Intramolecular Cyclizations via Arylnitrenium Ions
J . Org. Chem., Vol. 64, No. 16, 1999 5911
1-(3-Meth oxyph en yl)-2-(4-n itr oph en yl)eth an e (10). Acid
9 (4.06 g, 0.013 mol) was dissolved in quinoline (19 mL), and
copper chromite (0.359 g) was added. The mixture was heated
under reflux in an oil bath kept at 210-220 °C for 1.5 h. The
mixture was cooled, treated with 10% HCl (63 mL), and stirred
for 1 h. The aqueous solution was extracted with diethyl ether
and the combined organic layers were washed with 10% HCl
(20 mL) and water and dried (MgSO4). Silica gel (40-140
mesh) column chromatography of the crude product (petroleum
ether/EtOAc 95:5, v/v) gave 10 (2.05 g, 59%) as a pale yellow
(trifluoroacetate) (39 mg) was then added and stirring contin-
ued at -10 °C for 2 h. The temperature was gradually raised
to 0 °C and kept there for 3 h. The solution was then
transferred to a separating funnel with the help of toluene,
washed with water, and dried (MgSO4). Filtration and evapo-
ration of the solvent gave a crude product (39 mg). GC/MS
suggested that the main product could be 16: m/z 435 (M•+),
344, 328, 286, 238, 196, 132, 91 (see the Results and Discus-
sion).
If the reaction was carried out in carbon tetrachloride
solution, unchanged 12 was recovered, even after the reaction
time at 0 °C was extended to 7 h.
solid: mp 48-49 °C; GC-MS (70 eV) m/z 257 (M•+). Anal.
Calcd for C15H15NO3: C, 70.01; H, 5.89. Found: C, 69.93; H,
5.89.
1-(3-Ben zyloxyp h en yl)-2-(4-a zid op h en yl)et h a n e (17).
Amine 15 (74 mg, 0.24 mmol) was dissolved in warm dilute
HCl (0.5 mL concentrated HCl and 2.5 mL of H2O) with
heating. The mixture was cooled in ice and treated with
NaNO2 (28 mg) in H2O (1.8 mL). After being stirred for 1 h,
NaN3 (28 mg) in H2O (1.8 mL) was added to the mixture and
the solution was stirred for 4 h. Extraction with ethyl acetate,
washing the combined extracts with water, drying (MgSO4),
filtration, and evaporation yielded 17 (74.5 mg, 93%) as a white
solid: mp 74-75 °C; IR (NaCl) 2100 (N3) (s), 1285 (N3); GC-
1-(3-H yd r oxyp h en yl)-2-(4-n it r op h en yl)et h a n e
(11).
Methyl ether 10 (0.79 g, 3.07 mmol) was dissolved in a mixture
of glacial acetic acid (33 mL) and 48% aqueous HBr (33 mL).
The resulting solution was boiled under reflux for 3.5 h. The
solvent was removed in vacuo, and the residue was dissolved
in diethyl ether (100 mL). The organic layer was washed with
saturated aqueous NaHCO3 solution and then with water and
then dried (MgSO4). The ether solution was filtered, and the
solvent was removed in vacuo to give 11 (0.73 g, 98%) as a
pale yellow solid: mp 123-124 °C; IR (KBr) 3460 (bs) (OH),
1518 (NO2) (s), 1345 (NO2) cm-1 (s); GC-MS (70 eV) m/z 243
MS (70 eV) m/z 329 (M•+). Anal. Calcd for C21H19N3O: C,
76.56; H, 5.83. Found: C, 76.33; H, 5.79.
2-Ben zyloxy-6-tr iflu or oacetam ido-9,10-dih ydr oph en an -
th r en e (19). Azide 17 (106 mg, 0.32 mmol) was dissolved in
(M•+). Anal. Calcd for C14H13NO3: C, 69.11; H, 5.40. Found:
C, 68.92; H, 5.42.
1-(3-Ben zyloxyph en yl)-2-(4-n itr oph en yl)eth an e (4). Com-
pound 11 (0.60 g, 2.47 mmol) was added to a mixture of acetone
(10 mL) and anhydrous K2CO3 (1.69 g). Benzyl bromide (0.52
mL) was added to the suspension, and the resulting mixture
was boiled under reflux for 24 h. The mixture was filtered,
and the solvent was removed in vacuo. The crude product was
subjected to bulb-to-bulb distillation (0.6 mmHg, 100 °C) to
remove excess benzyl bromide, giving 4 (0.83 g, 100%) as a
pale yellow solid: mp 72-73 °C; IR (KBr) 1512 (NO2) (s), 1342
(NO2) (s), 745 (m) (Ph), 695 cm-1 (m) (Ph); 1H NMR (CDCl3) δ
8.14 (d, 2H, J ) 8.6 Hz) (2H ortho to NO2), 7.43-7.30 (m, 5H)
(2H ortho to OCH2), 7.26 (d, 2H, J ) 8.6 Hz) (2H meta to NO2),
7.21-7.16 (t, 1H) (H meta to CH2O), 6.84-6.71 (m, 3H) (3H
ortho and para to CH2O), 5.03 (s, 2H) (OCH2), 3.03-2.99 (m,
carbon tetrachloride (10 mL) at 0 °C under
a nitrogen
atmosphere. Trifluoroacetic acid (2 mL) was then added
dropwise to the solution, which was stirred at 0 °C for 1 h
and then at room temperature for 24 h. Trifluoroacetic
anhydride (2 mL) was added, and stirring was continued for
another 24 h. The solution was then washed with water and
dried (Na2SO4). Column chromatography of the crude product
on neutral alumina (20 g, column length 10") (hexane/EtOAc
9:1, v/v), followed by recrystallization from EtOH gave 19 (59.2
mg, 46.3%) as white solid: mp 164-165 °C; IR (KBr) 3278
(NH) (m), 1705 (CO) cm-1 (s); 19F NMR (CDCl3) δ -79.8; H
1
NMR (CDCl3) δ 7.94 (bs, 1H), 7.89 (d, 1H, J ) 2.1 Hz), 7.66
(d, 1H, J ) 8.5 Hz), 7.47-7.33 (m, 6H), 7.23 (d, 1H, J ) 8.1
Hz), 6.95-6.91 (m, 1H), 6.88 (d, 1H, J ) 2.6 Hz), 5.10 (s, 2H),
2H), 2.94-2.89 (m, 2H); GC-MS (70 eV) m/z 333 (M•+). Anal.
Calcd for C21H19NO3: C, 75.65; H, 5.76. Found: C, 75.61; H,
5.82.
2.85 (s, 4H); GC-MS (70 eV) m/z 397 (M•+). Anal. Calcd for
C
23H18F3NO: C, 69.50; H, 4.57. Found: C, 69.36; H, 4.64. Two
additional products were detected by GC-MS: the trifluoro-
1-(3-Ben zyloxyp h en yl)-2-(4-a m in op h en yl)eth a n e (15).
Nitro compound 4 (0.79 g, 2.37 mmol) was dissolved in
methanol (39 mL) containing hydrazine hydrate (1.55 mL). A
suspension of Raney Ni (ethanol) (0.4 mL) was added dropwise,
and the suspension was stirred and boiled under reflux for
1.5 h. After filtration, the solvent was removed in vacuo, and
the residue was dissolved in diethyl ether. The organic layer
was washed with water and dried (MgSO4). Filtration and
evaporation gave the crude product, which was recrystallized
from diethyl ether to give 15 (0.75 g, 99%) as a white solid:
mp 73-74 °C; IR (KBr) 3435 (NH2) (w), 3330 (NH2) cm-1 (m);
1H NMR (CDCl3) δ 7.43-7.34 (m, 5H), 7.22-7.17 (t, 1H), 6.98
(d, 2H, J ) 8.3 Hz), 6.82-6.80 (m, 3H), 6.63 (d, 2H, J ) 8.3
Hz), 5.04 (s, 2H), 3.56 (bs, 2H), 2.82 (s, 4H); GC-MS (70 eV)
acetylated hydrogen-abstraction product 18 (17%), GC-MS (70
eV) m/z 399 (M•+), and a product to which structure 20 or 21
is assigned (<1%), GC-MS (70 eV) m/z 397 (M•+), 210, 182,
165, 89.
1-(2-B r o m o -5-m e t h o x y )p h e n y l-2-(4-n it r o p h e n y l)-
eth a n e (26). Methyl ether 10 (0.75 g, 0.29 mmol) was
dissolved in acetonitrile (15 mL). N-Bromosuccinimide (0.54
g) was then added. The solution was stirred at room temper-
ature and monitored by TLC until the starting material had
disappeared (6 h). The solvent was then evaporated under
vacuum, and the crude product was repeatedly extracted with
small amounts of diethyl ether to afford pure 26 as a pale
yellow solid (97%): mp 80-81 °C; IR (KBr) 1508 (NO2) (s),
1335 (NO2) cm-1 (s); 1H NMR (CDCl3) δ 8.15 (d, 2H, J ) 8.65
Hz), 7.44 (d, 1H, J ) 9.49 Hz), 7.35 (d, 2H, J ) 8.64 Hz), 6.64-
6.68 (m, 2H), 3.74 (s, 3H), 3.01 (s, 4H); 13C NMR (CDCl3) δ
158.94, 149.04, 146.52, 140.68, 133.47, 129.37, 123.66, 116.28,
m/z 303 (M•+). Anal. Calcd for C21H21NO: C, 83.12; H, 6.99.
Found: C, 82.88; H, 7.03.
1-(3-Ben zyloxyp h en yl)-2-(4-a cet a m id op h en yl)et h a n e
(12). Triethylamine (0.4 mL) and acetyl chloride (0.15 g, 2.36
mmol) were added to 15 (0.21 g, 0.69 mmol) in methylene
chloride (4 mL) and the solution stirred at room temperature
for 4 h, transferred to a separating funnel, washed with 5%
aqueous NaHCO3 and then water, and dried (MgSO4). The
solvent was evaporated, and the crude product was recrystal-
lized (ethanol) giving pure 12 as a white solid (89%): mp 90-
91.5 °C; IR (Nujol) 3345 (NH) (w), 1658 (CO) cm-1 (s); GC-
1
114.72, 113.54, 55.41, 37.94, 35.92, 29.56; H-13C DEPT five
quaternary C's (δ 158.94, 149.04, 146.52, 140.68, 114.72); five
tertiary C's (δ 133.47, 129.37, 123.66, 116.28, 113.54); two
secondary C’s (δ 37.94, 35.92); one primary C (δ 55.41); 1D
NOE NOE (5%) between the peak at δ 3.74 and the peaks at
δ 6.64-6.68; GC-MS (70 eV) m/z 335 (337) (M•+), 256, 199
(201). Anal. Calcd for
C15H14BrNO3: C, 53.58; H, 4.21.
MS (70 eV) m/z 345 (M•+). Anal. Calcd for C23H23NO2: C,
79.96; H, 6.72. Found: C, 79.72; H, 6.76.
Attem p ted N-Oxid a tion of 12. To the solution of 12 (23
mg, 0.067 mmol) in toluene (5.6 mL) under N2 was added
sodium hydride (3 mg) at 0 °C. The mixture was cooled to -10
°C and stirred for 30 min. Pentafluorophenyliodine(III) bis-
Found: C, 53.45; H, 4.18.
1-(2-B r o m o -5-h y d r o x y )p h e n y l-2-(4-n it r o p h e n y l)-
eth a n e (27). A 50 mL three-necked, round-bottomed flask
equipped with a nitrogen inlet adapter, a rubber stopper, and
a pressure-equalizing dropping funnel was charged with a
solution of methyl ether 26 (0.86 g, 2.56 mmol) in methylene