresses aromatic properties.\nWith [nucleophiles](https://bliptext.com/articles/nucleophile), pyridine reacts at positions 2 and 4 and thus behaves similar to [imines](https://bliptext.com/articles/imine) and [carbonyls](https://bliptext.com/articles/carbonyl).\nThe reaction with many [Lewis acids](https://bliptext.com/articles/lewis-acid) results in the addition to the nitrogen atom of pyridine, which is similar to the reactivity of tertiary amines.\nThe ability of pyridine and its derivatives to oxidize, forming [amine oxides](https://bliptext.com/articles/amine-oxide) (N-oxides), is also a feature of tertiary amines.\nThe nitrogen center of pyridine features a basic [lone pair](https://bliptext.com/articles/lone-pair) of [electrons](https://bliptext.com/articles/electron).\nThis lone pair does not overlap with the aromatic π-system ring, consequently pyridine is [basic](https://bliptext.com/articles/base-chemistry), having chemical properties similar to those of [tertiary amines](https://bliptext.com/articles/tertiary-amine).\n[Protonation](https://bliptext.com/articles/protonation) gives [pyridinium](https://bliptext.com/articles/pyridinium), C5H5NH+.The pKa of the [conjugate acid](https://bliptext.com/articles/conjugate-acid) (the [pyridinium](https://bliptext.com/articles/pyridinium) cation) is 5.25.\nThe structures of pyridine and pyridinium are almost identical.\nThe pyridinium cation is [isoelectronic](https://bliptext.com/articles/isoelectronic) with benzene.\nPyridinium p-[toluenesulfonate](https://bliptext.com/articles/toluenesulfonic-acid) (PPTS) is an illustrative pyridinium salt; it is produced by treating pyridine with p-toluenesulfonic acid.\nIn addition to [protonation](https://bliptext.com/articles/protonation), pyridine undergoes N-centred [alkylation](https://bliptext.com/articles/alkylation), [acylation](https://bliptext.com/articles/acylation), and N-oxidation.\nPyridine and poly(4-vinyl) pyridine have been shown to form conducting [molecular wires](https://bliptext.com/articles/molecular-wire) with remarkable polyenimine structure on [UV irradiation](https://bliptext.com/articles/uv-irradiation), a process which accounts for at least some of the visible light absorption by aged pyridine samples.\nThese wires have been theoretically predicted to be both highly efficient electron donors and acceptors, and yet are resistant to air oxidation.\n\n## Electrophilic substitutions\nOwing to the decreased electron density in the aromatic system, [electrophilic substitutions](https://bliptext.com/articles/electrophilic-substitution) are suppressed in pyridine and its derivatives.\n[Friedel–Crafts alkylation or acylation](https://bliptext.com/articles/friedel-crafts-reaction), usually fail for pyridine because they lead only to the addition at the nitrogen atom.\nSubstitutions 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.\nDirect [nitration](https://bliptext.com/articles/nitration) of pyridine is sluggish.\nPyridine derivatives wherein the nitrogen atom is screened sterically and/or electronically can be obtained by nitration with [nitronium tetrafluoroborate](https://bliptext.com/articles/nitronium-tetrafluoroborate) (NO2BF4).\nIn this way, 3-nitropyridine can be obtained via the synthesis of 2,6-dibromopyridine followed by nitration and debromination.\n[Sulfonation](https://bliptext.com/articles/sulfonation) of pyridine is even more difficult than nitration.\nHowever, pyridine-3-sulfonic acid can be obtained.\nReaction with the SO3 group also facilitates addition of sulfur to the nitrogen atom, especially in the presence of a [mercury(II) sulfate](https://bliptext.com/articles/mercury-ii-sulfate) catalyst.\nIn contrast to the sluggish nitrations and sulfonations, the [bromination](https://bliptext.com/articles/bromination) and [chlorination](https://bliptext.com/articles/chlorination-reaction) of pyridine proceed well.\n# [substitution in the 2-position | upload.wikimedia.org/wikipedia/commons/5/50/Pyridine-EAS-2-position-2D-skeletal.png]\n# [substitution in the 3-position | upload.wikimedia.org/wikipedia/commons/e/e5/Pyridine-EAS-3-position-2D-skeletal.png]\n# [Substitution in 4-position | upload.wikimedia.org/wikipedia/commons/0/0a/Pyridine-EAS-4-position-2D-skeletal.png]\n# [500px | upload.wikimedia.org/wikipedia/commons/0/09/simple///chlorination.png]\n\n### Pyridine N-oxide\nOxidation of pyridine occurs at nitrogen to give pyridine N-oxide.\nThe oxidation can be achieved with [peracids](https://bliptext.com/articles/peracid):\nSome electrophilic substitutions on the pyridine are usefully effected using pyridine N-oxide followed by deoxygenation.\nAddition of oxygen suppresses further reactions at nitrogen atom and promotes substitution at the 2- and 4-carbons.\nThe oxygen atom can then be removed, e.g., using zinc dust.\n# [Structure of pyridine N-oxide | upload.wikimedia.org/wikipedia/commons/6/65/Pyridine///N-oxide.png]\n\n## Nucleophilic substitutions\nIn contrast to benzene ring, pyridine efficiently supports several nucleophilic substitutions.\nThe reason for this is relatively lower electron density of the carbon atoms of the ring.\nThese reactions include substitutions with elimination of a [hydride](https://bliptext.com/articles/hydride) ion and elimination-additions with formation of an intermediate [aryne](https://bliptext.com/articles/aryne) configuration, and usually proceed at the 2- or 4-position.\nMany 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.\nSo fluorine is the best leaving group for the substitution with [organolithium compounds](https://bliptext.com/articles/organolithium-compound).\nThe nucleophilic attack compounds may be [alkoxides](https://bliptext.com/articles/alkoxide), thiolates, [amines](https://bliptext.com/articles/amine), and ammonia (at elevated pressures).\nIn general, the hydride ion is a poor leaving group and occurs only in a few heterocyclic reactions.\nThey include the [Chichibabin reaction](https://bliptext.com/articles/chichibabin-reaction), which yields pyridine derivatives [aminated](https://bliptext.com/articles/amination) at the 2-position.\nHere, [sodium amide](https://bliptext.com/articles/sodium-amide) is used as the nucleophile yielding 2-aminopyridine.\nThe hydride ion released in this reaction combines with a proton of an available amino group, forming a hydrogen molecule.\nAnalogous to benzene, nucleophilic substitutions to pyridine can result in the formation of [pyridyne](https://bliptext.com/articles/pyridyne) intermediates as hetero[aryne](https://bliptext.com/articles/aryne).\nFor this purpose, pyridine derivatives can be eliminated with good leaving groups using strong bases such as sodium and [potassium tert-butoxide](https://bliptext.com/articles/potassium-tert-butoxide).\nThe subsequent addition of a nucleophile to the [triple bond](https://bliptext.com/articles/triple-bond) has low selectivity, and the result is a mixture of the two possible adducts.\n# [Nucleophilic substitution in 2-position | upload.wikimedia.org/wikipedia/commons/d/d8/Pyridine-NA-2-position.svg]\n# [Nucleophilic substitution in 3-position | upload.wikimedia.org/wikipedia/commons/6/6e/Pyridine-NA-3-position.svg]\n# [Nucleophilic substitution in 4-position | upload.wikimedia.org/wikipedia/commons/a/a2/Pyridine-NA-4-position.svg]\n\n## Radical reactions\nPyridine supports a series of radical reactions, which is used in its [dimerization](https://bliptext.com/articles/dimer-chemistry) to bipyridines.\nRadical dimerization of pyridine with elemental [sodium](https://bliptext.com/articles/sodium) or [Raney nickel](https://bliptext.com/articles/raney-nickel) selectively yields [4,4'-bipyridine](https://bliptext.com/articles/4-4-bipyridine), or [2,2'-bipyridine](https://bliptext.com/articles/2-2-bipyridine), which are important precursor reagents in the chemical industry.\nOne of the [name reactions](https://bliptext.com/articles/name-reactions) involving free radicals is the [Minisci reaction](https://bliptext.com/articles/minisci-reaction).\nIt can produce 2-tert-butylpyridine upon reacting pyridine with [pivalic acid](https://bliptext.com/articles/pivalic-acid), [silver nitrate](https://bliptext.com/articles/silver-nitrate) and [ammonium](https://bliptext.com/articles/ammonium) in [sulfuric acid](https://bliptext.com/articles/sulfuric-acid) with a yield of 97%.\n\n## Reactions on the nitrogen atom\n[Lewis acids](https://bliptext.com/articles/lewis-acid) easily add to the nitrogen atom of pyridine, forming pyridinium salts.\nThe reaction with [alkyl halides](https://bliptext.com/articles/alkyl-halide) leads to [alkylation](https://bliptext.com/articles/alkylation) of the nitrogen atom.\nThis creates a positive charge in the ring that increases the reactivity of pyridine to both oxidation and reduction.\nThe [Zincke reaction](https://bliptext.com/articles/[zinc](https://bliptext.com/articles/zinc)ke-reaction) is used for the selective introduction of radicals in pyridinium compounds (it has no relation to the chemical element [zinc](https://bliptext.com/articles/zinc)).\n# [Additions of various Lewis acids to pyridine | upload.wikimedia.org/wikipedia/commons/3/37/Pyridine-complex.svg]\n\n## Hydrogenation and reduction\n[Piperidine](https://bliptext.com/articles/piperidine) is produced by [hydrogenation](https://bliptext.com/articles/hydrogenation) of pyridine with a [nickel](https://bliptext.com/articles/nickel)-, [cobalt](https://bliptext.com/articles/cobalt)-, or [ruthenium](https://bliptext.com/articles/ruthenium)-based catalyst at elevated temperatures.\nThe hydrogenation of pyridine to piperidine releases 193.8 kJ/mol, which is slightly less than the energy of the hydrogenation of [benzene](https://bliptext.com/articles/benzene) (205.3 kJ/mol).\nPartially hydrogenated derivatives are obtained under milder conditions.\nFor example, reduction with [lithium aluminium hydride](https://bliptext.com/articles/lithium-aluminium-hydride) yields a mixture of 1,4-dihydropyridine, 1,2-dihydropyridine, and 2,5-dihydropyridine.\nSelective synthesis of 1,4-dihydropyridine is achieved in the presence of organometallic complexes of [magnesium](https://bliptext.com/articles/magnesium) and [zinc](https://bliptext.com/articles/zinc), and (Δ3,4)-tetrahydropyridine is obtained by electrochemical reduction of pyridine.\n[Birch reduction](https://bliptext.com/articles/birch-reduction) converts pyridine to dihydropyridines.\n# [Reduction of pyridine to piperidine with Raney nickel | upload.wikimedia.org/wikipedia/commons/2/20/Pyridine///hydrogenation.png]\n\n## Lewis basicity and coordination compounds\nPyridine is a [Lewis base](https://bliptext.com/articles/lewis-base), donating its pair of electrons to a Lewis acid.\nIts Lewis base properties are discussed in the [ECW model](https://bliptext.com/articles/ecw-model).\nIts relative donor strength toward a series of acids, versus other Lewis bases, can be illustrated by [C-B plots](https://bliptext.com/articles/ecw-model).\nOne example is the [sulfur trioxide pyridine complex](https://bliptext.com/articles/sulfur-trioxide-pyridine-complex) (melting point 175 °C), which is a [sulfation](https://bliptext.com/articles/sulfation) agent used to convert alcohols to [sulfate esters](https://bliptext.com/articles/sulfate-ester).\nPyridine-[borane](https://bliptext.com/articles/borane) (C5H5NBH3, melting point 10–11 °C) is a mild reducing agent.\n[Transition metal pyridine complexes](https://bliptext.com/articles/transition-metal-pyridine-complexes) are numerous.\nTypical octahedral complexes have the stoichiometry MCl2(py)4 and MCl3(py)3.\nOctahedral homoleptic complexes of the type M(py)6(+) are rare or tend to dissociate pyridine.\nNumerous square planar complexes are known, such as [Crabtree's catalyst](https://bliptext.com/articles/crabtree-s-catalyst).\nThe pyridine ligand replaced during the reaction is restored after its completion.\nThe η6 coordination mode, as occurs in η6 benzene complexes, is observed only in [sterically encumbered](https://bliptext.com/articles/steric-effects) derivatives that block the nitrogen center.\n# [structure of the Crabtree's catalyst | upload.wikimedia.org/wikipedia/commons/6/60/Crabtree.svg]\n\n# Applications\n\n## Pesticides and pharmaceuticals\nThe main use of pyridine is as a precursor to the herbicides [paraquat](https://bliptext.com/articles/paraquat) and [diquat](https://bliptext.com/articles/diquat).\nThe first synthesis step of insecticide [chlorpyrifos](https://bliptext.com/articles/chlorpyrifos) consists of the chlorination of pyridine.\nPyridine is also the starting compound for the preparation of [pyrithione](https://bliptext.com/articles/pyrithione)-based [fungicides](https://bliptext.com/articles/fungicide).\n[Cetylpyridinium](https://bliptext.com/articles/cetylpyridinium-chloride) and laurylpyridinium, which can be produced from pyridine with a [Zincke reaction](https://bliptext.com/articles/zincke-reaction), are used as [antiseptic](https://bliptext.com/articles/antiseptic) in oral and dental care products.\nPyridine is easily attacked by alkylating agents to give N-alkylpyridinium salts.\nOne example is [cetylpyridinium chloride](https://bliptext.com/articles/cetylpyridinium-chloride).\nIt is also used in the textile industry to improve network capacity of cotton.\n# [Synthesis of paraquat | upload.wikimedia.org/wikipedia/commons/c/ca/Synthesis///of///paraquat.png]\n\n## Laboratory use\nPyridine is used as a polar, basic, low-reactive solvent, for example in [Knoevenagel condensations](https://bliptext.com/articles/knoevenagel-condensation).\nIt is especially suitable for the dehalogenation, where it acts as the base for the [elimination reaction](https://bliptext.com/articles/elimination-reaction).\nIn [esterifications](https://bliptext.com/articles/esterification) and acylations, pyridine activates the carboxylic [acid chlorides](https://bliptext.com/articles/acid-chloride) and anhydrides.\nEven more active in these reactions are the derivatives [4-dimethylaminopyridine](https://bliptext.com/articles/4-dimethylaminopyridine) (DMAP) and 4-(1-pyrrolidinyl) pyridine.\nPyridine is also used as a base in some [condensation reactions](https://bliptext.com/articles/condensation-reaction).\n# [Elimination reaction with pyridine to form pyridinium | upload.wikimedia.org/wikipedia/commons/c/c0/Chlorocyclopentane///elimination.svg]\n\n## Reagents\nAs a base, pyridine can be used as the [Karl Fischer reagent](https://bliptext.com/articles/karl-fischer-titration), but it is usually replaced by alternatives with a more pleasant odor, such as [imidazole](https://bliptext.com/articles/imidazole).\n[Pyridinium chlorochromate](https://bliptext.com/articles/pyridinium-chlorochromate), [pyridinium dichromate](https://bliptext.com/articles/cornforth-reagent), and the [Collins reagent](https://bliptext.com/articles/collins-reagent) (the complex of [chromium(VI) oxide](https://bliptext.com/articles/chromium-trioxide)) are used for the oxidation of alcohols.\n# [Oxidation of an alcohol to aldehyde with the Collins reagent | upload.wikimedia.org/wikipedia/commons/3/38/Alcohol///oxidation///with///Collins///reagent.svg]\n\n# Hazards\nPyridine is a toxic, flammable liquid with a strong and unpleasant fishy odour.\nIts [odour threshold](https://bliptext.com/articles/odour-threshold) of 0.04 to 20 ppm is close to its [threshold limit](https://bliptext.com/articles/threshold-limit-value) of 5 ppm for adverse effects, thus most (but not all) adults will be able to tell when it is present at harmful levels.\nPyridine easily dissolves in water and harms both animals and plants in aquatic systems.\n\n## Fire\nPyridine has a [flash point](https://bliptext.com/articles/flash-point) of 20 °C and is therefore highly flammable.\nCombustion produces toxic fumes which can include [bipyridines](https://bliptext.com/articles/bipyridine), [nitrogen oxides](https://bliptext.com/articles/nitrogen-oxide), and [carbon monoxide](https://bliptext.com/articles/carbon-monoxide).\n\n## Short-term exposure\nPyridine can cause chemical burns on contact with the skin and its fumes may be irritating to the eyes or upon inhalation.\nPyridine depresses the [nervous system](https://bliptext.com/articles/nervous-system) giving symptoms similar to intoxication with vapor concentrations of above 3600 [ppm](https://bliptext.com/articles/parts-per-million) posing a greater health risk.\nThe effects may have a delayed onset of several hours and include dizziness, headache, [lack of coordination](https://bliptext.com/articles/ataxia), nausea, [salivation](https://bliptext.com/articles/saliva), and loss of appetite.\nThey may progress into abdominal pain, [pulmonary congestion](https://bliptext.com/articles/pulmonary-congestion) and unconsciousness.\nThe lowest known [lethal dose](https://bliptext.com/articles/lethal-dose) (LDLo) for the ingestion of pyridine in humans is 500 mg/kg.\n\n## Long-term exposure\nProlonged exposure to pyridine may result in liver, heart and kidney damage.\nEvaluations as a possible [carcinogenic](https://bliptext.com/articles/carcinogenic) agent showed that there is inadequate evidence in humans for the [carcinogenic](https://bliptext.com/articles/carcinogenic)ity of pyridine, although there is sufficient evidence in experimental animals.\nTherefore, [IARC](https://bliptext.com/articles/international-agency-for-research-on-cancer) considers pyridine as possibly carcinogenic to humans (Group 2B).\n\n# Occurrence\nTrace amounts of up to 16 μg/m3 have been detected in tobacco smoke.\nMinor amounts of pyridine are released into environment from some industrial processes such as steel manufacture, processing of [oil shale](https://bliptext.com/articles/oil-shale), [coal gasification](https://bliptext.com/articles/coal-gasification), [coking](https://bliptext.com/articles/coking) plants and [incinerators](https://bliptext.com/articles/incineration).\nThe atmosphere at oil shale processing plants can contain pyridine concentrations of up to 13 μg/m3, and 53 μg/m3 levels were measured in the [groundwater](https://bliptext.com/articles/groundwater) in the vicinity of a coal gasification plant.\nAccording to a study by the US [National Institute for Occupational Safety and Health](https://bliptext.com/articles/national-institute-for-occupational-safety-and-health), about 43,000 Americans work in contact with pyridine.\n\n## In foods\nPyridine has historically been added to foods to give them a bitter flavour, although this practise is now banned in the U.S. It may still be added to [ethanol](https://bliptext.com/articles/ethanol) to make it unsuitable for drinking.\n\n# Metabolism\nExposure to pyridine would normally lead to its inhalation and absorption in the lungs and gastrointestinal tract, where it either remains unchanged or is [metabolized](https://bliptext.com/articles/metabolism).\nThe 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](https://bliptext.com/articles/monooxygenase).\nIn humans, pyridine is metabolized only into N-methylpyridiniumhydroxide.\n# [Metabolism of pyridine | upload.wikimedia.org/wikipedia/commons/7/7f/Pyridin-Metabolisierung.png]\n\n# Environmental fate\nPyridine is readily degraded by bacteria to ammonia and carbon dioxide.\nThe unsubstituted pyridine ring degrades more rapidly than [picoline](https://bliptext.com/articles/picoline), [lutidine](https://bliptext.com/articles/lutidine), [chloropyridine](https://bliptext.com/articles/chloropyridine), or [aminopyridines](https://bliptext.com/articles/aminopyridine), and a number of pyridine degraders have been shown to overproduce [riboflavin](https://bliptext.com/articles/riboflavin) in the presence of pyridine.\nIonizable 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](https://bliptext.com/articles/soil-organic-matter), [cation exchange](https://bliptext.com/articles/cation-exchange), and surface complexation.\nSuch [adsorption](https://bliptext.com/articles/adsorption) to surfaces reduces bioavailability of pyridines for microbial degraders and other organisms, thus slowing degradation rates and reducing [ecotoxicity](https://bliptext.com/articles/ecotoxicity).\n\n# Nomenclature\nThe systematic name of pyridine, within the [Hantzsch–Widman nomenclature](https://bliptext.com/articles/hantzsch-widman-nomenclature) recommended by the [IUPAC](https://bliptext.com/articles/iupac), is .\nHowever, systematic names for simple compounds are used very rarely; instead, heterocyclic nomenclature follows historically established common names.\nIUPAC discourages the use of in favor of pyridine.\nThe numbering of the ring atoms in pyridine starts at the nitrogen (see infobox).\nAn allocation of positions by letter of the [Greek alphabet](https://bliptext.com/articles/greek-alphabet) (α-γ) and the [substitution pattern](https://bliptext.com/articles/arene-substitution-patterns) nomenclature common for homoaromatic systems (ortho, meta, para) are used sometimes.\nHere α (ortho), β (meta), and γ (para) refer to the 2, 3, and 4 position, respectively.\nThe systematic name for the pyridine derivatives is pyridinyl, wherein the position of the substituted atom is preceded by a number.\nHowever, the historical name pyridyl is encouraged by the IUPAC and used instead of the systematic name.\nThe [cationic](https://bliptext.com/articles/cation) derivative formed by the addition of an [electrophile](https://bliptext.com/articles/electrophile) to the nitrogen atom is called [pyridinium](https://bliptext.com/articles/pyridinium).","revisionCount":0},"hasMore":false,"nextCursor":null}