Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, 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".[4] In addition to pyrrolidine itself, many substituted pyrrolidines are known.
Pyrrolidine
Names
Pyrrolidine[1]
Azolidine
Azacyclopentane
Tetrahydropyrrole
Prolamine
Azolane
Identifiers
Y3D model (JSmol)
102395
Y1704
PubChem CID
1922
CompTox Dashboard (EPA)
InChI=1S/C4H9N/c1-2-4-5-3-1/h5H,1-4H2 Y
Key: RWRDLPDLKQPQOW-UHFFFAOYSA-N Y
InChI=1/C4H9N/c1-2-4-5-3-1/h5H,1-4H2
Key: RWRDLPDLKQPQOW-UHFFFAOYAX
C1CCNC1
Properties
C4H9N
71.123 g·mol−1
Appearance
Clear colorless liquid
0.866 g/cm3
−63 °C (−81 °F; 210 K)
87 °C (189 °F; 360 K)
Miscible
Acidity (pKa)
11.27 (pKa of conjugate acid in water),[2]
19.56 (pKa of conjugate acid in acetonitrile)[3]
-54.8·10−6cm3/mol
Refractive index (nD)
1.4402 at 28°C
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
highly flammable, harmful, corrosive, possible mutagen
Danger
H225, H302, H314, H332
P210, P233, P240, P241, P242, P243, P260, P261, P264, P270, P271, P280, P301+P312, P301+P330+P331, P303+P361+P353, P304+P312, P304+P340, P305+P351+P338, P310, P312, P321, P330, P363, P370+P378, P403+P235, P405, P501
NFPA 704 (fire diamond)
3 °C (37 °F; 276 K)
345 °C (653 °F; 618 K)
Safety data sheet (SDS)
Related compounds
Related nitrogen heterocyclic compounds
Pyrrole (aromatic with two double bonds)
Pyrroline (one double bond)
Pyrrolizidine (two pentagonal rings)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Pyrrolidine is prepared industrially by the reaction of 1,4-butanediol and ammonia 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.[5]
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.[5]
In the laboratory, pyrrolidine was usually synthesised by treating 4-chlorobutan-1-amine with a strong base:
Furthermore, 5-membered N-heterocyclic ring of the pyrrolidine derivatives can be synthesized via cascade reactions.[6]
Many modifications of pyrrolidine are found in natural and synthetic drugs and drug candidates.[6] The pyrrolidine ring structure is present in numerous natural alkaloids i.a. nicotine 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 acids proline and hydroxyproline are, in a structural sense, derivatives of pyrrolidine.
Pyrrolidine is a base. Its basicity is typical of other dialkyl amines.[7] 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 ketones and aldehydes toward nucleophilic addition by formation of enamines (e.g. used in the Stork enamine alkylation):[8]
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