1756
V. P. Glazunovet al. / Tetrahedron 58 -2002) 1751±1757
lit.25 Mp 154±1578C). IR 1CDCl3), n 1cm21): 3526 m, 3424
m 1b-OH), 1654 w, 1629 m, 1599 s1C vO), 1577 sh. m
1Aldrich, ,150 mesh, for chromatography) 1640 mg), abso-
lute MeOH 110 mL), and ethylene glycol dimethyl ether
³
1
1CvC). H NMR: 1.16 1t, J7.6 Hz, 3H, CH3); 2.64 1q,
12 mL) was stirred in a closed reaction vessel at 90±958C
for 10 h. After cooling, the absorbent was separated by
®ltration, washed successively with 5% HCl 10.5 mL) and
acetone 13 mL). The combined acidic ®ltrate wasconcen-
trated in vacuo, and the residue was treated with water
13 mL) and then Et2O. The organic layer waswashed with
water and brine, dried Na2SO4, ®ltered and concentrated.
Preparative TLC 1hexane/acetone3:1) afforded the
product 3e, 27 mg 142%), Rf0.32. Mp 234±2358C. IR
1CDCl3), n 1cm21): 3520 m, 3418 m 1b-OH), 1663 w,
J7.6 Hz, 2H, CH2); 3.96 1s, 3H, OCH3); 6.57 1s, 1H,
H16)); 7.13 1broad s, 1H, b-OH); 12.04 and 13.34 1both s,
on 1H each, a-OH). 1H NMR 1DMSO-d6): 1.05 1t,
J7.6 Hz, 3H, CH3); 2.50 1q, J7.6 Hz, 2H, CH2); 3.91
1s, 3H, OCH3); 6.76 1s, 1H, H16)); 11.11 1broad s, 1H,
b-OH); 12.27 and 13.50 1both s, on 1H each, a-OH).
EI-MS m/z: 264 [M]1 1100). In addition to product 3b,
3-ethyl-5,8-dihydroxy-2,7-dimethoxy-1,4-naphthoquinone
16) wasisolated from the reaction mixture in a yield 27 mg
132%), Rf0.45. Mp 146±1498C 1lit.22,24,26 Mp 145±
1
1620 m, 1606 s1C vO), 1575 m 1CvC). H NMR: 4.15
1
1478C). H NMR: 1.16 1t, J7.6 Hz, 3H, CH3); 2.73 1q,
1s, 3H, OCH3); 6.45 1s, 1H, H13)); 11.97 and 13.37 1both s,
on 1H each, a-OH). EI-MS m/z: 270/272 [M]1 1100), 269/
271 [M21]1 136). Anal. calcd for C11H7O6Cl: C, 48.82; H,
2.61. Found: C, 48.23; H, 2.60.
J7.6 Hz, 2H, CH2); 3.94 and 4.06 1both s, on 3H each,
OCH3); 6.26 1s, 1H, H16)); 12.80 and 13.31 1both s, on 1H
each, a-OH). EI-MS m/z: 278 [M]1 1100).
4.1.2.3. 3,6-Diethyl-2,5,8-trihydroxy-7-methoxy-1,4-
naphthoquinone -3d). From 5, 32 mg 136%), Rf0.56.
Mp 115±1178C. IR 1CDCl3), n 1cm21): 3519 w, 3417 m
In addition to product 3e, 7-chloro-2,5,8-trihydroxy-6-
methoxy-1,4-naphthoquinone 13g) wasioslated from the
reaction mixture in a yield of 13 mg 120%), Rf0.41. Mp
200±2048C. IR 1CDCl3), n 1cm21): 3515 m, 3409 m
1b-OH), 1661 w, 1624 sh. m, 1607 s 1CvO), 1580 m,
1
1b-OH), 1623 m, 1600 s1C vO), 1575 sh. m 1CvC). H
NMR: 1.15 and 1.18 1both t, on 3H each, J7.6 Hz, CH3);
2.62 and 2.76 1both q, on 2H each, J7.6 Hz, CH2); 4.03 1s,
3H, OCH3); 12.01 and 13.54 1both s, on 1H each, a-OH).
EI-MS m/z: 292 [M]1 117), 291 [M21]1 116), 258 137), 256
1100), 255 115). Anal. calcd for C15H16O6: C, 61.64; H, 5.52.
Found: C, 61.91; H, 5.68.
1
1567 m 1CvC). H NMR: 4.26 1s, 3H, OCH3); 6.44 1s,
1H, H13)); 12.32 and 13.24 1both s, on 1H each, a-OH).
EI-MS m/z: 270/272 [M]1 1100), 269/271 [M21]1 120),
252/254 139), 241/243 135), 235 122), 224/226 122). Anal.
calcd for C11H7ClO6: C, 48.82; H, 2.61. Found: C, 48.68; H,
2.69.
4.1.2.4.
6,7-Dichloro-5,8-dihydroxy-2-methoxy-1,4-
naphthoquinone -7b). Thiscompound wasprepared from
7a in quantitative yield. Mp 216±2188C. 1H NMR: 3.98 1s,
3H, OCH3); 6.29 1s, 1H, H13)); 12.77 and 13.28 1both s, on
1H each, a-OH). EI-MS m/z: 288/290/292 [M]1 1100), 287/
289/291 [M21]1 188), 273/275/277 123), 272/274/276 144),
270/272/274 175), 269/271/273 159), 258 110), 256 110), 223
114), 222 110). Anal. calcd for C11H6O5Cl2: C, 45.70; H,
2.09. Found: C, 45.92; H, 2.00.
4.1.5. 3-Chloro-2,5,8-trihydroxy-7-methoxy-1,4-naphtho-
quinone -3f). A mixture of well-dried 6,7-dichloro-2-
methoxynaphthazarin 17b) 170 mg, 0.24 mmol), anhydrous
KF 1150 mg, 2.6 mmol), and glacial acetic acid 115 mL) was
re¯uxed for 20 h. After cooling, the reaction mixture was
concentrated in vacuo. The residue was treated with 5%
Na2CO3 to pH 8±9 for about 15 min, monitoring by TLC.
The mixture wasacidi®ed by 10% HCl to pH 4±5 and
extracted with Et2O. The organic layer waswahsed with
water and brine, dried Na2SO4 and concentrated. Prepara-
tive TLC using CHCl3, yielded 3f, 35 mg 153%), Rf0.28.
Mp 207±2098C. IR 1CDCl3), n 1cm21): 3514 m, 3406 m
1b-OH), 1670 w, 1633 m, 1606 s1C vO), 1585 sh. m
4.1.3. Partial acid hydrolysis of substituted 2,7-
dimethoxynaphthazarin 6. To a boiling solution of
6-ethyl-5,8-dihydroxy-2,7-dimethoxy-1,4-naphthoquinone
16, 53 mg, 0.2 mmol) in MeOH 130 mL) wasadded drop-
wise over 3 min HCl 130 mL), and the mixture was heated at
re¯ux for 60 min monitored by TLC. After cooling, the
1
1CvC). H NMR: 3.99 1s, 3H, OCH3); 6.62 1s, 1H, H16));
12.02 and 12.99 1both s, on 1H each, a-OH). EI-MS m/z:
270/272 [M]1 1100), 269/271 [M21]1 196), 256/258 161),
191 127). Anal. calcd for C11H7O6Cl: C, 48.82; H, 2.61.
Found: C, 48.68; H, 2.98.
mixture wasdiluted by H O 150 mL), then extracted three
2
timeswith diethyl ether. The organic extract waswahsed
with brine, and dried over anhydrousNa SO4 and con-
2
centrated. Preparative TLC 1hexane/acetone3:1) yielded
6-ethyl-2,5,8-trihydroxy-7-methoxy-1,4-naphthoquinone
13c), 22 mg 142%), Rf0.42. Mp 160±1668C. IR 1CDCl3), n
1cm21): 3523 w, 3414 m 1b-OH), 1662 m, 1620 s, 1614 s
In addition to product 3f, 3-chloro-2,5,8-trihydroxy-6-
methoxy-1,4-naphthoquinone 13h) wasioslated from the
reaction mixture in a yield of 28 mg 142%), Rf0.29. Mp
.2508C 1subl.). IR 1CDCl3), n 1cm21): 3515 m, 3376 m
1b-OH), 1678 w, 1634 m, 1603 s1C vO), 1580 sh. m
1
1CvO), 1588 s, 1575 sh. s 1CvC). H NMR: 1.19 1s,
J7.5 Hz, 3H, CH3); 2.75 1q, J7.5 Hz, 2H, CH2); 4.04
1s, 3H, OCH3); 6.36 1s, 1H, H13)); 12.05 and 13.35 1both
s, on 1H each, a-OH). EI-MS m/z: 264 [M]1 1100), 250 117),
249 145). Anal. calcd for C13H12O6: C, 58.09; H, 4.58.
Found: C, 58.13; H, 4.59.
1
1CvC). H NMR: 4.02 1s, 3H, OCH3); 6.56 1s, 1H, H17));
12.04 and 13.19 1both s, on 1H each, a-OH). EI-MS m/z:
270/272 [M]1 1100), 269/271 [M21]1 192), 252/254 142),
241/243 122), 240/242 119), 236/238 119), 223 118). Anal.
calcd for C11H7O6Cl: C, 48.82; H, 2.61. Found: C, 48.90; H,
2.96.
4.1.4. 6-Chloro-2,5,8-trihydroxy-7-methoxy-1,4-naphtho-
quinone -3e). A mixture of well-dried 6,7-dichloro-2-
hydroxynaphthazarin 17a) 165 mg, 0.23 mmol), anhydrous
KF 1100 mg, 1.72 mmol), activated neutral alumina
³
27
Reagentswere prepared according to the early described procedure.