heterocyclic chemistry furan and thiophene. heterocyclic chemistry introduction
TRANSCRIPT
Heterocyclic Chemistry
Heterocyclic Chemistry
N
OS Furan and
Thiophene
Heterocyclic Chemistry
IntroductionIntroduction
N OS> >
Furan is not very aromatic therefore if there is a possibility of forming stable bondssuch as C-O bonds by addition, this may be preferred to substitution i.e. tendency to give addition products rather than substitution products increses as aromaticitydecreases.
In comparison to benzene the order of reactivity in electrophilic substitution is as follows: Pyrrole > Furan > Thiophene > Benzene
Regioselectivity: The 2 & 5 ( ) positions are more reactive than 3 & 4 ( ) PositionsAs in pyrrole the intermediate results from electrophilic attack at C2 can bestabillized by three resonance structure while the intermaediate results from theattack C3 is only satbilized by two resonance structures. Thus the former is morepreferred
>
Eelectrophilic substitution on furan requires very mild non acidic conditions (acidsmay induce polymerization or ring opening), however, for thiophene the acidity isless critical since it is stable to aqueous minral acids but not to 100 % strong acids or Lewis acids such as AlCl3.
Order of aromaticity
H
Heterocyclic Chemistry
Synthesis of Furan and ThiopheneSynthesis of Furan and Thiophene
O OH3C CH3
CH3H3Cdistl.P2O5
O S
1)
RR
H2S / weak base
S RR
Pentose
H2SO4/
O CHO
ZnO / 400 C°
O
1,4-Dicarbonylcompound
2)
3)
OH OHCHO
OHHO
- 3H2OFurfural
4)EtO2C
H3C
+
CH3
Cl
O pyridine
- H2OO
EtO2C
H2SO4 P4S10
O
- HCl,
Feist-Benary Furan Synthesis
Heterocyclic Chemistry
1- Addition Reactions1- Addition Reactions
a) Oxidation
Thiophene is oxidized by peracids to Thiophene-1-oxide and 2-hydroxythiophene oxide.
O
Br2 / CH3OHO OMeMeO
2,5-Dihydro-2,5-dimethoxyfuran
HH
cis / trans
This reaction involves electrophilic addition of bromine in presence of methanol at 2 & 5 positions which is characteristic of 1,3-dienes followed by substitution by methanol.
S
O
S
O
OH
Heterocyclic Chemistry
1- Addition Reactions1- Addition Reactions
b) Reduction
On the other hand thiophene can not be reduced under the sameconditions 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 / H2
O O
2-Methyltetrahydrofuran
S
Raney Ni / H2 + NiS
Zn / HCl
SS CH2CH3 CH2CH3
Heterocyclic Chemistry
11- - Addition ReactionsAddition Reactions
c) Diels- Alder Reaction:
Reaction of thiophene with maleic anhydride requires more drastic conditions than in case of furan and pyrrole (high pressure and temperature), this is because it is the most aromatic thus it is the least reactive as a diene. The order of reactivity in D.A reaction is as follows:
Furan > N-alkyl pyrrole > Pyrrole > Thiophene.
O O
O
O
O
S + O
O
O
S
O +O
CN
CNH3CO H3COZnI2
unsatble
Catalyst
+
100 Cpressure
°
HCl
Heterocyclic Chemistry
Electrophilic Aromatic substitution Electrophilic Aromatic substitution ReactionsReactions
1) Nitration
2) Sulphonation
O
CH3COONO2
S
CH3COONO2
O NO2
S NO2
Pyridine
AcOH / Ac2O
O
S
O SO3H
S SO3H
SO3 / Pyridine complex
95 % H2SO4
NSO3
HO3S
Heterocyclic Chemistry
Electrophilic Aromatic substitution Electrophilic Aromatic substitution ReactionsReactions
3) Halogenation
O
X2/ r.t
O
X
X
X
X
Cl2 / CH2Cl2
- 40 C°O Cl
x= Clor Br
Br2 / Dioxane
0 C ° O Br
Indirect insertion of iodine in furan ring
O COOH
I2 / KI
O IKOH
S
NBS
S Br
Heterocyclic Chemistry
Electrophilic Aromatic substitution Electrophilic Aromatic substitution ReactionsReactions
4) Acylation
5) AlkylationIt is very low yielding reaction due to formation of polyalkylated products or polymers.
S SCOCH3
O OCOCH3
Ac2O / SnCl4
(CH3CO)2O /
H3PO4
(CH3)2CCl / FeCl3
OO t-But-Bu
Heterocyclic Chemistry
Electrophilic Aromatic substitution Electrophilic Aromatic substitution ReactionsReactions
4) Lithiation
5) Diazocoupling: Furan and thiophene can not couple with diazonium salts which shows that they are less reactive than pyrrole.
O
S
Ar N=N +Cl- No Reaction
X LiX
X = O, S
BuLi RXX R
Heterocyclic Chemistry
Second Electrophilic Substitution in Second Electrophilic Substitution in Furan and ThiopheneFuran and Thiophene
(incoming E + is directed to m-position i.e. position 4)
S CN S CN
O2N
a) Monosubstituted furan & thiophene with electron withdrawing groups such asCOOH, CHO, CN, COR, SO3H are less reactive than unsubstitutted compounds
CH3COONO
2
Pyridine
(incoming E +is directed to position 5 mainly and to position 4
as well )
Less reactive than furan
O CHO O CHOO2N
Less reactive than thiopene
HNO3
O CHO+
O2N
X
E+EWG
i) EWG at position 2
ii) EWG at position 3
X
EWG
E(incoming E +is directed to position 5)
O COOH
Br2 / DioxaneO COOHBr O COOH
+
Br
3 : 1
Heterocyclic Chemistry
Second Electrophilic Substitution in Second Electrophilic Substitution in Furan and ThiopheneFuran and Thiophene
X E
EDG
E+
(incoming E +directed to 2 mainly or 5 due to steric effects )
b) Monosubstituted furan & thiophene with electron donating group such as CH3, OH, NH2, OCH3
More reactive than unsubstitutedcompound
orXE
i) EDG at position 2
X EDGX EDGE
(incoming E +is directed to position 5)
X
EDG
E+
O COCH3
CH3Ac2O / r.t.
25 % H3PO4O
CH3
+
OH3COC
EDG
CH3
ii) EDG at position 3
Heterocyclic Chemistry
Second Electrophilic Substitution in Second Electrophilic Substitution in Furan and ThiopheneFuran and Thiophene
SCOOH
(Replacement of leaving group takes place)
H3C S NO2H3C
Ac2O / HNO3