Pyrrolidine, also known as tetrahydropyrrole, is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

with the molecular formula (CH₂)₄NH. It is a cyclic secondary

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...

, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most organic solvents. It has a characteristic odor that has been described as "ammoniacal, fishy, shellfish-like". In addition to pyrrolidine itself, many substituted pyrrolidines are known.

Production and synthesis

Industrial production

Pyrrolidine is prepared industrially by the reaction of 1,4-butanediol and

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...

at a temperature of 165–200 °C and a pressure of 17–21 MPa in the presence of a cobalt- and nickel oxide catalyst, which is supported on alumina. : Industrial synthesis of pyrrolidine

The reaction is carried out in the liquid phase in a continuous tube- or tube bundle reactor, which is operated in the cycle gas method. The catalyst is arranged as a fixed-bed and the conversion is carried out in the downflow mode. The product is obtained after multistage purification and separation by extractive and

azeotropic distillation In chemistry, azeotropic distillation is any of a range of techniques used to break an azeotrope in distillation. In chemical engineering, ''azeotropic distillation'' usually refers to the specific technique of adding another component to gene ...

Laboratory synthesis

In the laboratory, pyrrolidine was usually synthesised by treating 4-chlorobutan-1-amine with a strong base: : Pyrrolidine synthesis

Furthermore, 5-membered ''N''-heterocyclic ring of the pyrrolidine derivatives can be synthesized via cascade reactions.

Occurrence

Many modifications of pyrrolidine are found in natural and synthetic drugs and drug candidates. The pyrrolidine ring structure is present in numerous natural

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of simila ...

s ''i.a.''

nicotine Nicotine is a naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and '' Duboisia hopwoodii'') and is widely used recreationally as a stimulant and anxiolytic. As a pharmaceutical drug, it is use ...

and hygrine. It is found in many drugs such as procyclidine and bepridil. It also forms the basis for the racetam compounds (''e.g.'' piracetam, aniracetam). The

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

and

hydroxyproline (2''S'',4''R'')-4-Hydroxyproline, or L-hydroxyproline ( C5 H9 O3 N), is an amino acid, abbreviated as Hyp or O, ''e.g.'', in Protein Data Bank. Structure and discovery In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gelatin ...

are, in a structural sense, derivatives of pyrrolidine. : Nicotine

Reactions

Pyrrolidine is a base. Its basicity is typical of other dialkyl amines. Relative to many secondary amines, pyrrolidine is distinctive because of its compactness, a consequence of its cyclic structure. Pyrrolidine is used as a building block in the synthesis of more complex organic compounds. It is used to activate

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double b ...

s and

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl gro ...

s toward nucleophilic addition by formation of enamines (e.g. used in the Stork enamine alkylation): : Enamine

References

External links

*{{Commonscat-inline Amine solvents