C. F. Chee et al. / Tetrahedron Letters 52 (2011) 3120–3123
3123
Upon further investigation of the reaction conditions, we found
that addition of an excess of benzoyl chloride in wet K2CO3/acetone
(containing 1% w/w water) gave essentially the same ratio of prod-
ucts as that found with the open K2CO3/acetone system. Various
combinations of 20,40-dihydroxy-, 20,50-dihydroxy-, 20,60-dihy-
droxy-, and 20,40,60-trihydroxyacetophenones and aroyl chlorides
7a–c gave flavones 4a–g (51–63%) and 3-aroylflavones 6a–g (11–
23%) (Scheme 6). These results suggested that the presence of an
additional OH group at the 60-position of the 20-hydroxyacetophe-
none was not a requirement for the formation of flavones, in con-
trast to the findings of Boumendjel.6 Table 2 shows the different
flavones and 3-aroylflavones prepared by this method and the
yields obtained.
of Higher Education (Fundamental Research Grant Scheme). We
would also like to thank Professor Naresh Kumar for giving
C.F.C. the opportunity to carry out some of this work at UNSW,
Sydney.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
1. Middleton, E., Jr.; Kandaswani, C.; Theoharides, T. C. Pharmacol. Rev. 2000, 52,
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Synthesis 1997, 195.
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M. Tetrahedron Lett. 2005, 46, 4119; (b) Ganguly, A. K.; Mahata, P. K.; Biswas, D.
Tetrahedron Lett. 2006, 47, 1347.
6. Bois, F.; Beney, C.; Mariotte, A. M.; Boumendjel, A. Synlett 1999, 1480.
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58, 7903.
8. Although b-ketoesters are expected to be mainly in the enolate form under the
reaction conditions, they are represented here in the keto form for clarity.
9. This is in contrast to Baker’s hypothesis that the acylation of a b-diketone might
be expected to occur on the methylene carbon atom to give the triketone
intermediate directly.
10. A higher conversion rate could be achieved by heating compound 10a in a
DBU/pyridine system (90% conversion after 8 h treatment).
11. Heating the pure compound 6a in NaHCO3 satd/MeOH for 2 h gave flavone 4a
in 85% yield.
12. (a) Jain, P. K.; Makrandi, J. K.; Grover, S. K. Synthesis 1982, 221; (b) Costantino,
L.; Rastelli, G.; Albasini, A. Eur. J. Med. Chem. 1996, 31, 693; (c) Looker, J. H.;
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In summary, we have investigated the reaction between 20-
hydroxyacetophenone and aroyl chlorides under different condi-
tions. We found that when 20-hydroxyacetophenone was heated
with a stoichiometric amount of aroyl chloride, either in a DBU/
pyridine system or in an open K2CO3/acetone system, only the fla-
vone was obtained, but in modest yield. However, when heated
with excess aroyl chloride in a DBU/pyridine system, the 3-aroylf-
lavone was the only product, while treatment in an open K2CO3/
acetone system afforded the flavone as the major product along
with a smaller amount of 3-aroylflavone. Control experiments un-
der the latter conditions gave evidence that the reaction proceeds
via a triketone intermediate. An extension of the method using wet
K2CO3/acetone (1% w/w water) has been successfully applied to the
synthesis of flavones bearing a variety of substituents.
Acknowledgements
This work was supported by grants from the Ministry of Sci-
ence, Technology and Innovation (Science Fund) and the Ministry