Substituted 3-(Aryl)- and 3-(Heteroaryl)indoles
247
of anhydrous ZnCl2 in dry ether (1.0 M) were added and stirred at room temp for 30 min. There-
after, 2.6 g 13 (10 mmol) were added to the reaction mixture, which was further stirred at room
temp for 4 h. The resulting mixture was then treated with 100 cm3 H2O and stirred for 15 min. The
ether layer was separated and the aqueous layer was extracted with ether (3ꢃ50 cm3). The com-
bined ethereal portions were dried (Na2SO4), and the solvent was evaporated. The residual solid
product was collected and recrystallized from CHCl3=petroleum ether (bp 60–80ꢂC) to afford 10
as yellow solid. Yield 1.6 g, (47%); mp 196–197ꢂC; MS-EI: m=z (%) ¼ 341 (Mþ, 100), 310 (8),
295 (16), 266 (7), 235 (12), 206 (18), 179 (20), 151 (13), 119 (9), 95 (23); HRMS: calcd for Mþ
1
341.0647, found 341.06554; H NMR (300 MHz, CDCl3): ꢁ ¼ 4.04 (s, CH3), 7.16 (dd, J ¼ 7.0,
7.5 Hz, H-5), 7.23 (d, J ¼ 7.0 Hz, H-4), 7.27 (dd, J ¼ 7.5, 8.2 Hz, H-6), 7.40 (d, J ¼ 2.8 Hz, H-2),
7.42 (d, J ¼ 8.2 Hz, H-7), 8.54 (br s, N-H), 8.59 (s, H-30 þ H-50) ppm; 13C NMR (75 MHz,
CDCl3): ꢁ ¼ 53.4 (OCH3), 104.9 (C-3), 111.9 (C-7), 118.1 (C-4), 121.5 (C-5), 123.6 (C-6),
124.8 (C-2), 125.8 (C-3a), 127.0 (C-30 þ C-50), 127.5 (C-10), 130.7 (C-40), 151.8 (C-20 þ C-60),
163.2 (C¼O) ppm.
3-(2,6-Diamino-4-methoxycarbonylphenyl)indole (11, C16H15N3O2)
Sodium borohydride (1.9 g, 40 mmol) was added portionwise to a stirred solution of 1.65 g 10
(5 mmol) in 60 cm3 MeOH at room temp and mixed with 20 cm3 of a saturated aqueous solution of
copper acetate, whereby the reduction was completed within 4–6 h. The resulting mixture was then
treated with 100 cm3 ether and washed with 10% aqueous Na2CO3 solution. The ether layer was
separated, and the aqueous layer was extracted with diethyl ether (2ꢃ40 cm3). The combined ether
fractions were dried (Na2SO4), and the solvent was then removed. The residual solid product was
collected and recrystallized from CH2Cl2=petroleum ether (bp 40–60ꢂC) to afford bright red
needles. Yield 1.1 g (76%); mp 192–193ꢂC; MS-EI: m=z (%) ¼ 281(Mþ, 100), 250 (7), 222
(14), 205 (7), 193 (3), 166 (13), 149 (10), 125 (8), 111 (28), 97 (18); HRMS: calcd for Mþ
1
281.116405, found 281.118015; H NMR (300 MHz, DMSO-d6): ꢁ ¼ 3.79 (s, OCH3), 4.49 (br s,
2NH2), 6.69 (s, H-30 þ H-50), 6.98 (dd, J ¼ 7.3, 7.7 Hz, H-5), 7.13 (dd, J ¼ 7.3, 7.8 Hz, H-6), 7.17
(d, J ¼ 7.7 Hz, H-4), 7.37 (br d, J ¼ 2.0 Hz, H-2), 7.45 (d, J ¼ 7.8 Hz, H-7), 11.37 (br s, N–H) ppm;
13C NMR (75 MHz, DMSO-d6): ꢁ ¼ 52.1 (OCH3), 104.4 (C-30=C-50), 107.9 (C-3), 109.4 (C-10),
112.3 (C-7), 119.3 (C-4), 119.8 (C-5), 121.9 (C-6), 125.5 (C-2), 126.1 (C-3a), 129.4 (C-40), 137.2
(C-7a), 147.9 (C-20=C-60), 167.7 (C¼O) ppm.
3-(2-Amino-4-trifluoromethyl-6-nitrophenyl)indole (9, C15H10F3N3O2)
An aqueous solution of sodium polysulfide was freshly prepared according to Ref. [9]: A solution
of 2.7 g crystalline Na2Sꢄ9H2O (11 mmol) in 10 cm3 H2O was treated with 0.65 g finely powdered
S8 (20 mmol) and warmed until a clear solution was produced. A stirred mixture of 3.5 g 7 [7]
(10 mmol), 15 cm3 H2O, and 10 cm3 EtOH was brought to gentle boiling in a beaker. To this
solution was dropwise added the freshly prepared aqueous solution of Na2SxꢄnH2O, and the
resulting reaction mixture was vigorously stirred and boiled for further 20 min. The resultant
mixture was cooled, filtered, and the filtrate was acidified with 13 cm3 20% aqueous HCl and
boiled for 15 min. The reaction mixture was filtered, cooled, and basified with an excess of 25%
aqueous NH3. The precipitated solid was collected and recrystallized from aqueous EtOH in the
form of fine orange needles. Yield 2.3 g (72%); mp 243–245ꢂC; MS-EI: m=z (%) ¼ 321 (Mþ, 100),
304 (23), 302 (6), 275 (49), 274 (56), 247 (25), 226 (5), 206 (18), 178 (5), 152 (7), 137 (11), 127
1
(7), 113 (6), 103 (7); HRMS: calcd for Mþ 321.072479, found 321.075226; H NMR (300 MHz,
DMSO-d6): ꢁ ¼ 4.33 (br s, NH2); 6.59 (dd, J ¼ 7.6, 7.8 Hz, H-5), 6.66 (d, J ¼ 7.8 Hz, H-4), 7.02 (m,
H-6 þ H-7), 7.92 (br d, J ¼ 2.0 Hz, H-2), 8.01 (br s, H-30), 8.18 (br s, H-50), 12.51 (br s, N1–H) ppm;
13C NMR (75 MHz, CDCl3): ꢁ ¼ 112.9 (q, 3JC-F ¼ 3.7 Hz, C-30), 114.0 (C-3), 114.7 (C-7), 114.8 (q,
3JC-F ¼ 3.8 Hz, C-50), 116.3 (C-4), 119.8 (C-10), 120.5 (C-3a), 120.7 (q, 2JC-F ¼ 34 Hz, C-40), 124.8
1
(q, JC-F ¼ 254 Hz, CF3), 128.0 (C-5), 129.9 (C-6), 133.7 (C-2), 136.8 (C-7a), 143.1 (C-20), 147.4
(C-60) ppm.