D. Maes et al. / Tetrahedron 64 (2008) 4438e4443
4443
with 10 ml of water. After drying over magnesium sulfate, fil-
tration and evaporation of the solvent in vacuo, 36 mg (86%)
of pure 2,3-methylenedioxy-4,6-dimethoxybenzaldehyde 14
was obtained as a white powder.
(s, 1H, CH ); 7.29e7.48 (m, 10H, CH ); 10.40 (s, 1H,
Ar Ar
1
3
CHO). C NMR (75 MHz, CDCl ): d 56.1 (OCH ); 62.2
3
3
(OCH ); 71.2 (OCH Ar); 75.6 (OCH Ar); 93.6 (CH );
3
2
2
Ar
113.2 (C ); 127.1 (CH ); 128.0 (CH ); 128.1 (CH );
q
Ar
Ar
Ar
ꢀ
22
ꢁ1
Mp ( C): 167 (lit. 166e167 ). IR (KBr, cm ): 1672
128.3 (CH ); 128.4 (CH ); 128.7 (CH ); 135.2 (C );
Ar Ar Ar q
1
C]O); 1639. H NMR (300 MHz, CDCl ): d 3.87 (s, 3H,
(
136.1 (C ); 137.3 (C ); 156.6 (C ); 158.3 (C ); 159.3 (C );
3
q
q
q
q
q
þ
þ
OCH ); 4.00 (s, 3H, OCH ); 6.04 (s, 1H, CH ); 6.08 (s, 2H,
187.9 (CHO). MS (70 eV, ES , m/z (%)): 379 (MþH ).
3
3
ar
1
3
eOCH Oe) 10.23 (s, 1H, CHO). C NMR (75 MHz,
Anal. Calcd for C H O : C, 73.00%; H, 5.86%. Found: C,
23 22 5
72.82%; H, 6.09%.
2
CDCl ): d 56.4 (OCH ); 57.0 (OCH ); 90.7 (CH ); 102.9
3
3
3
Ar
(
(
2
4
eOCH Oe); 105.7 (C ); 129.8 (C ); 148.1 (C ); 149.9
2 q q q
þ
C ); 158.1 (C ); 186.7 (CHO). MS (70 eV, ES , m/z (%)):
q q
Acknowledgements
þ
11 (MþH ). Anal. Calcd for C H O : C, 57.14%; H,
1
0 10 5
.80%. Found: C, 56.97%; H, 4.87%.
This work was financially supported by the Special
Research Fund (BOF) of Ghent University.
4
.2.5. 3,6-Dihydroxy-2,4-dimethoxybenzaldehyde 16
,6-Dibenzyloxy-2,4-dimethoxybenzaldehyde 18 (378 mg,
3
References and notes
1
3
mmol) was dissolved in 10 ml of absolute ethanol, and
8 mg (10w%) of Pd on carbon (10%) was added to the solu-
1. Murray, R. D. H. Prog. Chem. Org. Nat. Prod. 2002, 83, 673.
2. Kayser, O.; Kolodziej, H. Z. Z. Naturforsch. 1999, 54c, 169e174.
3. Wu, T.-S.; Tsang, Z.-J.; Wu, P.-L.; Lin, F.-W.; Li, C.-Y.; Teng, C.-M.; Lee,
K.-H. Bioorg. Med. Chem. 2001, 9, 77e83.
tion and the mixture was stirred at room temperature under hy-
drogen atmosphere (4.5 bar) for 3 h. The mixture was filtered
and the solvent was evaporated in vacuo, yielding 191 mg
(
low crystals after crystallization from diethyl ether/hexane.
97%) 3,6-dihydroxy-2,4-dimethoxybenzaldehyde 16 as yel-
4. Riveiro, M. E.; Shayo, C.; Monczor, F.; Fern a´ ndez, N.; Baldi, A.;
De Kimpe, N.; Rossi, J.; Debenedetti, S.; Davio, C. Cancer Lett. 2004,
210, 179e188.
ꢀ
ꢁ1
Mp ( C): 126e127. IR (KBr, cm ): 3422 (br, OH); 1630
5
6
. Kostova, I. Planta Med. 1992, 58, 484.
1
(
CHO). H NMR (300 MHz, CDCl ): d 3.94 (s, 3H, OCH );
3
3
. Abou Zeid, A. H. S. Food Chem. 2002, 76, 187e195.
4
1
.04 (s, 3H, OCH ); 5.10 (s, 1H, OH); 6.22 (s, 1H, CH );
3 Ar
7. Deng, Y.-R.; Song, A.-X.; Wang, H.-Q. J. Chin. Chem. Soc-TAIP 2004,
51, 629e636.
1
0.08 (s, 1H, CHO); 11.91 (s, 1H, OH). C NMR (75 MHz,
3
8
. Ishii, H.; Kobayashi, J.-I.; Ishikawa, T. Chem. Pharm. Bull. 1983, 31,
330e3333.
CDCl ): d 56.5 (OCH ); 61.9 (OCH ); 94.6 (CH ); 108.5
3
3
3
Ar
3
(
(
C ); 130.5 (C ); 147.9 (C ); 156.0 (C ); 158.3 (C ); 192.9
q q q q q
9
. Latt e´ , K. P.; Kayser, O.; Tan, N.; Kaloga, M.; Kolodziej, H.
þ
þ
CHO). MS (70 eV, ES , m/z (%)): 199 (MþH ). Anal. Calcd
Z. Naturforsch. 2000, 55c, 528e533.
for C H O : C, 54.55%; H, 5.09%. Found: C, 53.93%; H,
9
10
5
10. Wagner, H.; Bladt, S. Phytochemistry 1975, 14, 2061e2064.
11. Kayser, O.; Kolodziej, H. Planta Med. 1997, 63, 508e510.
5
.18%.
1
2. Dean, F. M.; Costa, A. M. B. S. R. C. S.; Harborne, J. B.; Smith, D. M.
Phytochemistry 1978, 17, 505e509.
4
.2.6. 3,6-Dibenzyloxy-2,4-dimethoxybenzaldehyde 18
Phosphorus(V) oxychloride (1.840 g, 12 mmol) was added
1
3. Ahluwalia, V. K.; Prakash, C. Indian J. Chem. 1977, 15B, 808.
4. Deshmukh, M. N.; Deshpande, V. H.; Rao, A. V. R. Phytochemistry 1976,
1
to N,N-dimethylformamide (4.380 g, 60 mmol) and the reac-
tion mixture was stirred for 10 min at room temperature.
Subsequently, 4 mmol (1.512 g) of 2,5-dibenzyloxy-1,3-dime-
1
5, 1419.
15. Szab o´ , G.; Greger, H.; Hofer, O. Phytochemistry 1985, 24, 537e541.
1
1
6. Hepworth, J. D. Coumarins (2H-1-benzopyran-2-ones). Comprehensive
Heterocyclic Chemistry II; Katritzky, A. R., Ed.; Elsevier: Amsterdam,
2
1
thoxybenzene 17 was added to the reaction mixture and the
reaction was left at room temperature for 16 h. The reaction
1
7. Harayama, T.; Nakatsuka, K.; Katsuno, K.; Nishioka, H.; Murakami, K.;
996; Vol. 5, pp 417e425.
ꢀ
was cooled to 0 C, 100 ml of a 2.5 N aqueous sodium hydrox-
Fujii, M.; Hayashida, N.; Takeuchi, Y. Chem. Express 1993, 8, 245e248.
18. Harayama, T.; Nakatsuka, K.; Nishioka, H.; Murakami, K.; Ohmori, Y.;
ide solution was added, and the reaction was left at room tem-
perature for 1 h. The reaction mixture was extracted three
times with 100 ml of ethyl acetate and the combined organic
layers were washed with 100 ml of 2 M aqueous hydrochloric
acid and 2ꢂ100 ml of water. After drying over magnesium
sulfate, filtration and evaporation of the solvent, 1.224 g
Takeuchi, Y.; Ishii, H.; Kenmotsu, K. Heterocycles 1994, 38, 2729e2738.
1
9. Demyttenaere, J.; Vervish, S.; Debenedetti, S.; Coussio, J.; Maes, D.;
De Kimpe, N. Synthesis 2004, 11, 1844e1848.
0. Maes, D.; Vervish, S.; Debenedetti, S.; Davio, C.; Mangelinckx, S.;
Giubellina, N.; De Kimpe, N. Tetrahedron 2005, 61, 2505e2511.
2
21. Iinuma, M.; Matoba, Y.; Tanaka, T.; Mizuno, M. Chem. Pharm. Bull.
986, 34, 1656e1662.
1
(
was obtained as a yellow oil.
81%) of 3,6-dibenzyloxy-2,4-dimethoxybenzaldehyde 18
2
2. Paul, E. G.; Wang, P. S. C. J. Org. Chem. 1979, 44, 2307e2308.
2
3. Paknikar, S. K.; Bhattacharjee, J.; Nadkarni, K. K. J. Indian Inst. Sci.
ꢁ
1
1
IR (KBr, cm ): 1682 (C]O); 1594; 1568. H NMR
300 MHz, CDCl ): d 3.83 (s, 3H, OCH ); 3.95 (s, 3H,
1
994, 74, 277e285.
(
3
3
24. Trost, B. M.; Toste, F. D.; Greenman, K. J. Am. Chem. Soc. 2003, 125,
4518e4526.
OCH ); 4.95 (s, 2H, OCH Ar); 5.08 (s, 2H, OCH Ar); 6.31
3
2
2