Reaction of Furan and Thiophene

Reaction of Furan and Thiophene
Assis.Prof.Dr.Mohammed Hassan
Lecture 6

a) Oxidation
Br 2 / CH 3 OH
H
O
MeO
H
O OMe
cis / trans
2,5-Dihydro-2,5-dimethoxyfuran
This reaction involves electrophilic addition of bromine in
presence of methanol at 2 & 5 positions followed by
substitution by methanol.
Thiophene is oxidized by peracids to Thiophene-1-oxide and
2-hydroxythiophene oxide.
S
O
S
O
OH

Raney Ni / H 2
b) Reduction
O
O
2-Methyltetrahydrofuran
On the other hand thiophene can not be reduced under the
same conditions due to sulfur poison the catalyst and
desulphurization occurs with ring opening.
However, partial reduction can take place by metals in
acidic medium.
Raney Ni / H 2
+ NiS
S
Zn / HCl
S CH 2 CH 3 S
CH 2 CH 3

Electrophilic Aromatic substitution Reactions
1) Nitration
O
CH 3 COONO 2
Pyridine
O
NO 2
S
CH 3 COONO 2
AcOH / Ac 2 O
2) Sulphonation
S
NO 2
O
N
SO 3
SO 3 / Pyridine complex
HO 3 S
O
SO 3 H
S
95 % H 2 SO 4
S
SO 3 H
Heterocyclic Chemistry

3) Halogenation
NBS
S
S
Br
X
X
O
X 2 / r.t
x= Clor Br
X
O
X
Cl 2 / CH 2 Cl 2
- 40 C°
Br 2 / Dioxane
O
Cl
0 C ° O Br
Indirect insertion of iodine in furan ring
I 2 / KI
O
COOH
KOH
O I
Heterocyclic Chemistry

4) Acylation
(CH 3 CO) 2 O /
S
S
COCH 3
H 3 PO 4
(CH 3 ) 2 CCl / FeCl 3
Ac 2 O / SnCl 4
O
O
COCH 3
5) Alkylation
It is very low yielding reaction due to formation of
polyalkylated products or polymers.
O
Heterocyclic Chemistry
t-Bu
O
t-Bu

4) Lithiation
X
X = O, S
BuLi
X
Li
RX
X
R
5) Diazocoupling:
Furan and thiophene can not couple with diazonium salts
which shows that they are less reactive than pyrrole.
O
Ar N=N + Cl -
No Reaction
S
Heterocyclic Chemistry

Second Electrophilic Substitution in Furan and
Thiophene
a) Monosubstituted furan & thiophene with electron withdrawing groups such as
COOH, CHO, CN, COR, SO 3 H are less reactive than unsubstitutted compounds
i) EWG at position 2
O 2 N
HNO 3 (incoming E + is directed to m-position i.e. position 4)
S CN S CN
Less reactive than thiopene
O 2 N
+
CH COONO 3 2
O CHO
O 2 N O CHO O CHO
Pyridine
Less reactive than furan
O
COOH
Br 2 / Dioxane
ii) EWG at position 3
3 : 1
(incoming E + is directed to position 5 mainly and to position 4
as well )
Br
+
Br O COOH
O COOH
X
EWG
E +
E
X
EWG
(incoming E + is directed to position 5)
Heterocyclic Chemistry

) Monosubstituted furan & thiophene with electron donating group such as CH 3 , OH, NH 2 ,
OCH 3
i) EDG at position 2
E + O COCH 3
X
EDG
More reactive than unsubstituted
compound
E
X
EDG
(incoming E + is directed to position 5)
ii) EDG at position 3
EDG
X
EDG
EDG
or
E + X E
E X
(incoming E + directed to 2 mainly or 5 due to steric effects )
CH 3 CH 3
Ac 2 O / r.t.
+
CH 3
O
25 % H 3 PO 4
H 3 COC
O
Heterocyclic Chemistry

Ac 2 O / HNO 3
H 3 C
S
COOH
H 3 C
S NO 2
(Replacement of leaving group takes place)
Heterocyclic Chemistry