D
C. Balakrishna et al.
Letter
Synlett
Table 2 (continued)
(4) (a) Desroses, M.; Wieckowski, K.; Stevens, M.; Odell, L. R. Tetra-
hedron Lett. 2011, 52, 4417. (b) Augustine, J. K.; Atta, A. N.;
Ramappa, B. K.; Boodappa, C. Synlett 2009, 3378.
(c) Ragghavendra, G. M.; Ramesha, A. B.; Revanna, C. N.;
Nandeesh, K. N. Mantelingu K.; Rangappa, K. S. Tetrahedron Lett.
2011, 52, 5571. (d) Wen, X.; El Bakali, J.; Deprez-Poulain, B.;
Deprez, B. Tetrahedron Lett. 2012, 53, 2440. (e) Poojari, S.;
Parameswar Naik, P.; Krishnamurthi, G. Tetrahedron Lett. 2012,
53, 4639. (f) Jida, M.; Deprez, B. New J. Chem. 2012, 36, 869.
(5) Desroses, M.; Jacques-Cordonnier, M. C.; Llona-Minguez, S.;
Jacques, S.; Koolmeister, T.; Helleday, T.; Scobie, M. Eur. J. Org.
Chem. 2013, 5879.
Entry
Acetophenone
Product
Yield (%)
74
Cl
O
Cl
O
O
19
OH
3s
1s
O
O
O
O
O
O
O
20
80
(6) Reis, J.; Gaspar, A.; Milhazes, N.; Borges, M. J. Med. Chem. 2017,
60, 7941.
OH
1t
3t
(7) Leahy, J. J. J.; Golding, B. T.; Griffin, R. J.; Hardcastle, I. R.;
Richardson, C.; Rigoreau, L.; Smith, G. C. M. Bioorg. Med. Chem.
Lett. 2004, 14, 6083.
(8) Griffin, R. J.; Fontana, G.; Golding, B. T.; Guiard, S.; Hardcastle, I.
R.; Leahy, J. J. J.; Martin, N.; Richardson, L.; Rigoreau, M.;
Stockley, G. C. M.; Smith, C. J. Med. Chem. 2005, 48, 569.
(9) Kim, H. P.; Son, K. H.; Chang, H. W.; Kang, S. S. J. Pharmacol. Sci.
(Tokyo, Jpn.) 2004, 14, 608310.1254/jphs.CRJ04003X.
(10) Bhat, A. S.; Whetstone, J. L.; Brueggemeier, R. W. Tetrahedron
Lett. 1999, 40, 2469.
(11) (a) Benett, C. J.; Caldwell, S. T.; McPhail, D. B.; Morrice, P. C.;
Duthie, G. G.; Hartley, R. C. Bioorg. Med. Chem. 2004, 12, 2079.
(b) Krishnamachari, V.; Levin, L. H.; Zhou, C.; Paré, P. W. Chem.
Res. Toxicol. 2004, 17, 795.
(12) Marder, M.; Viola, H.; Bacigaluppo, J. A.; Colombo, M. I.;
Wasowski, C.; Wolfman, C.; Medina, J. H.; Rúveda, E. A.; Paladini,
A. C. Biochem. Biophys. Res. Commun. 1998, 249, 481.
(13) Hoult, J. R. S.; Moroney, M. A.; Payá, M. Methods Enzymol. 1994,
234, 443.
(14) Parmar, V. S.; Bracke, M. E.; Philippe, J.; Wengel, J.; Jain, S. C.;
Olsen, C. E.; Bisht, K. S.; Sharma, N. K.; Courtens, A.; Sharma, S.
K.; Vennekens, K.; Van Marck, V.; Singh, S. K.; Kumar, N.; Kumar,
A.; Malhothra, S.; Kumar, R.; Rajwanshi, V. K.; Jain, R.; Mareel,
M. M. Bioorg. Med. Chem. 1997, 5, 1609.
(15) Galietta, L. J.; Springsteel, M. F.; Eda, M.; Neidzinsk, E. J.; By, K.;
Haddadin, M. J.; Nantz, M. H.; Verkman, A. S. J. Biol. Chem. 2001,
276, 19723.
(16) (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003,
103, 893. (b) Gaspar, A.; Matos, J. M.; Garrideo, J.; Uriarte, E.;
Borges, F. Chem. Rev. 2014, 114, 4960.
(17) Rangappa, S. K.; Srinivasa, B.; Pai, R. K.; Balakrishna, R. G. Eur. J.
Med. Chem. 2014, 78, 340.
A one-step synthesis of chromone was also attempted,
but when 1-(2-hydroxyphenyl)ethanone (1a) was treated
with (MeO)2CHNMe2 in the presence of T3P® in ethyl ace-
tate, and the mixture was heated to 110 °C for 16 hours or
subjected to microwave irradiation, no product was formed,
as evidenced by LC-MS analysis.
In summary, we have developed a novel, efficient and
easily reproducible T3P®-mediated formation of chromones
from readily available o-hydroxyacetophenones under
microwave irradiation. This protocol offers a useful alterna-
tive to the strongly acidic conditions that are generally
required for this conversion. The reaction conditions are
simple and sufficiently mild to tolerate various functional-
ities that can serve as platforms for further functionaliza-
tion of the chromone products. We believe that this metho-
dology will find widespread application in the synthesis of
chromone derivatives.
Funding Information
We are grateful to GVK Biosciences Pvt. Ltd., for financial support and
encouragement.
)(
Acknowledgements
The help from the analytical department is appreciated. We thank
Dr. Sudhir Kumar Singh for his invaluable support and motivation.
(18) Li, N.-G.; Shi, Z.-H.; Tang, Y.-P.; Ma, H.-Y.; Yang, J.-P.; Li, B.-Q.;
Wang, Z.-J.; Song, S.-L.; Duan, J.-A. J. Heterocycl. Chem. 2010, 47,
785.
(19) (a) Elassar, A.-Z. A.; Ei-Khair, A. A. Tetrahedron 2003, 59, 8463.
(b) Riyadh, S. M.; Abdelhamid, I. A.; Al-Matar, H. M.; Hilmy, N.
M.; Elnagdi, M. H. Heterocycles 2008, 75, 1849.
Supporting Information
Supporting information for this article is available online at
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(20) (a) Gammill, R. B. Synthesis 1979, 901. (b) Biegasiewicz, K. F.; St.
Denis, J. D.; Carrol, V. M.; Priefer, R. Tetrahedron Lett. 2010, 51,
4408. (c) Ravi Kumar, P.; Balakrishna, C.; Murali, B.; Gudipati,
R.; Hota, P. K.; Chaudhary, A. B.; Jaya Shree, A.; Yennam, S.;
Behera, M. J. Chem. Sci. 2016, 128, 441.
(21) Joussot, J.; Schoenfelder, A.; Larquetoux, L.; Nicolas, M.; Suffet,
J.; Blond, G. Synthesis 2016, 48, 3364.
(22) Lin, Y.-F.; Fong, C.; Peng, W.-L.; Tang, K.-C.; Liang, Y.-E.; Li, W.-T.
J. Org. Chem. 2017, 82, 10855.
References
(1) (a) Wissmann, H.; Kleiner, H. J. Angew. Chem. Int. Ed. Engl. 1980,
19, 133. (b) Escher, R.; Bünning, P. Angew. Chem. Int. Ed. Engl.
1986, 25, 277.
(2) Llanes García, A. L. Synlett 2007, 1328.
(3) Waghmare, A. A.; Hindupur, R. M.; Pati, H. N. Rev. J. Chem. 2014,
4, 53.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E