pyridine

Pyridine
IUPAC name	Pyridine
Other names	Azabenzene Azine py
Identifiers
CAS number	110-86-1 Y
PubChem	1049
EC number	203-809-9
SMILES	C1=NC=CC=C1
ChemSpider ID	1020
Properties
Molecular formula	C5H5N
Molar mass	79.1 g mol−1
Appearance	colourless liquid
Density	0.9819 g/cm3, liquid
Melting point	−41.6 °C
Boiling point	115.2 °C
Solubility in water	Miscible
Viscosity	0.94 cP at 20 °C
Hazards
MSDS	External MSDS
EU classification	Flammable (F) Harmful (Xn)
R-phrases	R20 R21 R22 R34 R36 R38
NFPA 704	3 2 0
Flash point	21 °C
Related compounds
Related amines	Picoline Quinoline
Related compounds	Aniline Pyrimidine Piperidine
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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

Preparation and occurrence

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

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

This process (Chichibabin pyridine synthesis) involves the intermediacy of acrolein. An estimated 26,000 tons were produced worldwide in 1989. Condensations of ammonia sources and related unsaturated carbon sources affords alkyl- and aryl-substituted pyridines, e.g. monomethyl compounds (picolines), dimethyl compounds (lutidines), and trimethyl derivatives (collidines).^[1] Pyridine occurs in numerous plants, although this can mostly recorded just by smell. Goris and Larsonneau^[2] did show definite evidence of its presence in belladonna leaves, while Kuhn and Schäfer^[3] of its presence in the roots of the same plant.

For specialized applications, the synthesis of the pyridine skeleton is well developed.^[4] The Hantzsch pyridine synthesis, for example, is a multicomponent reaction involving formaldehyde, a keto-ester and a nitrogen donor. The Kröhnke pyridine synthesis involves the condensation of 1,5-diketones with ammonium acetate in acetic acid followed by oxidation. The Ciamician-Dennstedt Rearrangement entails the ring-expansion of pyrrole with dichlorocarbene to 3-chloropyridine.^[5] In the Gattermann-Skita synthesis,^[6] a malonate ester salt reacts with dichloromethylamine.^[7]

Reactions

As a base

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

Pyridinium cation

The nitrogen atom on pyridine features a basic lone pair of electrons. Because this lone pair is not delocalized into the aromatic pi-system, pyridine is basic with chemical properties similar to tertiary amines. The pKa of the conjugate acid is 5.21. Pyridine is protonated by reaction with acids and forms a positively charged aromatic polyatomic ion called pyridinium. The bond lengths and bond angles in pyridine and the pyridinium ion are almost identical.^[8] In addition, the pyridinium cation is isoelectronic with benzene. Pyridinium p-toluenesulfonate (PPTS) is an illustrative pyridinium salt; it is formed by treating pyridine with p-toluenesulfonic acid.

As an N-nucleophile and ligand

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

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

Nucleophilic reactions at the ring

Nucleophilic aromatic substitution occurs at C-2 and at C-4. For example in the Chichibabin reaction, pyridine reacts with sodium amide to give 2-aminopyridine. In the Emmert reaction, named for Bruno Emmert), pyridine reacts with a ketone in presence of aluminium or magnesium and mercuric chloride to give the carbinol also at C2.^[9][10]

Applications

Role in chemical synthesis

Pyridine is an important solvent and reagent in organic synthesis.^[11] It is used as a solvent in Knoevenagel condensations. It is the precursor to myriad insecticides, herbicides, pharmaceuticals, food flavorings, dyes, rubber chemicals, adhesives, paints, explosives and disinfectants. Examples include paraquat^[1]

Pyridine as a solvent

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

Specialised uses

As a denaturant

Pyridine is also used as a denaturant for antifreeze mixtures, for ethyl alcohol, for fungicides, and as a dyeing aid for textiles.^[12]

Role in analytical chemistry

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

Safety and environmental aspects

Pyridine is harmful if inhaled, swallowed or absorbed through the skin.^[13] Effects of an acute pyridine intoxication include dizziness, headache, nausea and anorexia. Further symptoms include abdominal pain and pulmonary congestion.^[14] 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.^[14] 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".^[14] The LD₅₀ in rats (oral) is 891 mg kg⁻¹. Pyridine is flammable. Pyridine is readily degraded by bacteria to ammonia and carbon dioxide.^[15]

Other 6-membered aromatic rings

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

References

Wikimedia Commons has media related to: pyridine

External links

• International Chemical Safety Card 0323
• NIOSH Pocket Guide to Chemical Hazards
• Synthesis of pyridines (overview of recent methods)