Pyridine

Pyridine is a basic heterocyclic organic compound with the formula C5H5N. Its structure is similar to benzene, except one carbon-hydrogen group is replaced by a nitrogen atom. This liquid is highly flammable, weakly alkaline, and mixes with water, giving off a strong, unpleasant fishy odor. Fresh samples are colorless, but older or impure ones may turn yellow. The pyridine ring appears in many commercial products, such as agrochemicals, pharmaceuticals, and vitamins. Historically, it came from coal tar, and as of 2016, about 20,000 tons are synthesized worldwide each year.

The compound is diamagnetic. Its critical pressure is 5.63 MPa, critical temperature 619 K, and critical volume 248 cm³/mol. Between 340 and 426 K, its vapor pressure follows the Antoine equation with constants A = 4.16272, B = 1371.358 K, and C = −58.496 K.

The pyridine ring forms a C₅N hexagon, with slight variations in carbon-carbon and carbon-nitrogen bond lengths and angles. It crystallizes in an orthorhombic system, space group Pna2₁, with lattice parameters a = 1752 pm, b = 897 pm, c = 1135 pm, and 16 molecules per unit cell at 153 K. In comparison, benzene also crystallizes orthorhombically but with space group Pbca, smaller lattice dimensions, and only 4 molecules per cell. This difference partly comes from pyridine’s lower molecular symmetry (C₂v versus D₆h for benzene). A trihydrate form, pyridine·3H₂O, also crystallizes orthorhombically in space group Pbca, with a = 1244 pm, b = 1783 pm, c = 679 pm, and 8 formula units per cell at 223 K.

In hexane, pyridine’s optical absorption spectrum shows bands at 195, 251, and 270 nm, with extinction coefficients of 7500, 2000, and 450 L·mol⁻¹·cm⁻¹, assigned to π → π*, π → π*, and n → π* transitions. It has very low fluorescence. In ¹H NMR, signals appear for α-protons at δ 8.5, γ-protons at δ 7.5, and β-protons at δ 7, while benzene’s protons appear at δ 7.27. The larger chemical shifts for α and γ positions come from lower electron density there, as seen in resonance structures. Similarly, ¹³C NMR shows a triplet: α-carbon at δ 150 ppm, β-carbon at δ 124 ppm, and γ-carbon at δ 136 ppm, versus benzene’s single line at 129 ppm. Pyridine is typically detected by gas chromatography and mass spectrometry.

Pyridine has a conjugated system of six π electrons delocalized over the ring, making it planar and aromatic by Hückel’s rule. Unlike benzene, electron density is uneven due to nitrogen’s negative inductive effect, giving pyridine a dipole moment and lower resonance energy (117 kJ/mol versus 150 kJ/mol for benzene). All ring atoms are sp²-hybridized. Nitrogen uses its unhybridized p orbital in the π system, while its lone pair sits in an sp² orbital, projecting outward in the σ-bond plane. This lone pair does not participate in the aromatic system but readily forms bonds via electrophilic attack. However, nitrogen cannot show a positive mesomeric effect. Many analogues exist where nitrogen is replaced by other elements from the same column of the periodic table. Substituting one C–H with another nitrogen yields the diazines: pyridazine, pyrimidine, and pyrazine.

Impure pyridine was likely made by early alchemists heating animal bones, but the first documented reference is from Scottish scientist Thomas Anderson in 1849. He examined oil from high-temperature heating of animal bones and separated a colorless liquid with an unpleasant odor, isolating pure pyridine two years later. He noted it was highly soluble in water, readily soluble in hot concentrated acids and salts, and only slightly soluble in oils. Because it was flammable, Anderson named it pyridine from the Greek word for fire, πῦρ (pyr), adding the suffix -idine to indicate a nitrogen-containing cyclic compound, following conventions like toluidine. The structure was determined decades later: Wilhelm Körner in 1869 and James Dewar in 1871 proposed that pyridine is benzene with one C–H replaced by nitrogen, based on the analogy between quinoline and naphthalene. This was confirmed when pyridine was reduced to piperidine with sodium in ethanol. In 1876, William Ramsay synthesized pyridine by passing acetylene and hydrogen cyanide through a red-hot iron tube, the first such synthesis.