An Expeditious Synthesis of Flavones on Montmorillonite K 10 Clay with Microwaves

Article abstract of DOI:10.1039/a709146j

A manipulatively simple and rapid method for the synthesis of flavones is described via a solid-state dehydrative cyclizatton of o-hydroxydibenzoylmethanes on a clay surface using microwaves.

Full text of DOI:10.1039/a709146j

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3
48 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
An Expeditious Synthesis of Flavones on
Montmorillonite K 10 Clay with Microwaves$%
Rajender S. Varma,* Rajesh K. Saini and Dalip Kumar
1998, 348±349$
Department of Chemistry and Texas Regional Institute for Environmental Studies (TRIES),
Sam Houston State University, Huntsville, TX 77341-2117, USA
A manipulatively simple and rapid method for the synthesis of flavones is described via a solid-state dehydrative
cyclization of o-hydroxydibenzoylmethanes on a clay surface using microwaves.
Flavonoids are a group of naturally occurring phenolic
compounds widely distributed in the plant kingdom, the
most abundant being the ¯avones. Members of this class
have been shown to display a wide variety of biological
1
activities and have proven useful in the treatment of var-
2
ious diseases. There are number of methods available for
3
a±e
the synthesis of ¯avones and their analogues,
including
4
the Allan±Robinson synthesis, synthesis from chalcones
3c
5
and via an intramolecular Wittig strategy. The most com-
mon method, however, involves the Baker±Venkataraman
rearrangement wherein o-hydroxyacetophenone is benzoy-
lated to form the benzoyl ester which is treated with base
6,7
(
pyridine/KOH) to e€ect an acyl group migration, forming
a 1,3-diketone. The ensuing diketone is then cyclized under
strongly acidic conditions using acetic acid and sulfuric acid
to deliver the ¯avone. Consequently, there is a need for
the development of a milder protocol for the cyclization
process.
Scheme
In conclusion, we have developed a simple and mild
method for the solid-state cyclodehydration of o-hydroxy-
dibenzoylmethanes to ¯avones on a clay surface using
microwave irradiation.
Clay-catalysed organic reactions have generated consider-
able interest in recent years in view of their inexpensive
nature and special catalytic attributes under heterogeneous
7
reaction conditions. Microwave (MW) heating is used for a
wide variety of organic reactions and has found application
Experimental
8
±11
in rapid and cleaner synthesis of organic compounds.
More recently, the emphasis has shifted in favor of micro-
1
Mps are uncorrected. H NMR spectra were recorded in
CDCl3 solutions at 60 MHz, using TMS as an internal standard.
o-Hydroxydibenzoylmethanes 1a±g were obtained by rearrange-
9
±11
wave-assisted methods under solvent-free conditions
13
ment of the corresponding o-benzoyloxyacetophenones. A Sears
Kenmore household microwave oven operating at 2450 MHz was
used at its full power, 900 W, for all the experiments. Products were
identi®ed by comparison of their mp, IR and NMR spectra with
those of authentic samples.
which have special appeal as they provide an opportunity to
work with open vessels, thus avoiding the risk of high
pressure development. Further, this approach enhances the
possibility of upscaling the reactions on a preparative scale.
In continuation of our studies on microwave-accelerated
Typical Procedure: 4'-Methyl-6-methoxy¯avone 2f.Ð1-(2-Hydroxy-
5-methoxyphenyl)-3-(4-methylphenyl)propane-1,3-dione 1f (0.2 g,
10
solvent-free reactions on mineral solid supports, we now
report manipulatively simple and rapid microwave
0.70 mmol) was dissolved in a small amount of dichloromethane
a
(
1 ml) and adsorbed on montmorillonite K 10 clay (1.0 g). The
protocol for the solid-state cyclodehydration of o-hydroxy-
dibenzoylmethanes to ¯avones on a clay surface.
contents, in a test-tube, were placed in an alumina bath inside the
microwave oven and irradiated for 1.5 min. The crude product was
extracted in dichloromethane (2Â 15 ml) and then crystallized from
The method in its entirety involves the microwave
irradiation of o-hydroxydibenzoylmethanes adsorbed on
montmorillonite K 10 clay for 1±1.5 min (bulk temperature
of alumina bath reaches 80±120 8C). The exclusive for-
mation of cyclized ¯avones 2a±g occurs which are easily
extractable in good yields from the support (Table 1). The
alumina bath, in addition to being a container for the reac-
tion vessel, also serves as a heat sink for the microwaves in
view of the small amount of reactants normally employed.
Among the various other mineral supports explored, namely
silica gel, neutral or basic alumina, the formation of ¯avone
is ideally accomplished on K 10 clay; some reaction does
occur on neutral alumina and silica surfaces but it is not
complete.
1
methanol to a€ord 2f in 80% yield, mp 161±162 8C; H NMR
(
3 3 3
CDCl ) ꢀ 2.26 (3 H, s, C4'±CH ), 3.36 (3 H, s, C6-OCH ), 6.26
(
1 H, s, C3±H), 6.53±7.33 (7 H, m, aromatic H); m/z 266 (100%).
That the e€ect may not be purely thermal is supported by the
14
fact that the reaction could not be completed (65%) in 24 h at
the same bulk temperature of 80 8C using an alternate mode of
Table 1 Synthesis of flavones from o-hydroxydibenzoyl-
methanes on clay
a
mp (8C)
Yield
(%)
1
R
2
Entry
R
Observed
Reported
3
b
2a
H
H
H
H
OCH
OCH
OCH
H
75
77
76
78
73
80
72
96
95
3
110
d
2
2
2
2
2
2
b
c
d
e
f
CH
OCH
NO
H
CH
OCH
3
108±109
155±157
244±245
161
161±162
193±194
3
d
d
3
156±157
246±247
163±164
±
*To receive any correspondence (e-mail: chm_rsv@shsu.edu).
3
2
$This is a Short Paper as de®ned in the Instructions for Authors,
3e
3
3
3
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
3
12
g
3
195
%
Presented in part at the 6th International Conference on
a
Microwave and High frequency Heating, Fermo, Italy, 9±13th
September, 1997.
MW irradiated for 1 min (the bulk temperature of the alumina
bath reached 80 8C at full power of the MW oven, 900 W).

View Article Online
J. CHEM. RESEARCH (S), 1998 349
heating (oil-bath). The temperature of the reaction mixture inside
the alumina bath reached 180 8C after 1 min of irradiation in a
MW oven operating at full power of 900 W.
8 S. Caddick, Tetrahedron, 1995, 51, 10403.
9 R. S. Varma, in Microwaves: Theory and Application in Material
Processing IV, ed. D. Clark, W. Sutton and D. Lewis, American
Ceramic Society, Ceramic Transactions, 1997, vol. 80, pp. 357±
365.
We are grateful to Texas Advanced Research Program
(
ARP) in chemistry (Grant No. 003606-023) and TRIES,
Oce of Naval Research/SERDP (Grant No. N00014-96-1-
067) for ®nancial support.
10 R. S. Varma, M. Varma and A. K. Chatterjee, J. Chem. Soc.,
Perkin Trans. 1, 1993, 999; R. S. Varma, A. K. Chatterjee and
M. Varma, Tetrahedron Lett., 1993, 34, 3207; R. S. Varma, J. B.
Lamture and M. Varma, Tetrahedron Lett., 1993, 34, 3029; R. S.
Varma, A. K. Chatterjee and M. Varma, Tetrahedron Lett.,
1
1993, 34, 4603; R. S. Varma and R. K. Saini, Tetrahedron Lett.,
1997, 38, 2623; R. S. Varma and R. Dahiya, Tetrahedron Lett.,
1997, 38, 2043; R. S. Varma and H. M. Meshram, Tetrahedron
Received, 22nd December 1997; Accepted, 26th February 1998
Paper E/7/09146J
Lett., 1997, 38, 5427, 7973; R. S. Varma, R. Dahiya and
S. Kumar, Tetrahedron Lett., 1997, 38, 2039, 5131; R. S. Varma
and R. K. Saini, Synlett, 1997, 857; R. S. Varma, R. K. Saini
and H. M. Meshram, Tetrahedron Lett., 1997, 38, 6525; R. S.
Varma, R. Dahiya and R. K. Saini, Tetrahedron Lett., 1997, 38,
7029, 7823, 8819; R. S. Varma and R. K. Saini, Tetrahedron
Lett., 1997, 38, 4337; R. S. Varma and R. Dahiya, Tetrahedron
Lett., 1998, 39, 1307; R. S. Varma and R. K. Saini, Tetrahedron
Lett., 1998, 39, 1481; R. S. Varma and K. P. Naicker, Molecules
Online, 1998, 2, 94.
1 J. M. Lerestif, L. Toupet, S. Sinbandhit, F. Tonnard, J. P.
Bazureau and J. Hamelin, Tetrahedron, 1997, 53, 6351; A. L.
Marrero-Terrero and A. Loupy, Synlett, 1996, 245; A.
Benalloum, B. Labiad and D. Villemin, J. Chem. Soc., Chem.
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