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Pyridine
Pyridine
General
Systematic name	Pyridine
Other names	Azabenzene Azine py
Molecular formula	C5H5N
SMILES	C1=NC=CC=C1
Molecular Weight	79.10 g/mol
Appearance	colourless liquid
CAS number	110-86-1
Properties
Density and phase	0.9819 g/cm³, liquid
Solubility in water	Miscible
Solubility in ethanol	Miscible
Melting point	−41.6 °C
Boiling point	115.2 °C
Viscosity	0.94 cP at 20 °C
Thermodynamic data
Standard enthalpy of formation Δf''H''°liquid	101.2 kJ/mol
Standard enthalpy of combustion Δc''H''°liquid	−2783.2 kJ/mol
Standard molar entropy ''S''°liquid	? J.K−1.mol−1
'Hazards'
EU classification	Flammable ('F') Harmful ('Xn')
NFPA 704
R-phrases	, , ,
S-phrases	, ,
Flash point	21 °C
Supplementary data page
Structure and properties	''n'', ''εr'', etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Regulatory data	Flash point, RTECS number, etc.
Related compounds
Related amines	Picoline Quinoline
Related compounds	Aniline Pyrimidine
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

'Pyridine' is a chemical compound with the formula C₅H₅N. It is a liquid with a distinctively putrid odour. Pyridine is a simple and fundamentally important heterocyclic aromatic organic compound that is structurally related to benzene, wherein one CH group in the six-membered ring is replaced by a nitrogen atom. The pyridine ring occurs in many important compounds, including the nicotinamides. Pyridine is sometimes used as a ligand in coordination chemistry. As a ligand, it is usually abbreviated 'py'.

Contents

Basicity

Pyridine as a solvent

Role in chemical synthesis

Preparation and occurrence

Organic reactions

Safety and Environmental

Related compounds

See also

References

External links

Basicity

Pyridine has a lone pair of electrons at the nitrogen atom. Because this lone pair is not delocalized into the aromatic pi-system, pyridine is basic with chemical properties similar to tertiary amines. The pKa of the conjugate acid is 5.30. Pyridine is protonated by reaction with acids and forms a positively charged aromatic polyatomic ion called pyridinium cation. The bond lengths and bond angles in pyridine and the pyridinium ion are almost identical^[1] because protonation does not affect the aromatic pi system.

Pyridine as a solvent

Pyridine is widely used as a versatile solvent, since it is polar but aprotic. It is fully miscible with a very broad range of solvents including hexane and water. Deuterated pyridine, called 'pyridine-''d''₅', is a common solvent for ¹H NMR spectroscopy.

Role in chemical synthesis

Pyridine is important in industrial organic chemistry, both as a fundamental building block and as a solvent and reagent in organic synthesis.^[2] It is used as a solvent in Knoevenagel condensations.
Pyridine-borane, C₅H₅NBH₃ (m.p. 10–11 °C) is a mild reducing agent with improved stability vs NaBH₄ in protic solvents and improved solubility in aprotic organic solvents. Pyridine-sulfur trioxide, C₅H₅NSO₃ (mp 175 °C) is a sulfonation agent used to convert alcohols to sulfonates, which in turn undergo C-O bond scission upon reduction with hydride agents.
It is also a starting material in the synthesis of compounds used as an intermediate in making insecticides, herbicides, pharmaceuticals, food flavorings, dyes, rubber chemicals, adhesives, paints, explosives and disinfectants. Pyridine is also used as a denaturant for antifreeze mixtures, for ethyl alcohol, and for fungicides, and as a dyeing aid for textiles.

Preparation and occurrence

Many methods exist in industry and in the laboratory (some of them named reactions) for the synthesis of pyridine and its derivatives ^[3]:

★ Pyridine is obtained industrially from crude coal tar or is synthesized from acetaldehyde, formaldehyde and ammonia.

★ The Hantzsch pyridine synthesis is a multicomponent reaction involving formaldehyde, a keto-ester and a nitrogen donor.

★ Other examples of the pyridine class can be formed by the reaction of 1,5-diketones with ammonium acetate in acetic acid followed by oxidation. This reaction is called the 'Kröhnke pyridine synthesis'.

★ Pyridium salts can be obtained in the Zincke reaction.

★ The 'Ciamician-Dennstedt Rearrangement' (1881) is the ring-expansion of pyrrole with dichlorocarbene to 3-chloropyridine and HCl ^[4]

★ In the 'Chichibabin pyridine synthesis' (Aleksei Chichibabin, 1906) the reactants are three equivalents of a linear aldehyde and ammonia

Organic reactions

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

★ Pyridine is a good nucleophile with a donor number of 33.1. It is easily attacked by alkylating agents to give N-alkylpyridinium salts.

★ Nucleophilic aromatic substitution takes place at C2 and C4 for example in the Chichibabin reaction of pyridine with sodium amide to 2-aminopyridine. In the 'Emmert reaction' (B. Emmert, 1939) pyridine is reacted with a ketone in presence of aluminium or magnesium and mercuric chloride to the carbinol also at C2 ^[5].

Safety and Environmental

Pyridine is toxic with LD₅₀ in rats (oral) of 891 mg kg^–1. It is volatile and can be absorbed through skin. 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''". ^[6] Currently its evaluations as a possible carcinogenic agent showed there is inadequate evidence in humans for the carcinogenicity of pyridine, albeit there is limited evidence of carcinogenic effects on animals. Effects of an acute pyridine intoxication include dizziness, headache, nausea and anorexia. Further symptoms include abdominal pain and pulmonary congestion. Though resistant to oxidation, pyridine is readily degraded by bacteria, releasing ammonium and carbon dioxide as terminal degradation products. ^[7]

Related compounds

Structurally or chemically related compounds are

★ DMAP is short for 4-dimethylaminopyridine

★ Bipyridine and viologen are simple polypyridine compounds consisting of two pyridine molecules joined by a single bond

★ Terpyridine, a molecule of three pyridine rings connected together by two single bonds.

★ Quinoline and Isoquinoline have pyridine and a benzene ring fused together.

★ Aniline is a benzene derivative with an attached NH₂ group and NOT a pyridine

★ Diazines are compounds with one more carbon replaced by nitrogen such as Pyrazine and Pyramidine

★ Triazines are compounds with two more carbons replaced by nitrogen and a tetrazine has four nitrogen atoms

★ 2,6-Lutidine is a trivial name for 2,6-dimethylpyridine.

★ 'Collidine' is the trivial name for 2,4,6-trimethylpyridine.

★ Pyridinium ''p''-toluenesulfonate (PPTS) is a salt formed by proton exchange between pyridine and ''p''-toluenesulfonic acid

★ '2-Chloropyridine' is a toxic environmentally significant component of the breakdown of the pesticide imidacloprid.

See also

★ Simple aromatic rings

★ 6-Membered aromatic rings with one carbon replaced by another group: borabenzene, silabenzene, germanabenzene, stannabenzene, phosphorine, pyrylium salt

References

1. T. M. Krygowski, H. Szatyowicz, and J. E. Zachara J. Org. Chem. '2005' 70(22) 8859 - 8865; .
2. Sherman, A. R. “Pyridine” in Encyclopedia of Reagents for Organic Synthesis (Ed: L. Paquette) 2004, J. Wiley & Sons, New York. .
3. Gilchrist, T.L. (1997). Heterocyclic Chemistry ISBN 0470204818
4. Ciamician-Dennstedt Rearrangement @ drugfuture.com Link
5. ''Histamine Antagonists. Basically Substituted Pyridine Derivatives'' Charles H. Tilford, Robert S. Shelton, and M. G. van Campen J. Am. Chem. Soc.; '1948'; 70(12) pp 4001 - 4009;
6. Pyridine Summary & Evaluation
7. Degradation of pyridines in the environment, Sims, G.K. and O'Loughlin, E.J., , , CRC Critical Reviews in Environmental Control,

External links

★ International Chemical Safety Card 0323

★ NIOSH Pocket Guide to Chemical Hazards

★ Computational Chemistry Wiki

★ Examples of Pyridines

★ Synthesis of pyridines (overview of recent methods)