Five membered heterocyclic compounds

1. Heterocyclic Compounds
Dr Beena Negi
Assistant Professor
Department of Chemistry
Gargi College
University of Delhi

2. 2
Aromatic Five-Membered Heterocycles With
One Heteroatom

3. • Pyrrole, furan and thiophene are colorless liquids of boiling points 126o, 32o,
and 84o respectively.
• Pyrrole has a relatively high boiling point as compared to furan and
thiophene, this is due to the presence of intermolecular hydrogen bonding in
pyrrole.
N N N
H H H
N
H
N
H
Five-membered Rings with one Heteroatom

4. They tend to react by electrophilic substitution due appearance of –ve charge on
carbon atoms due to delocalization as shown in the following resonance structures
Resonance in Pyrrole

5. Hetero-Monocyclic Compounds
Resonance
Since thiophene has vacant d orbital of sulphur and it can expand its octet, thus it has
five more resonating structures.

6. Aromaticity
 Pyrrole furan and thiophene are
aromatic because:
they fulfill the criteria for aromaticity, the
extent of delocalization of the nonbonding
electron pair is decisive for the
aromaticity, thus the grading of
aromaticity is in the order of:
Furan < Pyrrole < Thiophene < Benzene
this order is consistent with the order of
electronegativity values for oxygen (3.44),
nitrogen (3.04) and thiophene (2.56).
Hetero-Monocyclic Compounds

7. 7

8. 8
the dipole moment of pyrrole compared with pyrolidine is reverted

9. By passing mixture of acetylene and ammonia through red hot tube.
By passing a mixture of furan, ammonia and steam over hot alumina
By distillation of succinamide over zinc dust
Synthesis of Pyrrole

11. Mechanism of pyrrole synthesis

12. Knorr Pyrrole synthesis

15. Hetero-Monocyclic Compounds
( C5H8O4 )n
H2O,H+
CHO
(CHOH)3
CH2OH
Pentose
O
CHO
O
Furfural Furan
-3H2O
400
Pentosan
Catalytic decarboxylation of furfural in steam in the presence of oxide catalyst.
Synthesis of Furan

17. Paal Knorr Synthesis

19. Synthesis of Thiophene

24. Reactions of Pyrrole, Furan and Thiophene

25. Electrophilic substitution reaction occurs preferentially at C-2
rather than at C-3.

27. 27
The increased reactivity is a result of resonance which pushes the
electrons from the hetero-atom into the ring making the C-atoms of
ring more electron rich than in case of benzene.
In fact pyrrole resembles most reactive benzene derivatives (phenols
and amines).
O is more EN than N hence O is not as effective as N in donating
electrons into the ring. S has non bonding electrons in 3p orbital and
hence less overlapping between 2p and 3p orbitals of C and S.
Relative reactivity towards electrophilic substitution reaction

28. There are some modifications in usual electrophilic reagents, for
instance, sulphonating and nitrating reagents have been modified to
avoid the use of strong acids (induce polymerization).
Also reaction with halogens requires no Lewis acid .
Halogenation
X
Br2
Dioxane
SOCl2
pyridine
X
X
Br
Cl
2-bromo.....
2-chloro.....

29. 29
Electrophilic aromatic substitution reactions:

30. 30
If both positions adjacent to the heteroatom are
occupied, electrophilic substitution occurs at C-3:

31. 31
The relative reactivities of the five-membered
heterocycles in Friedel–Crafts reaction:

32. Reactions of pyrrole
N
H
N
H
N
H
N
H
N
H
N
H
O H C
C O C H 3
C
O
C
O
O
H 3 C
H 3 C
A c 2
O
1 - D M F /P O C l3
2 - H
2 O
+ N a
2 C O
3
CH3
COO
-
NO2
+
N O 2
H
2 pt
A cO H 200
S O 3
p yridine
H O 3 S
2 -n itr o p y r ro le
p y r ro lid in e2 -p y rro le su lfo n ic a c id
2-a cety lp y rro le
p y rro le-2 -c arb ox a ld eh y d e
a ce tic a n h y d rid e
Acetylation
Vilsmier haack Rx
Nitration
ReductionSulfonation
HNO3
+Ac2o

33. with carbeneReactions of Pyrrole
Hetero-Monocyclic Compounds
Ciamiaci Dennstedt rearrangement
Riemer Tiemann reaction

34. Formylation reactions
Vilsmier Haack reaction
Gattermann reaction
Reimer Tiemann reaction

37. O
O
O
O
O
OHC
COCH3Ac2
O
1- DMF/POCl3
2- H
2 O
+ Na
2 CO
3
dil NHO3
CH3COOH,[0]
NO2
SO3 ,100
pyridine
HO3S
2-nitrofuran2-furan sulfonic acid
2-acetyl furae
furfulaldehyde
furfural BF3
NitrationSulfonation
Acetylation
Vilsmier Rx
Hetero-Monocyclic Compounds
Reactions of Furan

39. Reactions of Thiophene
S
S
S
S
COCH3
CH3COCl
dil NHO3
CH3COOH,[0]
NO2
SO
3 , 100pyridine
HO3S
2-thiophene-2- sulfonic acid
SOCL4
S
NO
2O2NHNO3
SS
S S S
Br
Br
Br
Cl Cl
Cl
Cl
Cl Cl
Cl
Br 2
AcOH
Cl2
50
major minor
Nitration
Sulfonation
Acetylation
Halogenation
Hetero-Monocyclic Compounds

43. Hetero-Monocyclic Compounds
The order of aromaticity
Benzene > Thiophene > Pyrrole > Furan
In case of Thiophene [S]
donate & accept electrons……
so delocalization as complete as benzene
S
In case of Furan [O]
electronegativity more.
Diene-like character CH2=CH-CH=CH2
O

44. O
O
O
O
Thermodynamic
exo-product forms as the
temperature is raised
endo-product
Furan being least aromatic has diene character,
It readily undergoes the Diels-Alder reaction with maleic anhydride
More stable due to less steric reasons

45. Aromaticity prevents thiophene from taking part in the Diels-Alder reaction
S
O
O
X
S O
O
X
X
+
- SO2
This sulfone is not aromatic & very reactive
Thiophene may undergo Diels Alder
reaction with very reactive dienophiles
(alkynes) or under high pressure

46. 46
Pyrrole is an extremely weak base:
Electrons not available for
protonation—hence not basic

47. 47
The resonance hybrid of pyrrole indicates that there is a
partial positive charge on the nitrogen:
Pyrrole is unstable in strongly acid solution because the
protonated pyrrole polymerizes:

51. 51
Pyrrole is more acidic than pyrrolidine because of
stabilization of its conjugated base by resonance
Five resonance
structures for the anion
Localized anion

52. Hetero-Monocyclic Compounds
N
H
N+
N N
CH3
H2
K+
Cl-
+ KICH3I
HCl
KOH
H2O +
Its exceptional lack of basicity and strong acidity as a secondary amine compared to
the aliphatic analog (pyrrolidine).
This can be explained on the basis of participation of N lone pair in aromatic sextet
N
H
N
-Na
+ NaNH2
Liq NH3
strong baseweak acid salt
N
H
NNNN
-H+
Pyrrole anion
( Conjugated base)

54. Acidic properties of pyrrole
Its exceptional lack of basicity and strong acidity as a secondary amine compared
to the aliphatic analog (pyrrolidine). This can be explained on the basis of
participation of N lone pair in aromatic sextet.
It can react with strong bases or Grignard reagent or potassium metal in inert
solvents, and with sodium amide in liquid ammonia, to give salt-like compounds
which can be used to alkylate or acylate the nitrogen atom as shown below

55. Five Membered Heterocycles
N
H
S O
Pyrrole
Thiophene Furan
The least aromatic:
The O atom is too electronegative
Can give addition, as well as substitution products when
reacted with E+
Less reactive than pyrrole,
but substitution always at 2-
position
More aromatic than Furan
Electrophilic Substitution, not addition
Least reactive
Thiophene has similar reactivity to benzene

69. Ans b

70. Ans (d)

71. Ans (d)
Increasing Order of acidity

72. Ans c

73. The reactivity of the following compounds with proton will be in the order of
Ans a

74. Ans (c)

75. Suggest suitable reagents to carry out the following transformations

76. Ans (a)

77. Ans c

78. 78