Pyridine
Overview
Pyridine is a basic heterocyclic
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....

 organic compound
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...

 with the chemical formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....

 C5
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...

H5
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...

N
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

. It is structurally related to benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....

, with one C-H group replaced by a nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

 atom. The pyridine ring occurs in many important compounds, including azine
Azine
Azines are a functional class of organic compounds, formed from the condensation reaction of two equivalents of an aldehyde or ketone with one equivalent of hydrazine...

s and the vitamins niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...

 and pyridoxal
Pyridoxal
Pyridoxal is one of the three natural forms of vitamin B6, along with pyridoxamine and pyridoxine . All of these forms are converted in the human body into a single biologically active form, pyridoxal 5-phosphate. All three forms of vitamin B6 are heterocyclic organic compounds...

.

Pyridine was discovered in 1849 by the Scottish chemist Thomas Anderson
Thomas Anderson (chemist)
thumb|280pxThomas Anderson was a noted 19th century chemist. In 1853 his work on alkaloids led him to discover the correct structure for codeine...

 as one of the constituents of bone oil
Dippel's oil
Dippel's Oil is a nitrogenous by-product of the destructive distillation manufacture of bone char . This liquid is dark colored and highly viscous with an unpleasant smell. The oil contains the organic base pyrrole. It is named after its inventor, Johann Conrad Dippel,Dippel's oil had a number...

. Two years later, Anderson isolated pure pyridine through fractional distillation
Fractional distillation
Fractional distillation is the separation of a mixture into its component parts, or fractions, such as in separating chemical compounds by their boiling point by heating them to a temperature at which several fractions of the compound will evaporate. It is a special type of distillation...

 of the oil.
Encyclopedia
Pyridine is a basic heterocyclic
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....

 organic compound
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...

 with the chemical formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....

 C5
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...

H5
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...

N
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

. It is structurally related to benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....

, with one C-H group replaced by a nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

 atom. The pyridine ring occurs in many important compounds, including azine
Azine
Azines are a functional class of organic compounds, formed from the condensation reaction of two equivalents of an aldehyde or ketone with one equivalent of hydrazine...

s and the vitamins niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...

 and pyridoxal
Pyridoxal
Pyridoxal is one of the three natural forms of vitamin B6, along with pyridoxamine and pyridoxine . All of these forms are converted in the human body into a single biologically active form, pyridoxal 5-phosphate. All three forms of vitamin B6 are heterocyclic organic compounds...

.

Pyridine was discovered in 1849 by the Scottish chemist Thomas Anderson
Thomas Anderson (chemist)
thumb|280pxThomas Anderson was a noted 19th century chemist. In 1853 his work on alkaloids led him to discover the correct structure for codeine...

 as one of the constituents of bone oil
Dippel's oil
Dippel's Oil is a nitrogenous by-product of the destructive distillation manufacture of bone char . This liquid is dark colored and highly viscous with an unpleasant smell. The oil contains the organic base pyrrole. It is named after its inventor, Johann Conrad Dippel,Dippel's oil had a number...

. Two years later, Anderson isolated pure pyridine through fractional distillation
Fractional distillation
Fractional distillation is the separation of a mixture into its component parts, or fractions, such as in separating chemical compounds by their boiling point by heating them to a temperature at which several fractions of the compound will evaporate. It is a special type of distillation...

 of the oil. It is a colorless, highly flammable, weakly alkaline, water-soluble liquid
Liquid
Liquid is one of the three classical states of matter . Like a gas, a liquid is able to flow and take the shape of a container. Some liquids resist compression, while others can be compressed. Unlike a gas, a liquid does not disperse to fill every space of a container, and maintains a fairly...

 with a distinctive, unpleasant fish-like odor.

Pyridine is used as a precursor
Precursor (chemistry)
In chemistry, a precursor is a compound that participates in the chemical reaction that produces another compound. In biochemistry, the term "precursor" is used more specifically to refer to a chemical compound preceding another in a metabolic pathway....

 to agrochemicals and pharmaceuticals and is also an important solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...

 and reagent
Reagent
A reagent is a "substance or compound that is added to a system in order to bring about a chemical reaction, or added to see if a reaction occurs." Although the terms reactant and reagent are often used interchangeably, a reactant is less specifically a "substance that is consumed in the course of...

. Pyridine is added to ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

 to make it unsuitable for drinking. It is used in the in vitro synthesis of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

, in the synthesis of sulfapyridine
Sulfapyridine
Sulfapyridine, original UK spelling Sulphapyridine, is a sulfonamide antibacterial. At one time it was commonly referred to as M&B....

 (a drug against bacterial and viral infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s), antihistaminic
Histamine antagonist
A histamine antagonist, commonly referred to as antihistamine, is a pharmaceutical drug that inhibits action of histamine by blocking it from attaching to histamine receptors.- Clinical effects :...

 drugs tripelennamine
Tripelennamine
Tripelennamine is psychoactive drug and member of the pyridine and ethylenediamine classes that is used as an antipruritic and first-generation antihistamine...

 and mepyramine
Mepyramine
Mepyramine, also known as pyrilamine, is a first generation antihistamine, targeting the H1 receptor. However, it rapidly permeates the brain often causing drowsiness. It also has anticholinergic properties. It is used in over-the-counter combination products to treat the common cold and menstrual...

, as well as water repellents, bactericides and herbicide
Herbicide
Herbicides, also commonly known as weedkillers, are pesticides used to kill unwanted plants. Selective herbicides kill specific targets while leaving the desired crop relatively unharmed. Some of these act by interfering with the growth of the weed and are often synthetic "imitations" of plant...

s. Some chemical compounds, although not synthesized from pyridine, contain its ring structure. They include B vitamins
B vitamins
B vitamins are a group of water-soluble vitamins that play important roles in cell metabolism. The B vitamins were once thought to be a single vitamin, referred to as vitamin B . Later research showed that they are chemically distinct vitamins that often coexist in the same foods...

 niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...

 and pyridoxal
Pyridoxal
Pyridoxal is one of the three natural forms of vitamin B6, along with pyridoxamine and pyridoxine . All of these forms are converted in the human body into a single biologically active form, pyridoxal 5-phosphate. All three forms of vitamin B6 are heterocyclic organic compounds...

, an anti-tuberculosis
Tuberculosis treatment
Tuberculosis treatment refers to the medical treatment of the infectious disease tuberculosis .The standard "short" course treatment for TB is isoniazid, rifampicin , pyrazinamide, and ethambutol for two months, then isoniazid and rifampicin alone for a further four months...

 drug isoniazid
Isoniazid
Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...

, nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...

 and other nitrogen-containing plant products. Historically, pyridine was produced from coal tar
Coal tar
Coal tar is a brown or black liquid of extremely high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal iscarbonized to make coke or gasified to make coal gas...

 and as a by-product of the coal gasification
Coal gasification
Coal gasification is the process of producing coal gas, a type of syngas–a mixture of carbon monoxide , hydrogen , carbon dioxide and water vapour –from coal...

. However, increased demand for pyridine resulted in the development of more economical methods of synthesis from acetaldehyde
Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...

 and ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...

, and more than 20,000 tonne
Tonne
The tonne, known as the metric ton in the US , often put pleonastically as "metric tonne" to avoid confusion with ton, is a metric system unit of mass equal to 1000 kilograms. The tonne is not an International System of Units unit, but is accepted for use with the SI...

s per year are manufactured worldwide.

History

Impure pyridine was undoubtedly prepared by early alchemists by heating animal bones and other organic matter, but the earliest documented reference is attributed to the Scottish scientist Thomas Anderson
Thomas Anderson (chemist)
thumb|280pxThomas Anderson was a noted 19th century chemist. In 1853 his work on alkaloids led him to discover the correct structure for codeine...

. In 1849, Anderson examined the contents of the oil obtained through high-temperature heating of animal bones. Among other substances, he separated from the oil a colorless liquid with unpleasant odor, from which he isolated pure pyridine two years later. He described it as highly soluble in water, readily soluble in concentrated acids and salts upon heating, and only slightly soluble in oils. Owing to its flammability, Anderson named the new substance pyridine, after (pyr) meaning fire. The suffix -idine was added in compliance with the chemical nomenclature, as in toluidine
Toluidine
There are three isomers of toluidine, which are organic compounds. These isomers are o-toluidine, m-toluidine, and p-toluidine. The o- stands for ortho- , m- stands for meta- , and p- stands for para-...

, to indicate a carbon cycle containing a nitrogen atom.

The chemical structure of pyridine was determined decades after its discovery. Wilhelm Körner
Wilhelm Korner
Wilhelm Körner, later a.k.a. Guglielmo Körner was a German chemist.-Life:Körner studied chemistry at Giessen, where he graduated in 1860. In 1866 he became assistant to Kekulé at Ghent...

 (1869) and James Dewar
James Dewar
Sir James Dewar FRS was a Scottish chemist and physicist. He is probably best-known today for his invention of the Dewar flask, which he used in conjunction with extensive research into the liquefaction of gases...

 (1871) independently suggested that, in analogy between quinoline
Quinoline
Quinoline is a heterocyclic aromatic organic compound. It has the formula C9H7N and is a colourless hygroscopic liquid with a strong odour. Aged samples, if exposed to light, become yellow and later brown...

 and naphthalene
Naphthalene
Naphthalene is an organic compound with formula . It is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08 ppm by mass. As an aromatic hydrocarbon, naphthalene's structure consists of a fused pair of benzene rings...

, the structure of pyridine is derived from benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....

 by substituting one C-H unit with a nitrogen atom. The suggestion by Körner and Dewar was later confirmed in an experiment where pyridine was reduced to piperidine
Piperidine
Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...

 with sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 alcohol. In 1876, William Ramsay
William Ramsay
Sir William Ramsay was a Scottish chemist who discovered the noble gases and received the Nobel Prize in Chemistry in 1904 "in recognition of his services in the discovery of the inert gaseous elements in air" .-Early years:Ramsay was born in Glasgow on 2...

 combined acetylene
Acetylene
Acetylene is the chemical compound with the formula C2H2. It is a hydrocarbon and the simplest alkyne. This colorless gas is widely used as a fuel and a chemical building block. It is unstable in pure form and thus is usually handled as a solution.As an alkyne, acetylene is unsaturated because...

 and hydrogen cyanide into pyridine in a red-hot
Red heat
The practice of using colours to determine the temperature of a piece of ferrous metal comes from blacksmithing. Long before thermometers were widely available it was necessary to know what state the metal was in for heat treating it and the only way to do this was to heat it up to a colour which...

 iron-tube furnace. This was the first synthesis of a hetero-aromatic compound.

The contemporary methods of pyridine production had a low yield, and the increasing demand for the new compound urged to search for more efficient routes. A breakthrough came in 1924 when the Russian chemist Aleksei Chichibabin
Aleksei Chichibabin
For the poet, see Boris Chichibabin.Alekséy Yevgényevich Chichibábin was a Soviet/Russian organic chemist. His name is also written Alexei Yevgenievich Chichibabin and Alexei Euguenievich Tchitchibabine.- Life :...

 invented a pyridine synthesis reaction
Chichibabin pyridine synthesis
The Chichibabin pyridine synthesis -chē-bā-bēn) is a method for synthesizing pyridine rings. In its general form, the reaction can can be described as a condensation reaction of aldehydes, ketones, α,β-Unsaturated carbonyl compounds, or any combination of the above, in ammonia or ammonia...

 which was based on inexpensive reagents. This method is still used for the industrial production of pyridine.

Occurrence

Pyridine is not abundant in nature, except for the leaves and roots of belladonna (Atropa belladonna) and in marshmallow (Althaea officinalis
Althaea officinalis
Althaea officinalis is a species indigenous to Africa, which is used as a medicinal plant and ornamental plant...

). Pyridine derivatives, however, are often part of biomolecules such as the eponymous pyridine nucleotides and alkaloids. In daily life, trace amounts of pyridine are components of the volatile organic compound
Volatile organic compound
Volatile organic compounds are organic chemicals that have a high vapor pressure at ordinary, room-temperature conditions. Their high vapor pressure results from a low boiling point, which causes large numbers of molecules to evaporate or sublimate from the liquid or solid form of the compound and...

s that are produced in roasting and canning
Canning
Canning is a method of preserving food in which the food contents are processed and sealed in an airtight container. Canning provides a typical shelf life ranging from one to five years, although under specific circumstances a freeze-dried canned product, such as canned, dried lentils, can last as...

 processes, e.g. in fried chicken, sukiyaki
Sukiyaki
Sukiyaki is a Japanese dish in the nabemono style.It consists of meat which is slowly cooked or simmered at the table, alongside vegetables and other ingredients, in a shallow iron pot in a mixture of soy sauce, sugar, and mirin...

, fried bacon
Bacon
Bacon is a cured meat prepared from a pig. It is first cured using large quantities of salt, either in a brine or in a dry packing; the result is fresh bacon . Fresh bacon may then be further dried for weeks or months in cold air, boiled, or smoked. Fresh and dried bacon must be cooked before eating...

, Beaufort cheese
Beaufort (cheese)
Beaufort is a hard, rather sharp cheese made from cow's milk and is similar to gruyère. It is produced in the area around Beaufort located high in the French Alps in the Savoie region of France...

, coffee aroma, black tea
Black tea
Black tea is a variety of tea that is more oxidized than the oolong, green, and white varieties.All four varieties are made from leaves of the shrub Camellia sinensis. Black tea is generally stronger in flavor and contains more caffeine than the less oxidized teas. Two principal varieties of the...

 and sunflower honey
Monofloral honey
Monofloral honey is a type of honey which has a high value in the marketplace because it has a distinctive flavor or other attribute due to its being predominantly from the nectar of one plant species....

. The smoke of tobacco
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...

 and of marijuana contains pyridine, as do vaginal secretions
Vaginal lubrication
Vaginal lubrication is a lubricating fluid that is naturally produced in a woman's vagina. Vaginal lubrication or moistness is present at all times, but production increases significantly during a woman's sexual arousal in anticipation of sexual intercourse...

.

Nomenclature

The systematic name of pyridine, within the Hantzsch–Widman nomenclature
Hantzsch–Widman nomenclature
Hantzsch–Widman nomenclature, also called the extended Hantzsch–Widman system, is a type of systematic chemical nomenclature used for naming heterocyclic parent hydrides having no more than ten ring members....

 recommended by the IUPAC, is azine. However, systematic names for simple compounds are used very rarely, instead heterocyclic nomenclature follows historically established common names. IUPAC discourages the use of azine in favor of pyridine. The numbering of the ring atoms in pyridine starts at the nitrogen (see infobox). An allocation of positions by letter of the Greek alphabet
Greek alphabet
The Greek alphabet is the script that has been used to write the Greek language since at least 730 BC . The alphabet in its classical and modern form consists of 24 letters ordered in sequence from alpha to omega...

 (α-γ) and the substitution pattern
Arene substitution patterns
Arene substitution patterns are part of organic chemistry IUPAC nomenclature and pinpoint the position of substituents other than hydrogen in relation to each other on an aromatic hydrocarbon.- Ortho, meta, and para substitution :...

 nomenclature common for homoaromatic systems (ortho, meta, para) are used sometimes. Here α (ortho), β (meta) and γ (para) refer to the 2, 3 and 4 position, respectively. The systematic name for the pyridine derivatives is pyridinyl, wherein the position of the substituted atom is preceded by a number. However, here again the historical name pyridyl is encouraged by the IUPAC and used instead of the systematic name. The cationic derivative formed by the addition of an electrophile
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...

 to the nitrogen atom is called pyridinium
Pyridinium
Pyridinium refers to the cationic form of pyridine. This can either be due to protonation of the ring nitrogen or because of addition of a substituent to the ring nitrogen, typically via alkylation. The lone pair of electrons on the nitrogen atom of pyridine is not delocalized, and thus pyridine...

.

Production

Historically, pyridine was extracted from coal tar or obtained as a by-product of coal gasification. The process was labor consuming and inefficient: coal tar
Coal tar
Coal tar is a brown or black liquid of extremely high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal iscarbonized to make coke or gasified to make coal gas...

 contains only about 0.1% pyridine, and therefore a multi-stage purification was required, which further reduced the output. Nowadays, most pyridine is produced synthetically using various name reaction
Name reaction
A name reaction is a chemical reaction named after its discoverers or developers. Well known examples include the Wittig reaction, the Claisen condensation, the Friedel-Crafts acylation, and the Diels-Alder reaction. Among the tens of thousands of organic reactions that are known, hundreds of such...

s, and the major ones are discussed below.

Chichibabin synthesis

The Chichibabin pyridine synthesis
Chichibabin pyridine synthesis
The Chichibabin pyridine synthesis -chē-bā-bēn) is a method for synthesizing pyridine rings. In its general form, the reaction can can be described as a condensation reaction of aldehydes, ketones, α,β-Unsaturated carbonyl compounds, or any combination of the above, in ammonia or ammonia...

 was reported in 1924 and is still in use industrially. In its general form, the reaction can be described as a condensation reaction
Condensation reaction
A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...

 of aldehydes, ketones, α,β-Unsaturated carbonyl compounds, or any combination of the above, in ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...

 or ammonia derivatives
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...

. In particular, unsubstituted pyridine is produced from formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...

 and acetaldehyde
Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...

, which are inexpensive and widely available. First, acrolein
Acrolein
Acrolein is the simplest unsaturated aldehyde. It is produced widely but is most often immediately reacted with other products due to its instability and toxicity...

 is formed in a Knoevenagel condensation
Knoevenagel condensation
The Knoevenagel condensation reaction is an organic reaction named after Emil Knoevenagel. It is a modification of the Aldol condensation.A Knoevenagel condensation is a nucleophilic addition of an active hydrogen compound to a carbonyl group followed by a dehydration reaction in which a molecule...

 from the acetaldehyde and formaldehyde. It is then condensed
Condensation reaction
A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...

 with acetaldehyde and ammonia into dihydropyridine, and then oxidized with a solid-state catalyst to pyridine. This process is carried out in a gas phase at 400–450 °C. The product consists of a mixture of pyridine, simple methylated
Methyl group
Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...

 pyridines (picoline
Picoline
Picoline refers to three different methylpyridine isomers, all with the chemical formula C6H7N and a molar mass of 93.13 g mol−1. All three are colourless liquids at room temperature and pressure and are miscible with water and most organic solvents...

) and lutidine; its composition depends on the catalyst used and can be adapted to the needs of the manufacturer. The catalyst is usually a transition metal salt such as cadmium(II) fluoride or manganese(II) fluoride
Manganese(II) fluoride
Manganese fluoride is the chemical compound composed of manganese and fluoride with the formula MnF2. It is a light pink crystalline solid, the light pink color being characteristic for manganese compounds. It is made by treating manganese and diverse compounds of manganese in hydrofluoric acid. ...

, but cobalt
Cobalt
Cobalt is a chemical element with symbol Co and atomic number 27. It is found naturally only in chemically combined form. The free element, produced by reductive smelting, is a hard, lustrous, silver-gray metal....

 and thallium
Thallium
Thallium is a chemical element with the symbol Tl and atomic number 81. This soft gray poor metal resembles tin but discolors when exposed to air. The two chemists William Crookes and Claude-Auguste Lamy discovered thallium independently in 1861 by the newly developed method of flame spectroscopy...

 compounds can also be used. The recovered pyridine is separated from by-products in a multistage process.
Practical application of the traditional Chichibabin pyridine synthesis are limited by its consistently low yield, typically about 20%. This low yield, together with the high prevalence of byproducts, render unmodified forms of Chichibabin's method unpopular.

Dealkylation of alkylpyridines

Pyridine can be prepared by dealkylation of alkylated pyridines, which are obtained as by-products in the syntheses of other pyridines. The oxidative dealkylation is carried out either using air over vanadium(V) oxide
Vanadium(V) oxide
Vanadium oxide is the chemical compound with the formula V2O5. Commonly known as vanadium pentoxide, this brown/yellow solid is the most stable and common compound of vanadium. Upon heating it reversibly loses oxygen...

 catalyst, by vapor-dealkylation on nickel
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...

-based catalyst, or hydrodealkylation with a silver
Silver
Silver is a metallic chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...

 or platinum
Platinum
Platinum is a chemical element with the chemical symbol Pt and an atomic number of 78. Its name is derived from the Spanish term platina del Pinto, which is literally translated into "little silver of the Pinto River." It is a dense, malleable, ductile, precious, gray-white transition metal...

 based catalyst. Yields of pyridine up to be 93% can be achieved with the nickel-based catalyst.

Hantzsch pyridine synthesis

The first major synthesis of pyridine derivatives was described in 1881 by Arthur Rudolf Hantzsch
Arthur Rudolf Hantzsch
Arthur Rudolf Hantzsch , was a German chemist.-Life and work:Hantzsch studied chemistry in Dresden and graduated at the University of Würzburg under Johannes Wislicenus...

. The Hantzsch pyridine synthesis
Hantzsch pyridine synthesis
The Hantzsch pyridine synthesis or Hantzsch dihydropyridine synthesis is a multi-component organic reaction between an aldehyde such as formaldehyde, 2 equivalents of a β-keto ester such as ethyl acetoacetate and a nitrogen donor such as ammonium acetate or ammonia. The initial reaction product is...

 typically uses a 2:1:1 mixture of a β-keto acid
Keto acid
Keto acids are organic compounds that contain a carboxylic acid group and a ketone group. The alpha-keto acids are especially important in biology as they are involved in the Krebs citric acid cycle and in glycolysis...

 (often acetoacetate
Acetoacetic acid
Acetoacetic acid is the organic compound with the formula CH3CCH2CO2H. It is the simplest beta-keto acid group and like other members of this class is unstable.- Synthesis and properties :...

), an aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....

 (often formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...

), and ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...

 or its salt as the nitrogen donor. First, a double hydrogenated
Hydration reaction
In organic chemistry, a hydration reaction is a chemical reaction in which a hydroxyl group and a hydrogen cation are added to the two carbon atoms bonded together in the carbon-carbon double bond which makes up an alkene functional group. The reaction usually runs in a strong acidic, aqueous...

 pyridine is obtained, which is then oxidized to the corresponding pyridine derivative. Emil Knoevenagel
Emil Knoevenagel
Heinrich Emil Albert Knoevenagel was the German chemist who established the Knoevenagel condensation reaction. The Knoevenagel condensation reaction of benzaldehydes with nitroalkanes is a classic general method for the preparation of nitroalkenes, which are very valuable synthetic...

 showed that unsymmetrically substituted pyridine derivatives can be produced with this process.

Bönnemann cyclization

The trimerization of a part of a nitrile
Nitrile
A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...

 molecule and two parts of acetylene
Acetylene
Acetylene is the chemical compound with the formula C2H2. It is a hydrocarbon and the simplest alkyne. This colorless gas is widely used as a fuel and a chemical building block. It is unstable in pure form and thus is usually handled as a solution.As an alkyne, acetylene is unsaturated because...

 into pyridine is called Bönnemann cyclization. This modification of the Reppe synthesis
Walter Reppe
Walter Julius Reppe was a German chemist. He is notable for his contributions to the chemistry of acetylene.-Education and career:...

 can be activated either by heat or light
Photochemistry
Photochemistry, a sub-discipline of chemistry, is the study of chemical reactions that proceed with the absorption of light by atoms or molecules.. Everyday examples include photosynthesis, the degradation of plastics and the formation of vitamin D with sunlight.-Principles:Light is a type of...

. While the thermal activation requires high pressures and temperatures, the photoinduced cycloaddition
Cycloaddition
A cycloaddition is a pericyclic chemical reaction, in which "two or more unsaturated molecules combine with the formation of a cyclic adduct in which there is a net reduction of the bond multiplicity." The resulting reaction is a cyclization reaction.Cycloadditions are usually described by the...

 proceeds at ambient conditions with CoCp2(cod) (Cp = cyclopentadienyl, cod = 1,5-cyclooctadiene
1,5-Cyclooctadiene
1,5-Cyclooctadiene is the organic compound with the chemical formula C8H12. Generally abbreviated COD, this diene is a useful precursor to other organic compounds and serves as a ligand in organometallic chemistry.- Synthesis :...

) as a catalyst, and can be performed even in water. A series of pyridine derivatives can be produced in this way. When using acetonitrile
Acetonitrile
Acetonitrile is the chemical compound with formula . This colourless liquid is the simplest organic nitrile. It is produced mainly as a byproduct of acrylonitrile manufacture...

 as the nitrile, 2-methylpyridine is obtained, which can be dealkylated to pyridine.

Other methods

The Kröhnke pyridine synthesis involves the condensation of 1,5-diketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...

s with ammonium acetate
Ammonium acetate
Ammonium acetate is a chemical compound with the formula CH3COONH4 . It is a white solid, which can be derived from the reaction of ammonia and acetic acid...

 in acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...

 followed by oxidation.
The Ciamician-Dennstedt rearrangement entails the ring-expansion of pyrrole
Pyrrole
Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH. It is a colourless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3...

 with dichlorocarbene
Dichlorocarbene
Dichlorocarbene is a carbene commonly encountered in organic chemistry. This reactive intermediate with chemical formula CCl2 is easily available by reaction of chloroform and a base such as potassium t-butoxide or sodium hydroxide dissolved in water...

 to 3-chloropyridine.
In the Gattermann-Skita synthesis, a malonate ester
Malonic ester synthesis
The malonic ester synthesis is a chemical reaction where diethyl malonate or another ester of malonic acid is alkylated at the carbon alpha to both carbonyl groups, and then converted to a substituted acetic acid. The major drawback of malonic ester synthesis is that the alkylation stage can also...

 salt reacts with dichloromethylamine
Methylamine
Methylamine is the organic compound with a formula of CH3NH2. This colourless gas is a derivative of ammonia, but with one H atom replaced by a methyl group. It is the simplest primary amine. It is sold as a solution in methanol, ethanol, THF, and water, or as the anhydrous gas in pressurized...

.

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
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

, fungi and mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s. Mammals synthesize nicotinic acid through oxidation of the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

, where an intermediate product, aniline
Aniline
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane...

, creates a pyridine derivative, kynurenine
Kynurenine
L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...

. On the contrary, the bacteria Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

and Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

produce nicotinic acid by condensation of glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...

 and aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...

.

Physical properties

Pyridine is a colorless liquid that boils at 115.2 °C and freezes at −41.6 °C. Its density, 0.9819 g/cm3, is close to that of water, and its refractive index
Refractive index
In optics the refractive index or index of refraction of a substance or medium is a measure of the speed of light in that medium. It is expressed as a ratio of the speed of light in vacuum relative to that in the considered medium....

 is 1.5093 at a wavelength
Wavelength
In physics, the wavelength of a sinusoidal wave is the spatial period of the wave—the distance over which the wave's shape repeats.It is usually determined by considering the distance between consecutive corresponding points of the same phase, such as crests, troughs, or zero crossings, and is a...

 of 589 nm and a temperature of 20 °C. Addition of up to 40 mol% of water to pyridine gradually lowers its melting point from −41.6 °C to −65.0 °C. The molecular electric dipole moment
Electric dipole moment
In physics, the electric dipole moment is a measure of the separation of positive and negative electrical charges in a system of charges, that is, a measure of the charge system's overall polarity with SI units of Coulomb-meter...

 is 2.2 Debye
Debye
The debye is a CGS unit of electric dipole momentElectric dipole moment is defined as charge times displacement: Historically the debye was defined as the dipole moment resulting from two charges of opposite sign but an equal magnitude of 10-10 statcoulomb10-10 statcoulomb is approximately 0.2083...

. Pyridine is diamagnetic
Diamagnetism
Diamagnetism is the property of an object which causes it to create a magnetic field in opposition to an externally applied magnetic field, thus causing a repulsive effect. Specifically, an external magnetic field alters the orbital velocity of electrons around their nuclei, thus changing the...

 and has a diamagnetic susceptibility
Magnetic susceptibility
In electromagnetism, the magnetic susceptibility \chi_m is a dimensionless proportionality constant that indicates the degree of magnetization of a material in response to an applied magnetic field...

 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
Viscosity
Viscosity is a measure of the resistance of a fluid which is being deformed by either shear or tensile stress. In everyday terms , viscosity is "thickness" or "internal friction". Thus, water is "thin", having a lower viscosity, while honey is "thick", having a higher viscosity...

 of 0.88 mPa/s and thermal conductivity
Thermal conductivity
In physics, thermal conductivity, k, is the property of a material's ability to conduct heat. It appears primarily in Fourier's Law for heat conduction....

 of 0.166 W·m−1·K−1. The enthalpy of vaporization is 35.09 kJ·mol−1 at the boiling point
Boiling point
The boiling point of an element or a substance is the temperature at which the vapor pressure of the liquid equals the environmental pressure surrounding the liquid....

 and normal pressure. The enthalpy of fusion
Enthalpy of fusion
The enthalpy of fusion is the change in enthalpy resulting from heating one mole of a substance to change its state from a solid to a liquid. The temperature at which this occurs is the melting point....

 is 8.28 kJ·mol−1 at the melting point
Melting point
The melting point of a solid is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends on pressure and is usually specified at standard atmospheric pressure...

.

Pyridine crystallizes in an orthorhombic crystal system
Orthorhombic crystal system
In crystallography, the orthorhombic crystal system is one of the seven lattice point groups. Orthorhombic lattices result from stretching a cubic lattice along two of its orthogonal pairs by two different factors, resulting in a rectangular prism with a rectangular base and height , such that a,...

 with space group
Space group
In mathematics and geometry, a space group is a symmetry group, usually for three dimensions, that divides space into discrete repeatable domains.In three dimensions, there are 219 unique types, or counted as 230 if chiral copies are considered distinct...

 Pna21 and lattice parameters a = 1752, b = 897, c = 1135 pm, and 16 formula unit
Formula unit
A formula unit in chemistry is the empirical formula of an ionic or covalent network solid compound used as an independent entity for stoichiometric calculations. It is the lowest whole number ratio of ions represented in an ionic compound...

s per unit cell (measured at 153 K). For comparison, benzene crystal 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
Hydrate
Hydrate is a term used in inorganic chemistry and organic chemistry to indicate that a substance contains water. The chemical state of the water varies widely between hydrates, some of which were so labeled before their chemical structure was understood....

 (pyridine·3H2O) is known; it also crystallizes in an orthorhombic system in the space group Pbca, lattice parameters a = 1244, b = 1783, c = 679 pm and eight formula units per unit cell (measured at 223 K).

The critical parameters
Critical point (thermodynamics)
In physical chemistry, thermodynamics, chemistry and condensed matter physics, a critical point, also called a critical state, specifies the conditions at which a phase boundary ceases to exist...

 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
Temperature
Temperature is a physical property of matter that quantitatively expresses the common notions of hot and cold. Objects of low temperature are cold, while various degrees of higher temperatures are referred to as warm or hot...

, A = 4.16272, B = 1371.358 K and C = -58.496 K.

The optical absorption spectrum of pyridine in hexane
Hexane
Hexane is a hydrocarbon with the chemical formula C6H14; that is, an alkane with six carbon atoms.The term may refer to any of four other structural isomers with that formula, or to a mixture of them. In the IUPAC nomenclature, however, hexane is the unbranched isomer ; the other four structures...

 contains three bands at the wavelength
Wavelength
In physics, the wavelength of a sinusoidal wave is the spatial period of the wave—the distance over which the wave's shape repeats.It is usually determined by considering the distance between consecutive corresponding points of the same phase, such as crests, troughs, or zero crossings, and is a...

s of 195 nm (π → π*transition, molar absorptivity
Molar absorptivity
The molar absorption coefficient, molar extinction coefficient, or molar absorptivity, is a measurement of how strongly a chemical species absorbs light at a given wavelength...

 ε = 7500 L·(mol·cm)−1), 251 nm (π → π*transition, ε = 2000 L·(mol·cm)−1) and 270 nm (n → π*transition, ε = 450 L·(mol·cm)−1). The 1H nuclear magnetic resonance
Nuclear magnetic resonance
Nuclear magnetic resonance is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation...

 (NMR) spectrum of pyridine contains three signals with the integral intensity ratio of 2:1:2 which correspond to the three chemically different protons in the molecule. These signals originate from the α-protons (chemical shift
Chemical shift
In nuclear magnetic resonance spectroscopy, the chemical shift is the resonant frequency of a nucleus relative to a standard. Often the position and number of chemical shifts are diagnostic of the structure of a molecule...

 8.5 ppm), γ-proton (7.5 ppm) and β-protons (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
Mass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...

 methods.

Chemical properties

Pyridine is miscible with water and virtually all organic solvents. It is weakly basic, and with hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....

 it forms a crystalline hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....

 salt which melts at 145–147 °C. Most chemical properties of pyridine are typical of a heteroaromatic compound. In organic reaction
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...

s, pyridine behaves both as a tertiary amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...

, undergoing protonation
Protonation
In chemistry, protonation is the addition of a proton to an atom, molecule, or ion. Some classic examples include*the protonation of water by sulfuric acid:*the protonation of isobutene in the formation of a carbocation:2C=CH2 + HBF4 → 3C+ + BF4−*the protonation of ammonia in the...

, alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...

, acylation
Acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....

, and N-oxidation at the nitrogen atom, and as an aromatic compound, undergoing nucleophilic substitution
Nucleophilic substitution
In organic and inorganic chemistry, nucleophilic substitution is a fundamental class of reactions in which an electron nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom or a group of atoms called the leaving group; the positive or partially positive...

s.

Because of the electronegative nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

 in the pyridine ring, the molecule is relatively electron deficient. It therefore enters less readily electrophilic aromatic substitution
Electrophilic aromatic substitution
Electrophilic aromatic substitution EAS is an organic reaction in which an atom, usually hydrogen, appended to an aromatic system is replaced by an electrophile...

 reactions, which are characteristic of benzene derivatives. However, unlike benzene and its derivatives, pyridine is more prone to nucleophilic substitution
Nucleophilic substitution
In organic and inorganic chemistry, nucleophilic substitution is a fundamental class of reactions in which an electron nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom or a group of atoms called the leaving group; the positive or partially positive...

 and metalation
Metalation
Metalation is a chemical reaction which results in a metal atom beingattached to a molecule.Lithium metal in contact with an organohalide lithiates the organic molecule and gives the organolithium reagent and lithium halide...

 of the ring by strong organometallic bases. The reactivity of pyridine can be distinguished for three chemical groups. With electrophile
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...

s, electrophilic substitution
Electrophilic substitution
Electrophilic substitution reactions are chemical reactions in which an electrophile displaces a group in a compound, typically but not always hydrogen. Electrophilic aromatic substitution is characteristic of aromatic compounds and is an important way of introducing functional groups onto benzene...

 takes place where pyridine expresses aromatic properties. With nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

s, pyridine reacts via its 2nd and 4th carbon atoms and thus behaves similar to imine
Imine
An imine is a functional group or chemical compound containing a carbon–nitrogen double bond, with the nitrogen attached to a hydrogen atom or an organic group. If this group is not a hydrogen atom, then the compound is known as a Schiff base...

s and carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....

s. The reaction with many Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...

s 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 oxide
Amine oxide
An amine oxide, also known as amine-N-oxide and N-oxide, is a chemical compound that contains the functional group R3N+-O−, an N-O bond with three additional hydrogen and/or hydrocarbon side chains attached to N. Sometimes it is written as R3N→O or, wrongly, as R3N=O.In the strict sense the...

s (N-oxides), is also a feature of tertiary amines.
The nitrogen center of pyridine features a basic lone pair
Lone pair
In chemistry, a lone pair is a valence electron pair without bonding or sharing with other atoms. They are found in the outermost electron shell of an atom, so lone pairs are a subset of a molecule's valence electrons...

 of electron
Electron
The electron is a subatomic particle with a negative elementary electric charge. It has no known components or substructure; in other words, it is generally thought to be an elementary particle. An electron has a mass that is approximately 1/1836 that of the proton...

s. Because this lone pair is not part of the aromatic ring, pyridine is a base
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...

, having chemical properties similar to those of tertiary amines. The pKa
PKA
PKA, pKa, or other similar variations may stand for:* pKa, the symbol for the acid dissociation constant at logarithmic scale* Protein kinase A, a class of cAMP-dependent enzymes* Pi Kappa Alpha, the North-American social fraternity...

 of the conjugate acid
Conjugate acid
Within the Brønsted–Lowry acid-base theory , a conjugate acid is the acid member, HX, of a pair of two compounds that transform into each other by gain or loss of a proton. A conjugate acid can also be seen as the chemical substance that releases, or donates, a proton in the forward chemical...

 is 5.25. Pyridine is protonated
Protonation
In chemistry, protonation is the addition of a proton to an atom, molecule, or ion. Some classic examples include*the protonation of water by sulfuric acid:*the protonation of isobutene in the formation of a carbocation:2C=CH2 + HBF4 → 3C+ + BF4−*the protonation of ammonia in the...

 by reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...

 with acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...

s and forms a positively charged aromatic polyatomic ion
Polyatomic ion
A polyatomic ion, also known as a molecular ion, is a charged species composed of two or more atoms covalently bonded or of a metal complex that can be considered as acting as a single unit in the context of acid and base chemistry or in the formation of salts. The prefix "poly-" means "many," in...

 called pyridinium
Pyridinium
Pyridinium refers to the cationic form of pyridine. This can either be due to protonation of the ring nitrogen or because of addition of a substituent to the ring nitrogen, typically via alkylation. The lone pair of electrons on the nitrogen atom of pyridine is not delocalized, and thus pyridine...

. The bond length
Bond length
- Explanation :Bond length is related to bond order, when more electrons participate in bond formation the bond will get shorter. Bond length is also inversely related to bond strength and the bond dissociation energy, as a stronger bond will be shorter...

s and bond angles in 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
P-Toluenesulfonic acid
p-Toluenesulfonic acid or tosylic acid is an organic compound with the formula CH3C6H4SO3H. It is a white solid that is soluble in water, alcohols, and other polar organic solvents. The 4-CH3C6H4SO2- group is known as the Tosyl group and is often abbreviated as Ts or Tos...

.

Pyridine can act as Lewis base, donating its pair of electron to a Lewis acid as in the sulfur trioxide pyridine complex
Sulfur trioxide pyridine complex
Sulfur trioxide pyridine complex is a complex formed where the lone pair on the nitrogen of the pyridine binds to the sulfur of the sulfur trioxide...

.

Pyridine itself is a relatively weak ligand in forming complexes with transition metal
Transition metal
The term transition metal has two possible meanings:*The IUPAC definition states that a transition metal is "an element whose atom has an incomplete d sub-shell, or which can give rise to cations with an incomplete d sub-shell." Group 12 elements are not transition metals in this definition.*Some...

 ions. For example, it forms a 1:1 complexes with nickel
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...

(II), Ni2+, and copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...

(II), Cu2+, with logK1 values of ca. 1.9 and 2.6, respectively. The infrared spectra of pyridine complexes have been discussed in detail. Picolinic acid, which is a substituted derivative of pyridine, forms strong complexes due to the chelate effect. 2,2'-bipyridine and 1,10-phenanthroline, which can also be viewed as substituted derivatives of pyridine, also form strong complexes, such as in Ferroin
Ferroin
Ferroin is the chemical compound with the formula [Fe3]SO4, where o-phen is an abbreviation for 1,10-phenanthroline, a bidentate ligand. The term "ferroin" is used loosely and includes salts of other anions such as chloride.-Redox indicator:...

 which can be used as an redox indicator
Redox indicator
A redox indicator is an indicator that undergoes a definite color change at a specific electrode potential....

 in the quantitative analysis
Quantitative analysis (chemistry)
In chemistry, quantitative analysis is the determination of the absolute or relative abundance of one, several or all particular substance present in a sample....

 of iron.

The η6 coordination mode, as occurs in η6 benzene complexes, is only observed in sterically encumbered
Steric effects
Steric effects arise from the fact that each atom within a molecule occupies a certain amount of space. If atoms are brought too close together, there is an associated cost in energy due to overlapping electron clouds , and this may affect the molecule's preferred shape and reactivity.-Steric...

 derivatives that block the nitrogen center.

Molecular properties

Pyridine has a conjugated system of six π-electrons
Pi bond
In chemistry, pi bonds are covalent chemical bonds where two lobes of one involved atomic orbital overlap two lobes of the other involved atomic orbital...

 that are delocalized over the ring. The molecule is planar and thus follows the Hückel criteria for aromatic systems. In contrast to benzene, the electron density
Electron density
Electron density is the measure of the probability of an electron being present at a specific location.In molecules, regions of electron density are usually found around the atom, and its bonds...

 is not evenly distributed over the ring, reflecting the negative inductive effect
Inductive effect
In chemistry and physics, the inductive effect is an experimentally observable effect of the transmission of charge through a chain of atoms in a molecule by electrostatic induction...

 of the nitrogen atom. For this reason, pyridine has a dipole moment and a weaker resonant stabilization
Resonance (chemistry)
In chemistry, resonance or mesomerism is a way of describing delocalized electrons within certain molecules or polyatomic ions where the bonding cannot be expressed by one single Lewis formula...

 than benzene (resonance energy 117 kJ·mol−1 in pyridine vs. 150 kJ·mol−1 in benzene). The electron localization in pyridine is also 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 bond
Double bond
A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...

s and are typical of aromatic compounds.

All the ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen atom "donates" its three hybridized electrons to the ring system, and its extra electron pair lies in the molecule plane, projecting outwards, in the plane of the ring. This lone pair
Lone pair
In chemistry, a lone pair is a valence electron pair without bonding or sharing with other atoms. They are found in the outermost electron shell of an atom, so lone pairs are a subset of a molecule's valence electrons...

 does not contribute to the aromatic system but importantly infuences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. However, because of the separation of the lone pair from the aromatic system of the ring affects, the nitrogen atom can not exhibit a positive mesomeric effect
Mesomeric effect
The mesomeric effect or resonance effect in chemistry is a property of substituents or functional groups in a chemical compound. The effect is used in a qualitative way and describes the electron withdrawing or releasing properties of substituents based on relevant resonance structures and is...

.

Many analogues of pyridine are known where N is replaced by other heteroatoms (see Figure). Substitution of one CH in pyridine with a second N gives rise to the "diaza" heterocycles (C4H4N2), with the names pyridazine
Pyridazine
Pyridazine is a heteroaromatic organic compound with the molecular formula C4H4N2, sometimes called 1,2-diazine. It contains a six-membered ring with two adjacent nitrogen atoms. It is a colorless liquid with a boiling point of 208 °C....

, pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...

, and pyrazine
Pyrazine
Pyrazine is a heterocyclic aromatic organic compound with the chemical formula C4H4N2.Pyrazine is a symmetrical molecule with point group D2h. Derivatives like phenazine are well known for their antitumor, antibiotic and diuretic activity. Pyrazine is less basic in nature than pyridine, pyridazine...

.

Reactions

Many reactions that are characteristic of benzene proceed with pyridine either at more complicated conditions or/and with low yield. Owing to the decreased electron density in the aromatic system, electrophilic substitution
Electrophilic substitution
Electrophilic substitution reactions are chemical reactions in which an electrophile displaces a group in a compound, typically but not always hydrogen. Electrophilic aromatic substitution is characteristic of aromatic compounds and is an important way of introducing functional groups onto benzene...

s are suppressed in pyridine and its derivatives in favor of addition
Addition reaction
An addition reaction, in organic chemistry, is in its simplest terms an organic reaction where two or more molecules combine to form a larger one....

 of nucleophiles at the electron-rich nitrogen atom. The nucleophilic addition at the nitrogen atom leads to a further deactivation of the aromatic properties and hindering of the electrophilic substitution. On the other hand, free-radical and nucleophilic substitutions
Nucleophilic aromatic substitution
right|300px|Aromatic nucleophilic substitutionA nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring...

 occur more readily in pyridine than in benzene.

Electrophilic substitutions

Many electrophilic substitutions on pyridine either do not proceed or proceed only partially; however, the heteroaromatic character can be activated by electron-donating functionalization. Common alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...

s and acylation
Acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....

s, such as Friedel–Crafts alkylation or acylation, usually fail for pyridine because they only lead to the addition at the nitrogen atom. Substitutions usually occur at the 3-position which is the electron-richest carbon atom in the ring and is therefore more susceptible to an electrophilic addition.
Substitutions to pyridine at the 2- or 4-position result in an energetically unfavorable σ complex. They can be promoted, however, using clever experimental techniques, such as conducting electrophilic substitution on the pyridine-N-oxide followed by deoxygenation of the nitrogen atom. Addition of oxygen reduces electron density on the nitrogen atom and promotes substitution at the 2- and 4-carbons. The oxygen atom can then be removed via several routes, most commonly with compounds of trivalent phosphorus
Phosphorus
Phosphorus is the chemical element that has the symbol P and atomic number 15. A multivalent nonmetal of the nitrogen group, phosphorus as a mineral is almost always present in its maximally oxidized state, as inorganic phosphate rocks...

 or divalent sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...

 which are easily oxidized. Triphenylphosphine
Triphenylphosphine
Triphenylphosphine is a common organophosphorus compound with the formula P3 - often abbreviated to PPh3 or Ph3P. It is widely used in the synthesis of organic and organometallic compounds. PPh3 exists as relatively air stable, colorless crystals at room temperature...

 is a frequently used reagent, which is oxidized in this reaction to triphenylphosphine oxide
Triphenylphosphine oxide
Triphenylphosphine oxide is the chemical compound with the formula OP3. Often chemists abbreviate the formula by writing Ph3PO or PPh3O . This white crystalline compound is a common side product in reactions involving triphenylphosphine...

. The following paragraphs describe representative electrophilic substitution reactions of pyridine.

Direct nitration
Nitration
Nitration is a general chemical process for the introduction of a nitro group into a chemical compound. The dominant application of nitration is for the production of nitrobenzene, the precursor to methylene diphenyl diisocyanate...

 of pyridine requires harsh conditions and has very low yields. The 3-nitropyridine can be obtained instead by reacting pyridine with dinitrogen pentoxide
Dinitrogen pentoxide
Dinitrogen pentoxide is the chemical compound with the formula N2O5. Also known as nitrogen pentoxide, N2O5 is one of the binary nitrogen oxides, a family of compounds that only contain nitrogen and oxygen...

 in presence of sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

. Pyridine derivatives where the nitrogen atom is screened sterically and/or electronically can be obtained by nitridation with nitronium tetrafluoroborate
Nitronium tetrafluoroborate
Nitronium tetrafluoroborate is an inorganic compound with formula NO2BF4. It is a salt of nitronium cation and tetrafluoroborate anion. It is a colorless crystalline solid, which reacts heavily with water to form the corrosive acids HF and HNO3. As such, it must be handled under water-free conditions...

 (NO2BF4). In this way, 3-nitropyridine can be obtained via the synthesis of 2,6-dibromopyridine followed by removal of the bromine atoms.
Direct sulfonation of pyridine is even more difficult than direct nitridation. However, pyridine-3-sulfonic acid can be obtained at acceptable yield by boiling pyridine in an excess of sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...

 at 320 °C. Reaction with the SO3 group also facilitates addition of sulfur to the nitrogen atom, especially in the presence of a mercury(II) sulfate
Mercury(II) sulfate
Mercury sulfate, commonly called mercuric sulfate is the chemical compound Hg S O4. It is an odorless solid that forms white granules or crystalline powder...

 catalyst.

In contrast to the nitration and sulfonation, the direct bromination and chlorination
Chlorination
Chlorination is the process of adding the element chlorine to water as a method of water purification to make it fit for human consumption as drinking water...

 of pyridine proceed well. The reaction of pyridine with molecular bromine
Bromine
Bromine ") is a chemical element with the symbol Br, an atomic number of 35, and an atomic mass of 79.904. It is in the halogen element group. The element was isolated independently by two chemists, Carl Jacob Löwig and Antoine Jerome Balard, in 1825–1826...

 in sulfuric acid at 130 °C readily produced 3-bromopyridine. The yield is lower for 3-chloropyridine upon chlorination with molecular chlorine
Chlorine
Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...

 in the presence of aluminium chloride
Aluminium chloride
Aluminium chloride is the main compound of aluminium and chlorine. It is white, but samples are often contaminated with iron trichloride, giving it a yellow colour. The solid has a low melting and boiling point. It is mainly produced and consumed in the production of aluminium metal, but large...

 at 100 °C. Both 2-bromopyridine and 2-chloropyridine can be produced by direct reaction with halogen with a palladium(II) chloride
Palladium(II) chloride
Palladium chloride, also known as palladium dichloride, are the chemical compounds with the formula PdCl2. PdCl2 is a common starting material in palladium chemistry – palladium-based catalysts are of particular value in organic synthesis. It is prepared by chlorination of...

 catalyst.

Nucleophilic substitutions

In contrast to benzene, pyridine efficiently supports several nucleophilic substitutions, and is regarded as a good nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

 (donor number
Donor number
In chemistry a donor number or DN is a qualitative measure of Lewis basicity. A donor number is defined as the negative enthalpy value for the 1:1 adduct formation between a Lewis base and the standard Lewis acid SbCl5 , in dilute solution in the noncoordinating solvent 1,2-dichloroethane with a...

 33.1). The reason for this is relatively lower electron density of the carbon atoms of the ring. These reactions include substitutions with elimination of a hydride
Hydride
In chemistry, a hydride is the anion of hydrogen, H−, or, more commonly, a compound in which one or more hydrogen centres have nucleophilic, reducing, or basic properties. In compounds that are regarded as hydrides, hydrogen is bonded to a more electropositive element or group...

 ion and elimination-additions with formation of an intermediate arine configuration, and usually proceed at 2- or 4-position.

Many nucleophilic substitutions occur easier not with bare pyridine, but with pyridine modified with bromine, chlorine, fluorine or sulfonic acid fragments which then become a leaving group. So fluorine is the best leaving group for the substitution with organolithium compounds. The nucleophilic attack compounds may be alkoxide
Alkoxide
An alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They can be written as RO−, where R is the organic substituent. Alkoxides are strong bases and, when R is not bulky, good nucleophiles and good ligands...

s, thiolates, amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...

s, and ammonia (at elevated pressures).

The hydride ion is generally a poor leaving group and occurs only in a few heterocyclic reactions. They include the Chichibabin reaction
Chichibabin reaction
The Chichibabin reaction -chē-bā-bēn) is a method for producing 2-aminopyridine derivatives by the reaction of pyridine with sodium amide. It was reported by Aleksei Chichibabin in 1914. The following is the overall form of the general reaction:...

 which yields pyridine derivatives aminated
Amination
Amination is the process by which an amine group is introduced into an organic molecule. Enzymes which catalyse this reaction, are termed aminases. This can occur in a number of ways including reaction with ammonia or another amine such as an alkylation, reductive amination and the Mannich reaction...

 at the 2-position. Here sodium amide
Sodium amide
Sodium amide, commonly called sodamide, is the chemical compound with the formula NaNH2. This solid, which is dangerously reactive toward water, is white when pure, but commercial samples are typically gray due to the presence of small quantities of metallic iron from the manufacturing process...

 is used as the nucleophile yielding 2-aminopyridine. The hydride ion released in this reaction combines with a proton of an available amino group forming a hydrogen molecule.

Analogous to benzene, nucleophilic substitutions to pyridine can result in the formation of heteroarine intermediates. For this purpose, pyridine derivatives can be eliminated with good leaving groups using strong bases such as sodium and potassium tert-butoxide
Potassium tert-butoxide
Potassium tert-butoxide is the chemical compound with the formula 3COK. This colourless solid is a strong base useful in organic synthesis. It exists as a tetrameric cubane-like cluster...

. The subsequent addition of a nucleophile to the triple bond
Triple bond
A triple bond in chemistry is a chemical bond between two chemical elements involving six bonding electrons instead of the usual two in a covalent single bond. The most common triple bond, that between two carbon atoms, can be found in alkynes. Other functional groups containing a triple bond are...

 has low selectivity and the result is a mixture of the two possible adducts.

Radical reactions

Pyridine supports a series of radical reactions, which is used in its dimerization to bipyridines. Radical dimerization of pyridine with elemental sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 or Raney nickel
Raney nickel
Raney nickel is a solid catalyst composed of fine grains of a nickel-aluminium alloy, used in many industrial processes. It was developed in 1926 by American]] engineer Murray Raney as an alternative catalyst for the hydrogenation of vegetable oils in industrial processes...

 selectively yields 4,4'-bipyridine
4,4'-Bipyridine
4,4'-Bipyridine is a bipyridine which is mainly used as a precursor to N,N'-dimethyl-4,4'-bipyridinium [2]2+, known as paraquat. This species is electroactive, and its toxicity arises from the ability of this dication to interrupt biological electron transfer...

 or 2,2'-bipyridine
2,2'-Bipyridine
2,2'-Bipyridine is a organic compound with the formula . This colorless solid, commonly abbreviated bipy or bpy , is an important isomer of the bipyridine family. It is a bidentate chelating ligand, forming complexes with many transition metals...

, which are important precursor reagents in the chemical industry. One of the name reactions involving free radicals is the Minisci reaction
Minisci reaction
The Minisci-Reaction is a named reaction in organic chemistry. It is a radical substitution to an aromatic compound, in particular to a heteroaromatic base, that introduces an alkyl group. The reaction was published about in 1971 by F. Minisci.. The aromatic compound is generally electron-deficient...

. It can produce 2-tert-butylpyridine upon reacting pyridine with pivalic acid
Pivalic acid
Pivalic acid is a carboxylic acid with a molecular formula of 3CCO2H. This colourless, odiferous organic compound is solid at room temperature.-Industrial route:...

, silver nitrate
Silver nitrate
Silver nitrate is an inorganic compound with chemical formula . This compound is a versatile precursor to many other silver compounds, such as those used in photography. It is far less sensitive to light than the halides...

 and ammonium
Ammonium
The ammonium cation is a positively charged polyatomic cation with the chemical formula NH. It is formed by the protonation of ammonia...

 in sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...

 with a yield of 97%.

Reactions on the nitrogen atom

Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...

s easily add to the nitrogen atom of pyridine forming pyridinium salts. The reaction with alkylhalides leads to alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...

 of the nitrogen atom. This creates a positive charge in the ring that increases the reactivity of pyridine to both oxidation and reduction. The Zincke reaction
Zincke reaction
The Zincke reaction is an organic reaction in which a pyridine is transformed into a pyridinium salt by reaction with 2,4-dinitro-chlorobenzene and a primary amine, named after Theodor Zincke....

 is used for the selective introduction of radicals in pyridinium compounds (it has no relation to the chemical element zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...

).

Hydrogenation and reduction

Hydrogen-saturated piperidine is obtained through reaction with hydrogen gas in the presence of Raney nickel
Raney nickel
Raney nickel is a solid catalyst composed of fine grains of a nickel-aluminium alloy, used in many industrial processes. It was developed in 1926 by American]] engineer Murray Raney as an alternative catalyst for the hydrogenation of vegetable oils in industrial processes...

. This reaction releases 193.8 kJ·mol−1 of energy, which is slightly less than the energy of the hydrogenation of benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....

 (205.3 kJ·mol−1).

Partially hydrogenated derivatives are obtained under milder conditions. For example, reduction with lithium aluminium hydride
Lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH or known as LithAl, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters,...

 yields a mixture of 1,4-dihydropyridine, 1,2-dihydropyridine and 2,5-dihydropyridine. Selective synthesis of 1,4-dihydropyridine is achieved in the presence of organometallic complexes of magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

 and zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...

, and (Δ3,4)-tetrahydropyridine is obtained by electrochemical reduction of pyridine.

Applications

Pyridine is an important raw material in of the chemical industry
Chemical industry
The chemical industry comprises the companies that produce industrial chemicals. Central to the modern world economy, it converts raw materials into more than 70,000 different products.-Products:...

, 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
Evonik Industries
Evonik Industries is an industrial corporation in Germany owned by RAG Foundation and one of the world´s leading specialty chemicals companies. It was created on 12 September 2007 as a result of restructuring of the mining and technology group RAG...

, Rütgers Chemicals, Imperial Chemical Industries
Imperial Chemical Industries
Imperial Chemical Industries was a British chemical company, taken over by AkzoNobel, a Dutch conglomerate, one of the largest chemical producers in the world. In its heyday, ICI was the largest manufacturing company in the British Empire, and commonly regarded as a "bellwether of the British...

 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
Joint venture
A joint venture is a business agreement in which parties agree to develop, for a finite time, a new entity and new assets by contributing equity. They exercise control over the enterprise and consequently share revenues, expenses and assets...

 Vertellus is currently the world leader in pyridine production.

Pyridine is used as polar, basic, low-reactive solvent, for example in Knoevenagel condensation
Knoevenagel condensation
The Knoevenagel condensation reaction is an organic reaction named after Emil Knoevenagel. It is a modification of the Aldol condensation.A Knoevenagel condensation is a nucleophilic addition of an active hydrogen compound to a carbonyl group followed by a dehydration reaction in which a molecule...

s. It is especially suitable for the dehalogenation, where it acts as the base of the elimination reaction
Elimination reaction
An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism...

 and bonds the resulting hydrogen halide to form a pyridinium salt. In esterifications and acylations pyridine activates the carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...

 halides or anhydrides. Even more active in these reactions are the pyridine derivatives 4-dimethylaminopyridine
4-Dimethylaminopyridine
4-Dimethylaminopyridine is a derivative of pyridine with the chemical formula 2NC5H4N. This colourless solid is a useful nucleophilic catalyst for a variety of reactions such as esterifications with anhydrides, the Baylis-Hillman reaction, hydrosilylations, tritylation, the Steglich...

 (DMAP) and 4-(1-pyrrolidinyl) pyridine. Pyridine is also used as a base in condensation reaction
Condensation reaction
A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...

s.
Pyridinium chlorochromate
Pyridinium chlorochromate
Pyridinium chlorochromate is a reddish orange solid reagent used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones. Pyridinium chlorochromate, or PCC, will not fully oxidize a primary alcohol to the carboxylic acid as does the Jones reagent. A disadvantage to using PCC is...

 was developed by Elias James Corey
Elias James Corey
Elias James Corey is an American organic chemist. In 1990 he won the Nobel Prize in Chemistry "for his development of the theory and methodology of organic synthesis", specifically retrosynthetic analysis...

 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
Chromic acid
The term chromic acid is usually used for a mixture made by adding concentrated sulfuric acid to a dichromate, which may contain a variety of compounds, including solid chromium trioxide. This kind of chromic acid may be used as a cleaning mixture for glass. Chromic acid may also refer to the...

 and concentrated hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....

:
C5H5N + HCl + CrO3 → [C5H5NH][CrO3Cl]


The carcinogenicity of the side-product chromyl chloride
Chromyl chloride
Chromyl chloride is a chemical compound with the formula CrO2Cl2. This compound is an opaque dark blood-red liquid at room temperature and pressure. It is tetrahedral, somewhat like SO2Cl2. CrO2Cl2 is similar to the most commonly encountered chromium derivative chromate, [CrO4]2−; both are...

 (CrO2Cl2) urged to look for alternative routes, such as treating chromium(VI) oxide with pyridinium chloride:
[C5H5NH+]Cl + CrO3 → [C5H5NH][CrO3Cl]


The Cornforth reagent
Cornforth reagent
The Cornforth reagent or pyridinium dichromate is a pyridinium salt of dichromate with the chemical formula [C5H5NH]2[Cr2O7]. This compound is named after the Australian-British chemist Sir John Warcup Cornforth who introduced it in 1962...

 (pyridinium dichromate, PDC), pyridinium chlorochromate
Pyridinium chlorochromate
Pyridinium chlorochromate is a reddish orange solid reagent used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones. Pyridinium chlorochromate, or PCC, will not fully oxidize a primary alcohol to the carboxylic acid as does the Jones reagent. A disadvantage to using PCC is...

 (PCC), the Collins reagent
Collins reagent
Collins reagent is the complex of chromium oxide with pyridine in dichloromethane. It is used to selectively oxidize primary alcohols to the aldehyde, and will tolerate many other functional groups within the molecule....

 (complex of chromium(VI) oxide
Chromium trioxide
Chromium trioxide is the inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name.This compound is a dark-red/orange brown solid, which dissolves in water concomitant with hydrolysis...

 with pyridine in dichloromethane
Dichloromethane
Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...

) and the Sarret reagent (complex of chromium(VI) oxide
Chromium trioxide
Chromium trioxide is the inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name.This compound is a dark-red/orange brown solid, which dissolves in water concomitant with hydrolysis...

 with pyridine in pyridine) are similar chromium-based pyridine compounds, which are also used for oxidation, namely conversion of primary
Primary alcohol
A primary alcohol is an alcohol which has the hydroxyl radical connected to a primary carbon. It can also be defined as a molecule containing a “–CH2OH” group.Examples include ethanol and butanol....

 and secondary alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

s to ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...

s. 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
Polymerization
In polymer chemistry, polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains...

 and hydrogenation reactions, using, for example, the Crabtree's catalyst
Crabtree's catalyst
Crabtree's catalyst is the name given to a complex of iridium with 1,5-cyclooctadiene, tris-cyclohexylphosphine, and pyridine. It is a homogeneous catalyst for hydrogenation reactions, developed by Robert H. Crabtree, a professor at Yale University...

. 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, insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...

s and herbicide
Herbicide
Herbicides, also commonly known as weedkillers, are pesticides used to kill unwanted plants. Selective herbicides kill specific targets while leaving the desired crop relatively unharmed. Some of these act by interfering with the growth of the weed and are often synthetic "imitations" of plant...

s. It was and is used in large quantities in the production of herbicides diquat
Diquat
Diquat is a contact herbicide that produces desiccation and defoliation most often available as the dibromide, diquat dibromide. Brand names for this formulation include Aquacide, Dextrone, Preeglone, Deiquat, Detrone, Reglone, Reglon, Reglox, Ortho-Diquat and Weedtrine-D.Diquat is a non-selective...

 and paraquat
Paraquat
Paraquat is the trade name for N,N′-dimethyl-4,4′-bipyridinium dichloride, one of the most widely used herbicides in the world. Paraquat, a viologen, is quick-acting and non-selective, killing green plant tissue on contact. It is also toxic to human beings and animals...

, which contain bipyridine fragments. The first synthesis step of insecticide chlorpyrifos
Chlorpyrifos
Chlorpyrifos is a crystalline organophosphate insecticide that inhibits acetylcholinesterase and is used to control insect pests. It is known by many trade names...

 consists of the chlorination of pyridine. Pyridine is also the starting compound for the preparation of pyrithione-based fungicide
Fungicide
Fungicides are chemical compounds or biological organisms used to kill or inhibit fungi or fungal spores. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality and profit. Fungicides are used both in agriculture and to fight fungal infections in animals...

s. Cetylpyridinium
Cetylpyridinium chloride
Cetylpyridinium chloride is a cationic quaternary ammonium compound in some types of mouthwashes, toothpastes, lozenges, throat sprays, breath sprays, and nasal sprays. It is an antiseptic that kills bacteria and other microorganisms. It has been shown to be effective in preventing dental plaque...

 and laurylpyridinium, which can be produced from pyridine with a Zincke reaction, are used as antiseptic
Antiseptic
Antiseptics are antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction...

 in oral and dental care products.
In addition to pyridines, piperidine
Piperidine
Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...

 derivatives are also important synthetic building blocks. A common synthesis of piperidine is the reduction of pyridine with a nickel
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...

, cobalt
Cobalt
Cobalt is a chemical element with symbol Co and atomic number 27. It is found naturally only in chemically combined form. The free element, produced by reductive smelting, is a hard, lustrous, silver-gray metal....

 or ruthenium
Ruthenium
Ruthenium is a chemical element with symbol Ru and atomic number 44. It is a rare transition metal belonging to the platinum group of the periodic table. Like the other metals of the platinum group, ruthenium is inert to most chemicals. The Russian scientist Karl Ernst Claus discovered the element...

-based catalyst at elevated temperatures.

Pyridine is used as a solvent in the manufacture of dyes and rubber
Rubber
Natural rubber, also called India rubber or caoutchouc, is an elastomer that was originally derived from latex, a milky colloid produced by some plants. The plants would be ‘tapped’, that is, an incision made into the bark of the tree and the sticky, milk colored latex sap collected and refined...

. It is also used in the textile industry to improve network capacity of cotton
Cotton
Cotton is a soft, fluffy staple fiber that grows in a boll, or protective capsule, around the seeds of cotton plants of the genus Gossypium. The fiber is almost pure cellulose. The botanical purpose of cotton fiber is to aid in seed dispersal....

. Pyridine is added to ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

 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
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

. The detection threshold for pyridine in solutions is about 1–3 mmole
Mole (unit)
The mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...

·L−1 (79–237 mg·L−1). As a base, pyridine can be used as the Karl Fischer reagent
Karl Fischer titration
Karl Fischer titration is a classic titration method in analytical chemistry that uses coulometric or volumetric titration to determine trace amounts of water in a sample. It was invented in 1935 by the German chemist Karl Fischer.-Coulometric titration:...

, but it is usually replaced by alternatives with a more pleasant odor, such as imidazole
Imidazole
Imidazole is an organic compound with the formula C3H4N2. This aromatic heterocyclic is a diazole and is classified as an alkaloid. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents...

.

Pyridine is widely used as a ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

 in coordination chemistry. Also important are its chelating derivatives 2,2'-bipyridine
Bipyridine
Bipyridines are a family of chemical compounds with the formula 2, which are formed by the coupling of two pyridine rings. Six isomers of bipyridine exist, but two isomers are prominent: 2,2'-bipyridine is a popular ligand in coordination chemistry and 4,4'-bipyridine is a precursor to the...

, consisting of two pyridine molecules joined by a single bond, and terpyridine
Terpyridine
Terpyridine is a heterocyclic compound derived from pyridine. This colourless solid is used as a ligand in coordination chemistry.-Synthesis:...

, 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
Cetylpyridinium chloride
Cetylpyridinium chloride is a cationic quaternary ammonium compound in some types of mouthwashes, toothpastes, lozenges, throat sprays, breath sprays, and nasal sprays. It is an antiseptic that kills bacteria and other microorganisms. It has been shown to be effective in preventing dental plaque...

, a cationic surfactant that is a widely used disinfection
Disinfection
Disinfectants are substances that are applied to non-living objects to destroy microorganisms that are living on the objects. Disinfection does not necessarily kill all microorganisms, especially nonresistant bacterial spores; it is less effective than sterilisation, which is an extreme physical...

 and antiseptic
Antiseptic
Antiseptics are antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction...

 agent. Pyridinium salts can be obtained in the Zincke reaction
Zincke reaction
The Zincke reaction is an organic reaction in which a pyridine is transformed into a pyridinium salt by reaction with 2,4-dinitro-chlorobenzene and a primary amine, named after Theodor Zincke....

. Useful adduct
Adduct
An adduct is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components. The resultant is considered a distinct molecular species...

s of pyridine include pyridine-borane
Borane
In chemistry, a borane is a chemical compound of boron and hydrogen. The boranes comprise a large group of compounds with the generic formulae of BxHy. These compounds do not occur in nature. Many of the boranes readily oxidise on contact with air, some violently. The parent member BH3 is called...

, 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
Sulfur trioxide pyridine complex
Sulfur trioxide pyridine complex is a complex formed where the lone pair on the nitrogen of the pyridine binds to the sulfur of the sulfur trioxide...

, C5H5NSO3 (melting point 175 °C) is a sulfonation agent used to convert alcohols to sulfonates, which in turn undergo C-O bond
Carbon-oxygen bond
A carbon–oxygen bond is a covalent bond between carbon and oxygen and one of the most abundant in organic chemistry and biochemistry. Oxygen has 6 valence electrons and prefers to share two electrons in bonding with carbon, leaving the remaining 4 nonbonding electrons in 2 lone pairs...

 scission
Beta scission
Beta scission is an important reaction in the chemistry of thermal cracking of hydrocarbons and the formation of free radicals. Free radicals are formed upon splitting the carbon-carbon bond. Free radicals are extremely reactive and short-lived...

 upon reduction with hydride agents.

Hazards

Pyridine has a flash point
Flash point
The flash point of a volatile material is the lowest temperature at which it can vaporize to form an ignitable mixture in air. Measuring a flash point requires an ignition source...

 (the lowest temperature at which it can vaporize to form an ignitable mixture in air) of only 17 °C and is therefore highly flammable. Its ignition temperature is 550 °C, and mixtures of 1.7–10.6 vol% of pyridine with air are explosive. The thermal modification of pyridine starts above 490 °C, resulting in bipyridine
Bipyridine
Bipyridines are a family of chemical compounds with the formula 2, which are formed by the coupling of two pyridine rings. Six isomers of bipyridine exist, but two isomers are prominent: 2,2'-bipyridine is a popular ligand in coordination chemistry and 4,4'-bipyridine is a precursor to the...

 (mainly 2,2'-bipyridine and to a lesser extent 2,3'-bipyridine and 2,4'-bipyridine), nitrogen oxide
Nitrogen oxide
Nitrogen oxide can refer to a binary compound of oxygen and nitrogen, or a mixture of such compounds:* Nitric oxide, also known as nitrogen monoxide, , nitrogen oxide* Nitrogen dioxide , nitrogen oxide...

s and carbon monoxide
Carbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...

. Pyridine easily dissolves in water and harms both animals and plants in aquatic systems. The permitted maximum allowable concentration
Threshold Limit Value
The threshold limit value of a chemical substance is a level to which it is believed a worker can be exposed day after day for a working lifetime without adverse health effects. Strictly speaking, TLV is a reserved term of the American Conference of Governmental Industrial Hygienists...

 of pyridine was 15–30
parts per million (ppm, or 15–30 mg·m−3 in air) in most countries in the 1990s, but was reduced to 5 ppm in the 2000s. For comparison, indoor air contaminated with tobacco smoke may contain up to 16 µg·m−3, and one cigarette contains 21–32 µg of pyridine.

Health issues

Pyridine is harmful if inhaled, swallowed or absorbed through the skin. Effects of an acute pyridine intoxication include dizziness, headache, lack of coordination
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

, nausea, saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...

tion and loss of appetite. They may progress into abdominal pain, pulmonary congestion and unconsciousness. One person died after accidental ingestion of half a cup of pyridine. The lowest known lethal dose
Lethal dose
A lethal dose is an indication of the lethality of a given substance or type of radiation. Because resistance varies from one individual to another, the 'lethal dose' represents a dose at which a given percentage of subjects will die...

 (LDLo) for the ingestion of pyridine in humans is 500 mg·kg−1. In high doses pyridine has a narcotic effect and its vapor concentrations of above 3600 ppm pose health risk. The LD50 in rats (oral) is 891 mg·kg−1. Pyridine is flammable.

Evaluations as a possible carcinogenic agent showed there is inadequate evidence in humans for the carcinogenicity of pyridine, albeit there is limited evidence of carcinogenic effects on animals. Available data indicate that "exposure to pyridine in drinking-water led to reduction of sperm motility at all dose levels in mice and increased estrous cycle length at the highest dose level in rats".

Pyridine might also have minor neurotoxic
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

, genotoxic and clastogenic
Clastogenic
Clastogenic is an adjective that describes the ability of an agent or process to act as a clastogen—an agent or process giving rise to or inducing disruption or breakages of chromosomes.-Biology:...

 effects. Exposure to pyridine would normally lead to its inhalation and absorption in the lungs and gastrointestinal tract, where it either remains unchanged or is metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

. The major products of pyridine metabolism are N-methylpyryliumhydroxide, which is formed by N-methyltransferase
N-methyltransferase
N-methyltransferase may refer to*-1-benzyl-1,2,3,4-tetrahydroisoquinoline N-methyltransferase*3-hydroxy-16-methoxy-2,3-dihydrotabersonine N-methyltransferase*Amine N-methyltransferase*Anthranilate N-methyltransferase...

s (e.g. pyridine N-methyltransferase
Pyridine N-methyltransferase
In enzymology, a pyridine N-methyltransferase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are S-adenosyl methionine and pyridine, whereas its two products are S-adenosylhomocysteine and N-methylpyridinium....

), as well as pyridine-N oxide, and 2-, 3- and 4-hydroxypyridine, which are generated by the action of monooxygenase
Monooxygenase
Monooxygenases are enzymes that incorporate one hydroxyl group into substrates in many metabolic pathways. In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of NADH.-Classification:...

. In humans, pyridine is metabolized only into N-methylpyryliumhydroxide. Pyridine is readily degraded by bacteria to ammonia and carbon dioxide. The unsubstituted pyridine ring degrades more rapidly than picoline
Picoline
Picoline refers to three different methylpyridine isomers, all with the chemical formula C6H7N and a molar mass of 93.13 g mol−1. All three are colourless liquids at room temperature and pressure and are miscible with water and most organic solvents...

, lutidine, chloropyridine, or aminopyridine
Aminopyridine
Aminopyridine may refer to any of several chemical compounds:* 2-Aminopyridine* 3-Aminopyridine* 4-Aminopyridine...

, and a number of pyridine degraders have been shown to overproduce riboflavin
Riboflavin
Riboflavin, also known as vitamin B2 or additive E101, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a...

 in the presence of pyridine.

Minor amounts of pyridine are released into environment from some industrial processes such as steel manufacture, processing of oil shale
Oil shale
Oil shale, an organic-rich fine-grained sedimentary rock, contains significant amounts of kerogen from which liquid hydrocarbons called shale oil can be produced...

, coal gasification, coking plants and incinerators
Incineration
Incineration is a waste treatment process that involves the combustion of organic substances contained in waste materials. Incineration and other high temperature waste treatment systems are described as "thermal treatment". Incineration of waste materials converts the waste into ash, flue gas, and...

. The atmosphere at oil shale processing plants can contain pyridine concentrations of up to 13 µg·m−3, and 53 µg·m−3 levels were measured in the groundwater
Groundwater
Groundwater is water located beneath the ground surface in soil pore spaces and in the fractures of rock formations. A unit of rock or an unconsolidated deposit is called an aquifer when it can yield a usable quantity of water. The depth at which soil pore spaces or fractures and voids in rock...

 in the vicinity of a coal gasification plant. According to a study by the US National Institute for Occupational Safety and Health
National Institute for Occupational Safety and Health
The National Institute for Occupational Safety and Health is the United States’ federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the Centers for Disease Control and Prevention within the U.S...

, about 43,000 Americans work in contact with pyridine.

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