Pyridine

Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one methine group (=CH−) replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-soluble liquid with a distinctive, unpleasant fish-like smell. Pyridine is colorless, but older or impure samples can appear yellow. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Historically, pyridine was produced from coal tar. Today it is synthesized on the scale of about 20,000 tonnes per year worldwide.4-bromopyridine2,2′-bipyridinepyridine-2,6-dicarboxylic acid (dipicolinic acid)General form of the pyridinium cation Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one methine group (=CH−) replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-soluble liquid with a distinctive, unpleasant fish-like smell. Pyridine is colorless, but older or impure samples can appear yellow. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Historically, pyridine was produced from coal tar. Today it is synthesized on the scale of about 20,000 tonnes per year worldwide. The molecular electric dipole moment is 2.2 debyes. Pyridine is diamagnetic and has a diamagnetic susceptibility of −48.7 × 10−6 cm3·mol−1. The standard enthalpy of formation is 100.2 kJ·mol−1 in the liquid phase and 140.4 kJ·mol−1 in the gas phase. At 25 °C pyridine has a viscosity of 0.88 mPa/s and thermal conductivity of 0.166 W·m−1·K−1. The enthalpy of vaporization is 35.09 kJ·mol−1 at the boiling point and normal pressure. The enthalpy of fusion is 8.28 kJ·mol−1 at the melting point. The critical parameters of pyridine are pressure 6.70 MPa, temperature 620 K and volume 229 cm3·mol−1. In the temperature range 340–426 °C its vapor pressure p can be described with the Antoine equation where T is temperature, A = 4.16272, B = 1371.358 K and C = −58.496 K. Akin to benzene, pyridine ring forms a C5N hexagon. Electron localization in pyridine is reflected in the shorter C–N ring bond (137 pm for the C–N bond in pyridine vs. 139 pm for C–C bond in benzene), whereas the carbon–carbon bonds in the pyridine ring have the same 139 pm length as in benzene. These bond lengths lie between the values for the single and double bonds and are typical of aromatic compounds. Pyridine crystallizes in an orthorhombic crystal system with space group Pna21 and lattice parameters a = 1752 pm, b = 897 pm, c = 1135 pm, and 16 formula units per unit cell (measured at 153 K). For comparison, crystalline benzene is also orthorhombic, with space group Pbca, a = 729.2 pm, b = 947.1 pm, c = 674.2 pm (at 78 K), but the number of molecules per cell is only 4. This difference is partly related to the lower symmetry of the individual pyridine molecule (C2v vs D6h for benzene). A trihydrate (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). The optical absorption spectrum of pyridine in hexane contains three bands at the wavelengths of 195 nm (π → π* transition, molar absorptivity ε = 7500 L·mol−1·cm−1), 251 nm (π → π* transition, ε = 2000 L·mol−1·cm−1) and 270 nm (n → π* transition, ε = 450 L·mol−1·cm−1). The 1H nuclear magnetic resonance (NMR) spectrum of pyridine contains three signals with the integral intensity ratio of 2:1:2 that correspond to the three chemically different protons in the molecule. These signals originate from the α-protons (positions 2 and 6, chemical shift 8.5 ppm), γ-proton (position 4, 7.5 ppm) and β-protons (positions 3 and 5, 7.1 ppm). The carbon analog of pyridine, benzene, has only one proton signal at 7.27 ppm. The larger chemical shifts of the α- and γ-protons in comparison to benzene result from the lower electron density in the α- and γ-positions, which can be derived from the resonance structures. The situation is rather similar for the 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. All shifts are quoted for the solvent-free substances. Pyridine is conventionally detected by the gas chromatography and mass spectrometry methods. Because of the electronegative nitrogen in the pyridine ring, the molecule is relatively electron deficient. It, therefore, enters less readily into electrophilic aromatic substitution reactions than benzene derivatives. Correspondingly pyridine is more prone to nucleophilic substitution, as evidenced by the ease of metalation by strong organometallic bases. The reactivity of pyridine can be distinguished for three chemical groups. With electrophiles, electrophilic substitution takes place where pyridine expresses aromatic properties. With nucleophiles, pyridine reacts at positions 2 and 4 and thus behaves similar to imines and carbonyls. The reaction with many Lewis acids results in the addition to the nitrogen atom of pyridine, which is similar to the reactivity of tertiary amines. The ability of pyridine and its derivatives to oxidize, forming amine oxides (N-oxides), is also a feature of tertiary amines. The nitrogen center of pyridine features a basic lone pair of electrons. This lone pair does not overlap with the aromatic π-system ring, consequently pyridine is a basic, having chemical properties similar to those of tertiary amines. Protonation gives pyridinium, C5H5NH+.The pKa of the conjugate acid (the pyridinium cation) is 5.25. The structures of pyridine and pyridinium are almost identical. The pyridinium cation is isoelectronic with benzene. Pyridinium p-toluenesulfonate (PPTS) is an illustrative pyridinium salt; it is produced by treating pyridine with p-toluenesulfonic acid. In addition to protonation, pyridine undergoes N-centered alkylation, acylation, and N-oxidation.