Dibenz[a,j]anthracene and Benzo[c]chrysene Metabolites
J . Org. Chem., Vol. 63, No. 23, 1998 8123
1, J ) 9.0 Hz), 6.16 (d, 1, J ) 10.1 Hz), 7.08 (d, 1, J ) 10.7
Hz), 7.27 (d, 1, J ) 10.2 Hz), 7.68-7.86 (m, 4), 8.07 (br d, 1, J
) 9.0 Hz), 8.31 (br d, 1, J ) 8.3 Hz); 13C NMR δ 73.17, 73.26,
73.95, 74.30, 76.29, 76.31, 76.54, 76.61, 121.88, 122.20, 122.30,
122.78, 123.02, 123.07, 124.47, 124.56, 127.63, 127.72, 127.80,
128.01, 128.20, 128.24, 128.51, 128.98, 129.09, 129.96, 130.03,
130.08, 130.12, 130.54, 130.59, 132.74, 132.79, 132.85, 133.01,
134.75, 135.28, 137.76, 139.28; UV (EtOH) λmax (ꢀ) 273 (4.6 ×
104), 287 (3.1 × 104), 297 (3.5 × 104), 310 (2.4 × 104), 334 (1.3
× 104) nm; MS m/e 346 (M+, 7), 310 (100); HRMS calcd for
to be incomplete after 3 days, additional NaBH4 (800 mg) was
added, and stirring was continued for 2 days. The usual
workup provided 5 (34 mg, 54%) as a white solid, mp 204-
206 °C: 1H NMR (DMSO-d6 + D2O) (data is for the major
isomer; the minor isomer showed slightly different chemical
shifts) δ 4.39 (d, 2, J ) 10.9 Hz), 4.75 (d, 2, J ) 10.9 Hz), 6.19
(d, 2, J ) 6.2 Hz), 7.47 (d, 1, J ) 9.9 Hz), 7.50 (d, 1, J ) 9.9
Hz), 7.70 (d, 2, J ) 8.5 Hz), 7.93 (d, 2, J ) 8.5 Hz), 8.44 (s, 1),
8.91 (s, 1); 13C NMR δ 74.48, 76.58, 117.24, 122.66, 124.03,
127.89, 128.12, 128.33, 129.06, 131.97, 134.64, 136.53; UV
(EtOH) λmax (ꢀ) 223 (1.95 × 104), 271.5 (1.21 × 104), 294.6 (1.03
× 104), 307 (0.8 × 104), 384.6 (0.3 × 104), 405 (0.5 × 104), 429
(0.38 × 104) nm. Anal. Calcd for C22H18O8: C, 70.58; H, 4.34.
Found: C, 70.49; H, 4.37. Acetylation of 5 by the procedure
employed for the preparation of 9d gave the tetraacetate as a
white solid, mp 230-231 °C (ether-hexane): 1H NMR δ 2.07
(s, 6), 2.15 (s, 6), 5.69 (m, 2), 6.35 (m, 4), 7.47 (d, 2, J ) 8.7
Hz), 7.67 (d, 2, J ) 10.1 Hz), 7.97 (d, 2, J ) 8.7 Hz), 8.44 (s,
1), 9.03 (s, 1).
1,3-Bis[2-(2,5-d ik etocycloh exyl)eth yl]ben zen e (12). To
50 mL of anhydrous THF in a flame-dried two-neck flask
cooled to -78 °C was added tert-BuLi (29.4 mL, 1.7 M in
pentane, 50 mmol) and 1,4-dimethylcyclohexa-1,4-diene (7.0
g, 50 mmol) in 8.5 mL of dry THF. The solution was stirred
for 1 h under argon, and then HMPA (8.7 mL) was added and
the red solution was stirred for 10 min. A solution of 1,3-bis-
(iodoethyl)benzene (7.72 g, 20 mmol) in 50 mL of THF was
added dropwise over 30 min. The reddish solution was stirred
for 10 min. Then the reaction was quenched with brine, ether
was added, and the organic layer was washed with brine, dried
over Na2SO4, and evaporated to dryness.
C
22H18O4 346.1205, found 346.1221.
Ben zo[c]ch r ysen e-1,2,9,10-tetr a on e (11). A solution of
6 (200 mg, 0.58 mmol) and o-chloranil (720 mg, 2.92 mmol) in
50 mL of anhydrous THF was stirred at room temperature
under argon for 72 h. The red precipitate was removed by
filtration, washed with ether and then with acetone, and dried
to yield 11 (200 mg, 99%) as a red solid, mp 330-331 °C: 1H
NMR (500 MHz, DMSO-d6) δ 6.51 (d, 1, J ) 10.7 Hz), 6.56 (d,
1, J ) 10.5 Hz), 8.02 (d, 1, J ) 8.9 Hz), 8.13-8.22 (m, 3), 8.28
(d, 1, J ) 10.1 Hz), 8.43 (d, 1, J ) 9.0 Hz), 8.58-8.63 (m, 2).
Anal. Calcd for C22H10O4: C, 78.10; H, 2.18. Found: 78.24;
H, 2.32.
7-Ch lor o-3,4,10,11-t e t r a m e t h oxyd ib e n z[a ,j]a n t h r a -
cen e (9b). Argon was bubbled through a solution of 8c (570
mg, 1.3 mmol), iodine (1.0 g, 3.9 mmol), and 1,2-epoxypropane
(50 mL) in 500 mL of ether, while the mixture was irradiated
with a Hanovia 450 W medium-pressure lamp through a Vycor
filter for 2 h. The reaction was monitored by TLC, and then
most of the solvent was removed under vacuum and the
product was purified by chromatography on a Florisil column.
Elution with CH2Cl2-hexane afforded 9b (120 mg, 21.4%) as
a white solid, mp 248-250 °C: 1H NMR δ 4.06 (s, 6), 4.08 (s,
6), 7.43 (d, 2, J ) 9.0 Hz), 8.18 (d, 2, J ) 9.6 Hz), 8.40 (d, 2, J
) 9.6 Hz), 8.68 (d, 2, J ) 9.0 Hz), 9.76 (s, 1). Anal. Calcd for
The crude product was dissolved in 100 mL of acetone, and
20 mL of 1 N HCl was added (both acetone and hydrochloric
acid were purged with argon for 30 min before use). The
solution was stirred at room temperature under argon for 1
h. Acetone was evaporated under reduced pressure, and the
residue was extracted with CH2Cl2. The usual workup and
chromatography on Florisil elution with hexane-CH2Cl2 af-
forded pure 12 as a white solid (2.5 g, 36%): 1H NMR δ 1.64-
1.72 (m, 2), 2.14-2.24 (m, 2), 2.41-2.90 (m, 12), 6.99 (s, 1),
7.01 (d, 2, J ) 7.5 Hz), 7.20 (t, 1, J ) 7.5 Hz). Anal. Calcd for
C
26H21O4Cl: C, 72.14; H, 4.89; Cl, 8.19. Found: C, 72.13; H,
4.91; Cl, 8.27.
3,4,10,11-Tetr a m eth oxyd iben z[a ,j]a n th r a cen e (9a ). To
a suspension of 9b (120 mg, 0.28 mmol) in THF under argon
was added NiCl2 (181 mg, 1.4 mmol), and the mixture was
stirred at ambient temperature for 20 min. To this was added
2.8 mL of a 1 M solution of LiAlH4 in THF (2.8 mmol). Gas
was evolved, and the solution turned black. The reaction was
monitored by TLC. After it was complete (∼1 h), the mixture
was quenched by addition of a small amount of distilled water
and stirred for an additional 20 min, and then the solution
was dried over MgSO4, filtered, and evaporated to dryness.
The crude product was dissolved in a small amount of CH2Cl2
and chromatographed on a silica gel column. Elution with 1:1
CH2Cl2-hexane yielded 9a (100 mg, 91%) as a white solid,
mp 255-256 °C: 1H NMR δ 4.05 (s, 6), 4.07 (s, 6), 7.42 (d, 2,
J ) 9.0 Hz), 7.85 (d, 2, J ) 9.3 Hz), 8.07 (d, 2, J ) 9.2 Hz),
8.30 (s, 1), 8.70 (d, 2, J ) 9.0 Hz), 9.80 (s, 1). Anal. Calcd for
C
22H26O4: C, 74.55; H, 7.39. Found: C, 74.55; H, 7.42.
3,11-Dih yd r oxyd iben z[a ,j]a n th r a cen e (14a ). A mixture
of 12 (2.51 g, 7.08 mmol) in 4.5 mL of methanesulfonic acid
and 50 mL of CH2Cl2 was stirred for 24 h. The usual workup
followed by chromatography on a silica gel column eluted with
hexane-CH2Cl2 gave 13 as a pale yellow solid (220 mg): 1H
NMR δ 2.20 (t, 4, J ) 7.5 Hz), 2.64 (t, 4, J ) 7.0 Hz), 2.78 (t,
4, J ) 8.0 Hz), 2.87 (t, 4, J ) 6.5 Hz), 3.02 (s, 4), 6.90 (s, 1),
7.00 (s, 1H). Compound 13 was used directly in the next step.
A mixture of 13, Pd/C (250 mg, 10%), and 50 mL of triglyme
was refluxed for 5 h, and then the reaction mixture was cooled
to room temperature and poured onto ice. The usual workup
and chromatography on silica gel eluted with CH2Cl2/EtOAc
gave 14a (154 mg, 70% for the two steps) as white solid, mp
281-283 °C: 1H NMR (acetone-d6) δ 7.31 (dd, 2, J ) 2.5, 8.8
Hz), 7.34 (d, 2, J ) 2.5 Hz), 7.64 (d, 2, J ) 9.0 Hz), 7.86 (d, 2,
J ) 9.0 Hz), 8.38 (s, 1H), 8.78 (s, 1.2, exchangeable with D2O),
9.09 (d, 2, J ) 8.8 Hz), 9.97 (s, 1).
C
26H22O4: C, 78.37; H, 5.57. Found: C, 78.27; H, 5.61.
3,4,10,11-Tetr a h yd r oxy- a n d 3,4,10,11-Tetr a a cetoxy-
d iben z[a ,j]a n th r a cen e (9c,d ). To a stirred solution of 9a
(120 mg, 0.3 mmol) in 100 mL of CH2Cl2 was added 6 mL of a
1 M solution of BBr3 in CH2Cl2. When TLC showed the
reaction to be complete (1 h), it was quenched by the addition
of water. The solvent was removed by evaporation, and the
precipitate was dried to furnish 9c (100 mg, 97%) which,
because of its air sensitivity, was used directly in the next step.
A solution of 9c (100 mg, 0.30 mmol) in 4.5 mL of Ac2O and
0.5 mL of pyridine was stirred at room temperature under
argon for 16 h, and then 9d (150 mg) was precipitated by the
addition of ice-water, filtered out, and chromatographed on
a Florisil column eluted with CH2Cl2. Trituration with 1%
CH2Cl2 in ether gave pure 9d (102 mg, 65%), mp 289-290 °C:
1H NMR (500 MHz) δ 2.37 (s, 6), 2.48 (s, 6), 7.53 (d, 2, J ) 8.9
Hz), 7.67 (d, 2, J ) 9.1 Hz), 7.81 (d, 2, J ) 9.3 Hz), 8.25 (s, 1),
8.76 (d, 2, J ) 9.0 Hz), 9.74 (s, 1). Anal. Calcd for C30H22O8:
C, 70.58; H, 4.34. Found: C, 70.49; H, 4.37.
Compound 14a was further characterized by conversion to
its diacetate 14b, white solid, mp 252-254 °C: 1H NMR δ 2.41
(s, 6), 7.49 (dd, 2, J ) 2.4, 8.9 Hz), 7.65 (d, 2, J ) 2.3 Hz), 7.69
(d, 2, J ) 9.0 Hz), 7.88 (d, 2, J ) 9.0 Hz), 8.35 (s, 1), 8.97 (d,
2, J ) 8.9 Hz), 9.88 (s, 1); MS m/e 394 (M+, 45), 310 (100);
HRMS calcd for C26H18O4 394.1205, found 394.1198.
11-Hyd r oxyd iben z[a ,j]a n th r a cen e-3,4-d ion e (15).
A
solution of 14a (45.0 mg, 0.15 mmol) in 10 mL of benzene was
added with 2 drops of Adogen 464 and Fremy’s salt (374 mg,
1.45 mmol in 10 mL of 0.167 M KH2PO4 buffer). The reaction
mixture was stirred with O2 bubbled through for 2 h. The
precipitate was collected, washed with water and Et2O, and
dried. Compound 15 (40 mg, 85%) was obtained as a black
solid, mp 218-220 °C: 1H NMR (DMSO-d6) δ 6.57 (d, 1, J )
10.5 Hz), 7.20 (d, 1, J ) 8.5 Hz), 7.22 (s, 1), 7.68 (d, 1, J ) 9.0
Hz), 7.79 (d, 1, J ) 9.0 Hz), 7.94 (d, 1, J ) 8.6 Hz), 8.17 (d, 1,
tr a n s-3,4-tr a n s-10,11-Tetr a h yd r oxy-3,4,10,11-tetr a h y-
d r od iben z[a ,j]a n th r a cen e (5). Reduction of 9d (90 mg, 0.18
mmol) with NaBH4 (800 mg) was carried out by the procedure
employed for the reduction of 10c. When TLC showed reaction