Unit 3 Pyrrole

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
WHATISPYRROLE?
Pyrroleisanunsaturatedfivememberedheterocycliccompoundconsistsof
nitrogenasheteroatomat1
st
position.
Oneoftheimportantheterocycliccompoundbecausemanynaturallyoccurring
substancescontainpyrrolering.
Eg:Alkaloids,haemoglobin,chlorophyll
Itsnamederivedfromthefactthatitsvapoursproduceabrightredcolour
whenbroughtincontactwithapinesplintmoistenedwithcon.HCl.
Greekword-Pyrroswhichmeansfieryoil
Molecularformula:C
4H
5N

4. SOURCE:
Pyrroleoccursincoal-tarand
inboneoil.
Obtainedfromdrydistillationorpyrolysis
ofanimalby-productssuchashorns,hooves
andbones.
EhrlichTest:
Pyrrole+p-dimethylaminobenzaldehyde
IntenseRedcolour
PYRROLE
Steam distillation
Potassium salt of pyrrole formed
Pyrrole removed by boiling with KOH
Fractional distillation
Washing with dil.alkalito remove acidic
substances
Washing with Sulphuric acid to remove basic
substances
Isolated Bone oil

5. SYNTHESIS\PREPARATION
1) Paal-Knorr synthesis
1,4-dicarbonylcompoundsreactswithammoniaorprimary
aminestogivepyrrolederivatives.CH
2
CH
2
CC
O O
R
1
R
C
NH
C
CHCH
R
1
R
NH
3
-2H
2
O

6. 2) Hantzschpyrrole synthesis
Reactionofα-haloketoneswithβ-ketoesterinpresenceof
ammoniagivespyrrolederivatives.C CH
3
O
CHCH
3
Cl
+
CH
2
C
O CH
3
COOC
2
H
5
NH
3
-HCl
-2H
2
O
C
NH
C
CC
CH
3
CH
3
CH
3
COOC
2
H
5

7. 3) Knorr synthesis
Cycliccondensationofα-aminoketonewithβ-ketoester
givespyrrolederivatives.C CH
3
O
CHCH
3
NH
2
+
CH
2
C
O CH
3
COOC
2
H
5
C
NH
C
CC
CH
3
CH
3
CH
3
COOC
2
H
5
-2H
2
O

8. 4) From Furan (Commercial method)
FuranpassingoverammoniainpresenceofAluminium
oxidecatalystathightemperature480-490°CgivesPyrrole.O
CH
CH
CH
CH NH
3
Al
2
O
3
Δ
NH
CH
CH
CH
CH O
NH
3
Al
2
O
3
Δ
NH
Furan Pyrrole

9. 5) From acetylene
Bypassingamixtureofacetyleneandammoniathrougha
redhottube.CH
CH
CH
CH
+
NH
3
Δ
NH
Acetylene
Pyrrole

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

11. NH
HNO
3
(CH
3
CO)
2
O
Nitration
NH
NO
2
SO
3
in pyridine
Sulphonation
NH
SO
3
H
Pyrrole
2-nitropyrrole
2-pyrrolesulphonic acid
SO
2
Cl
2
Chlorination
NH
Cl
ClCl
Cl
2,3,4,5-tetrachloropyrrole
NH
I
II
I
I
2
aq.KI
Iodination
2,3,4,5-tetraiodopyrrole
CH
3
COOH+

12. NH
(CH
3
COO)
2
O
Friedel
-
Crafts Acylation
NH
COCH
3
CH
3
COOH+
2-acetylpyrrole
aq.K
2
CO
3
Kolbe
-
schmitt Reaction
NH
COOH
Pyrrole-2-carboxylic acid
CHCl
3
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) OxidationNH
Pyrrole
Zn
CH
3
COOH
H
2
/Pt
NH
NH
2,5-dihydropyrrole
Tetrahydropyrrole/
Pyrrolidine NH
Cr
2
O
3
CH
3
COOH
NH
OO
Maleic imide

14. 4) Ring expansion reactionNH
+2CH
3
ONaCH
2
I
2+
N
2NaI2CH
3
OH++
Pyrrole
Sodium
methoxide
Pyridine
Methylene
iodide

15. MEDICINAL USES
1.Proline
✓Amajoraminoacidfoundincartilageandisimportantfor
maintainingyouthfulskinaswellasrepairofmuscle,
connectivetissueandskindamage.
✓Anessentialcomponentofcollagenandisimportantfor
properfunctioningofjointsandtendons.
2.Nicotine
✓Astimulantandpotentparasympathomimetic
(Cholinergic)alkaloid.Itisusedforsmokingcessationto
relievewithdrawalsymptoms.

16. 3.Procyclidine
Ananticholinergicdrugusedtotreatthestiffness,
tremors(involuntarymovements)andpoormuscle
controlofParkinson'sdisease.

17. 4.Glycopyrrolate
Ananticholinergicdrugwhichisusedinpeptic
ulcer.
5.Atorvastatin
BelongstoagroupofdrugsknownasStatins.Used
toreducehighcholesterollevelinbloodandalso
reducetheriskofheartattackandstroke.