Heterocyclic Compounds
3rd Year Students
Special Chem, Chem-Phys, Geo-chem, Zoo-Chem, Bot-Chem,
1
Synthesis Of Furan
1. From cyclodehydration of 1, 4-diketones by acidic reagents, e.g., H2SO4, ZnCl2, Ac2O and
P2O3
I2 EtOOC COOEt
2CH3COCH2COOEt + 2C2H5ONa CH3COCHCOOEt HC HC
Na+ CH3 C C CH3
O O
COOEt
EtOOC C CH3 H2SO4
C C H3C O H3C
C OH
H3C OH
2. From knorr-pyrrole synthesis
2
Synthesis Of Furan
3. Feist’s synthesis
H3C
H3C C O H3C C OH HC COOEt
CH2Cl CH Cl C CH3 O CH3
OH
Chloroacetone
E.A.A
4. From decarboxylation of furoic acid.
+ CO2
O COOH
O
3
Synthesis Of Furan
5. Furfural (furan 2-carboxaldehyde)
Furfural is commercially obtained from pentose (occurred in oat hulls) by stream distillation
HO OH
CHO CHO CHO
OH OH OH OH O
6. By treatment of α-hydroxyketones and acetylenic compounds
R C=O CO2CH3 OH CO CH
C K2CO3 2 3 + R CO2CH3
R H
H2C C
OH CO2CH3 -H2O CO2CH3
CO2CH3 O O
4
Synthesis Of Pyrrole
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Reactions Of Furan
1. Ring opening of furan:
The mildest acidic conditions required to affect the hydrolysis of furan into succinaldehyde to
prevent the polymerization
H+ H2O
O OHC CHO
O
H
2. Addition reactions of furuan:
a) Reduction:
+ H2
O O
THF
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Reactions Of Furan
b) Diels-Alder reaction:
O O
H
C
O + O O O
C
H
O O
c) Addition of carbenes (with diazomethane):
CH2N2
-N2
O O
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Reactions Of Furan
d) Furanis not stable in presence of air and usually stabilized by addition of small amount of
hydroquinone. Air oxidation takes place by 2, 5 addition forming peroxide. Hydrogenation of
furan peroxide gives succinaldehyde.
O2 [H] H2C CH2
O O
O O OHC CHO
3. Electrophilic substitution of furan:
*Furan cannot be directly nitrated with nitric acid (is very readily attack by oxidizing agents).
2-Nitrofuran may be prepared by nitrating furan with acetyl nitrate (CH3COONO2). Similarly,
furan cannot be directly sulphonated, but 2-sulphonic acid may be prepared by action of
SO3/pyridine on furan.
*If (-I) group is present in the ring, then sulphonation can be carried out directly, e.g., furoic
acid gives furoic 5-sulphonic acid.
*Furan reacts readily with halogen, but the liberated (HX) causes polymerization, because of
this halogenated furan prepared by indirect method, e.g., by brominating furoic acid and
decarboxylating the product, 5-bromofuroic acid to 2-bromofuran by heating in quinolone in
the presence of copper bronze. Aluminum chloride attacks furan ring, and Friedel-Crafts is
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best carried with SnCl4.
Reactions Of Furan
NH3/Al 2O3
450°C N
H
SO3/pyridine
O SO3H
f uran-2-sulphonic acid
RCOCI/SnCl 2
O COR
2-acylf uran
O
Furan CH3COONO 2
+
° O NO2 O2N O NO2
0C
2-nitrof uran 2,5-dinitrof uran
H2/Ni H 2O/H+
HO(CH2)4OH
O
Tetrahydrof uran Tetramethyleneglycol
Hg(OAC) 2 Br 2
O HgOAc O Br
2-Bromof uran
C 4H 9Li 1-CO 2
O Li 2-HCl O COOH
HCl/HCN
O CHO 9
Synthesis Of Furfural
1. From dehydration of aldopentoses
HCl
CH2OH-(CHOH)3-CHO
CHO
O
CHO CHO CHO CHO
H OH C OH C O C O
HO H - H2O C H HC H H C
H OH H OH H OH H C
CH 2OH CH 2OH CH 2OH CH 2OH
H OH - H2O
H CHO
CHO
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Synthesis Of Furfural
2. From Gattermann’s reaction:
+ H2O
+ HCl/HCN CH=NH2 CHO
O O O
+ HCl + H-CN H2O
O H-C=NH CH=NH CHO
O O
Cl
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Reactions Of Furfural
Furfural is chemically very similar to benzaldehyde as the following
1. It undergoes oxidation (KMnO4) to furoic acid.
2. When it was submitted to react with sodium hydroxide it undergoes cannizzaro reaction
and gives a mixture from furfuryl alcohol and sodium salt of furoic acid.
3. It under goes benzoin condensation and gives furoin.
4. It reacts with aniline in the presence of acetic acid and gives Schiff’s base.
NH2
O
2 + O Ph-NHCH=CH-CH
C
aniline f urf ural
HO
Schif f 's base NPh
Brilliant red
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Reactions Of Furfural
5. It reacts with acetone and yields furfurylidene acetone.
O
f urf urylidene acetone
6. It reacts with CaO/400ºC, it loses carbon monoxide and gives furan by steam decomposition.
7. With ammonia and ammonium chloride gives 3-hydroxypyridine.
NH3/NH4Cl H OH
C
CHO
O O
H2N
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Reactions Of Furfural
H2/CuO
O CH2 OH
f urf uryl alcohol
H2/Ni
O CH 2 OH
O tetrahydrof urf uryl alcohol
CHO
furf ural
NaOH
+
(cannizzaro O CH 2OH O COOH
reaction)
f urf uryl alcohol f uroic acid
KMnO4
O COOH
f uroic acid
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Reactions Of Furfural
AC2O/AcONa
(perkin O
reaction) CH CH COOH
O
CHO f urylacrylic acid
f urf ural
Alc./KCN
CH
(benzoin O O
condensation) O OH f uroin
OXID
O O
O O
f uril
NaOH
OH
O
COOH
2
f urilic acid
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