, 2005, 15(3), 100–101
Facile oxidation of flavanones to flavones using [hydroxy(tosyloxy)iodo]benzene in
an ionic liquid
Murugan Muthukrishnan,* Pratap S. Patil, Shivaji V. More and Ramesh A. Joshi*
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411008, India.
E-mail: mmk@dalton.ncl.res.in
DOI: 10.1070/MC2005v015n03ABEH001997
A method for the oxidation of flavanones to flavones has been developed using [hydroxy(tosyloxy)iodo]benzene (HTIB) in the
room-temperature ionic liquid 1,3-di-n-butylimidazolium bromide ([bbim]+Br–).
Ionic liquids are an attractive alternative to conventional organic
solvents because of their negligible vapour pressure, high
Table 1 Oxidation of flavanones in an ionic liquid.
thermal stability and reusability. They are non hazardous and
non explosive. Organic reactions such as Diels–Alder reaction,1
Wittig reaction,2 Friedel–Crafts reaction,3 Heck reaction,4 Suzuki
coupling5 and many biotransformations6 have been successfully
carried out in ionic liquids.7
Product
R, R'
Time/h
Yielda (%)
2a
2b
2c
2d
2e
2f
2g
2h
2i
R = R' = H
2 (16)b
3
2
3
84 (68)b
82
91
84
78
85 (70)b
74 (65)b
75 (75)b
90
R = H, R' = 4-Me
R = 4-Me, R' = H
R = R' = 4-Me
R = 4-Cl, R' = 4-Me
R = 4-Cl, R' = H
R = H, R' = 4-Cl
R = R' = 4-Cl
Flavones are widespread phenolic compounds of plant origin.8
Flavones are of interest because of their pharmacological activities
including antioxidant, anti-inflammatory, antiviral, antineoplastic
and anticancer properties.9–11 The biomimetic oxidation of fla-
vanone to flavone was carried out using a variety of reagents
such as thallium(III) acetate, CuCl2–DMSO, DDQ, nickel peroxide
and pyrrolidone hydrotribromide in DMSO,12 which are either
hazardous or expensive. Prakash et al.13 reported the utility of
hypervalent iodine as an oxidising agent for the conversion of
flavanone to flavone. Even though hypervalent iodine-mediated
oxidative reactions are mild and efficient, these methods are
time-consuming and characterised by low yields and unwanted
by-products such as 2-aryl-2,3-dihydrobenzofuran-3-carboxylates
and cis-3-methoxy-flavanones. Here, we report the oxidation14
of flavanones to flavones using [hydroxy(tosyloxy)iodo]benzene
(HTIB) in a room-temperature ionic liquid.† We obtained
flavones in high yields within 2–4 h (Scheme 1).‡
4
2 (16)b
3 (16)b
3 (16)b
2
R = H, R' = 3-NO2
aIsolated and unoptimised yields. bTime and yield given in parentheses are
reported for HTIB oxidation in methanol.13(a)
excellent yields were obtained in all cases (Table 1). The pro-
ducts were characterized by IR and NMR spectroscopy.§ No
by-products were detected. To verify the reusability of the ionic
liquid, water was completely removed from a used ionic liquid,
which was recycled in subsequent reactions. Second and third
reactions using the recovered ionic liquid afforded yields similar
to those obtained in the first run.
In conclusion, we have developed an efficient methodology
for the rapid oxidation of flavanones to flavones using HTIB in
the ionic liquid [bbim]+Br–.
R'
References
O
1
HTIB
60–70 °C; 2–4 h
R
2
3
4
5
6
V. L. Boulaire and R. Gree, Chem. Commun., 2000, 2195.
D. E. Kaufmann, M. Nouroozian and H. Henze, Synlett., 1996, 1091.
C. J. Mathews, P. J. Smith and T. Welton, Chem. Commun., 2000, 1249.
R. M. Lau, R. Van Rantwijk, K. R. Seddon and R. A. Sheldon, Org.
Lett., 2001, 2, 4189.
N
N
O
Br
1
R'
7
Seddon, Pure Appl. Chem., 2000, 72, 1391; (c) P. Wasserscheid and
W. Keim, Angew. Chem., Int. Ed. Engl., 2000, 39, 3773; (d) R. Sheldon,
Chem. Commun., 2001, 2399.
R. Brouillard and O. Dangles, in The Flavonoids: Advances in Research
Since 1986, ed. J. B. Harborne, Chapman and Hall, London, 1993,
p. 565.
A. F. Welton, L. D. Tobias, C. Fiedler-Nagy, W. Anderson, W. Hope,
K. Meyers and J. W. Coffey, in Plant Flavonoids in Biology and
Medicine, eds. V. Cody, E. Middleton Jr. and J. B. Harborne, Alan R.
Liss, New York, 1986, p. 231.
O
O
R
8
9
2
Scheme 1
To study the general applicability of this simple protocol,
flavanones differently substituted at ring A and ring B were
successfully oxidised to their corresponding flavones. Good to
(b) G. Litkei, K. Gulacsi, S. Antus and G. Blasko, Liebigs Ann. Chem.,
1995, 1, 1711 and references cited therein.
The ionic liquid [bbim]+Br– was prepared according to ref. 15. All the
flavanones used in this study were prepared according to the procedures
†
described in ref. 16.
‡
In a typical experiment, a flavanone was stirred with 2 equiv. of HTIB in
3 ml of [bbim]+Br– at 60–70 °C for 2–4 h. The reaction was monitored
by TLC. After completion of the reaction, 10 ml of water was added, and
the reaction mixture was extracted with dichloromethane. The dichloro-
methane layer was seperated, washed with water and dried over Na2SO4.
After filtration, the solvent was removed under reduced pressure to yield
a flavone. The flavone thus obtained was further crystallised using
petroleum ether in ethyl acetate. We performed few reactions with the
ionic liquid [bbim]+BF4–, but the yields were good only with [bbim]+Br–.
Spectroscopic data for 2e: crystalline solid, mp 197–198 °C (lit.,17
§
196 °C). 1H NMR (200 MHz, CDCl3) d: 2.45 (s, 3H), 6.79 (s, 1H), 7.33
(d, 2H), 7.50 (q, 2H), 7.82 (d, 2H), 8.02 (s, 1H). 13C NMR (75 MHz,
CDCl3) d: 177.23, 163.92, 154.57, 142.60, 140.22, 133.84, 131.11,
129.84 (2C), 127.24, 126.27 (2C), 125.17, 119.77, 106.87, 21.55. Found
(%): C, 69.22; H, 3.81. Calc. for C16H11ClO2 (%): C, 70.99; H, 4.10.
100 Mendeleev Commun. 2005
Muthukrishnan, Murugan
