A Scientific Report On Pyridine

The heterocyclic organic compound, pyridine [Diagram 1] also known as Azine or Azabenzene (Robinson, 1932) in the pharmaceutical industry has the empirical formula C5H5N. Pyr comes from the word "Pyro" (Joule J.A.b, 1978) in Latin, which means fire and "idine" (Joule J.A.c, 1978) is the suffix given to aromatic compounds. Anderson (Anderson, 1849) was the first to isolate pyridine [Diagram 1] from bone oil in the mid-nineteenth century. The ? and ?`(alpha and pseudo alpha) [Diagram 1] positions were implemented by Scholtz and Wiedermann (Scholtz, 1903).

Processing Coal Tar Before the synthetic age of manufacturing, pyridine was obtained from coal tar.

Industrial Process Processing coal tar [Diagram 2] commences by cooking coal at > 800°C. The non-condensed gases undergo "scrubbing" (Considine,a. 1974) which is the term used when it passes a NH4 separator containing H2SO4. After the crude tar is separated from NH4 it undergoes "topping" (Considine,c. 1974) (i.e. distillation) which further separates it into chemical oils and low boiling tar constituents. The chemical oils with a boiling point of approximately 250°C contain tar acids, tar bases and naphthalene. Dephenolized acid-free oil is separated from the tar acids using aqueous alkali (e.g. NaOH) normally with caustic solution (e.g. H2SO4). Extraction from the acid-free oils using aqueous solutions of mineral acids is normally used to retrieve tar bases at 130-196°C/atm. The lower boiling bases consist of lutidines and picolines whereas, higher boiling bases consist of quinolines and isoquinolines. Pyridine consists only 35% of the lower boiling bases and 10% (Considine,d. 1974) are picolines, but the majority remain the lutidines. Further separation occurs through steam distillation because alkyl pyridines and liquid pyridine form aezotropes [Table 1]. Sadly, this process is very expensive and pyridine consists of only 0.1-0.2% (Joule J.A.d, 1978) of crude tar. It is not viable to use this method of production to produce large quantities of pyridines. Hence, synthesis is the way ahead. Uses of Pyridine Pyridine is used for extraction of antibiotics and dehydrochlorination (Joule J.A.b, 1978) reactions. Herbicides (e.g. paraquat), fungicides (e.g. pyrithione) and insecticides (e.g. chloropyrifos) contain pyridine. Pyridines and alkyl pyridines can only be shipped in bulky containers like super-sacks or tank cars. The Department of Transportation (DOT) regulates the transportation of pyridine and the Drug Enforcement Agency (DEA) (Kroschwitz, 1981) set the standard for the quality [Table 2] of pyridine transported. The Production of Pyridine and Alkyl Pyridines through Synthesis The most common low cost synthesis reaction to produce pure pyridine is acetaldehyde and formaldehyde reacting with ammonia to produce pyridine, water and hydrogen gas. [Figure 1] Chemical Equations of various Synthesis Reactions 2 CH3CHO + HCHO + NH3 ? C5H5N + 3 H2O + H2 Figure 1 - acetaldehyde and formaldehyde reacting with ammonia to produce pyridine, water and hydrogen gas (Elves,b. 1993)

When acetaldehyde and formaldehyde settle for a long time, they form Acrolein. [Figure 2]

CH3CHO + HCHO ? CH2CHCHO + H2O Figure 2 - acetaldehyde and formaldehyde form Acrolein (Elves,c. 1993)

Then Acrolein and acetaldehyde react with ammonia to produce pyridine and by-products water and hydrogen gas. This is known as the Chichibabin reaction. [Figure 3, 7] CH2CHCHO + CH3CHO + NH3 ? C5H5N + 2 H2O + H2 Figure 3 - Acrolein and acetaldehyde react with ammonia to produce pyridine, water and hydrogen gas (Elves,d. 1993) At the same time 2-, 3- and 4-methylpyridine are formed as shown in [Figure 4, 5, 6]. Figure 5 - acetaldehyde react with ammonia to produce 4-methylpyridine, water and hydrogen gas (Elves,f. 1993) Figure 6 - acrolein react with ammonia to produce 3-methylpyridine and water (Elves,g. 1993) Figure 7 - acrolein and acetaldehyde react with ammonia to produce pyridine, water and hydrogen gas (Elves,h. 1993) Catalysts used for the synthesis reactions The ?-, ?- and ?-methyl pyridine instantaneously also undergo demethylation to produce pyridine. The catalysts for each reaction affect the percentage yield dramatically. Industrial Process On an industrial scale [Diagram 3], preheated acetaldehyde is fed along with 36% (Elves, k.1993) formaldehyde and ammonia. These reactants pass through a reactor (a) filled with a catalyst at approximately 450°C (Elves,l. 1993). A collector (b) separates the ammonia and hydrogen from the reacting mixture. Then an extractor (c) extracts the mixture with a solvent (e.g. benzene). Then the solvent is removed from the extract (d) and the alkyl pyridines and pure pyridine are isolated within continuous distillation columns (e). Air continuously regenerates the catalysts. Uses of Alkyl Pyridines ?- and ?-methyl pyridine is used in the agrochemical and pharmaceutical industry to make products like feed additives (e.g. nicotinic acid and nicotine carboxamide) and herbicides (e.g. picloram). ?-methyl pyridine is polymerized to produce 2-vinylpyridine which is mixed with butadiene and styrene to create an adhesive for textile tire cords (Elves,m. 1993). ? -methyl pyridine is used for the production of an antituberculosis agent which is isonicotinic hydrazide. The polymer of ? - methyl pyridine is 4-vinyl pyridine, which is used as an anion exchangers. Polyalkylpyridines like MEP (see below) is used as a starting material for nicotinic acid. Diagram 3 - Flow sheet of the production of pyridine and alkyl pyridine (Elves,k. 1993) Industrial Process for MEP Another famous alkyl pyridine is 5-ethyl-2-methylpyridine (MEP) . Paraldehyde (a) is produced from reacting sulphuric acid and acetaldehyde (b) at temperatures of 230°C with pressures of 20MPa (Schofield,a. 1967) , the presence of ammonia and acetic acid. [Diagram 5] The reaction is separated in 2 phases in a separator (c). The stripper (d) retrieves the ammonia. Paraldehyde and ammonia react at temperatures reaching 300°C with pressures of 12-13MPa (Schofield,b. 1967) and the presence of an ammonium salt (e.g. ammonium phosphate).Further on, other reactions as shown in [Figure 4, 5] take place. The ?- and ?-methyl pyridines and MEP are isolated and recovered by distillation (f). Diagram 5 - Flow sheet of the production of MEP, 2- and 4- methyl pyridine (Elves,l. 1993) Economic Development of the Pyridine Industrial Market In the 20th century, the two major companies in the US that produce pyridine are Nepera Chemical Company Inc in Indiana and they have Cambrex Chemicals in New York. Reilly Industries own both these companies, which is the biggest producer of pyridine in the world. Prices of pyridine reflect on the price of petroleum-based raw materials and the chemistry related to produce the desired product of pyridine. The price of pyridine bases can cost from no lower than $5/kg going up to$150/kg (Feng,a. 2002) with an inverse relationship between price and volume. The Nantong Company in China is the biggest supplier and producer of pyridine in Asia. In March 2001, they produced 11 kt/a (Feng,b. 2009) of pyridine synthetically which is only 83% of their total production. The demand for pyridine has increased dramatically as Nantong`s output reached 19300 tons in 2007; with an increase of 36.9% (Feng,c. 2009). This is due to the expansion of the pyridine consumer market.