Synthesis of Carbazoles
J . Org. Chem., Vol. 66, No. 25, 2001 8615
205 °C (lit.16 198-199 °C). 2-Ch lor o-9H-ca r ba zole (3c): mp
242-244 °C (lit.17 241 °C). 4-Ch lor o-9H-ca r ba zole (4c): mp
94-95 °C (lit.17 95 °C). 1-Br om o-9H-ca r ba zole (3d ): mp
110-111 °C (lit.18 111-112 °C). 3-Met h yl-9H -ca r b a zole
(3e): mp 204-206 °C (lit.19 207-208 °C). 2-Meth yl-9H-
ca r ba zole (3f): mp 269-274 °C (lit.19 264-266 °C). 1,4-
Dim eth yl-9H-ca r ba zole (3g): mp 97-98 °C (lit.19 98.2-98.3
°C). N-(Bip h en yl-4-yl)-N-p h en yla m in e (4a ): mp 113 °C
(lit.20 112 °C).
Gen er al P r ocedu r e: Reaction of N-(N,N-Diar ylam in o)-
p h th a lim id es (1) w ith AlCl3. Meth od A. To a solution of 1
(1 mmol) in benzene (10 mL) was added AlCl3 (5 equiv) at room
temperature, and the progress of the reaction was monitored
by TLC. When TLC indicated the disappearance of starting
material, the reaction was quenched with 10% NaOH under
ice cooling, and the aqueous layer was extracted with EtOAc.
The organic layer was washed with brine, dried over Na2SO4,
filtered, and concentrated. Purification by column chromatog-
raphy over silica gel (n-hexane/EtOAc ) 5:1-2:1) afforded the
corresponding products.
δ 20.26, 21.19, 103.70, 111.18, 112.81, 116.87, 118.61, 119.44,
119.49, 124.10, 124.76, 125.59, 128.09, 128.76, 129.21, 130.41,
131.20, 133.02, 133.26, 135.56, 136.80, 138.59, 138.63, 141.09;
EI-MS m/z 522 (M+ + 2, 51.7), 520 (M+, 100), 518 (50.5), 260
(10.4). Anal. Calcd for C26H20N2Br2: C, 60.02; H, 3.87; N, 5.38.
Found: C, 59.89; H, 3.82; N, 5.11.
8,8′-Dibr om o-6,6′-d im eth yl-9H,9′H-[3,3′]bica r ba zoyl (9).
White solid: mp 260-268 °C; IR (KBr) 3420, 1570, 1510, 1300
cm-1; 1H NMR (DMSO-d6) δ 2.50 (s, 6H), 7.48 (s, 2H), 7.64 (d,
J ) 8.6 Hz, 2H), 7.85 (dd, J ) 8.6, 2.0 Hz, 2H), 8.07 (s, 2H),
8.51 (s, 2H), 11.33 (br s, 2H); 13C NMR (CDCl3) δ 20.57, 103.09,
111.80, 118.47, 119.64, 123.09, 124.47, 125.44, 128.79, 129.13,
132.54, 136.76, 139.15; EI-MS m/z 520 (M+ + 2, 51.7), 518 (M+,
100), 516 (50.8), 439 (8.8), 437 (10.6), 357 (8.4), 259 (9.0), 218
(7.3), 179 (12.9); HR-MS (FAB) m/z for C26H18N2Br2 calcd
515.9836, found 515.9841.
Rea ction of N-[N-(2-Br om o-4-m eth ylp h en yl)-N-p h en yl-
a m in o]p h th a lim id e (1i) w ith AlCl3. Meth od C. A solution
of 1i (0.600 g, 1.47 mmol) in 1,2-dichloroethane (10 mL) was
added dropwise to a mixture of AlCl3 (2.79 g, 22.1 mmol) and
1,2-dichloroethane (700 mL) over 40 min at room temperature.
After the mixture was stirred for 20 min, the reaction was
quenched with 10% NaOH under ice cooling. The organic layer
was washed with brine (2 × 100 mL), dried over Na2SO4,
filtered, and concentrated. Purification by column chromatog-
raphy over silica gel (n-hexane/THF ) 10:1) afforded 3i (0.199
g, 52%) as a white solid: mp 71-72 °C (n-hexane); IR (KBr)
Meth od B. To a mixture of AlCl3 (5 equiv) and 1,2-
dichloroethane (10 mL) was added dropwise a solution of 1 (1
mmol) in 1,2-dichloroethane (2 mL) at room temperature, and
the progress of the reaction was monitored by TLC. When TLC
indicated the disappearance of starting material, the reaction
was quenched with 10% NaOH under ice cooling, and the
aqueous layer was extracted with CH2Cl2. The organic layer
was washed with brine, dried over Na2SO4, filtered, and
concentrated. Purification by column chromatography over
silica gel (n-hexane/EtOAc ) 5:1-2:1) afforded the correspond-
ing products.
1
3400, 2920, 1620, 1570, 1500 cm-1; H NMR (CDCl3) δ 2.51
(s, 3H), 7.20-7.28 (m, 1H), 7.38-7.50 (m, 3H), 7.80 (s, 1H),
8.01 (d, J ) 7.7 Hz, 1H), 8.15 (br s, 1H); 13C NMR (CDCl3) δ
21.15, 103.59, 110.97, 119.36, 119.81, 120.71, 123.51, 124.61,
6-Br om o-1,4-dim eth yl-9H-car bazole (3h ).21 Colorless crys-
tals: mp 137-138 °C (EtOAc/n-hexane); IR (KBr) 3400, 1590,
126.34, 129.04, 130.29, 136.32, 139.40; EI-MS m/z 261 (M+
+
2, 96.4), 259 (M+, 100), 180 (68.8), 152 (11.1), 90 (15.9). Anal.
Calcd for C13H10NBr: C, 60.02; H, 3.87; N, 5.38. Found: C,
60.07; H, 3.87; N, 5.21.
1
1460 cm-1; H NMR (CDCl3) δ 2.53 (s, 3H), 2.82 (s, 3H), 6.95
(d, J ) 7.7 Hz, 1H), 7.16 (d, J ) 7.3 Hz, 1H), 7.36 (d, J ) 8.1
Hz, 1H), 7.50 (dd, J ) 8.4, 1.8 Hz, 1H), 8.10 (br s, 1H), 8.26 (s,
1H); 13C NMR (CDCl3) δ 16.50, 20.38, 111.78, 112.12, 117.17,
120.47, 121.21, 125.03, 126.15, 126.82, 127.64, 130.98, 137.89,
139.11; EI-MS m/z 275 (M+ + 2, 99.9), 273 (M+, 100), 260
(16.4), 194 (28.8). Anal. Calcd for C14H12NBr: C, 61.33; H, 4.41;
N, 5.11. Found: C, 61.54; H, 4.36; N, 4.99.
1-Meth oxy-3-m eth yl-9H-ca r ba zole (Mu r r a ya folin e A)
(10). DMF (10 mL), CuI (95%, 0.373 g, 1.86 mmol), and 3i
(0.242 g, 0.930 mmol) were added to a solution of metallic
sodium (0.214 g, 18.6 mmol) in absolute MeOH (2.5 mL). The
reaction mixture was refluxed (oil bath temperature ) 120 °C)
for 3 h under an argon atmosphere. After the reaction, EtOAc
(40 mL) was added to the reaction mixture and the insoluble
materials were filtered through Celite and washed with EtOAc.
The filtrate was washed with brine, dried over Na2SO4,
filtered, and concentrated. The residue was chromatographed
on a column of silica gel using 10:1 n-hexane/EtOAc to give
10 (0.181 g, 92%) as a white powder: mp 51-53 °C (n-hexane)
(lit.22 52-54 °C); IR (KBr) 3425, 1600, 1510, 1460, 1310, 1235
N-(Bip h en yl-4-yl)-N-(4-ch lor op h en yl)a m in e (4b). White
solid: mp 119-120 °C (n-hexane); IR (KBr) 3430, 1610, 1500
cm-1 1H NMR (CDCl3) δ 6.98-7.18 (m, 4H), 7.19-7.36 (m,
;
3H), 7.42 (t, J ) 7.5 Hz, 2H), 7.48-7.62 (m, 4H); 13C NMR
(CDCl3) δ 118.08, 119.05, 125.72, 126.54, 126.71, 128.06,
128.75, 129.32, 134.26, 140.68, 141.59, 142.04; EI-MS m/z 281
(M+ + 2, 33.5), 279 (M+, 100), 243 (11.9). Anal. Calcd for C18H14
-
NCl: C, 77.28; H, 5.04; N, 5.01. Found: C, 77.22; H, 5.03; N,
5.01.
cm-1 1H NMR (CDCl3) δ 2.53 (s, 3H), 4.00 (s, 3H), 6.74 (s,
;
1H), 7.20 (t, J ) 7.8 Hz, 1H), 7.34-7.46 (m, 2H), 7.47 (s, 1H),
8.02 (d, J ) 7.9 Hz, 1H), 8.15 (br s, 1H). EI-MS m/z 211 (M+,
100), 196 (71.7), 168 (37.5), 167 (27.0).
N-[4-(8-Br om o-6-m et h yl-9H -ca r b a zol-3-yl)p h en yl]-N-
(2-br om o-4-m eth ylp h en yl)a m in e (8). Colorless crystals:
mp 167-168 °C (EtOAc/n-hexane); IR (KBr) 3430, 2920, 1610,
1530, 1330 cm-1; 1H NMR (CDCl3) δ 2.28 (s, 3H), 2.51 (s, 3H),
5.98 (br s, 1H), 7.02 (d, J ) 8.3 Hz, 1H), 7.13-7.28 (m, 3H),
7.34-7.42 (m, 2H), 7.48 (d, J ) 8.3 Hz, 1H), 7.57-7.68 (m,
3H), 7.83 (s, 1H), 8.14 (s, 1H), 8.17 (s, 1H); 13C NMR (CDCl3)
N-(4-Br om op h en yl)-N-(2,5-d im eth ylp h en yl)a m in e (11).
Pale yellow oil: IR (neat) 3400, 1590, 1490, 1320 cm-1 1H
;
NMR (CDCl3) δ 2.19 (s, 3H), 2.27 (s, 3H), 5.31 (br s, 1H), 6.74-
6.82 (m, 3H), 7.01 (s, 1H), 7.09 (d, J ) 7.7 Hz, 1H), 7.31 (d, J
) 8.8 Hz, 1H); 13C NMR (CDCl3) δ 17.40, 21.70, 111.75, 118.41,
120.53, 123.66, 126.17, 130.86, 132.05, 136.56, 140.21, 143.52;
EI-MS m/z 277 (M+ + 2, 98.5), 275 (M+, 100), 194 (27.9), 181
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(17) Rosa, M. D.; P., A. Q.; Dodsworth, D. J . J . Org. Chem. 1987,
52, 173.
(23.2); HR-MS m/z for
C14H14NBr calcd 275.0307, found
275.0310.
(18) Barclay, B. M.; Campbell, N. J . Chem. Soc. 1945, 530.
(19) Kuroki, M.; Tsunashima, Y. J . Heterocycl. Chem. 1981, 18, 709.
(20) Piccard, J . J . Am. Chem. Soc. 1926, 48, 2878.
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J .-F.; Le Talaer, J .-Y.; Rault, S.; Robba, M. Eur. J . Med. Chem. 1989,
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