Structure, reactivity, synthesis and reactions of benzofuran

PRESENTED BY:
SHAMA TM
MSc 1st
year
Analytical chemistry

CONTENT:
 Introduction.
 Structure.
 Synthesis of Pyrone.
 Reaction.
 Conclusion
 Reference.

Introduction:
• Pyrones are the six membered unsaturated heterocyclic compounds containing oxygen atom in
the ring.
• Pyrones are also called Pyranone.
• This kind of structure are found in bacteria's ,plants ,animal and insects.
• They are two major isomeric forms of pyrone they are.
• 2H – pyrone [2- pyrone] and 4H – pyrone [4-pyrone].
• Pyrones are insignificantly basic and their basicity are comparable to those of urea and nitro
aniline.

Structure of Pyrones:
• The 2- pyrone can be viewed as conjugated enol- lactone , the extent to which they
additionally ,stabilized by resonance is not clear. Therefore 4 – pyrones have greater degree of
aromaticity than 2- pyrone.
• The parent compounds for both types of pyrone ring system are susceptible to ring opening by
nucleophilic reagent.
O
O
O
O
O
O
O
O
2-Pyrone 4-Pyrone
O
O
O
O

Some of simple 2-pyrone, 4-pyrone and their structures:
Benzannulated pyrone derivatives of :
O
O
O O
O
O
O
O
Isocoumarin
Coumarin
chromone
xanthone

Some pyrones found in nature:
O

O
O
O


O O




4-hydroxy 6-methyl 2-pyrone 3-acetyl 4-hydroxy 6-methyl 2-pyrone
Gibepyrone-A
Bufalin-A

Synthetic method of pyrones:
1. Vonpechmann method:
Reaction starts with malic acid, which converted into formyl acetic acid by reaction with
fuming sulphuric acid
The two moles of formyl acetic acid on self condensation gives coumalic acid which on
decarboxylation gives 2-pyrones its
CH2COOH
CH(OH)COOH
H2SO4
900
C
H OH
H
HOOC
H
O
H
COOH
Malic acid
formyl acetic acid

H
O
H
COOH
O
HO
O
+
H
H+
H
HO
HOOC H
O
O
H HO
-H2O
HOOC H
O
O
H HO
H
HOOC H
O
OH
H HO
Formyl pent-2 enedoic acid
O O
HOOC
O O
-H2O
Cu , 6500
c
-co2
Coumalic acid
2-pyrone

2.By acetone and diethyl oxalate: O
C
CH3
H3C
+
C
O
COOET
OET C
O
COOET
OET
Base
O
H
H
TEOOC
OET
COOET
OET
O O
O
H
H
TEOOC COOET
O O
H2O
O
TEOOC COOET
O
Hydrolisis
O
HOOC COOH
O
Cu , Tetralin
Heat
O
O

Reaction/chemical properties of pyrone:
1. Electrophilic substitution :-
 The aromatic character is reflect in their reaction towards electrophilic substitution
Both α and γ pyrones undergo substitution at 3- (or) 5- position to carbonyl group.
Halogenation:
α-pyrone is brominated at the 3-position via an addition elimination reaction and is not
result of direct electrophilic substitution.
O
O O
O
Br2
Br
Br
O
O
Br
Br
-HBr

 Nitration of the ring can be nitrated and sulfonated reaction of
alpha-pyrone with nitronium tetra fluoroborate ,reversibly from a o-
nitro salt which is slowly converted to 5-nitro alpha-pyrone.
O
O
O
O
Br, FeCl3
900C
[Perbromide]
H2O
1000
C
O
O
Br Br
Br
+
Bromination of 4-pyrone,
O
O ONO2
O
NO2
+
BF4
-
O
O
O2N

Acetylation:
4 – pyrones gives 3 – and 5 –substituted product.
 4-pyrone is weak base that is protonated at the carbonyl carbon in the
presence of (HCLO4) to from 4-hydroxy-pyrylium chlorate , crystalline salt.
O
O
O
O
O
O
Me
Me Me Me
O O
O
Me Me
RCOCl
CF3COOH
RCOCl
O
O
O
OH
HClO4
ClO4
In contrast,2-pyrone is a much weaker base and does not form
crystalline salt with strong acid.

2. Reaction with reducing agent:
Catalytic hydrogenation (H2/Ni) occurs at the c-c double bonds to give
saturated lactose hydrogenation further support the olefinic nature of both
alpha-and gamma pyrones.
O O
H2 , Ni
O O
O
O
Copper chromate
H2
O
O
O
+

NaBH4 do not react with pyrones.
LiAlH4 breaks the 4–pyrones ring to from an acid but an alcohol is obtained in
case gamma-pyrone due to redaction of the carbonyl moiety.
O O O O
Me
Me
Me
Me
H
LiAlH4
COO
Me
Me
H
O
O
O
Ph Ph
OH
H
Ph Ph
LiAlH4
Ether

3. Nucleophilic reaction:
Pyrones easily attacked by nucleophilic reagent.
Weak nucleophiles add at 2-position while strong ones add at 6-position.
Grignard reagent reacts preferentially at the carbonyl group to yield initially an alcohol
which is converted to a substituted pyrylium ion on acidification.
O O
O O
AgNH3
 H2N
H
COO
H2N H N O
H
-H2O
O
O
O
Me-MgX
Ether
OMgX
Me
O
Me
ClO4
HClO4 . H2O
-400
C

2- and 4- pyrones are easily hydrolysed in aqueous space which simultaneous ring
opening.
4. Photo chemical reaction:
Pyrones have been widely investigated photochemically and they have been shown
to give interesting product on Photolysis 2-pyrones lose carbon dioxide to yield
cyclobutadiene.
O O
Aq. NaOH
O
COO
2H+
OH
COOH
O
O
Aq.(BaOH)2
O
O O
Ba2
O
OH HO
O
O O
h
Pyrex
O
CO2
h
+

4. Diels alder reaction:
In this kind of reactions for 2-Pyrone functions as a diene for instance with Maleic
anhydride and two pyrones forms an adduct which suffers a pericyclic decarboxylation
to form a new diene Which reacts with the second molecule of Maleic anhydride to
form a new adduct.
There seems to be no case of 4-pyrone serving as a diene in a Diels alder reaction.
O O
O
O
O
O
H
H
O
O
O
C
O
1500
C
O
H
H
O
O
- CO2
O
H
H
O
O
O
O
O
H
H
O
O
O

Conclusion:
pyrone motif often shows biological activity in the form of defence against foreign bodies.
It is also found in bio synthetic precursors/intermediates and can be easily metabolised.
This particular fact of the Pyrone ring system makes them very interesting to study
potential pharma critical agent.
The structural derivative shown by 2-pyrone containing natural product is mirrored
through their biological effects,
example. as anti-bacterial anti-fungal agents acting against Alzheimer’s disease, HIV,
cholesterol-lowering and cancer treatment.

Reference:
Heterocyclic chemistry (5th
edition).
-Raj K Bansal

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