Sodium perborate tetrahydrate-mediated transformations of 2′-hydroxychalcones to flavanones, flavones, and 3′, 5′-diiodoflavone under mild, environmentally friendly conditions

Article abstract of DOI:10.1080/00397911.2011.633734

Sodium perborate tetrahydrate has been utilized as a nucleophilic catalyst for facile conversion of 2′-hydroxychalcones to flavanones in warm aqueous acetonitrile, and then these chalcones, upon oxidative cyclization in warm acetic acid with an excess of the same reagent, afforded flavones in acceptable yields. One-pot synthesis of 3′,5′-diiodoflavone has been accomplished by diacetoxyiodobenzene-catalyzed iodination of 2′-hydroxychalcone with tetra-n-butylammonium iodide in acetic acid in the presence of sodium perborate as a terminal oxidant.

Full text of DOI:10.1080/00397911.2011.633734

This article was downloaded by: [University of Glasgow]
On: 21 March 2013, At: 11:21
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Sodium Perborate Tetrahydrate–Mediated
Transformations of 2′-Hydroxychalcones
to Flavanones, Flavones, and
3′, 5′-Diiodoflavone Under Mild,
Environmentally Friendly Conditions
Nemai C. Ganguly a , Sumanta Chandra a & Sujoy Kumar Barik a
a Department of Chemistry, University of Kalyani, Kalyani, India
Accepted author version posted online: 08 Aug 2012.Version of
record first published: 05 Mar 2013.
To cite this article: Nemai C. Ganguly , Sumanta Chandra & Sujoy Kumar Barik (2013): Sodium
Perborate Tetrahydrate–Mediated Transformations of 2′-Hydroxychalcones to Flavanones, Flavones,
and 3′, 5′-Diiodoflavone Under Mild, Environmentally Friendly Conditions, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 43:10, 1351-1361
To link to this article: http://dx.doi.org/10.1080/00397911.2011.633734
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 43: 1351–1361, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.633734
SODIUM PERBORATE TETRAHYDRATE–MEDIATED
TRANSFORMATIONS OF 2’-HYDROXYCHALCONES TO
FLAVANONES, FLAVONES, AND 3’,
5’-DIIODOFLAVONE UNDER MILD,
ENVIRONMENTALLY FRIENDLY CONDITIONS
Nemai C. Ganguly, Sumanta Chandra, and Sujoy Kumar Barik
Department of Chemistry, University of Kalyani, Kalyani, India
GRAPHICAL ABSTRACT
Abstract Sodium perborate tetrahydrate has been utilized as a nucleophilic catalyst for
facile conversion of 20-hydroxychalcones to flavanones in warm aqueous acetonitrile, and
then these chalcones, upon oxidative cyclization in warm acetic acid with an excess of
the same reagent, afforded flavones in acceptable yields. One-pot synthesis of
30,50-diiodoflavone has been accomplished by diacetoxyiodobenzene-catalyzed iodination
of 20-hydroxychalcone with tetra-n-butylammonium iodide in acetic acid in the presence
of sodium perborate as a terminal oxidant.
Keywords 30,50-Diiodoflavone; flavanone; flavone; 20-hydroxychalcone; sodium
perborate tetrahydrate
INTRODUCTION
Flavonoids (C6–C3–C6 compounds of natural origin) are a versatile class of
secondary plant metabolites that are widely distributed in vascular plants and
endowed with a broad range of bioactivities including antitumor,[1] antimetastatis,[2]
Received September 7, 2011.
Address correspondence to Nemai C. Ganguly, Department of Chemistry, University of Kalyani,
Kalyani 741235, India. E-mail: suj.ykumarbarik@yahoo.co.in
1351

1352
N. C. GANGULY, S. CHANDRA, AND S. K. BARIK
Scheme 1. Biosynthesis of flavonoids catalyzed by chalcone isomerase enzme.
antioxidant,[3] antimicrobial,[4] antiviral,[5] and neuron protection[6] properties.
Flavanones are characterized by a 2-arylchroman-4-one core and constitute an
important subclass of flavonoids. Because of their antitumor and anti-inflammatory
properties, flavanones have currently attracted interest as promising selective
estrogen receptor modulators[7] and tumor necrosis factor (TNF)-a inhibitors.[8]
They occupy a crucial position in the biosynthetic route of flavonoids connecting
20-hydroxychalcones as precursors to other substructures of this group, such as fla-
vones, isoflavones, cyanidins, and dihydroflavonols. The oxa-Michael type cycliza-
tion of 20-hydroxychalcones that generates the chroman core of flavanones is a
fundamental step in the biosynthesis of flavonoids (Scheme 1) and is catalyzed by
the chalcone isomerase enzyme in plant, fungi, and bacteria with astonishing high
levels of enantioselectivity. However, the isomerization is typically sluggish, parti-
cularly for nonsubstituted 20-hydroxychalcones under ambient and neutral con-
ditions.
An unabated search for efficient and selective procedures to realize the trans-
formation has continued over the years, leading to the development of a host of pro-
tocols employing various reagents and conditions ranging from aqueous buffers at
variable pH values,[9] mineral acids,[10] acidic ion-exchange resin,[11] NaOH with
and without phase-transfer catalysts,[12] CH3CO2Na,[13] KF,[14] amino acids,[12]
CoIII-salen complex catalyst,[15] and Lewis acids[16] to photoirradiation,[17] thermal
reaction in the solid state,[18] and electrochemical reactions.[19] However, a good
number of reported methods employ either stoichiometric or excess of reagents
and some of them have serious environmental constraints such as solvent-intensive
separation of products from unreacted starting materials and by-products. In con-
tinuation of our interest in developing environmentally friendly synthetic proto-
cols,[20] we felt the need to develop an efficient protocol for cyclization under
environmentally compatible conditions. To this end, we identified sodium perborate
tetrahydrate (NaBO3, 4H2O; SPB) as a nucleophilic oxidant in view of its ability to
deliver perhydroxyl anion through the associated species [B(OH)3OOH]- at a lower
pH than is available from H2O2 in aqueous organic solvents.[21a] It is an inexpensive,
nontoxic, and shock-insensitive reagent with good storage stability and has been
widely used in the detergent industry as a safe bleaching and antiseptic agent on large
scale without any waste disposal problem. Despite versatile applications as a nucleo-
philic oxidizing agent in functional group oxidations,[21a–d] the catalytic role of SPB
is rarely exploited.[21e] This prompted us to assess the hitherto unexplored efficacy of
SPB for the transformation of 20-hydroxychalcones to flavanones, particularly under
catalytic or substoichiometric conditions.

FLAVANONES AND FLAVONES
1353
RESULTS AND DISCUSSION
For initial optimization experiments, 20-hydroxychalcone (1a) was allowed to
undergo SPB-mediated cyclization to flavanone (1b) under various conditions
(Table 1).
The reaction did not proceed to completion with a suspension of SPB
(40 mol%) in dry acetonitrile at 50–60 ꢀC, providing an unsatisfactory yield (52%)
of 1b. Gratifyingly, aqueous acetonitrile proved to be the medium of choice, with
the yield of 1b showing modest dependence on the composition of the solvent.
The most rewarding result was obtained in CH3CN-H2O (6:1) with an exclusive yield
of 1b (86%) in a clean reaction within 1 h (entry 4). Optimization of catalyst loading
revealed that use of neither lower nor stoichiometric amounts of SPB delivered better
result (entries 5 and 6). Protic solvents such as aqueous ethanol, methanol, and acetic
acid were also screened, but with poor results. The optimized reaction conditions
[40 mol% SPB, CH3CN-H2O (6:1), 50–60ꢀC] were successfully extended to a good
number of 20-hydroxychalcones to demonstrate generality and compatibility with
a number of common functional and protecting groups (Cl, OH, OMe, allyloxy, pro-
pargyloxy, methylenedioxy). 20-Hydroxychalcone analogs derived from heterocyclic
aldehydes such as furfural and thiophene-2-aldehyde were also accommodated in the
protocol, albeit the yields of the corresponding flavanone analogs were on the lower
side (entries 9 and 10, Table 2). The results of these experiments are summarized in
Table 2.
The stereoelectronic requirement for the 6-endo-trig mode of ring closure is
the decisive factor in the cyclization process. Earlier model studies of
20-hydroxychalcone system revealed that the optimum Burgi–Dunitz trajectory[23a]
¨
for this mode of six-membered ring closure was not attainable as the hydroxy group
is well offline for a 109o approach of its lone pairs with respect to the plane of the
Table 1. Optinization experiments on SPB-mediated concersion of 20-hydroxychalcone 1 to flavanone 1a
Entry
Amount of SPB (mol%)
Solvent (4 mL)
Reaction timea (h)
Yield of 1bb
1
2
3
4
5
6
7
8
9
40
40
dry CH3CN
3
3
3
1
1
1
1
1
1
52
64
85
86
68
75
70
78
10
CH3CN-H2O (4:1)
CH3CN-H2O (6:1)
CH3CN-H2O (6:1)
CH3CN-H2O (6:1)
CH3CN-H2O (6:1)
EtOH-H2O (6:1)
MeOH-H2O
40
40
30
100
40
40
40
CH3CO2H-H2O
aThe reactions were carried out on a 1-mmol scale of 1a at 50–60 ꢀC using 4 mL of solvent each case.
bIsolated yield after chromatographic separation.

1354
N. C. GANGULY, S. CHANDRA, AND S. K. BARIK
Table 2. SPB-catalyzed conversion of 20-hydroxy chalcone to flavanone in aqueous acetonitrile
Entry
Ar
Producta
Time (h)
Yieldb (%)
Mp (ꢀC) (lit. mp)
1
2
3
4
5
6
7
C6H5
3-Cl C6H4
4-Cl C6H4
1b
1c
1d
1e
1f
1
86
74
80
54
68
76
64
74–76 (75–76)[12]
98–100 (98–99)[22a]
82–84 (84–85)[22b]
192–194 (190–192)[22c]
96–98 (96–97)[22b]
70–72
2.5
1
4-OH C6H4
4
4-OMe C6H4
4-O-ally C6H4
3,4-(-OCH2O-)C6H3
2
1g
1h
2
3
118–120
8
1i
2.5
1.5
50
72–74 (74–75)[22d]
9
1j
54
86–88
10
11
3-OMe, 4-O-propargyl C6H3
4-MeC6H4
1k
1l
4
1.5
72
76
80–82
82–84 (82–83)[22a]
aThe known compounds exhibit spectral data (FT-IR, 1H CNMR, 13CNMR, MS) and melting points in
agreement with those reported in the literature.
bIsolated yield after column chromatographic separation.
double bond, due to the unfavorable nature of the connecting chain comprising sp2-
hybridized carbons with larger bond angle of 120ꢀ coupled with the rigidity of the
conjugated system to remain in plane.[23b] Consequently upon the stereoelectronic
restriction imposed upon the 20-hydroxy group as a intramolecular Michael donor,
perhydroxyl anion from SPB initiates external nucleophilic attack on the enone
moiety. This softens the rigidity of the connecting chain, making the b-carbon end
sp3-hybridized and paving the way for subsequent oxyanion-mediated Michael ring
closure to 1b by 6-exo-tet mode (Scheme 2). Thus SPB essentially functions as a
nucleophilic catalyst rather than an oxidant in this reaction.
Complete nonformation of epoxychalcones was somewhat surprising in view of
the reported epoxidation of a, b-unsaturated ketones with SPB (2 mol equiv.) in the
presence of phase-transfer catalyst under aqueous conditions.[24a] Presumably, this is
due to the presence of 20-OH, which plays a key facilitatory role to bias the reaction
toward cyclization by fast evicting the perhydroxyl anion. To test this hypothesis, the
chalcone 2, which lacks the 20-OH group, was treated under the optimized conditions
to afford the corresponding epoxide[24b] 2a in 20% yield, which vastly improved to
80% with an excess of the reagent (Scheme 3).
The success of SPB-induced flavanone cyclization motivated us to evaluate its
oxidizing potential for entry into other subclasses of flavonoids of greater oxidation

FLAVANONES AND FLAVONES
1355
Scheme 2. Oxyanion-mediated Michael ring closure by 6-exo-tet mode.
Scheme 3. Epoxidation fo unsubtituted chaclone 2 with SPB.
level. To realize this, SPB in warm acetic acid, which generates powerful peracetox-
yboron anion species,[21a] was envisaged to be a suitable oxidant for electron-
deficient chalcones. Exposure of the chalcone 3a to an excess of SPB in warm acetic
acid for 3 h afforded the flavone 4a in 60% yield (Scheme 4). The results of some
similar conversions are shown in Table 3
Despite varied biological activities of iodinated heteroaromatic compounds,[26]
only sporadic attempts toward synthesis of iodoflavones by way of oxidative conden-
sation of iodinated flavones is documented in literature.[27] There is no literature pre-
cedence, to the best our knowledge, of one-pot conversion of 20-hydroxychalcone to
iodoflavones. Encouraged by the report of iodolactonization[28] catalyzed by diace-
toxyiodobenzene in the presence of tetra-n-butylammonium iodide (TBAI) and
sodium perborate in acetic acid, we reasoned that the reagent combination might
accomplish iodination of activated phenolic ring of 20-hydroxychalcone with
Scheme 4. Oxidative cycllization of 20-hydroxychalcone to flavones with SPB.

1356
N. C. GANGULY, S. CHANDRA, AND S. K. BARIK
Table 3. SPB-mediated synthesis of flavones
Entry
R
Product
Time (h)
Yield of flavones (%)
Mp (ꢀC) (lit. mp)
[25a,b]
1
2
3
4
H
4b
4c
4d
4e
3
65
58
55
55
98–99 (97–99)
4-HCl
4-CH3
4-OMe
3
186–188 (185–187)[25c]
106–107 (108–109)[25d]
156–158 (157–158)[25d]
3.5
4
concomitant cyclization and oxidation to iodoflavone. Treatment of
20-hydroxychalcone (1a) with TBAI (2.2 mol equiv.) in the presence of 20 mol% of
diacetoxyiodobenzene, PhI(OAc)2, and an excess of SPB in warm acetic acid resulted
in a one-pot formation of 30,50-diiodoflavone (5c) in 84% yield. Attempted controlled
monoiodination using 1 mol equiv. of TBAI while maintaining other conditions
indentical was unsuccessful, giving 5c only in poor yield. In the absence of TBAI,
no iodoflavone was formed, but the flavone was isolated in 58% yield. On the other
hand, exclusion of SPB from the reagent combination resulted in a sluggish, unclean
conversion of 1a to the corresponding flavanone 1b in a disappointingly poor yield of
30% along with unconverted starting material. This observation attests to the key
role of SPB as terminal oxidant in the hypervalent iodine–catalyzed oxidation of
TBAI to iodonium ion equivalent for iodination of 1a (Scheme 5).
Scheme 5. One-pot synthesis of 3’,50-diiodoflavone from 20-hydroxychalcone.

FLAVANONES AND FLAVONES
1357
In conclusion, the biogenetically relevant transformation of 20-hydroxychalcones
to flavanones has been accomplished using sodium perborate as a nucleophilic
catalyst in warm aqueous acetonitrile. Utilization of an excess of the reagent in warm
acetic acid provided access to flavones from the same precursor. One-pot synthesis of
30,50-diiodoflavone in excellent yield (by employing a catalytic amount of diacetoxyio-
dobenzene in the presence of TBAI as iodide source and SPB as a terminal oxidant)
adds to synthetic utility of the protocol.
EXPERIMENTAL
Typical Procedure for the Conversion of 2’-Hydroxychalcone 1a into
Flavanone 1b
20-Hydroxychalcone 1a (1.1 mmol, 246 mg) was added slowly to a stirred sus-
pension of sodium perborate tetrahydrate (40 mol%, 61 mg) in CH3CN-H2O (6:1,
4 mL) maintained at 50–60 ꢀC. The reaction mixture was thoroughly stirred for 1 h
[thin-layerchramatography (TLC)monitoring]. The residue remaining after removal
of organic solvent was extracted with ethyl acetate (3 ꢁ 5 mL) and the combined
extract was washed with water (2 ꢁ 3 mL), dried (Na2SO4), and concentrated. It
was subjected to column chromatography over silica gel (60–120 mesh) using light
petrol–ethyl acetate (50:1) as eluent to afford 1b (211 mg, 86%), as white solid, mp
74–76 ꢀC, (lit.[12] 75–76 ꢀC); IR (KBr): 3039, 2896, 1689, 1605, 1462, 1322, 1303,
1227, 1114, 1067, 907, 7066 cmꢂ1 1H NMR (300 MHz, CDCl3): d 7.94 (dd,
;
J ¼ 1.5, 8.1 Hz, 1H), 7.54–7.39 (m, 6H), 7.09–7.04 (m, 2H), 5.49 (dd, J ¼ 2.7,
13.2 Hz, 1H), 3.00 (dd, J ¼ 13.5, 16.8 Hz, 1H), 2.90 (dd, J ¼ 3, 16.8 Hz); 13C NMR
(75 MHz, CDCl3): d 191.9, 161.5, 138.7, 1360.1, 128.8, 128.7, 127.0, 126.1, 121.6,
120.9, 118.1, 79.5, 44.6. Anal. calcd. for C18H16O3: C, 80.03; H, 5.39. Found: C,
80.12; H, 5.46.
General Procedure for the Synthesis of Flavones from
2’-Hydroxychalcones
Sodium perborate tetrahydrate (3 mmol) was added to a stirred solution of
20-hydroxychalcone (1 mmol) in acetic acid (4 mL), and the mixture was stirred at
50–60 ꢀC for an appropriate time (TLC monitoring; Table 3). The reaction was
quenched by pouring in ice-cold water and then neutralized by NaHCO3. It was
extracted with ethyl acetate (3 ꢁ 6 mL); the combined extract was washed with water,
dried (Na2SO4), and concentrated. Column chromatographic purification over silica
gel (60–120 mesh) using light petrol–ethyl acetate as eluent afforded the correspond-
ing flavone.
Representative Procedure for the Conversion of 2’-Hydroxychalcone
1a into 3’,5’-Diiodoflavone 5c
20-Hydroxychalcone 1a (1 mmol, 224 mg) was added to a stirred suspension of
sodium perborate tetrahydrate (8 mmol, 1.232 g) in glacial acetic acid (3 mL) fol-
lowed by TBAI (2.2 molar equiv., 812 mg) and diacetoxyiodobenzene (20 mol%,

1358
N. C. GANGULY, S. CHANDRA, AND S. K. BARIK
33 mg). The mixture was vigorously stirred at 50–60 ꢀC for 8 h (TLC monitoring).
The reaction was quenched by pouring the mixture in ice-cold water (15 mL) and
then neutralized with solid NaHCO3. It was extracted by ethyl acetate (3 ꢁ 6 mL)
and the combined extract was washed with water (2 ꢁ 3 mL), dried over anhydrous
Na2SO4, and concentrated. Column chromatography of the concentrated extract
over silica gel (60–120 mesh) using light petrol–ethyl acetate (50:1) as eluent afforded
5c (398 mg, 84%) as white solid; mp 188–190 ꢀC; IR (KBr): 2922, 1653, 1439, 1346,
1
1249, 1097, 775 cmꢂ1; H NMR (400 MHz, CDCl3): d 8.50 (d, J ¼ 2.0 Hz, 1H), 8.41
(d, J ¼ 2.0 Hz, 1H), 8.05–8.03 (m, 2H), 7.57 (d, J ¼ 6.8 Hz, 3H), 6.88 (s, 1H); 13C
NMR (100 MHz, CDCl3): d 176.4, 163.9, 154.7, 150.5, 135.0, 132.2, 130.8, 129.2,
126.7, 125.8, 107.1, 89.7, 86.6; ESI-MS: m=z ¼ 475 [M þ 1]þ. Anal. calcd. for
C18H16O3: C, 38.01; H, 1.70. Found: C, 38.10; H, 1.76.
ACKNOWLEDGMENTS
S. C. thanks to the Council of Scientific and Industrial Research (SRF-NET),
New Delhi, and S. K. B. thanks the University of Kalyani for financial assistance by
way of a research fellowship. Facilities provided by a great from the Department of
Science and Technology–Funing for Infrastructure in Science and Technology,
government of India, are also acknowledged.
REFERENCES
1. (a) Agarwal, C.; Tyagi, A.; Kaur, M.; Agarwal, R. Silibinin inhibits constitutive activation
of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma
DU145 cells. Carcinogenesis 2007, 28, 1463–1470; (b) Cabrera, M.; Simoens, M.; Falchi,
G.; Lavaggi, M. L.; Piro, O. E.; Castellano, E. E.; Vidal, A.; Azqueta, A.; Monge, A.;
Lopez de Cerain, A.; Sagrera, G.; Seoane, G.; Cerecetto, H.; Gonzalez, M. Synthetic chal-
cones, flavanones, and flavones as antitumoral agents: Biological evaluation and struc-
ture–activity relationships. Bioorg. Med. Chem. 2007, 15, 3356–3367.
2. Hsiao, Y. C.; Kuo, W. H.; Chen, P. N.; Chang, H. R.; Lin, T. H.; Yang, W. E.; Hsieh, Y.
S.; Chu, S. C. Flavanone and 20-OH flavanone inhibit metastasis of lung cancer cells via
down-regulation of proteinases activities and MAPK pathway. Chem-Biol. Interact. 2007,
167, 193–206.
3. (a) Varga, Z.; Seres, I.; Nagy, E.; Ujhelyi, L.; Balla, G.; Balla, J.; Antus, S. Structure pre-
requisite for antioxidant activity of silybin in different biochemical systems in vitro. Phy-
tomedicine 2006, 13, 85–93; (b) Sun, J. M.; Yang, J. S.; Zhang, H. Two new flavanone
glycosides of Jasminum lanceolarium and their anti-oxidant activities. Chem. Pharm. Bull.
2007, 55, 474–476; (c) Jung, H. A.; Jeong, D. M.; Chung, H. Y.; Lim, H. A.; Kim, J. Y.;
Yoon, N. Y.; Choi, J. S. Re-evaluation of the antioxidant prenylated flavonoids from the
roots of Sophora flavescens. Biol. Pharm. Bull. 2008, 31, 908–915.
4. Ward, F. E.; Garling, D. L.; Buckler, R. T.; Lawler, D. M.; Cummings, D. P. Antimicro-
bial 3-methylene flavanones. J. Med. Chem. 1981, 24, 1073–1077.
5. (a) Paredes, A.; Alzuru, M.; Mendez, J.; Rodriguez-Ortega, M. Anti-sindbis activity of fla-
vanones hesperetin and naringenin. Biol. Pharm. Bull. 2003, 26, 108–109; (b) Kim, H. K.;
Jeon, W. K.; Ko, B. S. Flavanone glycosides from Citrus junos and their anti-influenza
virus activity. Planta Med. 2001, 67, 548–549.

FLAVANONES AND FLAVONES
1359
6. Vauzour, D.; Vafeiadou, K.; Rice-Evans, C.; Williams, R. J.; Spencer, J. P. E. Activation
of pro-survival Akt and ERK1=2 signalling pathways underlie the anti-apoptotic effects of
flavanones in cortical neurons. J. Neurochem. 2007, 103, 1355–1367.
7. Chen, H. Y.; Dykstra, K. D.; Birzin, E. T.; Frisch, K.; Chan, W.; Yang, Y. T.; Mosley, R.
T.; DiNino, F.; Rohrer, S. P.; Schaeffer, J. M.; Hammond, M. L. Estrogen receptor
ligands, part 1: The discovery of flavanoids with subtype selectivity. Bioorg. Med. Chem.
Lett. 2004, 14, 1417–1421.
8. Biddle, M. M.; Lin, M.; Scheidt, K. A. Catalytic enantioselective synthesis of flavanones
and chromanones. J. Am. Chem. Soc. 2007, 129, 3830–3831.
´
9. Gonzalez, E. A.; Nazareno, M. A.; Borsarelli, C. D. Enthalpy–entropy compensation
effect in the chalcone formation from naringin in water–ethanol mixtures. J. Chem.
Soc., Perkin Trans. 2002, 2, 2052–2056, and references cited therein.
10. Kagawa, H.; Takahashi, T.; Uno, M.; Ohta, S.; Harigaya, Y. Synthesis of
deuterium-labeled flavanones. Chem. Pharm. Bull. 2004, 52, 953–956.
11. Patonay, T.; Litkei, G.; Zsuga, M.; Kiss, A. A simple procedure for the cyclization of
20-hydroxychalcone into flavanones. Org. Prep. Proced. Int. 1984, 16, 315–319.
12. Tanaka, K.; Sugino, T. Efficient conversion of 20-hydroxychalcones into flavanones and
flavanols in a water suspension medium. Green Chem. 2001, 3, 133–134.
´
´
13. Litkei, G.; Bognar, R.; Dinya, Z.; David, E. R. In Topics in Flavonoid Chemistry and Bio-
´
´
chemistry; L. Farkas, M. Gabor, F. Kallay (Eds.); Elsevier: Amsterdam, 1975, 110.
14. (a) Macquarrie, D. J.; Nazih, R.; Sebti, S. KF=natural phosphate as an efficient catalyst
for synthesis of 20-hydroxychalcones and flavanones. Green Chem. 2002, 4, 56–59; (b)
Harwood, L. M.; Loftus, G. C.; Oxford, A.; Thomson, C. An improved procedure for
cyclisation of chalcones to flavanones using celite-supported potassium fluoride in meth-
anol: Total synthesis of bavachinin. Synth. Commun. 1990, 20, 649–657.
15. Maruyama, K.; Tamanaka, K.; Nishinaga, A.; Inada, A.; Nakanishi, T. Conversion of
20-hydroxychalcones to flavanones catalyzed by cobalt Schiff base complex. Tetrahedron
Lett. 1989, 30, 4145–4148.
16. Ahmed, N.; Ali, H.; van Lier, J. E. Silica gel–supported InBr3 and InCl3: New catalysts for
the facile and rapid oxidation of 20-hydroxychalcones and flavanones to their correspond-
ing flavones under solvent-free conditions. Tetrahedron Lett. 2006, 46, 253–256.
17. (a) Kaneda, K.; Arai, T. Mechanistic approach to the cyclization reaction of a
20-hydroxychalcone analogue with light and solvent. Org. Biomol. Chem. 2003, 1, 2041–
2043; (b) Maki, Y.; Shimada, K.; Sako, M.; Hirota, K. Photo-oxidative cyclisation of
20-hydroxychalcones leading to flavones induced by heterocycle N-oxides: High efficiency
of pyrimido[5,4-g]pteridine N-oxide for the photochemical dehydrogenation. Tetrahedron
1988, 44, 3187–3194; (c) Pandey, G.; Krishna, A.; Kumaraswamy, G. Photosensitized (set)
conversion of 20-hydroxychalcones to flavonoids: A probable biogenetic pathway. Tetra-
hedron Lett. 1987, 28, 4615–4616; (d) Matsushima, R.; Kageyama, H. Photochemical
cyclization of 20-hydroxychalcones. J. Chem. Soc. Perkin Trans. 1985, 2 743–748; (e)
Matsushima, R.; Hirao, I. Photocyclization of 20-hydroxychalcones to 4-flavanones. Bull.
Chem. Soc. Jpn. 1980, 53, 518–522; (f) Stermitz, F. R.; Adamovics, J. A.; Geigert, J.
Synthesis and photoreactions of sorbophenones: A photochemical synthesis of flavone.
Tetrahedron 1975, 31, 1593–1595.
18. Goud, B. S.; Panneerselvam, K.; Zacharias, D. E.; Desiraju, G. R. Intramolecular
Michael-type addition in the solid state. J. Chem. Soc., Perkin Trans. 2 1995, 325–330.
19. Sanicanin, Z.; Tabakovic, I. Electrochemical transformations of 20-hydroxychalcones into
flavanoids. Tetrahedron Lett. 1986, 27, 407–408.
20. (a) Ganguly, N. C.; Barik, S. K.; A facile efficient mild deprotection protocol of
1,3-dithianes and 1,3-dithiolanes with 30% hydrogen peroxide and iodine catalyst in aque-
ous micellar system. Synthesis 2009, 1393–1399; (b) Ganguly, N. C.; Nayek, S.; Barik,

1360
N. C. GANGULY, S. CHANDRA, AND S. K. BARIK
S. K. Convenient, mild catalytic deprotection of oximes to carbonyl compounds with
hydrogen peroxide and iodine catalyst in aqueous acetonitrile. Synth. Commun. 2009,
39, 4053–4061; (c) Ganguly, N. C.; Mondal, P. Iodine-mediated efficient Beckmann
rearrangement of ketoximes to amides under mild neutral conditions. Synthesis 2010,
3705–3709; (d) Ganguly, N. C.; Barik, S. K.; Dutta, S. Ecofriendly iodination of activated
aromatics and coumarins using potassium iodide and ammonium peroxodisulfate. Syn-
thesis 2010, 1467–1472; (e) Ganguly, N. C.; Mondal, P. Mild, efficient, and greener
dethioacetalization protocol using 30% hydrogen peroxide in catalytic combination with
ammonium iodide. Synth. Commun. 2011, 41, 2374–2384 (f) Ganguly, N. C.; Mondal,
P.; Barik, S. K. Iodine in aqueous micellar environment: A mild, effective, ecofriendly
catalytic system for expedient synthesis of bis(indolyl)methanes and 3-substituted indolyl
ketones. Green Chem. Lett. Rev. 2012, 5, 73–81.
21. (a) McKillop, A.; Sanderson, W. R. Sodium perborate and sodium percarbonate: Further
applications in organic synthesis. J. Chem. Soc, Perkin Trans. 1 2000, 471–476; (b)
Muzart, J. Sodium perborate and sodium percarbonate in organic synthesis. Synthesis
1995, 1325–1347; (c) McKillop, A.; Sanderson, W. R. Sodium perborate and sodium per-
carbonate: Cheap, safe, and versatile oxidizing agents for organic synthesis. Tetrahedron
1995, 51, 6145–6166; (d) Gomez, M. V.; Caballero, R.; Vazquez, E.; Moreno, A.; de la
´ ´
Hoz, A.; Dıaz-Ortiz, A. Green and chemoselective oxidation of sulfides with sodium per-
´
borate and sodium percarbonate: Nucleophilic and electrophilic character of the oxidation
system. Green Chem. 2007, 9, 331–336; (e) There is one literature precedent of use of SPB
as a substoichiometric co-oxidant in combination with trifluoromethanesulfonic acid for
monohydroxylation of arenes; see Prakash, G. K. S.; Krass, N.; Wang, Q.; Olah, G. A.
Oxyfunctionalization of hydrocarbons, 15: Electrophilic hydroxylation of aromatics with
sodium perborate=trifluorometahne-sulfonic acid. Synlett 1991, 39–40.
22. (a) Kumar, K. H.; Perumal, P. T. A simple and facile solventless procedure for the cycliza-
tion of 20-amino- and 20-hydroxy-chalcones using silica-supported sodium hydrogen sul-
phate as heterogenous catalyst. Canadian J. Chem. 2006, 84, 1079–1083; (b) Lee, J. I..;
Jung, M. G.; Jung, H. J. A novel synthesis of flavanones from 2-hydroxybenzoic acids.
Bull. Korean Chem. Soc. 2007, 28, 859–862; (c) Sagreraa, G.; Seoane, G. Acidic rearrange-
ment of (benzyloxy)chalcones: A short synthesis of chamanetin. Synthesis 2009, 4190–
4202; (d) Kumar, D.; Patel, G.; Mishra, B. G.; Varma, R. S. Eco-friendly polyethylene
glycol–promoted Michael addition reactions of a, b-unsaturated carbonyl compounds.
Tetrahedron Lett. 2008, 49, 6974–6976.
23. (a) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; John Wiley & Sons:
New York, 1994; p. 684; (b) Bradley, P. J.; Jarvis, T. C.; Johnson, D.; Mcdonnell, P. D.;
Weathestone, T. A. P. Stereoelectronic effects in ring closure reactions. Tetrahedron Lett.
1983, 24, 2851–2854.
24. (a) Straub, T. S. Epoxidation of a, b-unsaturated ketones with sodium perborate. Tetra-
hedron Lett. 1995, 36, 663–664; (b) Kim, D. Y.; Choi, Y. J.; Park, H. Y.; Joung, C. U.;
Koh, K. O.; Mang, J. Y.; Jung, K.-Y. Enantioselective epoxidation of a, b-unsaturated
ketones by phase-transfer catalysis using chiral quaternary ammonium salts. Synth.
Commun. 2003, 33, 435–443.
25. (a) Huang, X.; Tang, E.; Xu, W.-M.; Cao, J. Lewis acid–catalyzed solid-phase synthesis of
flavonoids using selenium-bound resin. J. Comb. Chem. 2005, 7, 802–805; (b)Cui, S.-L.;
Lin, X.-F. Wang, Y.-G. Novel and efficient synthesis of iminocoumarins via
copper-catalyzed multicomponent reaction. Org. Lett. 2006, 8, 4517–4520; (c) Sarda, S.
R.; Pathan, M. Y.; Paike, V. V.; Pachmase, P. R.; Jadhav, W. N.; Pawar, R. P. A facile
synthesis of flavones using recyclable ionic liquid under microwave irradiation. Arkivoc
2006, 16, 43–48; (d) Kumar, K. H.; Perumal, P. T. A novel one-pot oxidative cyclization

FLAVANONES AND FLAVONES
1361
of 20-amino and 20-hydroxychalcones employing FeCl3 ꢁ 6H2O–methanol: Synthesis of
4-alkoxy-2-aryl-quinolines and flavones. Tetrahedron 2007, 63, 9531–9535
26. (a) Butler, A.; Walker, J. V. Marine haloperoxidases. Chem. Rev. 1993, 93, 1937–1944; (b)
Sovak, M. Radiocontrast Agents: Handbook of Experimental Pharmacology; Springer:
Berlin, 1993.
27. Chen, F. C.; Chang, T. C.; Chen, T. S. Synthesis of 8- and 30-iodoflavones and related
compounds. J. Org. Chem. 1962, 27, 85–87, and references cited therein.
28. Liu, H.; Tan, H.-C. Iodobenzene-catalysed iodolactonisation using sodium perborate
monohydrate as oxidant. Tetrahedron Lett. 2007, 48, 8220–8222.