Applications
Pyridine is an important raw material in of the chemical industry, with the 1989 production of 26,000 tonnes in world-wide. Among major 25 production sites for pyridine eleven are located in Europe (as of 1999). The major producers of pyridine include Evonik Industries, Rütgers Chemicals, Imperial Chemical Industries and Koei Chemical. The pyridine production has significantly increased in the early 2000s, with an annual production capacity of 30,000 tonnes in mainland China alone. The US-Chinese joint venture Vertellus is currently the world leader in pyridine production.
Pyridine is used as polar, basic, low-reactive solvent, for example in Knoevenagel condensations. It is especially suitable for the dehalogenation, where it acts as the base of the elimination reaction and bonds the resulting hydrogen halide to form a pyridinium salt. In esterifications and acylations pyridine activates the carboxylic acid halides or anhydrides. Even more active in these reactions are the pyridine derivatives 4-dimethylaminopyridine (DMAP) and 4-(1-pyrrolidinyl) pyridine. Pyridine is also used as a base in condensation reactions.
Pyridinium chlorochromate was developed by Elias James Corey and William Suggs in 1975 and is used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones. It is obtained by adding pyridine to a solution of chromic acid and concentrated hydrochloric acid:
- C5H5N + HCl + CrO3 →
The carcinogenicity of the side-product chromyl chloride (CrO2Cl2) urged to look for alternative routes, such as treating chromium(VI) oxide with pyridinium chloride:
- Cl− + CrO3 →
The Cornforth reagent (pyridinium dichromate, PDC), pyridinium chlorochromate (PCC), the Collins reagent (complex of chromium(VI) oxide with pyridine in dichloromethane) and the Sarret reagent (complex of chromium(VI) oxide with pyridine in pyridine) are similar chromium-based pyridine compounds, which are also used for oxidation, namely conversion of primary and secondary alcohols to ketones. The Collins and Sarret reagents are both difficult and dangerous to prepare, they are hygroscopic and can inflame during preparation. For this reason, the use of PCC and PDC was preferred. Those reagents were rather popular in the 1970s–1980s, but because of their toxicity and confirmed carcinogenic status, they are rarely used nowadays.
When a pyridine ligand is part of a metal complex, it can be easily replaced by a stronger chelating Lewis base. This property is exploited in catalysis of polymerization and hydrogenation reactions, using, for example, the Crabtree's catalyst. The pyridine ligand replaced during the reaction is restored after its completion.
In the pharmaceutical industry pyridine serves as a building block for making a variety of drugs, insecticides and herbicides. It was and is used in large quantities in the production of herbicides diquat and paraquat, which contain bipyridine fragments. The first synthesis step of insecticide chlorpyrifos consists of the chlorination of pyridine. Pyridine is also the starting compound for the preparation of pyrithione-based fungicides. Cetylpyridinium and laurylpyridinium, which can be produced from pyridine with a Zincke reaction, are used as antiseptic in oral and dental care products.
In addition to pyridines, piperidine derivatives are also important synthetic building blocks. A common synthesis of piperidine is the reduction of pyridine with a nickel, cobalt or ruthenium-based catalyst at elevated temperatures.
Pyridine is used as a solvent in the manufacture of dyes and rubber. It is also used in the textile industry to improve network capacity of cotton. Pyridine is added to ethanol to make it unsuitable for drinking. In low doses, pyridine is added to foods to give them a bitter flavor, and such usage is approved by the US Food and Drug Administration. The detection threshold for pyridine in solutions is about 1–3 mmole·L−1 (79–237 mg·L−1). As a base, pyridine can be used as the Karl Fischer reagent, but it is usually replaced by alternatives with a more pleasant odor, such as imidazole.
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. Pyridine 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 (melting point 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 (melting point 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.
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