Five Membered Heteroaromatic Rings Their aromaticity derived from delocalization of lone pair of X...

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 +


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


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


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


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


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


Sources & Synthesis

Pyrrole & Thiophene …. Coal Tar

Pyrrole ring …. Prophyrin system….. Chlorophyll & Hemoglobin

Furan ….. Decarbonylation of Furfuraldehyde ……. Oat hulls, corncobs or rice hulls


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


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]


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


N

N

H

Pyridine like nitrogen( basic character )

Pyrrole like nitrogen( involved in aromaticity)

Aromaticity & Bascisity


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


Synthesis Fischer ndole Synthesis

NHNH2

+C

O

CH3

Ph

Phenylhydrazine acetophenon

NHN

CH3

Ph

NH

Ph

2-phenyl indole

AcOH

or ZnCl 2

- H2O


Basicity of Indole

Not basic because lone pair is delocalized and contributed to the Aromatic system

NH


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


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

Five Membered Heteroaromatic Rings Their aromaticity derived from delocalization of lone pair of X...

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