4856
S. Chimichi et al. / Tetrahedron 58 *2002) 4851±4858
4.3.4.
2-[,3,4-Dimethyl-2-oxo-2H-chromen-7-yl)oxy]-
®ed as ethyl 2-[-6-hydroxy-2-oxo-2H-chromen-7-yl)oxy]-
acetate 9 -0.12 g, 0.47 mmol, 17%); some starting material
8 -0.039 g, 8%) was recovered from the slowest moving
fraction. A mixture of compounds 10 and 11 -0.23 g,
0.98mmol, 35%, 25:1) was then obtained by eluting with
methanol.
acetaldehyde 7d. Yellowish powder; 0.23 g -98%); mp
148±1498C; IR -KBr) 3007, 2977, 2957, 1707,
1607 cm21; H NMR -300 MHz, CDCl3) d 9.87 -1H, t,
1
3J0.9 Hz, CHO), 7.54 -1H, d, 3J8.9 Hz, H-5), 6.89
-1H, dd, 3J8.9 Hz, 4J2.4 Hz, H-6), 6.77 -1H, d,
4J2.4 Hz, H-8), 4.65 -2H, d, J0.9 Hz, 20-CH2), 2.38
3
-3H, s, 4-CH3), 2.19 -3H, s, 3-CH3); 13C NMR
-75.43 MHz, CDCl3) d 197.6 -s, C-10), 162.1 -s, C-2),
159.2 -s, C-7), 153.4 -s, C-8a), 145.9 -s, C-4), 125.7 -d,
C-5), 119.8-s, C-3), 115.3 -s, C-4a), 112.0 -d, C-6), 101.7
-d, C-8), 72.7 -t, C-20), 15.1 -q, 4-CH3), 13.2 -q, 3-CH3);
EI-MS m/z -%) 232 -M1, 34), 204 -14), 161 -100), 117 -50).
Anal. calcd for C13H12O4: C, 67.23; H, 5.21. Found: C,
67.45; H, 5.21.
4.4.1. Ethyl 2-[,6-hydroxy-2-oxo-2H-chromen-7-yl)-
oxy]acetate 9. Colourless crystals; mp 155±1568C; IR
1
-KBr) 3480±3000, 1752, 1685 cm21; H NMR -200 MHz,
3
CDCl3) d 7.60 -1H, d, J9.5 Hz, H-4), 7.03 -1H, s, H-5),
6.81 -1H, s, H-8), 6.32 -1H, d, 3J9.5 Hz, H-3), 4.73 -2H, s,
3
20-CH2), 4.30 -2H, q, J7.3 Hz, CH2CH3), 1.33 -3H, t,
3J7.3 Hz, CH2CH3); EI-MS m/z -%) 264 -M1, 30), 218
-62), 190 -49), 162 -100). Anal. calcd for C13H12O6: C,
59.09; H, 4.58. Found: C, 59.22; H, 4.66.
4.3.5. 2-[,2-Oxo-2H-chromen-4-yl)oxy]acetaldehyde 7e.
White powder; 0.20 g -98%); mp 157±1588C; IR -KBr)
4.4.2. Ethyl 2-[,6-,2-ethoxy-2-oxoethoxy)-2-oxo-2H-
chromen-7-yl)oxy]acetate 12. Colourless crystals; mp
3032, 2984, 1715, 1618 cm21
;
1H NMR -400 MHz,
3
1
111±1128C; IR -KBr) 3062, 1747, 1615 cm21; H NMR
CDCl3) d 9.89 -1H, t, J0.7 Hz, CHO), 7.93 -1H, dd,
3J7.8Hz, 4J1.6 Hz, H-5 or H-8), 7.60 -1H, m, H-7 or
H-6), 7.35 -1H, m, H-8or H-5), 7.32 -1H, m, H-6 or H-7),
3
-200 MHz, CDCl3) d 7.60 -1H, d, J9.5 Hz, H-4), 7.01
3
-1H, s, H-5), 6.76 -1H, s, H-8), 6.30 -1H, d, J9.5 Hz,
3
5.60 -1H, s, H-3), 4.80 -2H, d, J0.7 Hz, 20-CH2); 13C
H-3), 4.76 -2H, s, OCH2), 4.73 -2H, s, OCH2), 4.28-2H,
q, 3J7.3 Hz, CH2CH3), 4.27 -2H, q, 3J7.3 Hz, CH2CH3),
NMR -100.58MHz, CDCl 3) d 194.6 -d, C-10), 164.4 -s,
C-4), 162.2 -s, C-2), 153.4 -s, C-8a), 132.9 -d), 124.2 -d),
123.0 -d), 116.9 -d), 115.0 -s, C-4a), 91.5 -d, C-3), 72.5 -t,
C-20); EI-MS m/z -%) 204 -M1, 40), 162 -12), 105 -16), 89
-100). Anal. Calcd for C11H8O4: C, 64.71; H, 3.95. Found:
C, 64.84; H, 3.87.
3
3
1.32 -3H, t, J7.3 Hz, CH2CH3), 1.30 -3H, t, J7.3 Hz,
CH2CH3); EI-MS m/z -%) 350 -M1, 40), 277 -30), 203
-100). Anal. calcd for C17H18O8: C, 58.28; H, 5.18. Found:
C, 58.42; H, 5.16.
4.4.3. 2-[,6-Methoxy-2-oxo-2H-chromen-7-yl)oxy]acetic
acid 13. -a) To a solution of compound 9 -0.30 g,
1.1 mmol) and dimethyl sulfate -0.24, 2.5 mmol) in acetone
-15 mL) potassium carbonate -0.28g) was added and the
mixture was re¯uxed for 5 h. Removal of the solvent left
a white solid which was suspended in water, collected by
®ltration and dried. To a solution of this product -0.30 g) in
ethanol -10 mL), was added NaOH 5% -1.3 mL) and the
mixture was stirred under re¯ux for 2 h. Removal of the
solvent left a residue that was dissolved in water and acidi-
®ed with 6 M HCl to give the acid 13 as a white solid
-0.26 g, 96%); mp 218±2208C; IR -KBr) 3600±1900,
4.3.6. 2-[,2-Oxo-2H-chromen-7-yl)oxy]propanal 7f.
Yellowish waxy solid; 0.21 g -95%); IR -nujol) 2925,
1
2857, 1713, 1614 cm21; H NMR -200 MHz, CDCl3) d
3
3
9.71 -1H, d, J1.5 Hz, CHO), 7.64 -1H, d, J9.5 Hz,
H-4), 7.41 -1H, d, 3J8.6 Hz, H-5), 6.85 -1H, dd,
3J8.6 Hz, 4J2.4 Hz, H-6), 6.79 -1H, d, 4J2.4 Hz,
H-8), 6.29 -1H, d, 3J9.5 Hz, H-3), 4.74 -1H, qd,
3
3
3J7.0 Hz, J1.5 Hz, CHCH3), 1.55 -3H, d, J7.0 Hz,
CHCH3); 13C NMR -50.29 MHz, CDCl3) d 200.0 -d,
C-10), 160.7 -s, C-2), 160.1 -s, C-7), 155.4 -s, C-8a),
143.1 -d, C-4), 129.0 -d, C-5), 113.5 -d, C-3), 113.2 -s,
C-4a), 112.7 -d, C-6), 102.3 -d, C-8), 78.0 -d, C-20), 15.0
-q, CHCH3); EI-MS m/z -%) 218-M 1, 16), 189 -48), 133
-38), 105 -39), 89 -100). Anal. calcd for C12H10O4: C, 66.05;
H, 4.62. Found: C, 66.00; H, 4.55.
1
1743, 1684 cm21; H NMR -200 MHz, DMSO-d6) d 7.96
3
-1H, d, J9.5 Hz, H-4), 7.30 -1H, s, H-5), 6.99 -1H, s,
3
H-8), 6.31 -1H, d, J9.5 Hz, H-3), 4.84 -2H, s, 20-CH2),
3.82 -3H, s, OCH3); EI-MS m/z -%) 206 -M1244, 100), 191
-45), 178-23), 163 -41). Anal. calcd for C 12H10O6: C, 57.61;
H, 4.03. Found: C, 57.55; H, 4.35.
4.4. Reaction of 6,7-dihydroxycoumarin ,8) with ethyl
bromoacetate
-b) Operating as above starting from the acid 10 -0.26 g,
1.1 mmol) compound 13 was obtained in 98% yield.
To a solution of 6,7-dihydroxycoumarin -8) -0.50 g,
2.8mmol) and ethyl bromoacetate -0.3 mL, 2.8mmol) in
DMF -15 mL) potassium carbonate -0.39 g) was added
and the reaction mixture was maintained at room tempera-
ture for 4 h under stirring. Removal of the solvent left a
yellow residue that was dissolved in water -10 mL) and
acidi®ed with 6 M HCl under cooling. The white precipitate
was collected by ®ltration, washed with cooled water and
dried in vacuo. The obtained material resulted in a
mixture of compounds 9±12 that were separated by ¯ash-
chromatography -petroleum ether/ethyl acetate1:2, as
eluant). The fastest running band gave ethyl 2-[-6--2-
ethoxy-2-oxoethoxy)-2-oxo-2H-chromen-7-yl)oxy]acetate
12 -0.18g, 0.52 mmol, 19%), the second band was identi-
4.4.4. 2-[,6-Methoxy-2-oxo-2H-chromen-7-yl)oxy]acetal-
dehyde 14. Operating as for 5a±f, starting from compound
13 -0.23 g, 0.92 mmol), the aldehyde 14 -0.20 g, 95%) was
obtained as a white powder: mp 138±1408C; IR -KBr) 3063,
1723, 1615 cm21; 1H NMR -300 MHz, CDCl3) d 9.89 -1H,
3
3
t, J0.9 Hz, CHO), 7.62 -1H, d, J9.5 Hz, H-4), 6.92
3
-1H, s, H-5), 6.74 -1H, s, H-8), 6.32 -1H, d, J9.5 Hz,
3
H-3), 4.71 -2H, d, J0.9 Hz, 20-CH2), 3.94 -3H, s,
OCH3); 13C NMR -100.58MHz, CDCl 3) d 197.2 -d,
C-10), 160.9 -s, C-2), 150.1 -s), 149.4 -s), 146.6 -s), 142.9
-d, C-4), 114.5 -d, C-3), 112.8-s, C-4a), 109.0 -d, C-5),
102.2 -d, C-8), 73.6 -t, C-20), 56.4 -q, OCH3); EI-MS m/z