Pyrrole

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Pyrrole
Chemical structure of pyrrole
IUPAC name Pyrrole
Pyrrol
Identifiers
CAS number [109-97-7]
SMILES C1=CC=CN1
InChI 1/C4H5N/c1-2-4-5-3-1/h1-5H
Properties
Molecular formula C4H5N
Molar mass 67.09 g/mol
Density 0.967 g/cm3
Melting point

−23 °C
Boiling point

129–131 °C
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Pyrrole, or pyrrol, is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH.[1] Substituted derivatives are also called pyrroles. For example, C4H4NCH3 is N-methylpyrrole. Porphobilinogen is a trisubstituted pyrrole, which is the biosynthetic precursor to many natural products.[2]

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

Contents

[edit] Properties

Pyrrole has very low basicity compared to amines and other aromatic compounds like pyridine, wherin the ring nitrogen is not bonded to a hydrogen atom. 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 −4. Protonation results in loss of aromaticity, and is, therefore, unfavorable.

[edit] Synthesis

Many methods exist for the organic synthesis of pyrrole and its derivatives. Classic named reactions are the Knorr pyrrole synthesis, the Hantzch pyrrole synthesis, and the Paal-Knorr synthesis.

The starting materials in the Piloty-Robinson pyrrole synthesis are 2 equivalents of an aldehyde and hydrazine[4][5]. 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 reacted first with hydrazine and then with benzoyl chloride at high temperatures and assisted by microwave irradiation[6]:

Piloty-Robinson reaction Milgram 2007

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

[edit] Reactivity

Both NH and CH protons in pyrroles are moderately acidic and can be deprotonated with strong bases such as butyllithium and the metal hydrides. The resulting "pyrrolides" are nucleophilic. Trapping of the conjugate base with an electrophile (e.g., an alkyl or acyl halide) reveals which sites were deprotonated based on which ring positions actually react as nucleophiles. The product distribution of such a reaction can often be complex and depends on the base used (especially the counterion, such as lithium from butyllithium or sodium from sodium hydride), existing substitution of the pyrrole, and the electrophile.

The resonance contributors of pyrrole provide insight to the reactivity of the compound. Like furan and thiophene, pyrrole is more reactive than benzene towards nucleophilic aromatic substitution because it is able to stabilize the positive charge of the intermediate carbanion. This is because the nitrogen can donate a lone pair into the ring by resonance Resonance Contributors of Pyrrole

Pyrrole undergoes electrophilic aromatic substitution predominantly at the 2 and 5 positions, though the substitution product at positions 3 and 4 is obtained in low yields. Two such reactions that are especially significant for producing functionalized pyrroles are the Mannich reaction and the Vilsmeier-Haack reaction (depicted below) [7] [8], both of which are compatible with a variety of pyrrole substrates. Reaction of pyrroles with formaldehyde form porphyrins.

Forlylation of a pyrrole derivative Garabatos-Perera 2007

Pyrrole compounds can also participate in cycloaddition (Diels-Alder) reactions under certain conditions, such as Lewis acid catalysis, heating, or high pressure.

[edit] Commercial Uses

In a 1994 report released by five top cigarette companies, pyrrole is one of the 599 additives to cigarettes. Its use or purpose, however, is unknown, like that of most cigarette additives. [9]

[edit] See also

[edit] External links

[edit] References

  1. ^ # Loudon, Marc G. (2002). "Chemistry of Naphthalene and the Aromatic Heterocycles.", Organic Chemistry, Fourth Edition, New York: Oxford University Press, 1135–1136. ISBN 0-19-511999-1. 
  2. ^ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6.
  3. ^ The aromatic pathways of porphins, chlorins and bacteriochlorins Jonas Juse lius and Dage Sundholm Phys. Chem. Chem. Phys., 2000, 2, 2145–2151 doi:10.1039/b000260g Open access
  4. ^ Piloty, O. Chem. Ber. 1910, 43, 489.
  5. ^ Robinson, R.; Robinson, G. M. J. Chem. Soc. 1918, 43, 639–644.
  6. ^ Microwave-Assisted Piloty-Robinson Synthesis of 3,4-Disubstituted Pyrroles Benjamin C. Milgram, Katrine Eskildsen, Steven M. Richter, W. Robert Scheidt, and Karl A. Scheidt J. Org. Chem.; 2007; 72(10) pp. 3941–3944; (Note) doi:10.1021/jo070389+
  7. ^ Comparison of Benzene, Nitrobenzene, and Dinitrobenzene 2-Arylsulfenylpyrroles Jose R. Garabatos-Perera, Benjamin H. Rotstein, and Alison Thompson J. Org. Chem. 2007, 72, 7382–7385 doi:10.1021/jo070493r
  8. ^ The 2-sulfenyl group in the pyrrole substrate acts as an activating group and as a protective group that can be removed with Raney nickel
  9. ^ quitsmoking.about.com Link