Synthesis of Flavanone
Synthesis of Flavanone
Synthesis of Flavanone
106-110
ISSN 2049-954X
Research Paper
Abstract
Flavanones are important biosynthetic precursors for the synthesis of flavones, isoflavones, flavonols and dihydroflavonols.
The flavanone skeleton is present in a wide range of synthetic and naturally occurring products exhibiting various
interesting pharmacological activities. The present paper describes the use of methane sulphonic acid as an efficient
organocatalyst for the synthesis of substituted flavanones from 2-Hydroxy Chalcones in good yields and in short reaction
time. The catalytic efficiency of methane sulphonic acid in cyclization of chalcones to flavanones has been demonstrated
with a variety of substrates bearing electrondeficient to electron rich groups on chalcones and the yields obtained are
higher than the reported methods with triflluoroacetic acid / mineral acids. Methane sulphonic acid is an inexpensive, safe,
eco-friendly acid catalyst with low LD50. The present protocol could find wide spread application in the synthesis of
flavanones bearing free hydroxyl groups on the aromatic moiety. At the same time the methodology would be useful for the
synthesis of naturally occurring bioactive flavanones.
Keywords: Methane Sulphonic Acid, 2-Hydroxy Chalcone, Flavanone, Cyclization, Acetic acid
1. Introduction
Flavanones (2,3-dihydro-2-phenyl-4H-1-benzo-pyran-4one derivatives) are the main biosynthetic precursors for
major flavonoids such as flavones or isoflavones and for
two important flavonoid intermediates: the flavan-4-ols
(biosynthetic precursors for the formation of 3deoxyanthocyanins)
and
the
dihydroflavonols
(biosynthetic intermediates in the formation of catechins,
flavonols, anthocyanins and proanthocyanidins) (Heller &
Forkmann, 1988; Haslam, 1993 and Mann, 1994). The
flavanone skeleton is present in a wide range of synthetic
or naturally occurring products exhibiting various
interesting pharmacological activities (Bertram, 1989;
Pathak et al, 1991; Spilkova & Hubik, 1992 and Manach et
al, 1996). Flavanones widely distributed in nature,
continue to attract attention due to their ample range of
biological activities (like hypotensive, antifungal,
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P. Zubaidha et al / Chemistry Journal (2012), Vol. 02, Issue 03, pp. 106-110
column
R4
R3
R3
R2
OH
CH3SO3H
R2
R2
R2
R2
R1
Acetic acid
R1
Reflux
R1
O
2
Sr.No.
Solvent
Temperature
% Yieldb
1
2
3
4
Acetic acid
Ethanol
DMF
DMSO
110
70
140
140
89
50
40
No Reaction
Reaction Condition:
Sulphonic Acid
by
2. Experimental
ISSN 2049-954X
2-hydroxychalcone
(1mmole),
Methane
107
P. Zubaidha et al / Chemistry Journal (2012), Vol. 02, Issue 03, pp. 106-110
ISSN 2049-954X
A possible reaction mechanism for the intramolecular oxaMichael addition in 1a, promoted by Bronsted acid, as
given by Johnsons group, is outlined in Scheme 2 (Ellis et
al, 1982 and 1983). The carbonyl oxygen of 1a accepts
Entry
Chalcone (1)
R1
R2
R3
R4
R5
R6
Flavanone (2)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
1s
1t
1u
1v
1w
H
H
H
H
H
H
H
H
H
H
H
H
OH
OH
H
H
H
H
H
H
H
OH
OH
H
H
H
H
H
H
H
H
H
H
H
H
OH
H
H
OH
OH
H
H
H
H
H
OH
H
H
H
H
H
H
OMe
CH3
Cl
H
Cl
H
H
H
H
H
H
H
H
H
OMe
H
H
H
OMe
H
H
OMe
OMe
H
H
H
H
H
H
H
H
NO2
H
H
H
OMe
H
OMe
OMe
H
H
OMe
Cl
CH3
H
H
H
H
Cl
Br
H
F
H
Cl
H
OMe
Cl
OMe
OMe
NO2
H
OMe
OMe
H
OMe
H
H
H
OMe
OMe
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
2s
2t
2u
2v
2w
Time
(hrs)
2
1.45
2.30
2.10
2.25
2.15
2
2.40
2.45
2.30
2.30
3
1.5
1.45
1.20
1.05
1.40
1.35
1.50
3.15
3.40
3.50
3.45
%Yield
89
86
82
80
73
78
75
69
65
73
68
82
64
73
79
76
71
85
82
62
76
73
72
Reaction Condition : 2-Hydroxychalcone (1 mmole), Methane Sulphonic Acid (10% v/v) in Solvent b : Isolated Yield
OH
H+
OH
O+
OH
+
OH
+
O
OH
H+
H+
III
OH
OH
II
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P. Zubaidha et al / Chemistry Journal (2012), Vol. 02, Issue 03, pp. 106-110
ISSN 2049-954X
4. Conclusion
In conclusion, here in we report simple and an efficient
method for the synthesis of flavanone from 2hydroxychalcone by the use of methane sulphonic acid an
inexpensive and safe acid catalyst. This protocol will be a
good addition to the most recent environmentally friendly
methods reported for the synthesis of flavanones. This
protocol is also useful for the synthesis of phloroglucinol
type flavanone. Other advantages of this method are high
yield and shorter reaction time compare to other reaction
conditions. Merits of this method over trifluroacetic acid
and mineral acid are that 1) this acid is biodegradable and
can be recycled while trifluroacetic acid is not
biodegradable 2) example reported with trifluroacetic acid
includes only methoxy group while this method is
applicable to all types of functional groups.
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