LETTER
Synthesis of Novel 1-Aryl-9H-xanthen-9-one
1405
(12) Franklin, G.; Conceição, L. F. R.; Kombrink, E.; Dias, A. C.
P. Phytochemistry 2009, 70, 60.
(13) Sousa, M. E.; Pinto, M. M. M. Curr. Med. Chem. 2005, 12,
2447.
(14) (a) Mahal, H. S.; Venkataraman, K. J. Chem. Soc. 1934,
1767. (b) Baker, W. J. Chem. Soc. 1933, 1381.
(15) Santos, C. M. M.; Silva, A. M. S.; Cavaleiro, J. A. S. Eur. J.
Org. Chem. 2003, 4575.
mesomeric deshielding effects of the carbonyl group, and
the lowest frequency aromatic signals corresponding to
the resonance of protons H-2, at dH = 7.13–7.18 ppm. The
structure of xanthones 6a–e was also supported by the
main connectivities found in their HMBC spectra
(Figure 1).
In conclusion, we have established a simple synthetic
methodology for preparing 1-aryl-9H-xanthen-9-ones
6a–e, by the electrocyclization and oxidation reactions of
the new (E,E)-2-(4-arylbuta-1,3-dien-1-yl)-4H-chromen-
4-ones 5a–e. The latter compounds were obtained by con-
densation of 2-methylchromone (2) with cinnamalde-
hydes 4a–e.
(16) Battistuzzi, G.; Cachi, S.; Fabrizi, G. Org. Lett. 2003, 5, 777.
(17) Ibrahim, M. A.; Ali, T. E.; Alnamer, Y. A.; Gabr, Y. A.
ARKIVOC 2010, (i), 98.
(18) Typical Experimental Procedure
Sodium (0.11 g, 4.8 mmol) was gradually added to dry EtOH
(5 mL), and the mixture was stirred until it reached r.t. 2-
Methylchromone (2, 0.2 g, 1.2 mmol) and the appropriate
cinammaldehyde 4a–e (1.5 mmol) were added and the
reaction mixture allowed to stand at r.t. until complete
disappearance of chromone 2 (TLC). The solution was then
poured into ice (20 g) and H2O (30 mL) and adjusted to pH
4 with dilute HCl. The solid was removed by filtration,
dissolved in CH2Cl2, and purified by silica gel column
chromatography using CH2Cl2 as eluent. The solvent was
evaporated the residue were recrystallized from EtOH to
give the (E,E)-2-(4-arylbuta-1,3-dien-1-yl)-4H-chromen-4-
ones 5a–e in good yields (Table 1).
Acknowledgment
Thanks are due to the University of Aveiro, ‘Fundação para a
Ciência e a Tecnologia’, and FEDER for funding the Organic Che-
mistry Research Unit and the Portuguese National NMR Network
(RNRMN). One of us (C. I. C. Esteves) is also grateful to FCT for
her fellowship (SFRH/BI/51098/2010).
(19) Physical Data of (E,E)-2-[-4-(4-methoxyphenyl)buta-1,3-
dien-1-yl]-4H-chromen-4-one (5c)
References and Notes
Mp 137–139 °C. 1H NMR (300,13 MHz, CDCl3): d = 3.84
(s, 3 H, OCH3), 6.24 (s, 1 H, H-3), 6.32 (d, 1 H, J = 15.3 Hz,
H-a), 6.84–6.87 (m, 1 H, H-d), 6.90 (d, 2 H, J = 8.8 Hz, H-
3¢,5¢), 6.90–6.96 (m, 1 H, H-g), 7.38 (ddd, 1 H, J = 8.2, 7.1,
0.9 Hz, H-6), 7.41–7.44 (m, 1 H, H-b), 7.43 (d, 2 H, J = 8.8
Hz, H-2¢,6¢), 7.49 (d, 1 H, J = 8.1 Hz, H-8), 7.67 (ddd, 1 H,
J = 8.1, 7.1, 1.7 Hz, H-7), 8.18 (dd, 1 H, J = 8.2, 1.7 Hz, H-
5). 13C NMR (75.47 MHz, CDCl3): d = 55.3 (OCH3), 109.9
(C-3), 114.3 (C-3¢-5¢), 117.7 (C-8), 122.3 (C-a), 124.1 (C-
10), 124.8 (C-6), 125.0 (C-g), 125.5 (C-5), 128.5 (C-2¢,6¢),
128.6 (C-1¢), 133.6 (C-7), 137.8 (C-b), 138.9 (C-d), 140.4
(C-9), 160.3 (C-4¢), 162.0 (C-2), 178.4 (C-4). ESI-MS: m/z
(rel. int.) = 305 (100) [M + H]+, 327 (110) [M + Na]+, 343
(20) [M + K]+, 631 (11) [2 M + Na]+. Anal. Calcd for
C20H16O3: C, 78.93; H, 5.30. Found: C, 78.86; H, 5.30.
(20) Physical Data of 1,4-Dihydro-1-phenyl-9H-xanthen-9-
one (7a)
(1) (a) Hostettman, K.; Hostettman, M. Plant Phenolics, In
Methods in Plant Biochemistry, Vol. 1; Dey, P. M.; Harbone,
J. B., Eds.; Academic Press: San Diego, 1989, 493.
(b) Gales, L.; Damas, A. M. Curr. Med. Chem. 2005, 12,
2499.
(2) Vieira, L. M. M.; Kijjoa, A. Curr. Med. Chem. 2005, 12,
2413.
(3) Fukawa, I.; Yoneda, H.; Asahi, K. K. K. K. EP 0237004,
1987.
(4) Kelkar, A. S.; Letcher, R. M.; Cheung, K.-K.; Chiu, K.-F.;
Brown, G. D. J. Chem. Soc., Perkin Trans. 1 2000, 3732.
(5) (a) Santos, C. M. M.; Silva, A. M. S.; Cavaleiro, J. A. S. Eur.
J. Org. Chem. 2009, 2642. (b) Santos, C. M. M.; Silva, A.
M. S.; Cavaleiro, J. A. S. Synlett 2007, 3113. (c) Santos,
C. M. M.; Silva, A. M. S.; Cavaleiro, J. A. S. Synlett 2005,
3095.
(6) (a) El-Seedi, H. R.; El-Barbary, M. A.; El-Ghorab, D. M.;
Bohlin, L.; Borg-Karlson, A. K.; Göransson, U.; Verpoorte,
R. Curr. Med. Chem. 2010, 17, 854. (b) Pinto, M. M. M.;
Sousa, M. E.; Nascimento, M. S. J. Curr. Med. Chem. 2005,
12, 2517.
(7) (a) Park, H. H.; Park, Y.-D.; Han, J.-M.; Im, K.-R.; Lee,
B. W.; Jeong, I. Y.; Jeong, T.-S.; Lee, W. S. Bioorg. Med.
Chem. Lett. 2006, 16, 5580. (b) Jiang, D.-J.; Dai, Z.; Li,
Y.-J. Cardiovasc. Drug Rev. 2004, 22, 91.
(8) (a) Na, Y. J. Pharm. Pharmacol. 2009, 61, 707. (b) Ee, G.
C. L.; Daud, S.; Izzaddin, S. A.; Rahmani, M. J. Asian Nat.
Prod. Res. 2008, 10, 475.
Yellow oil. 1H NMR (300.13 MHz, CDCl3): d = 2.76 (ddd,
1 H, J = 18.6, 5.8, 1.3 Hz, H-4trans), 3.01 (ddd, 1 H, J = 18.6,
9.7, 2.8 Hz, H-4cis), 4.56 (d, 1 H, J = 9.7 Hz, H-1), 6.39 (dd,
1 H, J = 9.7, 2.8 Hz, H-2), 6.44–6.51 (m, 1 H, H-3), 7.14–
7.26 (m, 3 H, H-3¢,4¢,5¢), 7.33–7.35 (m, 2 H, H-2¢,6¢), 7.33–
7.37 (m, 1 H, H-7), 7.45 (d, 1 H, J = 7.9 Hz, H-5), 7.62 (ddd,
1 H, J = 7.9, 7.7, 1.6 Hz, H-6), 8.17 (dd, 1 H, J = 7.9, 1.6 Hz,
H-8). 13C NMR (75.47 MHz, CDCl3): d = 31.5 (C-4), 33.4
(C-1), 116.6 (C-9b), 117.9 (C-5), 121.9 (C-2), 124.3 (C-8a),
124.8 (C-7), 125.9 (C-8), 125.9 (C-4¢), 127.1 (C-2¢,6¢), 128.4
(C-3¢,5¢), 133.1 (C-6), 138.4 (C-3), 143.3 (C-1¢), 155.4 (C-
4b), 159.3 (C-4a), 176.4 (C-9).
(9) (a) Riscoe, M.; Kelly, J. X.; Winter, R. Curr. Med. Chem.
2005, 12, 2539. (b) Portela, C.; Afonso, C. M. M.; Pinto, M.
M. M.; Ramos, M. J. Bioorg. Med. Chem. 2004, 12, 3313.
(10) (a) Santos, C. M. M.; Freitas, M.; Ribeiro, D.; Gomes, A.;
Silva, A. M. S.; Cavaleiro, J. A. S.; Fernandes, E. Bioorg.
Med. Chem. 2010, 18, 6776. (b) Pothitirat, W.;
Chomnawang, M. T.; Supabphol, R.; Gritsanapan, W.
Fitoterapia 2009, 80, 442.
(21) Typical Experimental Procedure
Iodine (18 mg, 0.07 mmol) was added to a solution of the
appropriated chomone 5a–e (0.35 mmol) in 1,2-4-
trichlorobenzene (5 mL), and the mixture was refluxed for
48 h. After this period the solution was directly purified by
silica gel column chromatography using light PE as eluent to
remove 1,2,4-trichlorobenzene and then CH2Cl2 to recover
the product. The solvent was evaporated to dryness and the
residue were recrystallized from EtOH to give the 1-aryl-
9H-xanthen-9-ones 6a–e in moderated yields (Table 1).
(11) Khan, M. T. H.; Orhan, I.; Şenol, F. S.; Kartal, M.; Sener, B.;
Dvorská, M.; Šmejkal, K.; Šlapetová, T. Chem. Biol.
Interact. 2009, 181, 383.
Synlett 2011, No. 10, 1403–1406 © Thieme Stuttgart · New York