stirred on a magnetic stirrer at 90–95°C for 12 h. The solvent was removed. The residue was treated with NaOH solution
(10%, 40 mL) and acidified with HCl (15%) to pH 3. The products were extracted with EtOAc (5 ꢅ 20 mL). The combined
extracts were rinsed with saturated NaCl solution (2 ꢅ 25 mL) and dried over Na SO . The solvent was removed at reduced
2
4
pressure. The residue was chromatographed over a column of SiO with elution by hexane–Me CO (5:1) to afford of 16
2
2
(51 mg, 21%).
1
2,5,8-Trihydroxy-7-methoxy-6-chloro-1,4-naphthoquinone (16), red plates, mp 216–219°C. Í NMR spectrum
(ÑDCl , ꢇ, ppm): 6.44 (1Í, s, Í-3), 7.71 (1Í, br.s, 2-ÎÍ), 4.26 (3Í, s, ÎÌå), 11.99 (1Í, s, 8-ÎÍ), 13.23 (1Í, s, 5-ÎÍ).
3
Elution by hexane–Me CO (4:1) gave 15 (66 mg, 27%).
2
1
2,5,8-Trihydroxy-6-methoxy-7-chloro-1,4-naphthoquinone (15), red plates, mp 220–223°C. Í NMR spectrum
(ÑDCl , ꢇ, ppm): 6.45 (1Í, s, Í-3), 7.83 (1Í, br.s, 2-ÎÍ), 4.15 (3Í, s, ÎÌå), 12.34 (1Í, s, 8-ÎÍ), 13.37 (1Í, s, 5-ÎÍ).
3
Elution by hexane–Me CO (3:1) gave starting 14 (28 mg, 10%).
2
O-Ethylation of 14 by Et SO . A solution of 14 (275 mg, 1.0 mmol), Et SO (1 mL), and Et N (1.2 mL) in MeCN
2
4
2
4
3
(15 mL) was refluxed for 4 h, cooled to room temperature, treated with NaOH solution (10%, 15 mL) and HCl (20%, 20 mL),
diluted with H O (20 mL), and extracted with EtOAc (4 ꢅ 20 mL). The usual work up of the extract gave a mixture of products
2
that was chromatographed over a column of SiO with elution by benzene–Me CO (10:1) to afford 17 (24 mg, 8%).
2
2
5,8-Dihydroxy-6,7-dichloro-2-ethoxy-1,4-naphthoquinone (17), reddish-orange plates, 188–190°C (crystallization
1
with sublimation), mp 232–235°C. Í NMR spectrum (ÑDCl , ꢇ, ppm, J/Hz): 1.56 (3Í, t, J = 6.8, Me), 4.16 (2H, q, J = 6.8,
3
13
ÎÑÍ ), 6.24 (1Í, s, Í-3), 12.79 (1Í, s, 5-ÎÍ), 13.28 (1Í, s, 8-ÎÍ). C NMR spectrum (ÑDCl , ꢇ, ppm): 13.96 (Ìå), 66.27
2
3
(ÎÑÍ ), 108.51 (Ñ-8à), 110.00 (Ñ-3), 110.19 (Ñ-4à), 132.99 (Ñ-6), 135.53 (Ñ-7), 156.49 (Ñ-8), 157.81 (Ñ-5), 159.94 (Ñ-2),
2
178.58 (Ñ-4), 184.65 (Ñ-1).
Elution by benzene–Me CO (8:1) gave 18 (40 mg, 12%).
5-Hydroxy-6,7-dichloro-2,8-diethoxy-1,4-naphthoquinone (18), orange needles, mp 237–239°C. Í NMR spectrum
2
1
(CDCl , ꢇ, ppm, J/Hz): 1.42 (3Í, t, J = 6.8, OCH CH -8), 1.54 (3Í, t, J = 6.8, OCH CH -2), 4.12 (2Í, q, J = 6.8, OCH CH -2),
3
2
3
2
3
2
3
4.33 (2Í, q, J = 6.8, OCH CH -8), 6.08 (1H, s, H-3), 13.63 (1H, s, 5-OH).
2
3
O-Methylation of 14 by MeI. A solution of 14 (1.10 g, 4.0 mmol) and MeI (22 mL) in DMF (80 mL) was stirred
vigorously and treated in small portions over 4 h with calcined K CO (1.67 g), saturated aqueous NaCl (170 mL), and HCl
2
3
(10%, 170 mL). The products were extracted with EtOAc (6 ꢅ 50 mL). The usual work up of the extract gave a product
mixture that was chromatographed over a column of SiO with elution by benzene–Me CO (9:1) to afford 19 (1.05 g, 91%).
2
2
5,8-Dihydroxy-2-methoxy-6,7-dichloro-1,4-naphthoquinone (19), reddish-orange plates, 179–180°C
1
(recrystallization with sublimation), mp 227–230°C. Í NMR spectrum (ÑDCl , ꢇ, ppm): 3.97 (3H, s, OMe), 6.28 (1Í, s,
3
13
Í-3), 12.76 (1H, s, 5-OH), 13.27 (1H, s, 8-OH). C NMR spectrum (CDCl , ꢇ, ppm): 56.99 (OMe), 108.39 (C-8à), 109.59
3
(C-3), 110.03 (C-4a), 133.02 (C-6), 134.95 (C-7), 156.61 (C-8), 157.91 (C-5), 160.53 (C-2), 178.02 (C-4), 184.17 (C-1).
Elution by benzene–Me CO (4:1) gave of 20 (46 mg, 4%).
2,5,8-Trihydroxy-3-methyl-6,7-dichloro-1,4-naphthoquinone (20), red needles, mp 192–193°C. Í NMR spectrum
2
1
(CDCl , ꢇ, ppm): 2.16 (3H, s, Me), 9.61 (1Í, br.s, 2-OÍ), 12.07 (1H, br.s, 8-OH), 13.55 (1H, s, 5-OH). Mass spectrum,
3
+
m/z (I ,%): 288/290/292 ([M] (100)).
rel
Nucleophilic Substitution of Cl Atoms in 19. Conditions analogous to those described above for conversion of 14
into the mixture of 15 and 16 (with the exception that the reaction time was 30 h) were used with 19 (1.45 g, 5.0 mmol) to give
a product mixture that was chromatographed over a column of SiO with elution by hexane–Me CO (12:1) to afford 22
2
2
(29 mg, 2%).
1
5,8-Dihydroxy-2,7-dimethoxy-6-chloro-1,4-naphthoquinone (22), red plates, mp 199–201°C. Í NMR spectrum
(CDCl , ꢇ, ppm): 3.97 (3H, s, 2-OMe), 4.18 (3H, s, 7-OMe), 6.35 (1Í, s, Í-3), 12.68 (1H, s, 8-OH), 13.26 (1H, s, 5-OH).
3
13
C NMR spectrum (CDCl , ꢇ, ppm): 57.09 (2-OMe), 61.84 (7-OMe), 105.73 (C-4à), 109.11 (C-3), 110.83 (C-8a), 128.06
3
(C-6), 154.47 (C-7), 158.92 (C-2), 164.07 (C-5), 171.52 (C-8), 172.74 (C-4), 177.71 (C-1).
Elution by hexane–Me CO (10:1) gave 21 (114 mg, 8%).
5,8-Dihydroxy-2,6-dimethoxy-7-chloro-1,4-naphthoquinone (21), red plates, mp 195–197°C. Í NMR spectrum
2
1
(CDCl , ꢇ, ppm): 3.97 (3H, s, 2-OMe), 4.26 (3H, s, 6-OMe), 6.34 (1Í, s, Í-3), 13.02 (1H, s, 8-OH), 13.09 (1H, s, 5-OH).
3
13
C NMR spectrum (CDCl , ꢇ, ppm): 57.09 (2-OMe), 62.11 (6-OMe), 107.78 (C-4à), 108.43 (C-3), 108.70 (C-8a), 124.97
3
(Ñ-7), 156.41 (C-6), 160.33 (C-2), 163.60 (C-5), 167.25 (C-4), 168.71 (C-8), 177.54 (C-1).
Elution by hexane–Me CO (5:1) gave 10 (1.12 g, 80%).
2
216