SEMESTER-IV

Section (B): Organic Chemistry-III Paper No: CHB-401

1. Heterocyclic Compounds: Synthesis and chemistry of furan, pyrrole, thiophene and pyridine.

U
O N
H S N
furan pyrrole thiophene Pyridine

H
2. Poly nuclear Hydrocarbons: Chemistry of naphthalene and anthracene.
naphthalene anthracene

-B
3. Carbohydrates: Characteristic reactions of aldoses and ketoses. Glucose-structure (Open and Cyclic),
Mutarotation. H H OH H
O H HO OH
HOH2C CHO
HOH2C C CH2OH
OH OH H OH

M D(+) Glucose
OH H H
Fructose
4. Colour and Constitution: Synthesis of malachite green, flurorescein, synthesis and structure of Indigotin.
N
SK
HO O O

O O
C O
OH N N
N
H H
Malachite Green
Fluorescein Indigotin
Books Recommended
1. Organic Chemistry, R. T. Morrison and R. N. Boyd, 6th Edition (1992), Prentice-Hall of India (P) Ltd., New Delhi.
2. Organic Chemistry, I. L. Finar, Vol. I, 6th Edition (1973), Reprinted in 1980 & Vol. II, 5th Edition (1975),
Reprinted in1996], ELBS and Longman Ltd., New Delhi.
Heterocyclic compounds are cyclic compounds with the ring containing carbon and
other elements, the commonest being oxygen, nitrogen and sulphur

U
Furan

H
' 
4 3

-B
' 5 2 
1
M O
SK
furan Oxole Furfuran

Furan is colourless volatile liquid with 32oC boiling point

Furan occurs in Pine wood
 Furan Preparation
1. Dry distillation of Mucic acid

COOH
HO OH

U
H OH
HO H  Quinoline/ Cu
H H
HO H
-CO2 COOH -CO2
H OH HOOC COOH

H
OH HO -3H2O O O
COOH

Mucic acid

-B
2. From Furfural (Catalytic decomposition)
CHO OH
HO
H OH
HO
H
H
OH
CH2OH
H
M OH HO
H
CHO
H2SO4 
-3H2O
O
CHO
Steam 400oC
ZnO/Cr2O3
O
SK
-CO
Aldopentose Furfural

3. Furan Derivatives from 1,4-diketones H2SO4 or P2O5

R R -H2O R R
O O O

R R R
:

OH O R
O OH
4. Furan Derivatives from EAA
' COOH
HOOC

H2SO4

U
O O
O O -H2O
O
EtONa OEt
2 2,5-dimethyl furan 3,4-dicarboxylic acid

H
OEt '
I2 OEt HOOC COOH
NH3
O O

-B
N
H
2,5-dimethyl pyrrole 3,4-dicarboxylic acid

5. Feist-Benary Synthesis

M O
OEt

+
O
Pyridine
EtOOC
SK
CH2Cl
O O
 keto ester  keto ester  chloro ketone 2,4-Dimethyl-furan-3-
Pyridine

carboxylic acid ethyl ester

-H2O

OEt
HO EtOOC HO
O EtOOC EtOOC HO
O
+
CH2Cl CH2Cl CH2Cl
:

O OH O H
O
 Structure of Furan

O O O

U
O O
:

(I) (II) (III) (IV) (V)

H
Resonance Energy: 71.1 – 96.2 KJmole-1

-B
Planar (4n+2) π electron molecule - Aromatic

To provide six π electrons for the ring system, one of the lone pairs of electrons
of the oxygen atom is involved

M
SK

SP2 SP2
 Electrophilic Substitution

1. Charge distribution O O O O O

:
(I) (II) (III) (IV) (V)

U
Larger the charge seperation, the less stable is that structure. Hence II and V contribute
less than the III and IV and consequently the resonance hybrid has a larger electron

H
density at position 2 or 5 than at 3 or 4 positions
Thus on the basis of charge distribution, electrophilic substitution expected to occur at
2 or 5 positions.

-B
2. Stability of Carbonium ion intermediate
2 or 5 E E E
+ E
O
M attack
O H O H O H
:

:
E E
H H
SK
E 3 or 4
+
attack
O O O
:

If we consider the contributing resonating structures of the intermediate carbonium ion,
then there are three for 2 or 5 subtitution and two for 3 or 4 substitution
Thus on the basis of Carbonium ion intermediate Stability, the electrophilic substitution
expected to occur at 2 or 5 positions.
Because of the oxygen lone pair, the ring becomes activated. Substitution occurring faster
than in bezene.
 Reactions of Furan
1. Diels-alder reaction

Furan behaves chemically as an aromatic compound but also behaves as a 1,3-diene

O O O

U

O O O O

H
O
O O O

-B
Furan O
Maleic anhydride

2. Reduction
M
SK
NH 3
Raney Ni (or) N
2H2 H
HC Pyrrolidine
Pd-PdO l
O O
Tetrahydro furan OH
(THF) Cl
Tetramethylene
chlorohydrine
 3. Nitration and Sulphonation

Direct nitration (HNO3/H2SO4) and sulphonation (H2SO4) leads to resinified product

U
Conc. Acids
n * *
O O n
Poly furan

H
AcONO2

-B
acetyl nitrate NO2
O O
2-nitro furan

M O
Py-SO3
Pyridinium
O
SO3H
SK
sulphonate
2-furan
sulphonic acid

If a –I group present in the ring, sulphonation can be carried out directly

Conc. H2SO4
COOH HO3S COOH
O O
Furoic acid furoic -5-
sulphonic acid
4. Halogenation

Furan reacts readily with halogens (X2), but the liberated halogen acid (HX) causes
polymerization. Indirect method is used for halogenation.

U
Br2 
COOH Br COOH -CO2 Br
O O O
2-bromo-furan

H
Furoic acid

-B
Cl2
+
-40oC Cl Cl Cl
O O O
2-chloro-furan 2,5-dichloro furan
5. Gattermann reaction (formylation)

M
SK
SnCl4 H2O
HC N O
HCl + Cl CH NH
CHO
imino formyl CH NH O
O
chloride

NaOH

+
COONa CH2OH
O O
6. Friedel Crafts acylation
Ac2O SnCl4
+ (Or) CH3
O CH3COCl
O
O

U
7. Mercuration

H
X2
HgCl2 X
O

-B
AcONa HgCl RCOCl
O O
2-chloro mercuric
furan COR
O

8. Organo metallic compound

M nC4H9Li CO2
SK
Li H+ COOH
O O O

9. Gomberg reaction

PhN2Cl

NaOH Ph
O O
10. Ring Opening O
aq. H2SO4
Me
 Me 1,4-diketone
O
O

- H+

U
H+

:
H+

:
H2O OH2 OH OH
- H+

H
O O O O O
:

OMe
HCl

-B
OMe
1,4-dioxo
O CH3OH MeO compound
MeO

:
MeO
:
H+ MeOH MeOH
H
:
MeO MeO MeO
O O O HO
O
:

SK
MeO H+ MeO MeOH MeO
OMe MeO
MeO MeO HO MeO HO
H2O OMe MeO O

MeOH

MeO OMe
MeO OMe
 Thiophene

' 

U
4 3
' 5

H
2 
1

-B
S

Thiophene Thiole
M
SK
Furan is colourless liquid with 84oC boiling point
Furan occurs in Coal Tar
Thiophene boiling point (84oC) is close to benzene (80oC) and hence it is difficult to
separate from the benzene fraction obtained from coal tar

Coal Tar
(Benzene + Thiophene)

U
Cold H2SO4 aq. (CH3COO)2Hg

H
-B
Bezene Thiophene Mercurated Bezene
sulphonic acid Thiophene

M
Presence of Thiophene in benzene is detected by Indophenin reaction
Isatin
Blue Colour
SK
Benzene + Thiophene
H2SO4
O

O + S S
N S O
H N O N
H H
Isatin Blue Colour
 Thiophene Preparation
1. From acetylene
Passing a acetylene and H2S through a tube containing alumina at 400oC

U
Al2O3
2 HC CH + H2S + H2

H
o
400 C S

-B
2. From n-butane

CH2 CH2 600oC

CH3
M CH3
+ 4S
S
+ 3H2S
SK
3. From sodium Succinate

CH2 COONa P2S3

+ 2NaPO2S + S
CH2 COONa S
 Structure of Thiophene

S S S S S

U
:

(I) (II) (III) (IV) (V)

H
-B
S S S S S

(vi) (vii) (viii) (ix) (x)

M Resonance Energy: 117 – 130 KJmole-1

Planar (4n+2) π electron molecule - Aromatic

SK
To provide six π electrons for the ring system, one of the lone pairs of electrons
of the sulphur atom is involved

SP2 SP2
 Electrophilic Substitution
Electrophilic substitution expected on the basis of charge distribution and stability of
carbonium oin intermediate, to take place at 2 or 5 positions.

Reactions of Thiophene

U
1. Nitration Fuming HNO3

H
in Ac2O NO2
S S
2-nitro thiophene

-B
2. Sulphonation
Cold
SO3H

3. Halogenation M S Conc. H2SO4 S

2-thiophene
sulphonic acid
SK
Cl2
+
o Cl Cl
-30 C Cl
s s s
2-chlorothiophene 2,5-dichloro thiophene

O O
N
Br I2
Br HgO I
s s s s
2-bromo thiophene
2-iodo thiophene
4. Acylation CH3COCl Ac2O
CH3 CH3
SnCl4 H3PO4
S S S S
O O
methyl 2-thienyl ketone
HCHO

U
5. Chloro methylation HCl
Cl
S S

H
2-Chloromethyl-
thiophene

DMF

-B
6. Formylation (Vilsmeier- Haack Reaction)
POCl3 CHO
O O S S
Cl P Cl P
Cl Cl
O

M Cl O O

P N CH Cl
:

N H Cl +
N H Cl
Cl O
SK
dimethyl
formamide (DMF) H

:
N CH Cl N CH Cl OPOCl2 CH N
S
Cl

-HCl

Hyd.
CHO CH N
S
S
7. Mercuration
HgCl2
AcONa HgCl
S S
2-chloro mercuric
thiophene

8. Organometalic compound

U
nC4H9Li
in ether Li

H
S S

Mg CO2

-B
Br MgBr H+ COOH
S S S

9. Reduction Pd
Na in

M S
liq. NH3
S
2,3-dihydro
thiophene
+
S
2,5-dihydro
S
2H2
S
tetrahydro
thiophene
SK
thiophene
9. Desulphurization
Raney Ni
+
H2
S NiS

Raney Ni COOH
COOH aq.NaOH 4
S
 Pyrrole
Pyrrole is a very important five membered heterocyclic ring because its nuclear occurs in
many natural compounds (Alkaloids, chloropyll, Haematic) .

U
' 

H
4 3

-B
' 5 2 
1
N

M Pyrrole
H

Azole
SK

Pyrrole is colourless volatile liquid with 131oC boiling point

Furan occurs in Coal Tar and Bone oil
 Pyrrole Extraction

Washing with dil.alkali Washing with acid Fractional distillation Pyrrole

Bone Oil
Fraction
acid substances basic substances 100 to 150oC

U
Fusing with KOH

H
Steam distillation
Pure Pyrrole Pottasium
Pyrrole

-B
Pyrrole Preparation

1. From acetylene
M
Passing mixture of acetylene and ammonia through red hot tube
SK
2 HC CH + NH3 + H2
N
H
2. From ammonium mucate

200oC
H4NOOC CHOH COONH4 + 2CO2 + NH3 + 4H2O
4
N
H
3. From Succinimide
distilled with Zn
O O
N N
H H
4. From furan and ammonia

U
Al2O3
+ NH3
-H2O
O N

H
H

Pyrrole Derivatives synthesis

-B
1. Paal-Knorr synthesis

M
:

RNH2 HO
OH
R R R -H2O R

:
:
O O O HN R O HN R R N R
SK
R R R

-H2O

H H + NH3
O O N
H R N R
R
2. Knorr pyrrole synthesis
O O O
HNO2 Zn

AcOH
EtO2C EtO2C NOH EtO2C NH2

U
 keto ester  amino ketone

O Y

H
Y
+
-2H2O
NH2

-B
EtO2C O EtO2C
N
 amino ketone  diketone (y = COR) H
3,5-Dimethyl 2,4
 keto ester (y = COOR) dicarboxylic ester

M
3. Hantzsch Synthesis O
NH3
NH NH2
SK
EtO2C EtO2C EtO2C

 keto ester 1o amine

EtO2C EtO2C
EtO2C
EtO2C Cl H
+ OH
:

NH2 O O -H2O
NH N N
H H
Chloro acetone
2,5-Dimethyl-pyrrole-3-
carboxylic ethyl ester
 Structure of Pyrrole

U
N N N N N
H H H H H

(I) (II) (III) (IV) (V)

H
Resonance Energy: 87.8 – 130 KJmole-1

-B
Planar (4n+2) π electron molecule - Aromatic

To provide six π electrons for the ring system, the lone pairs of electrons
of the nitrogen atom is involved

M
SK
SP2 SP2

Aromaticity: Thiophene > Pyrrole > Furan

Electronegativity: S (2.56) > N (3.04) > O (3.44)
 Basicity of Pyrrole
Because of the contribution of the lone pair of electrons of the nitrogen atom to the
Formation of a (4n+2) π electron molecule, the availability of this lone pair for
protonation is very much decreased.

U
In acid solution, protonation also occurs at 2 & 3 position
H
H

H
pKb = 13.6

-B
N
H
Conc. Acids
+ n * *
H
N N n
H H
H+ H+
Pyrrole Red
H

M
:

N H N N
H H H H
SK
When in contact with dilute acid for a brief period, pyrrole forms the trimer
:

:
N N N
H H H
 Electrophilic Substitution
Electrophilic substitution expected on the basis of charge distribution and stability of
carbonium oin intermediate, to take place at 2 or 5 positions.

Reactions of pyrrole

U
1. Nitration HNO3

H
in Ac2O NO2
N N
H 2-nitroHpyrrole

-B
2. Sulphonation Py-SO3

in dichloro ethane SO3H

N N
H H

3. Halogenation M 2-pyrrole
sulphonic acid
SK
SO2Cl2

Sulphuryl Cl Cl
N chloride N
H H
2,5-dichloro pyrrole

Br Br
2Br2

Br Br
N N
H H
2,3,4,5-tetrabromo
pyrrole
4. Reaction with KOH Solid KOH

N N
H K
Potassio pyrrole
Kolbe-Schmitt reaction
COOH

U
CO2
+
H+
COOH

H
N N N
K H H
Potassio pyrrole 2-pyrrole 3-pyrrole
carboxylic acid carboxylic acid

-B
O H H+
O O
C + C
C HOOC
O

M N
K K+
O
N
K+O
N
H
N
H
SK
O K+ O K+ O
C O C O COOH
C
H H+
+ O
N N N N
K H H
Reimer-Tiemann Reaction Cl
CHCl3
+
KOH
N CHO
N N
K H
Pyrrole 2- 3-chloro
aldehyde pyridine
K+

U
CHCl3 + KOH CCl3 : CCl2
-H2O -KCl

H
Cl
Cl
C
K+ Cl

-B
CCl2 N
N N
K+

N
K
:CCl2
M N
H
K+
CCl2
H2O
-KOH N
H
CHCl2 N
H
CHCl2
SK
KOH -KCl

O H
C C Cl
N -HCl N
H
H H OH
Cl
CHCl3
3-chloro
EtONa pyridine
N
K N
 RCOCl Hofmann-martius O
(or) Ac2O Rearrangement C
N N N R
K RT HT H
O R

U
RX Hofmann-martius
Rearrangement R
N RT N N

H
K HT H
R
5. Houben-Hoesh Synthesis

-B
ZnCl2 H+ O
+ CH3CN
C NH C
HCl
N N N
H

M CH3CN + HCl
H CH3

CH3C=NH
H
CH3
SK
Cl

6. Vilsmeier-Haack reaction

DMF

POCl3 CHO
N N
H H
7. Reaction with diazonium salt
ArN2Cl
ArN2Cl base N N NAr
N ArN N
Weak acid N NAr H H
N N
H H

U
R
8. Grignard reaction MeMgBr RX
+
R

H
N N N N
H MgBr H H

-B
9. Oxidation CrO3
maleinimide
[O] O O
N N
H H

10. Reduction
M N
H
Zn
AcOH
N
H
HI
P 
N
H pKb = 2.7
SK
2,5-dihydro pyrrole Pyrollidine
(pyrroline)

Ni
200oC
N N
H H
11. Reaction with NH2OH Pyrollidine

Reflux with CH2 CH NOH

+ NH3
N 2NH2OH/EtOH
CH2 CH NOH
H
Succinaldehyde
dioxime
 Pyridine
The pyridine ring occurs in many important compounds, including agrochemicals,
pharmaceuticals, and vitamins.

U
Coal Tar Fractions
5 3

H
Up to 170oC Crude light oil
170oC to 230oC Middle (or) Carbolic oil

-B
6 2 230oC to 270oC Heavy oil (or) Creosote
270oC to 360oC Green oil (or) Anthracene oil
N
1

M
Pyridine Azine
SK
Pyridine is colourless flammable liquid with 115oC boiling point
Pyridine occurs in light oil fraction of Coal Tar and Bone oil

treating with dil.H2SO4 Neutralized with NaOH

Light Oil dissolved pyridine with
Pyridine
basic substances
 Pyridine Preparation

1. From acetylene
Passing mixture of acetylene and hydrogen cyanide through red hot tube

U
2 HC CH + HCN

H
N

2. From pentamethylene diamine hydrochloride

-B
 Conc.H2SO4/300oC
ClH3N CH2 NH3Cl
5 -NH4Cl (or) Pd-C

M -HCl N
H
Piperidine
N
SK
3. From Furyl ketone
OH OH
:

NH3 + R
C H2N R OH
C

:
O O O
O NH2 N R
O R H
H
-H2O

N
4. Hantzsch synthesis

O O OH O NH2 O
NH3
OEt OEt -H2O OEt
H2N

U
O
O O O O

H
O O O O
NH3 H3C H
OEt OEt OEt OEt

-B
OH

EtO2C CO2Et EtO2C CO2Et EtO2C CO2Et

+
M H

:
O
:

NH2 NH2 O NH2 O

SK
EtO2C CO2Et EtO2C CO2Et
KOH HNO3 EtO2C CO2Et

N CaO  N [O]
N -H2O OH
H N
H
 Structure of Pyridine

U
N N N N

H
Resonance Energy: 125.5 KJmole-1
4

-B
5 3

6
N
1 M 2
SP2 SP2
SK
Substitution in Pyridine

Resonance contributing structures of pyridine show that 3 and 5 will be sites for
electrophilic attack whereas position 2,4 &6 will be sites for nucleophilic attack.
 Electrophilic Substitution

E E E

U
+ N N N
E
ttack H H H
r) 6a
2 (o

H
E E E
E+ H H H

-B
3 (or) 5 attack
N N N N

4a E+ H E H E H E
tta
ck

M N N N
SK
In 2 , 4 & 6 position electrophilic substitution of the intermediate carbonium ion has one
Contributing structure has a positively charged nitrogen atom. This makes these ions
less stable than the electrophilic substitution at position 3 (or) 5.
 Because of the withdrawal of electrons from the ring –carbon atoms towards nitrogen
atom, the ring is deactivated towards electrophilic reagents.
 In strong acid solution, pyridine is protonated, and so the positively charged nitrogen atom
Deactivates the ring even more than the unprotonated nitrogen atom. This is clearly shown

U
By the difficulty in nitration and sulphonation of pyridine.

H
 If a +I group is present, electrophilic reactions are accelerated. When the subtsituent group
Is in the 3 (or) 5 position, the entering group takes up the 2 or 6 position. If in the 2 or 4

-B
Position then the 3 or 5 position is the site of atteck.

M OCH3
OCH3
SK
N N N OCH3
 Nucleophilic Substitution

U
Nu Nu Nu
Nu ack
N H N H N H
t t
6a

H
or)
2( Nu Nu Nu
Nu

-B
H H H
3 (or) 5 attack
N N N N

4a Nu H Nu H Nu H Nu

M tta
ck
SK
N N N

Consideration of the anions in nucleophilic substitution shows that the 2 and 4 anions
have a nitrogen carrying a negative charge, so these anions will be more stable than
the 3 and 5 anions.
 Basicity of Pyridine

R-NH2 > >

U
N N
H
pKb 3.38 8.77 13.6

H
-B
Pyridine is more basic than pyrrole since in pyridine the lone pair of electrons of the
nitrogen atom is completely available for protonation, whereas the lone pair of electrons

M
of the nitrogen atom in pyrrole is involving the formation of (4n+2) π electron molecule.
Pyridine is less basic than the alkyl amines, since the nitrogen atom in pyridine is
SK
SP2 hybridized, it is more electron attracting than nitrogen in alkyl amine which is
SP3 hybridized, concequently, the lone pair of electrons in pyridine is more title held
and so is less available for protonation.
 Reactions of Pyridine
1. Dehydrohalogenation
Br
CH COOR CH COOR
N
+
CH2 COOR CH COOR N

U
bromosuccinic H Br
ester Maleic acid
ester

H
If we use KOH/EtOH solution, it also hydrolysis ester at the same time

-B
2. Acylation of –OH and –NH2

RCOCl ROH
RCOOR +

M N

O
N
Cl
R
N
H Cl
SK
N-acyl pyridinium
chloride
3. Reaction with RX
CH3

CH3I 300oC
+
HMR N CH3
N N N
I
CH3
4. Halogenation
cold X2
1 - halo pyridinium
halide
N N
X
X

U
Br Br Br
Br2
+ Electrophilic

H
300oC
N N N

-B
Br2
+ Free radical
500oC
N

M N Br Br N Br
SK
Cl
Cl2
AlCl3
N N
5. Nitration

NO2
conc. H2SO4 NO2
6% conc. H2SO4
fuming HNO3 90%
N N

U
fuming HNO3
300oC N N

H
H2O2
H2SO4
N NH2 NO2

-B
N

6. Sulphonation SO3H
20% Oleum

M N
o
220 C
N
Low yield
SK
SO3H
H2SO4 
70%
HgSO4
N N N
HgSO3

KSH [O]

N Cl N SH N SO3H
7. Mercuration Hg
(AcO)2Hg

N N

8. Ring openening

U
HIO4
o
CH3CH2CH2CH2CH3 + NH3
300 C
N

H
Nucleophilic substitution
1. TschiTschi babin reaction

-B
NaNH2 NaNH2

in toluene Excess
N

M N NH2
2-amino pyridine
N H2N N NH2
2,6-diamino pyridine
SK
H2O
NH2 H
-H+
N N -H- N N N NH2
NH2 NH2 NH
:

COCl CONH2 NH2

NH3/NaOH Br2/KOH
Shotten Hofmann
ClOC N COCl baumann H2NOC CONH2 rearrangement H2N NH2
N N
2. Reaction KOH
1. KOH/320oC
2.H3O+
N N OH N O
2-hydroxy pyridine H
(Pyridol) Pyridone

U
3. Reaction t-BuLi

H
C4H9Li
H + LiH
100oC C4H9
N N N
C4H9

-B
Li

Reduction

N
M
Na / EtOH
(or) Ni
N N
Na / liq.NH3

N
SK
H H
Piperidine 1,4-dihydro pyrdine

LiAlH4

N N
H
1,2-dihydro pyrdine
 Oxidation

Peracids N

:
PAA pyridine - 1-oxide
N PBA N O

U
MCPBA O H
O

H
 Pyridine oxide is more reactive towards electrophilic and nucleophilic reagent than pyridine

-B
N
O
M N
O
N
O
N
O
SK

:
N N N
N
O O O
O
 OH-
+ RCHO
N N
N O CH2R
H2/Ni

U
2X
PPh3 PCl3

H
RC
(or) PCl3
NO2 NH2 NH2

H
HNO3 H2/Pd H2/Pd

H2SO4 HCl

-B
N N Ac N N
2O
O O -A O
Ni cO
H
Ac2O NO2

M O
RONa HX
SK
OR X N X
N O RONa Fe

H3O+ AcOH
N N N
O O

N OH N O
H