Pyrrole

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Pyrrole
Explicit structural formula of pyrrole, with aromaticity indicated by dashed bonds Numbered skeletal formula of pyrrole
Ball-and-stick model of the pyrrole molecule Space-filling model of the pyrrole molecule
Identifiers
CAS number 109-97-7 YesY
PubChem 8027
ChemSpider 7736 YesY
UNII 86S1ZD6L2C YesY
EC number 203-724-7
UN number 1992, 1993
ChEBI CHEBI:19203 YesY
ChEMBL CHEMBL16225 YesY
RTECS number UX9275000
Beilstein Reference 1159
Gmelin Reference 1705
Jmol-3D images Image 1
Image 2
Properties
Molecular formula C4H5N
Molar mass 67.09 g mol−1
Density 0.967 g cm–3
Melting point −23 °C (−9 °F; 250 K)
Boiling point 129 to 131 °C (264 to 268 °F; 402 to 404 K)
Vapor pressure 7 mmHg at 23 °C
Viscosity 0.001225 Pa s
Thermochemistry
Specific
heat capacity
C
1.903 J k–1 mol k–1
Std enthalpy of
formation
ΔfHo298
108.2 kJ mol–1 (gas)
Std enthalpy of
combustion
ΔcHo298
2242 kJ mol–1
Hazards
NFPA 704
Flammability code 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g., diesel fuel Health code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroform Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
Flash point 33.33 °C (91.99 °F; 306.48 K)
Explosive limits 3.1–14.8%
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH.[1] It is a colourless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3. Porphobilinogen, a trisubstituted pyrrole, is the biosynthetic precursor to many natural products such as heme.[2]

Pyrroles are components of more complex macrocycles, including the porphyrins of heme, the chlorins, bacteriochlorins, chlorophyll, porphyrinogens.[3]

Properties[edit]

Pyrrole has very low basicity compared to conventional amines and some other aromatic compounds like pyridine. This decreased basicity is attributed to the delocalization of the lone pair of electrons of the nitrogen atom in the aromatic ring. Pyrrole is a very weak base with a pKaH of about –1 to –2. Protonation results in loss of aromaticity, and is, therefore, unfavorable.

Like many amines, pyrrole slowly decomposes on exposure to air and light. It turns brown over time due to accumulation of impurities such as polypyrrole and various amine oxides. It is usually purified by distillation immediately before use.[4]

Synthesis[edit]

Pyrrole is prepared industrially by treatment of furan with ammonia in the presence of solid acid catalysts.[5]

Synthesis of pyrrole from furan

One synthetic route to pyrrole involves the decarboxylation of ammonium mucate, the ammonium salt of mucic acid. The salt is typically heated in a distillation setup with glycerol as a solvent.[6]

Synthesis of pyrrole from ammonium mucate

Substituted pyrroles[edit]

Many methods exist for the organic synthesis of pyrrole derivatives. Classic "named reactions" are the Knorr pyrrole synthesis, the Hantzsch pyrrole synthesis, and the Paal–Knorr synthesis. More specialized methods are listed here.

The starting materials in the Piloty–Robinson pyrrole synthesis are 2 equivalents of an aldehyde and hydrazine.[7][8] The product is a pyrrole with specific substituents in the 3 and 4 positions. The aldehyde reacts with the diamine to an intermediate di-imine (R–C=N−N=C–R), which, with added hydrochloric acid, gives ring-closure and loss of ammonia to the pyrrole.

In one modification, propionaldehyde is treated first with hydrazine and then with benzoyl chloride at high temperatures and assisted by microwave irradiation:[9]

Piloty–Robinson reaction[9]

In the second step, a [3,3]sigmatropic reaction takes place between two intermediates.

Pyrrole can be polymerized to form polypyrrole.

Reactivity[edit]

The NH proton in pyrroles is moderately acidic with a pKa of 16.5. Pyrrole can be deprotonated with strong bases such as butyllithium and sodium hydride. The resulting alkali pyrrolide is nucleophilic. Treating this conjugate base with an electrophile such as methyl iodide gives N-methylpyrrole.

Resonance Contributors of Pyrrole

The resonance contributors of pyrrole provide insight to the reactivity of the compound. Like furan and thiophene, pyrrole is more reactive than benzene towards electrophilic aromatic substitution because it is able to stabilize the positive charge of the intermediate carbocation.

Pyrrole undergoes electrophilic aromatic substitution predominantly at the 2 and 5 positions. Two such reactions that are especially significant for producing functionalized pyrroles are the Mannich reaction and the Vilsmeier-Haack reaction (depicted below),[10][11] both of which are compatible with a variety of pyrrole substrates.

Formylation of a pyrrole derivative (Garabatos-Perera 2007[10])

Pyrroles react with aldehydes to form porphyrins. For example, benzaldehyde condenses with pyrrole to give tetraphenylporphyrin. Pyrrole compounds can also participate in cycloaddition (Diels-Alder) reactions under certain conditions, such as under Lewis acid catalysis, heating, or high pressure.

Pyrrole polymerizes in light. An oxidizing agent, such as ammonium persulfate, can also be used, typically at 0 °C and in darkness to control the polymerization.

Commercial uses[edit]

Pyrrole is essential to the production of many different chemicals. N-methylpyrrole is a precursor to N-methylpyrrolecarboxylic acid, a building-block in pharmaceutical chemistry.[5] Although there is a claim that pyrrole is used as an additive to cigarettes[citation needed], it is typically listed as a constituent of tobacco smoke and not as an ingredient.[12]

Analogs and derivatives[edit]

Structural analogs of pyrrole include:

  • Pyrroline, a partially saturated analog with one double bond
  • Pyrrolidine, the saturated hydrogenated analog
  • Kryptopyrrole, a pyrrole derivative once thought to be associated with schizophrenia

Heteroatom structural analogs of pyrrole include:

Derivatives of pyrrole include indole, a derivative with a fused benzene ring.

See also[edit]

References[edit]

  1. ^ Loudon, Marc G. (2002). "Chemistry of Naphthalene and the Aromatic Heterocycles.". Organic Chemistry (Fourth ed.). New York: Oxford University Press. pp. 1135–1136. ISBN 0-19-511999-1. 
  2. ^ Cox, Michael; Lehninger, Albert L; Nelson, David R. (2000). Lehninger principles of biochemistry. New York: Worth Publishers. ISBN 1-57259-153-6. 
  3. ^ Jonas Jusélius and Dage Sundholm (2000). "The aromatic pathways of porphins, chlorins and bacteriochlorins". Phys. Chem. Chem. Phys. (Open access) 2 (10): 2145–2151. doi:10.1039/b000260g. 
  4. ^ Armarego, Wilfred, L.F.; Chai, Christina, L.L. (2003). Purification of Laboratory Chemicals (5th ed.). Elsevier. p. 346. 
  5. ^ a b Albrecht Ludwig Harreus "Pyrrole" in Ullmann's Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH, Weinheim. doi:10.1002/14356007.a22_453
  6. ^ Practical Organic Chemistry, Vogel, 1956, Page 837, Link (12 MB)
  7. ^ Piloty, O. (1910). "Synthese von Pyrrolderivaten: Pyrrole aus Succinylobernsteinsäureester, Pyrrole aus Azinen". Chem. Ber. 43: 489. doi:10.1002/cber.19100430182. 
  8. ^ Robinson, Gertrude Maud; Robinson, Robert (1918). "LIV.—A new synthesis of tetraphenylpyrrole". J. Chem. Soc. 113: 639. doi:10.1039/CT9181300639. 
  9. ^ a b Benjamin C. Milgram, Katrine Eskildsen, Steven M. Richter, W. Robert Scheidt, and Karl A. Scheidt (2007). "Microwave-Assisted Piloty–Robinson Synthesis of 3,4-Disubstituted Pyrroles" (Note). J. Org. Chem. 72 (10): 3941–3944. doi:10.1021/jo070389. PMC 1939979. PMID 17432915. 
  10. ^ a b Jose R. Garabatos-Perera, Benjamin H. Rotstein, and Alison Thompson (2007). "Comparison of Benzene, Nitrobenzene, and Dinitrobenzene 2-Arylsulfenylpyrroles". J. Org. Chem. 72 (19): 7382–7385. doi:10.1021/jo070493r. PMID 17705533. 
  11. ^ The 2-sulfenyl group in the pyrrole substrate serves as an activating group and as a protective group that can be removed with Raney nickel
  12. ^ Fowles, Jefferson; Michael Bates and Dominique Noiton (March 2000). "The Chemical Constituents in Cigarettes and Cigarette Smoke: Priorities for Harm Reduction". Porirua, New Zealand: New Zealand Ministry of Health. pp. 20, 49–65. Retrieved 2012-09-23. 

External links[edit]