Pharmaceutical Organic Chemistry 3 B.Pharm IV SEM

1. UNIT 3
SYNTHESIS REACTIONS &
MEDICINAL USES OF
PYRROLE
Presented by
SOWMIYA PERINBARAJ
Assistant Professor
Dept. of Pharmaceutical Chemistry
SVCP

2. PYRROLE

3. PYRROLE
WHAT IS PYRROLE ?
 Pyrrole is an unsaturated five membered heterocyclic compound consists of
nitrogen as heteroatom at 1st position.
 One of the important heterocyclic compound because many naturally occurring
substances contain pyrrole ring.
 Eg: Alkaloids, haemoglobin, chlorophyll
 Its name derived from the fact that its vapours produce a bright red colour
when brought in contact with a pine splint moistened with con. HCl.
 Greek word- Pyrros which means fiery oil
 Molecular formula: C4 H5 N

4. SOURCE:
 Pyrrole occurs in coal- tar and
in bone oil.
 Obtained from dry distillation or pyrolysis
of animal by-products such as horns, hooves
and bones.
 Ehrlich Test:
Pyrrole + p-dimethylaminobenzaldehyde
Intense Red colour
PYRROLE
Steam distillation
Potassium salt of pyrrole formed
Pyrrole removed by boiling with KOH
Fractional distillation
Washing with dil.alkali to remove acidic
substances
Washing with Sulphuric acid to remove basic
substances
Isolated Bone oil

5. SYNTHESIS PREPARATION
1) Paal-Knorr synthesis
1,4-dicarbonyl compounds reacts with ammonia or primary
amines to give pyrrole derivatives.
CH2
CH2
C
C
O O R1
R C
NH
C
CH
CH
R1
R
NH3
-2H2O

6. 2) Hantzsch pyrrole synthesis
Reaction of α-haloketones with β-ketoester in presence of
ammonia gives pyrrole derivatives.
C CH3
O
C
H
C
H3
Cl
+
C
H2
C
O CH3
COOC2H5
NH3
-HCl
-2H2O C
NH
C
C
C
CH3
C
H3
C
H3
COOC2H5

7. 3) Knorr synthesis
Cyclic condensation of α-aminoketone with β-ketoester
gives pyrrole derivatives.
C CH3
O
C
H
C
H3
NH2
+
C
H2
C
O CH3
COOC2H5
C
NH
C
C
C
CH3
C
H3
C
H3
COOC2H5
-2H2O

8. 4) From Furan (Commercial method)
Furan passing over ammonia in presence of Aluminium
oxide catalyst at high temperature 480-490 °C gives Pyrrole.
O
C
H
CH
CH
CH NH3
Al2O3
Δ
NH
C
H
CH
CH
CH
O
NH3
Al2O3
Δ
NH
Furan Pyrrole

9. 5) From acetylene
By passing a mixture of acetylene and ammonia through a
red hot tube.
CH
CH
CH
CH
+
NH3
Δ
NH
Acetylene
Pyrrole

10. REACTIONS
1.ELECTROPHILIC SUBSTITUTION:
Pyrrole undergoes electrophilic substitution reaction at 2nd position
C2 attack gives more resonance structures than C3
C2 Attack – more
stable
C3 attack – less
stable

11. NH
HNO3
(CH3CO)2O
Nitration NH
NO2
SO3 in pyridine
Sulphonation
NH
SO3H
Pyrrole
2-nitropyrrole
2-pyrrolesulphonic acid
SO2Cl2
Chlorination
NH
Cl
Cl
Cl
Cl
2,3,4,5-tetrachloropyrrole
NH
I
I
I
I
I2
aq.KI
Iodination
2,3,4,5-tetraiodopyrrole
CH3COOH
+

12. NH
(CH3COO)2O
Friedel-
Crafts Acylation
NH
COCH3
CH3COOH
+
2-acetylpyrrole
aq.K2CO3
Kolbe-
schmitt Reaction
NH
COOH
Pyrrole-2-carboxylic acid
CHCl3
aq.KOH
Reimer-
Tiemann Reaction NH
CHO
2-formylpyrrole
Diazo coupling reaction NH
N N
N
+
N
+
Cl
2-phenylazopyrrole
+ HCl
Pyrrole

13. 2) Reduction
3) Oxidation
NH
Pyrrole
Zn
CH3COOH
H2/Pt
NH
NH
2,5-dihydropyrrole
Tetrahydropyrrole/
Pyrrolidine
NH
Cr2O3
CH3COOH
NH
O
O
Maleic imide

14. 4) Ring expansion reaction
NH
+ 2CH3ONa CH2I2
+
N
2NaI 2CH3OH
+ +
Pyrrole
Sodium
methoxide Pyridine
Methylene
iodide

15. MEDICINAL USES
1. Proline
✓ A major amino acid found in cartilage and is important for
maintaining youthful skin as well as repair of muscle,
connective tissue and skin damage.
✓ An essential component of collagen and is important for
proper functioning of joints and tendons.
2. Nicotine
✓ A stimulant and potent parasympathomimetic
(Cholinergic) alkaloid. It is used for smoking cessation to
relieve withdrawal symptoms.

16. 3. Procyclidine
An anticholinergic drug used to treat the stiffness,
tremors (involuntary movements) and poor muscle
control of Parkinson's disease.

17. 4. Glycopyrrolate
An anticholinergic drug which is used in peptic
ulcer.
5. Atorvastatin
Belongs to a group of drugs known as Statins. Used
to reduce high cholesterol level in blood and also
reduce the risk of heart attack and stroke.