Paal-Knorr synthesis

Named after Carl Paal Ludwig Knorr

Reaction type Ring forming reaction

The furan synthesis requires an acid catalyst:[5]

Paal–Knorr furan synthesis

In the pyrrole synthesis a primary amine

participates:
Paal–Knorr Pyrrole Synthesis

And in that of thiophene for instance the compound

phosphorus pentasulfide:
Paal-Knorr thiophene synthesis
 1. FURAN
Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with
four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also
referred to as furans.

Furan is a colorless, flammable, highly volatile liquid with a boiling point close to room
temperature. It is soluble in common organic solvents, including alcohol, ether, and acetone,
and is slightly soluble in water.[2] Its odor is “strong, ethereal; chloroform-like”.[3] It is toxic and
may be carcinogenic in humans. Furan is used as a starting point for other speciality chemicals.
[4]
 Names

Preferred IUPAC name

Furan[1]

Systematic IUPAC name

1,4-Epoxybuta-1,3-diene
1-Oxacyclopenta-2,4-diene

Other names
Oxole
Oxa[5]annulene
1,4-Epoxy-1,3-butadiene
5-Oxacyclopenta-1,3-diene
5-Oxacyclo-1,3-pentadiene
Furfuran
Divinylene oxide

Related compounds

Related heterocycles Pyrrole
Thiophene
 Related compounds Tetrahydrofuran (THF)
2,5-Dimethylfuran
Benzofuran
Dibenzofuran

FURAN
Furan is a Heterocyclic organic compound, consisting of a five-membered
aromatic ring with four carbon atoms and one oxygen atom. The class of
compounds containing such rings are also referred to as furans.

Synthesis of Furan:
 1. From Pentosans:

Pentosans are hydrolyzed to Xylose followed by dehydration and cyclization to

Give furfural

2. From Oxidation of cis-but-2-ene-1,4-diol:

3. From Alkynes:

4. From diacetosuccinic ester:

When diacetosuccinic ester is heated with dilute sulphuric acid,

2,5-dimethylfuran-3,4-dicarboxylic acid is obtained.

5. Ring opening of Epoxide in presence of Lewis acid BF3:

Name Reactions for Furan Synthesis:

1. Paal-Knorr Synthesis:

The acid-catalyzed cyclisation of 1,4-dicarbonyl compounds in presence of acid

Or lewis acid is known as Paal-Knorr Synthesis.

Mechanism
 2. Feist–Benary synthesis:

The organic reaction between α-haloketones and β-dicarbonyl compounds to

Form substituted furan compounds is known as Feist–Benary synthesis. This

Condensation reaction is catalyzed by base.

Mechanism
Q 2. Pyrrole
Pyrrole synthesis
The mechanism for the synthesis of the pyrrole was investigated by V.
Amarnath et al. in 1991.[4] His work suggests that the protonated carbonyl is
attacked by the amine to form the hemiaminal. The amine attacks the other
carbonyl to form a 2,5-dihydroxytetrahydropyrrole derivative which undergoes
dehydration to give the corresponding substituted pyrrole.

The reaction is typically run under protic or Lewis acidic conditions, with a
primary amine. Use of ammonium hydroxide or ammonium acetate (as
reported by Paal)
gives the N-unsubstituted pyrrole.

Paal-Knorr Pyrrole Synthesis

The Paal-Knorr Pyrrole Synthesis is the condensation of a 1,4-dicarbonyl
compound with an excess of a primary amine or ammonia to give a pyrrole.

The reaction can be conducted under neutral or weakly acidic conditions.

Addition of a weak acid such as acetic acid accelerates the reaction, but the use
of amine/ammonium hydrochloride salts or reactions at pH < 3 lead to furans as
main products (Paal-Knorr Furan Synthesis).

Mechanism of the Paal-Knorr Pyrrole Synthesis

Venkataraman Amarnath has shown (J. Org. Chem., 1991, 56, 6924) that meso-
and dl-3,4-diethyl-2,5-hexanediones cyclize at unequal rates, and that the
stereochemical configuration of the unchanged dione is preserved during the
reaction. Any mechanism such as the following one that involves the formation
of an enamine before the rate-determining step – the cyclization – must be
ruled out.
If the ring is formed from an imine that is generated from a primary amine, a
charged immonium ion must be an intermediate. Amarnath tried to stabilize or
destabilize the immonium ion with different aryl groups as substituents:

The use of ammonia should give an uncharged intermediate and is therefore

less affected by the choice of substitutents. The substituents also influence the
basicity of the imine, with the nitro group leading to a more basic nucleophile.
The rates of cyclization have been compared using ammonia and methylamine.
The nitro group has in every situation had a positive effect on the reaction rate.
The methoxy group has a negative effect on the cyclization rate in each case.
Comparison of the relative reaction rates of all substrates (R: H, Me) showed no
specific stabilization/destabilization effect for a possible mechanism involving
an immonium ion.

A mechanism that accounts for the influence of different substitution patterns

(meso, dl) and explains the influence of a p-nitrophenyl group making a
nucleophile more reactive (although not as the imine) includes the cyclization of
a hemiacetal which is followed by different dehydration steps:
A more detailed description can be found in the work by Venkataraman
Amarnath, and references cited therein (J. Org. Chem., 1991, 56, 6924).
3. Thiophene synthesis
Thiophene synthesis is achieved via a mechanism very similar to the furan synthesis. The initial
diketone is converted to a thioketone with a sulfurizing agent, which then undergoes the same
mechanism as the furan synthesis.[8]