a catalyst, and can be performed even in water. A series of pyridine derivatives can be produced in this way. When using acetonitrile as the nitrile, 2-methylpyridine is obtained, which can be dealkylated to pyridine. Other methods The Kröhnke 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. The reaction of pyridine with bromomethyl ketones gives the related pyridinium salt, wherein the methylene group is highly acidic. This species undergoes a Michael-like addition to α,β-unsaturated carbonyls in the presence of ammonium acetate to undergo ring closure and formation of the targeted substituted pyridine as well as pyridinium bromide. The Ciamician–Dennstedt rearrangement entails the ring-expansion of pyrrole with dichlorocarbene to 3-chloropyridine. In the Gattermann–Skita synthesis, a malonate ester salt reacts with dichloromethylamine. Other methods include the Boger pyridine synthesis and Diels–Alder reaction of an alkene and an oxazole. Biosynthesis Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals. Mammals synthesize nicotinic acid through oxidation of the amino acid tryptophan, where an intermediate product, the aniline derivative kynurenine, creates a pyridine derivative, quinolinate and then nicotinic acid. On the contrary, the bacteria Mycobacterium tuberculosis and Escherichia coli produce nicotinic acid by condensation of glyceraldehyde 3-phosphate and aspartic acid. Reactions Because of the electronegative nitrogen in the pyridine ring, pyridine enters less readily into electrophilic aromatic substitution reactions than benzene derivatives. Instead, in terms of its reactivity, pyridine resembles nitrobenzene. 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 basic, having chemical properties similar to those of tertiary