Manganese(III) acetate mediated oxidation of flavanones: A facile synthesis of flavones

Article abstract of DOI:10.1080/00397910500214490

Oxidation of flavanones (1a-o) with manganese(III) acetate by heating in acetic acid in presence of perchloric acid afforded exclusively flavones (2a-o) by dehydrogenation in almost quantitative yields. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1080/00397910500214490

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Manganese(III) Acetate
Mediated Oxidation of
Flavanones: A Facile Synthesis
of Flavones
Om V. Singh a , M. Muthukrishnan a & Gopan Raj a
a Phytochemistry Division, Tropical Botanic Garden
and Research Institute, Thiruvananthapuram-695
562, Kerala, India
Published online: 22 Aug 2006.
To cite this article: Om V. Singh , M. Muthukrishnan & Gopan Raj (2005)
Manganese(III) Acetate Mediated Oxidation of Flavanones: A Facile Synthesis
of Flavones, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:20, 2723-2728
To link to this article: http://dx.doi.org/10.1080/00397910500214490
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Synthetic Communicationsw, 35: 2723–2728, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500214490
Manganese(III) Acetate Mediated Oxidation
of Flavanones: A Facile
Synthesis of Flavones
Om V. Singh, M. Muthukrishnan, and Gopan Raj
Phytochemistry Division, Tropical Botanic Garden and Research
Institute, Pacha Palode, Thiruvananthapuram-695 562, Kerala, India
Abstract: Oxidation of flavanones (1a–o) with manganese(III) acetate by heating in
acetic acid in presence of perchloric acid afforded exclusively flavones (2a–o) by
dehydrogenation in almost quantitative yields.
Keywords: Manganese(III) acetate, flavanone, oxidation, flavone, dehydrogenation
Flavones are one of the important subgroups of flavonoids, which are widely
distributed in nature from ferns to higher plants and also have diverse biologi-
cal activities.[1] Over the years many synthetic methods have been developed
for their synthesis and have been reviewed from time to time.[1] The most
widely used approach for their synthesis is either oxidative cyclization of
20-hydroxychalcones or nondegradative oxidation of flavanones. The
oxidation of flavanones to flavones has been reported using different
reagents such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone,[2] DMSO/I2,[3]
selenium dioxide,[4] nickel peroxide,[5] disulfide,[6] thallium(III) salts,[7] and
hypervalent iodine reagents.[8] The oxidation of flavanone with lead(IV)
acetate[9] gave a mixture of 3-acetoxyflavanone, flavone, and isoflavone
with former being the major product.
Received in the USA May 18, 2005
Address correspondence to Om V. Singh, Department of Chemistry, University of
Texas at San Antonio, 6900 N. Loop 1604 West, San Antonio, TX 78249, USA.
E-mail: omvir.singh@utsa.edu
2723

2724
O. V. Singh, M. Muthukrishnan, and G. Raj
Mangnese(III) acetate (MTA), a one-electron oxidant, has been utilized
for the synthesis of numerous natural products via oxidative radical cycliza-
tions.[10] MTA generates a-oxo and a,a-dioxoalkyl radicals by regioselective
oxidation of carbonyl compounds, which leads to different products by radical
cyclization to other functional groups.[10b] The a-acylation of ketones and
enolizable a,b-unsaturated ketones with MTA have also been
reported.[10c,11] Furthermore, the oxidation of flavanone with MTA gave a
mixture of 3,3-dichloroflavanone and 3-chloroflavone in the presence of
potassium chloride as chloride source, with the former being the major
product[12] and the later formed by dehydrohalogenation of the former. We
have reported the oxidation of flavanones with thallium(III) acetate, which
exclusively gave flavones[7a] and isoflavones[13] by the addition of perchloric
acid to the reaction mixture. As the addition of perchloric acid has changed the
course of this reaction, it was thought worthwhile to investigate the effect of
perchloric acid for the oxidation of flavanones with MTA. We describe the
results of our findings.
Treatment of flavanone (1a) with MTA in acetic acid at 1008C for 10 h
afforded flavone (2a) in only 20% yield (based on H NMR of the reaction
1
mixture). After addition of perchloric acid to the reaction mixture, 1a
was completely converted to 2a and no trace of 1a could be detected by
1H NMR (Scheme 1). Hence, the addition of perchloric acid to the reaction
mixture increases the conversion (20% to 100%) and also decreases the
reaction time (10 h to 1 h). The generality of this transformation was
checked by treating different flavanones (1b–o) with MTA under similar
reaction conditions. In all the cases flavones (2b–o) were obtained as the
1
sole product. The identities of all flavones were established by H NMR
and IR spectral data by comparison with those reported in the literature.
The most plausible mechanism for this transformation is depicted in
Scheme 2. The electophillic attack of MTA at the enol form of 1 afforded
flavanone-Mn(III) adduct either by Mn(III)-O bond or Mn(III)-C3 bond
formation. The reductive elimination of Mn(II) from flavanone-Mn(III)
adduct generated a-oxoradical 3,[10c] which on further reaction with second
molecule of MTA furnished carbocation 4. The deprotonation of carbocation
Scheme 1.

Oxidation of Flavanones
2725
Scheme 2.
4 under reaction conditions produced the respective flavone 2. The formation
of 3 through enol form 1 can be explained by the fact that the addition of
perchloric acid to the reaction mixture enhanced the reaction rate several
fold (ꢀ50 times).
In summary an efficient method has been developed for the synthesis of
flavones by oxidation of flavanones using manganese(III) acetate in
presence of perchloric acid, which replaces the toxic reagents such as thal-
lium(III), selenium dioxide, and nickel peroxide for this transformation.
Furthermore, the method has been utilized for the synthesis of bioactive
flavones such as 6-chloro-30-nitroflavone (2i)[17] and 6-methyl-30-nitroflavone
(2o),[16] which have been demonstrated as potent ligands for the benzo-
diazepine binding site of GABAA receptor.
EXPERIMENTAL
General
Melting points were taken in open capillaries in a sulfuric acid bath and are
uncorrected. IR spectra (nmax in cm21) were recorded on Perkin Elmer 283
IR spectrophotometer, 1H NMR spectra were recorded on JEOL FX90Q
(90 MHz) using CDCl3 as solvent and tetramethylsilane as an internal
standard. Manganese(III) acetate was purchased from Aldrich Chemical Co
(USA). Substituted flavanones (1 a–n) were prepared by cyclization of
respective 20-hydroxychalcones using literature procedure.[18]
Oxidation of Flavanones with Manganese(III) Acetate in Presence
of Perchloric Acid, General Procedure
Perchloric acid (70%, 0.1 mL) and flavanones (1 mmol) were added to a
solution of manganese(III) acetate (0.563 g, 2.1 mmol) in acetic acid (5 mL).
The resultant mixture was heated at 1008C for 1 h, then cooled to room

2726
O. V. Singh, M. Muthukrishnan, and G. Raj
Table 1. Oxidation of flavanones (1a–n) with manganese(III) acetate
Yieldsa
(%)
Entry
Products
Mp (lit. mp) (8C)
1
2
2a, R1 ¼ R2 ¼ R3 ¼ H
92
95
90
96
95
95
96
92
94
96
90
92
92
94
92
97–98 (98)[14]
2b, R1 ¼ R2 ¼ H, R3 ¼ Cl
188–189 (188)[14]
3
2c, R1 ¼ R2 ¼ H, R3 ¼ CH3
2d, R1 ¼ R2 ¼ H, R3 ¼ NO2
2e, R1 ¼ R3 ¼ H, R2 ¼ NO2
2f, R1 ¼ Cl, R2 ¼ R3 ¼ H
110 (110)[14]
245–246 (246)[14]
199–200 (194–195)[14]
182–183 (182)[14]
4
5
6
7
2g, R1 ¼ R3 ¼ Cl, R2 ¼ H
226–227 (226–227)[14]
183–184 (183–184)[14]
235–236 (235–236)[14]
.285 (.285)[14]
8
2h, R1 ¼ Cl, R3 ¼ CH3, R2 ¼ H
2i, R1 ¼ Cl, R2 ¼ NO2, R3 ¼ H
2j, R1 ¼ Cl, R2 ¼ H, R3 ¼ NO2,
2k, R1 ¼ CH3, R2 ¼ R3 ¼ H
2l, R1 ¼ CH3, R2 ¼ H, R3 ¼ Cl
2m, R1 ¼ R3 ¼ CH3, R2 ¼ H
2n, R1 ¼ CH3, R2 ¼ NO2, R3 ¼ H
2o, R1 ¼ CH3, R2 ¼ H, R3 ¼ NO2
9
10
11
12
13
14
15
122 (121–122)[14]
198–199 (198–199)[14]
150–151 (151)[15]
222–223 (221–223)[16]
275–277 (276–278)[16]
aYield are based on isolated products.
temperature, and added slowly to ice cold water with constant stirring. The
obtained solid was filtered, washed with water, dried, and recrystallized
from ethanol to afford the respective flavones (2a–o). The characterization
data of flavones (2a–o) are given in Table 1.
ACKNOWLEDGMENTS
Authors are grateful to the International Foundation of Science, Sweden,
and State Committee on Science, Technology and Environment,
Thiruvananthapuram, Government of Kerala, India, for financial support.
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2727
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