1
13
Spectrum RXI FT-IR spectrometer. H and C NMR spectra were measured in CDCl with a Varian 200 MHz NMR spectrometer
3
with chemical shift values represented as (ppm) relative to the internal standard TMS. High-resolution EI mass spectra were
obtained using a JEOL JMS–AX505 double-focusing mass spectrometer. The non-radioactive HIV-RT colorimetric ELISA kit
was obtained from Roche Diagnostic, Germany.
General Procedure for the Preparation of 8-Halogen Derivatives 1–4. A mixture of anhydrous AlCl (40 g,
3
300 mmol) and NaCl (8 g, 137 mmol) was heated to 180ꢅC. A mixture of the appropriate 4-halo-3-methylphenol (2 g, 10.7 mmol)
or 4-halo-2-methylphenol and maleic anhydride (4 g, 40.8 mmol) was added to the above melt with vigorous stirring for 2 min,
and then poured into a mixture of ice and 12 M HCl. The mixture was kept for 30 min, and the precipitate was filtered and dried
at room temperature overnight. The residue obtained was powdered and extracted with n-hexane with vigorous stirring at
50ꢅC. The extract was concentrated under reduced pressure and crystallized from chloroform to afford the corresponding
halogenated products.
8-Fluoro-5-hydroxy-7-methyl-1,4-naphthoquinone (1). Obtained as dark orange needles from CHCl , yield 25%,
3
–1
1
mp 150ꢅC. IR (KBr, cm ): 1663, 1642 (C=O). H NMR (200 MHz, CDCl , , ppm): 12.59 (1H, s, 5-OH), 7.31 (1H, s, H-6),
6.95 (2H, s, H-2, H-3), 2.53 (3H, s, CH ). C NMR (CDCl , 50 MHz, ) 189.51 (C-4), 183.22 (C-1), 160.54 (C-5), 148.99 (C-8),
3
13
3
3
140.85 (C-2), 140.36 (C-3), 137.61 (C-7), 136.62 (C-9), 125.89 (C-6), 114.53 (C-10), 21.89 (C-11). HR-EI-MS m/z 206.0372
(calcd for C H FO 206.0379).
11
7
3
8-Chloro-5-hydroxy-7-methyl-1,4-naphthoquinone (2). Obtained as dark orange shining needles from CHCl ,
3
–1
1
yield 30%, mp 159ꢅC. IR (KBr, cm ): 1662, 1646 (C=O). H NMR (200 MHz, CDCl , , ppm): 12.54 (1H, s, 5-OH), 7.18
3
(1H, s, H-6), 6.88 (2H, s, H-2, H-3), 2.46 (3H, s, CH ). HR-EI-MS m/z 222.0088 (calcd for C H ClO 222.0084).
3
11
7
3
8-Bromo-5-hydroxy-7-methyl-1,4-naphthoquinone (3). Obtained as dark red needles from CHCl , yield 27%,
3
–1
1
mp 154ꢅC. IR (KBr, cm ): 1663, 1642 (C=O). H NMR (200 MHz, CDCl , , ppm):ꢂ12.54 (1H, s, 5-OH), 7.18 (1H, s, H-6),
6.88 (2H, s, H-2, H-3), 2.47 (3H, s, CH ). C NMR (50 MHz, CDCl , ):ꢂ189.50 (C-4), 183.21 (C-1), 160.54 (C-5), 148.99
3
13
3
3
(C-8), 140.84 (C-2), 140.69 (C-3), 136.61 (C-7), 136.52 (C-9), 125.88 (C-6), 114.53 (C-10), 21.89 (C-11). HR-EI-MS m/z 265.9574
(calcd for C H BrO 265.9579).
11
7
3
8-Chloro-5-hydroxy-6-methyl-1,4-naphthoquinone (4). Obtained as dark orange shining needles from CHCl ,
3
–1
1
yield 30%, mp 162ꢅC. IR (KBr, cm ): 1663, 1655 (C=O). H NMR (200 MHz, CDCl , , ppm): 12.99 (1H, s, 5-OH), 7.48
3
(1H, s, H-7), 6.89 (2H, s, H-2, H-3), 2.32 (3H, s, CH ).
3
General Procedure for the Preparation of 5-Hydroxy-7- and 6-methyl-1,4-naphthoquinones (5 and 6).Asolution
of the appropriate 8-chloro-1,4-naphthoquinones (200 mg, 0.90 mmol) in THF (20 mL) was added dropwise to a solution of
SnCl (1.0 g, 51 mmol) in 4 M HCl (70 mL) and THF (20 mL) at 60ꢅC and stirred for 3 h. It was then cooled and filtered into
2
a solution of FeCl . The resulting precipitate was filtered and dried to afford the required products.
3
5-Hydroxy-7-methyl-1,4-naphthoquinone (5). Obtained as orange needles from CHCl , yield 65%, mp 125ꢅC.
3
–1
1
IR (KBr, cm ): 1670, 1645 (C=O). H NMR (200 MHz, CDCl , , ppm):ꢂ11.84 (1H, s, 5-OH), 7.42 (1H, s, H-8), 7.06 (1H, s,
3
H-6), 6.89 (2H, s, H-2, H-3), 2.41 (3H, s, CH ). HR-EI-MS m/z 188.0475 (calcd for C H O 188.0473).
3
11 8 3
5-Hydroxy-6-methyl-1,4-naphthoquinone (6). Obtained as dark orange needles from CHCl , yield 60%, mp 104ꢅC.
3
–1
1
IR (KBr, cm ): 1663, 1655 (C=O). H NMR (200 MHz, CDCl , , ppm): 13.0 (1H, s, 5-OH), 7.48 (1H, s, H-7), 7.23 (1H, s,
H-8), 6.89 (2H, s, H-2, H-3), 2.32 (3H, s, CH ). C NMR (50 MHz, CDCl , ): 15.81 (CH ), 115.00, 124.64, 126.04, 136.60,
3
13
3
3
3
136.76, 140.24, 140.94, 160.22 (C-5), 182.62 (C=O), 190.10 (C=O). HR-EI-MS m/z 188.0462 (calcd for C H O 188.0473).
11
8 3
General Procedure for the Preparation of 5-Alkoxyderivatives 7 and 8. A mixture of compound 2 100 mg, Ag O
2
(130 mg, 0.56 mmol), and either methyl- or ethyl iodide (48.19 mmol) in acetone (3 mL) was refluxed at 60ꢅC for 2–4 h. The
reaction mixture was then filtered and concentrated under reduced pressure. It was purified by silica gel chromatography and
then crystallized (from hexane–chloroform) to afford the respective 5-methoxy- and 5-ethoxy- 1,4-naphthoquinone derivatives.
8-Chloro-5-methoxy-7-methyl-1,4-naphthoquinone (7). Obtained as yellow amorphous powder, yield 70%,
–1
1
mp 142ꢅC. IR (KBr, ꢆ , cm ): 1657 (C=O). H NMR (200 MHz, CDCl , , ppm): 7.28 (1H, s, H-6), 6.85 (1H, s, H-3), 6.83
max
3
(1H, s, H-2), 4.02 (3H, s, OCH ), 2.56 (3H, s, CH ). HR-EI-MS m/z 236.0252 (calcd for C H ClO 236.0240).
3
3
12
9
3
–1
8-Chloro-5-ethoxy-7-methyl-1,4-naphthoquinone (8). Obtained as a brown semisolid, yield 70%. IR (KBr, ꢆ , cm ):
max
1
1658 (C=O). H NMR (200 MHz, CDCl , , ppm): 7.31 (1H, s, H-6), 6.85 (1H, s, H-3), 6.84 (1H, s, H-2), 4.24 (2H, q, J = 7.5,
3
13
OCH ), 2.56 (3H, s, 7-CH ), 1.62 (3H, t, J = 7.5, CH CH ). C NMR (50 MHz, CDCl , ): 185.58 (C=O), 183.92 (C=O),
2
3
2
3
3
159.18 (C-5), 146.17, 140.95, 140.94, 135.88, 133.70, 119.82, 119.43, 65.02 (OCH ), 22.19 (CH ), 14.61 (CH ). HR-EI-MS
2
3
3
m/z 250.0137 (calcd for C H ClO 250.0397).
13 11
3
886