J. Chil. Chem. Soc., 59, Nº 1 (2014)
IODINE CATALYZED CASCADE SYNTHESIS OF FLAVONE DERIVATIVES FROM 2’-ALLYLOXY-α,
β-DIBROMOCHALCONES
BEENA R. NAWGHARE, SUNIL V. GAIKWAD, ABDUL RAHEEM AND PRADEEP D. LOKHANDE*
The Centre for Advanced Studies, Department of Chemistry, University of Pune, Pune 411007 India.
(Received: January 30, 2013 - Accepted: October 2, 2013)
ABSTRACT
Synthesis of flavones from 2’-allyloxy-α, β-dibromochalcones has been described. The iodine induced oxidative cyclization of 2’-allyloxy-α,
β-dibromochalcones results into the formation of 3-bromoflavanones which ultimately gives flavones. Dehydrobromination of 3-bromoflavanone to give flavone
is the preferred reaction over dehydrogenation.
Key words: Flavones, cyclization, oxidation, dehydrobromination, iodine, dimethyl sulfoxide
allyl bromide in presence of potassium carbonate and dimethylsulphoxide at rt
for 24 h. Bromination of 2’-allyloxy chalcones by bromine water in presence
of acetic acid resulted into formation of 2’-allyloxy-α, β-dibromochalcones
(1) at rt in 24 h.
2’-allyloxy-α, β-dibromochalcones (1) when reacted with iodine (1
mmol) in presence of dimethylsulfoxide, it was expected to follow the
steps deallylation, cyclization, debromination and dehydrogenation to give
3-bromoflavones (5). But it is surprise to see that under given condition
2’-allyloxy-α, β-dibromochalcones (1) converted to flavones (2) with high
yield (Scheme 1).
INTRODUCTION
1
Flavones are mainly found in wide variety of natural sources and
known to posses many biological activities such as free radical scavengers,2
anti-HIV3 and anticancer agent.4 Glycosides isolated from the whole plant of
Anaphalis aureo-punctata, Chrysanthemum morifolium shows antitumor,5
antibacterial, antifungal, antiviral, antispirochetal and anti-inflammatory
activities.6 3-Bromoflavones are used in drugs and for synthesis of alkylated
and arylated flavones. It is observed that variety of chalcones, flavones
and flavanones with bromo substituent exhibits anti-tuberculosis activity.7
6-Bromoflavone has shown binding affinity to central benzodiazepine
receptors and anxiolytic effect in mice.8 3-Haloflavones are used in the
synthesis of biflavonoids.9 Debromination of 1,2-bis(bromomethyl)arenes by
using tetrakis(dimethylamino)ethylene (TDAE) in the presence of olefins and
catalytic amount of iodine has been reported.10
As an extension of previous studies11 we have been interested in
the synthesis of 2’-allyloxy-α, β-dibromochalcones, which leads to the
corresponding 3-bromoflavones by using iodine in dimethylsulfoxide reagent.
In earlier work 2’-allyloxy chalcones when reacted with DMSO-I2 reagent, allyl
group was smoothly removed followed by cyclization and dehydrogenation to
give flavones. We envised that α, β-dibromochalcones expected to eliminate
HBr and then dehydrogenation to give 3-bromoflavones. Same study is
reported in present work.
Scheme 1
From the above results it is seen that flavones (2) could be formed from
2’-allyloxy-α,β-dibromochalcones(1)withtheintermediate3-bromoflavanones
(4) which have undergone dehydrobromination in DMSO- I2 reagent (Scheme
2).
EXPERIMENTAL
TLC was performed on E-Merck precoated 60 F254 plates and the spots
were rendered visible by exposing to UV light and iodine. Melting points were
determined with an Electro thermal model 9100 apparatus and are uncorrected.
IR spectra were recorded on a Shimadzu 8000 spectrophotometer. The 1H and
13C NMR spectra were recorded on Varian spectrometer. Chemical shifts (δ) are
reported in ppm and with reference to tetramethyl silane as internal standard.
Mass spectra (GCMS) were recorded on a Shimadzu Q 5050 spectrometer.
Typical procedure for the synthesis of flavones (2a-t): To a solution
of 2’-allyloxy-α, β-dibromochalcones (1 mmol) in DMSO (5 mL) was added
iodine (1 mmol) and the reaction mixture was heated in an oil bath at 130 °C
for 30 min. After cooling, iodine was removed by washing with a saturated
solution of sodium thiosulphate and water. The product was then extracted with
ethyl acetate and purified by column chromatography (hexane/ethyl acetate,
9:1).
Spectral data
6,8-Dichloro-2-phenyl-4H-chromene-4-one (Table, 2i)
Scheme 2
White solid; M.p. 160-161 °C, 1H-NMR (CDCl 300 MHz) δ 8.10 (d, 1H,
J=2.3 Hz, Ar-H), 7.99 (dd, 2H, J=1.4, 7.4 Hz, Ar-H),37.74 (d, 1H, J=2.7 Hz, Ar-
H), 7.58-7.54 (m, 3H, Ar-H), 6.86 (S, 1H, =CH); 13C-NMR (CDCl3) δ 176.2,
163.2, 133.6, 132.1, 130.7, 130.6, 129.1, 126.2, 125.5, 124.3, 123.7, 106.9; IR
(KBr/cm-1): 3390, 3065, 2914, 1725, 1662, 1602, 1567, 1451; MS(m/z): 290
(M+ ion); Anal. calcd for C15H8Cl2O2: C, 61.88; H, 2.67% Found: C, 61.47;
H, 2.91%
In reported method 2-iodoxybenzoic acid (IBX) selectively oxidize
substituted flavanones to flavones.12 Synthesis of Bromo-substituted flavone-
like troponoid compounds by oxidative cyclization of 3-cinnamoyl-5,7-
dibromotropolones was reported by using DMSO/I2/H2SO4 system.13 Earlier,
we have reported the use of DMSO- I2 reagent for deallylation,14a,b oxidation of
flavanones to flavones14c and dihydrochalcones to chalcones.14d
Result and discussion
2’-allyloxy chalcones were prepared by reacting 2’-hydroxy chalcones with
In present methodology, to verify whether deallylation of 2’-allyloxy-α,
β-dibromochalcones (1) is the first reaction followed by cyclization and then
e-mail: pdlokhande@chem.unipune.ernet.in
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