Five Membered Heteroaromatic Rings
X
X = NH Pyrrole
= O Furan
= S Thiophene
Their aromaticity derived from delocalization of lone pair of X
so X is electron deficient ring is electron rich
Five Membered Heteroaromatic RingsFacts
1- aromaticity inversely proportion to electro negativity
Thiophene > Pyrrole > Furan
2- Electrons not available for protonation—hence not basic
NH
N+
N N
CH3
H2
K+
Cl-
+ KICH3I
HCl
KOH
H2O +
Five Membered Heteroaromatic Rings
X
X = NH Pyrrole
= O Furan
= S Thiophene
Facts
3- 6 electrons over 5 ring atoms ….. Electron rich… so more reactive than benzene towered electrophilic substitution
Pyrrole > Furan >Thiophene>benzene
Five Membered Heteroaromatic Rings
Aromaticity
X X X X X X
Rasonance Explanation
1-
6 electrons distributed over 5 ring atoms
each 2e make coupling …. So is planner, all sp2
Five Membered Heteroaromatic Rings
X
X = NH Pyrrole
= O Furan
= S Thiophene
Aromaticity
2- Their protons show the same sort of chemical shift in NMR
as the protons of benzene with δ = 6.5 ppm-8 ppm
Five Membered Heteroaromatic Rings
Only for pyrrole
3-Its weak acid not basic as the secondary amines
NH
NNNN
-H+
Pyrrole anion( Conjugated base)
NH
N-Na
+ NaNH2Liq NH3
strong baseweak acid salt
Lone pair of N is involved in cloud and not
Available for sharing with acids
4-the patteren of reactivity
The pattern of reactivity with Electrophilic reagents
Cycloalkanes …… by addition reaction
Aromatic compounds ……. By substitution addition followed by proton loss [ onium intermediate]
Ordre of reactivityPyrrole > Furan >Thiophene>benzene
X
X X X
X X X
X
+ E+
H
EHE
HE
E- H+
HE
HE E
- H+
C2-attack
C3-attack
At what position Es take place
5-The order of aromaticity
Thiophene > Pyrrole > Furan
Why?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
Five Membered Heteroaromatic Rings
6- The pattern of reactivity with Electrophilic reagents
Cycloalkanes …… by addition reaction
Aromatic compounds ……. By substitution addition followed by proton loss [ onium intermediate]
Ordre of reactivityPyrrole > Furan >Thiophene>benzene
Five Membered Heteroaromatic Rings
Sources & Synthesis
Pyrrole & Thiophene …. Coal Tar
Pyrrole ring …. Prophyrin system….. Chlorophyll & Hemoglobin
Furan ….. Decarbonylation of Furfuraldehyde ……. Oat hulls, corncobs or rice hulls
Five Membered Heteroaromatic Rings
Synthesis Thiophene
Pyrrole
CH3-CH2-CH2-CH3 + 4 SS
560 + 3 H2S
n- butane
HC CH + 2 HCHOCu2C2 HOH2CC CCH2OH
NH
NH3pressure
1,2-butyldiolFormaldehydeEthyne
Five Membered Heteroaromatic Rings
Synthesis Furan
( C5H8O4 )nH2O,H+
CHO
(CHOH)3
CH2OH
Pentose
O CHOO
Furfural Furan
-3H2O 400
Pentosan
Pyrrole
Reactions ESR
NH
NH
NH
NH
NH
NH
OHCCOCH3
CO
C
O
O
H3C
H3CAc2O
1- DMF/POCl3
2- H2 O + Na
2 CO3
CH
3 CO
O-N
O2 +
NO2
H2 \pt
AcOH\200
SO 3
pyridine
HO3S
2-nitropyrrole
pyrrolidine2-pyrrole sulfonic acid
2-acetylpyrrolepyrrole-2-carboxaldehyde
acetic anhydride
Acetylation
Vilsmier Rex
Nitration
Reduction
Sulfonation
NH
:CCl2
HCCl3 / NaOH NH
CCl
Cl
ring openning
enlargementN
Cl
3-chloropyridine
Rex with carbene
Halogenation
X
Br2
Dioxane
SOCl2
pyridine
X
X
Br
Cl
2-bromo.....
2-chloro.....
Pyrrole
Furan
O
O
OO
O
OHCCOCH3Ac2
O
1- DMF/POCl32- H
2 O + Na2 CO
3
dil NHO3CH3COOH,[0]
NO2
SO 3 ,100
pyridine
HO3S
2-nitrofuran2-furan sulfonic acid
2-acetyl furaefurfulaldehyde furfural BF3
NitrationSulfonation
Acetylation
Vilsmier Rex
Rex of furfural
O
OCOOH
OO
CH3 CH2OH
+
NaOH
30 c
CO
H
N2 H
2base2-methyl furan
+ Furfural
KCN
OC
O
CH
OH
O
furoin
[O]
OC
O
C
O
Ofuril
O CHO COOH
O
furfulic acid
NaOH
Cannizaro Rex
Walf-Kishnerreduction
Benzoin-condensation
Thiophene
S
S
S
SCOCH3CH3COCl
dil NHO3CH3COOH,[0]
NO2
SO3 , 100pyridine
HO3S
2-thiophene-2- sulfonic acid
SOCL4
SNO2O2N
HNO3
SS
S S S
BrBr
Br
Cl ClCl
Cl
Cl Cl
Cl
Br 2
AcOHCl2
50
major minor
Nitration
Sulfonation
Acetylation
Halogenation
Five Membered Heteroaromatic RingsContaining 2X , at least one nitrogen
X
N
X
N
X = S ,O ,or N
1,3-Azoles 1,2-Azoles
Thiazole [ 1,3-thiazole]
Oxazole [ 1,3-oxazole]
Imidazole [ 1,3-diazole]
Isothiazole [ 1,2-thiazole]
Isoxazole [ 1,2-oxazole]
Pyrazole [ 1,2-diazole]
Five Membered Heteroaromatic RingsContaining 2X , at least one nitrogen
NH
N
Imidazole
Aromaticity & Bascisity
Strong base, due to the greater electron releasing capacity of the two nitrogen's
NH
N
2ry amine
3ry amine
NH
N H
N
N H
H
3ry amine ismore basic than 2ry amine
Five Membered Heteroaromatic RingsContaining 2X , at least one nitrogen
N
N
H
Pyridine like nitrogen( basic character )
Pyrrole like nitrogen( involved in aromaticity)
Aromaticity & Bascisity
Five Membered Heteroaromatic RingsContaining 2X , at least one nitrogen
Importance of the ring
Building blockes as Histidine and Histamine
It exist in two tautomeric forms ….. As base & weak acid
NH
N
N
NH
50 % 50 %
Fused Five Membered Heteroaromatic RingsWith one X
NH
NH
benzo[b]pyrroleIndole
benzo[c]pyrroleIsoindole
Found in coal tar & orange blossoms, humane feces
In amino acids as Tryptophan, alkaloid * pigments
NH
CH2CH
COOH
NH2
Tryptophan
NH
Carbazole
Fused Five Membered Heteroaromatic RingsWith one X
Synthesis Fischer ndole Synthesis
NHNH2
+C
O
CH3
Ph
Phenylhydrazine acetophenon
NHN
CH3
Ph
NH
Ph
2-phenyl indole
AcOH
or ZnCl 2
- H2O
Fused Five Membered Heteroaromatic RingsWith one X
Basicity of Indole
Not basic because lone pair is delocalized and contributed to the Aromatic system
NH
Fused Five Membered Heteroaromatic RingsWith one X
It undrego Electrophilic Subistitution at
Position 3
NH
+ E+
NH
NH
NH
NH
H
E
HE
H
E
HE
Not favoureddestroy aromatic str.of benzene
C-3attack
C-2attack
Fused Five Membered Heteroaromatic RingsWith one X
Rex with carbene
Vilsmier RexNH
DMF / POCl3
tolueneNH
CHO
Indole-3-carboxylaldehyde
NH
:CCl 2
(HCCl 3/NaOH)
:CHCl(H2 CCl
2 /NaOH)
N
Cl
Cl
HN
Cl
N
Cl
H
HN
3-chloroquinoline
quinoline
Fused Five Membered Heteroaromatic RingsWith tow X
NH
N
Benzimidazole
In nature as N-ribosyl-dimethyl benzimidazole …. In Vit B12
Commercially as an parasisticide