Pyrrole

Chembox new
Name = Pyrrole
ImageFile = Pyrrole.png ImageSize = 300px
ImageName = Chemical structure of pyrrole
IUPACName = Pyrrole
Pyrrol
Section1 = Chembox Identifiers
CASNo = 109-97-7
SMILES = C1=CC=CN1
InChI=1/C4H5N/c1-2-4-5-3-1/h1-5H
Section2 = Chembox Properties
Formula = C₄H₅N
MolarMass = 67.09 g/mol
Density = 0.967 g/cm³
MeltingPt = −23 °C
BoilingPt = 129–131 °C

Pyrrole, or pyrrol, is a heterocyclic aromatic organic compound, a five-membered ring with the formula C₄H₄NH. [cite book
author = Loudon, Marc G.
year = 2002
title = Organic Chemistry
chapter = Chemistry of Naphthalene and the Aromatic Heterocycles.
edition = Fourth Edition
pages = 1135–1136
publisher = Oxford University Press
location = New York
id = ISBN 0-19-511999-1] 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. [cite book |author=Cox, Michael; Lehninger, Albert L; Nelson, David R. |title=Lehninger principles of biochemistry |publisher=Worth Publishers |location=New York |year=2000 |pages= |isbn=1-57259-153-6 |oclc= |doi= ]

Pyrroles are components of more complex macrocycles, including the porphyrins of heme, the chlorins and bacteriochlorins [cite journal | title = The aromatic pathways of porphins, chlorins and bacteriochlorins | author = Jonas Jusélius and Dage Sundholm | journal = Phys. Chem. Chem. Phys. | year = 2000 | volume = 2 | pages = 2145–2151 | doi = 10.1039/b000260g | format = Open access] of chlorophyll, and porphyrinogens.

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 pK_aH of about −4. Protonation results in loss of aromaticity, and is, therefore, unfavorable.

ynthesis

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. [cite journal | author = Piloty, O. | journal = Chem. Ber. | year = 1910 | volume = 43 | pages = 489 | doi = 10.1002/cber.19100430182 | title = Synthese von Pyrrolderivaten: Pyrrole aus Succinylobernsteinsäureester, Pyrrole aus Azinen] [cite journal | journal = J. Chem. Soc. | year = 1918 | volume = 113 | pages = 639| doi = 10.1039/CT9181300639 | title = LIV.—A new synthesis of tetraphenylpyrrole | author = Robinson, Gertrude Maud] 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: [cite journal | title = Microwave-Assisted Piloty-Robinson Synthesis of 3,4-Disubstituted Pyrroles | author = Benjamin C. Milgram, Katrine Eskildsen, Steven M. Richter, W. Robert Scheidt, and Karl A. Scheidt | journal = J. Org. Chem. | year = 2007 | volume = 72 | issue = 10 | pages = 3941–3944 | format = Note | doi = 10.1021/jo070389]

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

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

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) [cite journal | title = Comparison of Benzene, Nitrobenzene, and Dinitrobenzene 2-Arylsulfenylpyrroles | author = Jose R. Garabatos-Perera, Benjamin H. Rotstein, and Alison Thompson | journal = J. Org. Chem. | year = 2007 | volume = 72 | pages = 7382–7385 | doi = 10.1021/jo070493r] [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 ] , both of which are compatible with a variety of pyrrole substrates. Reaction of pyrroles with formaldehyde form porphyrins.

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

Commercial Uses

In a 1994 report released by five top cigarette companies, pyrrole is one of the 599 additives to cigarettes. [quitsmoking.about.com [http://quitsmoking.about.com/cs/nicotineinhaler/a/cigingredients.htm Link] ]

ee also

* Arsole, a moderately-aromatic arsenic analog
* Furan, an analog with an oxygen instead of the nitrogen
* Indole, a derivative with a fused benzene ring
* Phosphole, a non-aromatic phosphorus analog
* Polypyrrole
* Pyroluria
* Pyrroline, a partially saturated analog with one double bond
* Pyrrolidine, the saturated hydrogenated analog
* Simple aromatic rings
* Thiophene, an analog with a sulfur instead of the nitrogen atom.

References

External links

* [http://chemistry.tidalswan.com/index.php?title=Heteroaromatics#Pyrrole_.28Azole.29 General Synthesis and Reactivity of Pyrrole]
* [http://www.organic-chemistry.org/synthesis/heterocycles/pyrroles.shtm Synthesis of pyrroles (overview of recent methods)]
* [http://users.ox.ac.uk/~mwalter/web_05/year2/arom2/hetarom_rxn_mech.shtml Substitution reaction mechanisms of nitrogen-containing heteroaromatics]
* [http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey=%23TOC%235289%232006%23999379949%23636416%23FLA%23&_cdi=5289&_pubType=J&view=c&_auth=y&_acct=C000043357&_version=1&_urlVersion=0&_userid=789722&md5=b22786bd8332b5d556d8620f8928ca28 Recent Review on Pyrrole Protection ]