10.1002/ejoc.201900772
European Journal of Organic Chemistry
FULL PAPER
1-Phenyl-2-(trifluoromethyl)-1H-indole (2j): Following the general
procedure A, 2j was obtained as a light-yellow crystalline solid from
2.793 g of 2,2,2-trifluoro-N-phenyl-N-o-tolylacetamide (1j). Yield: 1.899 g
(73%). MP 54-57 °C (lit. 53 °C).[25b] 1H NMR (600 MHz, Chloroform-d) δ
7.75 (d, J = 7.9 Hz, 1H), 7.57 – 7.52 (m, 3H), 7.45 – 7.42 (m, 2H), 7.29 (t,
J = 7.6 Hz, 1H), 7.26 – 7.22 (m, 1H), 7.14 – 7.12 (m, 1H), 7.10 – 7.08 (m,
1H). 13C{1H} NMR (151 MHz, Chloroform-d) δ 140.2 , 137.1 , 129.5 ,
129.1 , 128.7 , 128.5 (q, J = 37.3 Hz), 125.8 , 125.0 , 122.2 , 121.5 ,
121.4 (q, J = 268.7 Hz), 111.4 , 105.9 (q, J = 3.7 Hz). 19F NMR (188 MHz,
Chloroform-d) δ -59.0 . The 1H, 13C NMR spectra were identical to the
previously reported in the literature.[25b]
of aqueous HCl with subsequent passing through a pad of silica,
corresponding 1-(1-adamantyl)-2-(2-(phenylamino)phenyl)ethanone (2n’)
in mixture with 1-phenyl-2-(1-adamantyl)-1H-indole (2n) was observed in
1H NMR spectrum in 1:1.8 ratio. 1H NMR (600 MHz, Chloroform-d) δ 7.40
(s, 1H), 7.26 – 7.22 (m, 2H), 7.22 – 7.13 (m, 2H), 7.00 – 6.93 (m, 4H),
6.87 (t, J = 7.1 Hz, 1H), 3.84 (s, 2H), 2.10 (s, 3H), 1.91 (s, 6H), 1.80 (d, J
= 12.6 Hz, 3H), 1.73 (d, J = 12.5 Hz, 3H).
2-tert-Butyl-1-phenyl-1H-indole (2o): Following the general procedure
A, 2o was obtained as a white crystalline solid from 2.673 g of N-phenyl-
N-o-tolylpivalamide (1o). Yield: 2.478 g (>99%). Following the general
procedure D, 2-tert-butyl-1-phenyl-1H-indole (2o) was obtained as a
white crystalline solid from 1.833 g of 2-methyl-N-phenylaniline (7a) and
1.206 g of pivaloyl chloride. Yield: 2.344 g (94%). MP 74-76 °C. 1H NMR
(600 MHz, Chloroform-d) δ 7.60 (d, J = 7.7 Hz, 1H), 7.55 – 7.50 (m, 3H),
7.43 – 7.38 (m, 2H), 7.11 (t, J = 7.4 Hz, 1H), 7.07 – 7.03 (m, 1H), 6.67 (d,
J = 8.1 Hz, 1H), 6.50 (s, 1H), 1.29 (s, 9H). 13C{1H} NMR (151 MHz,
Chloroform-d) δ 150.8 , 141.0 , 140.4 , 130.9 , 129.1 , 128.7 , 127.0 ,
121.3 , 119.9 , 119.7 , 110.3 , 99.3 , 33.4 , 31.2 . The 1H, 13C NMR
spectra were identical to the previously reported in the literature.[32]
1-(2-Methoxyphenyl)-2-(trifluoromethyl)-1H-indole (2k): Following the
general procedure A, 2k was obtained as a colorless oil from 3.091 g of
2,2,2-trifluoro-N-(2-methoxyphenyl)-N-o-tolylacetamide (1k). Yield: 2.364
g (81%). HRMS (APPI) calcd for C16H12F3NO [M+]: 291.0871, found:
291.0868. IR (KBr) 3060, 2966, 2947, 2842, 1599, 1556, 1507, 1465,
1414, 1318, 1271, 1194, 1162, 1121, 1046, 1026, 972, 808, 753, 674,
635, 445 cm-1. 1H NMR (600 MHz, Chloroform-d) δ 7.73 (d, J = 7.9 Hz,
1H), 7.51 (td, J = 8.3, 1.7 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 7.28 – 7.24
(m, 1H), 7.21 (td, J = 7.5, 7.1, 0.9 Hz, 1H), 7.13 – 7.06 (m, 4H), 6.98 –
6.93 (m, 1H), 3.70 (s, 2H). 13C{1H} NMR (151 MHz, CDCl3) δ 156.7,
139.8, 130.9, 130.7, 128.5 (q, J = 36.9 Hz), 125.6, 125.2, 124.7, 122.0,
121.3 (q, J = 268.5 Hz),121.1, 120.7, 118.6, 112.2, 111.2, 105.4 (q, J =
3.8 Hz), 55.8. 19F NMR (376 MHz, CDCl3) δ -59.2.
1-Cyclohexyl-2-phenyl-1H-indole (2p): Following the general
procedure A, 2p was obtained as a white crystalline solid from 2.934 g of
N-cyclohexyl-N-o-tolylbenzamide (1p). Yield: 1.246 g (45%). MP 105-
106 °C (lit. 104 °C).[7c] 1H NMR (600 MHz, Chloroform-d) δ 7.68 (d, J =
8.3 Hz, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.51 – 7.41 (m, 5H), 7.20 (t, J = 7.7
Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.49 (s, 1H), 4.23 (tt, J = 12.5, 3.8 Hz,
1H), 2.45 – 2.35 (m, 2H), 1.96 – 1.88 (m, 4H), 1.76 – 1.71 (m, 1H), 1.33 –
1.27 (m, 3H). 13C{1H} NMR (151 MHz, Chloroform-d) δ 141.7 , 136.0 ,
134.0 , 129.7 , 129.1 , 128.5 , 128.0 , 121.0 , 120.9 , 119.5 , 112.8 ,
102.4 , 56.5 , 31.6 , 26.4 , 25.7 . The 1H, 13C NMR spectra were identical
to the previously reported in the literature.[7c]
5-Methyl-1-phenyl-2-(trifluoromethyl)-1H-indole (2l): Following the
general procedure A, 2l was obtained as a yellow oil from 2.931 g of N-
(2,4-dimethylphenyl)-2,2,2-trifluoro-N-phenylacetamide (1l). Yield: 1.882
g (68%). HRMS (APPI) calcd for C16H12F3N [M+]: 275.0922, found:
275.0917. IR (KBr) 3030, 2923, 2862, 1598, 1556, 1500, 1415, 1304,
1271, 1221, 1204, 1166, 1120, 805, 761, 698 cm-1. 1H NMR (600 MHz,
Chloroform-d) δ 7.56 – 7.49 (m, 4H), 7.41 (d, J = 6.7 Hz, 2H), 7.11 (d, J =
8.5 Hz, 1H), 7.03 (s, 1H), 6.97 (d, J = 8.5 Hz, 1H), 2.48 (s, 3H). 13C{1H}
NMR (151 MHz, CDCl3) δ 138.5, 137.0, 130.8, 129.5, 129.0, 128.6,
128.2 (q, J = 36.9 Hz), 126.8, 125.9, 121.5, 121.4 (q, J = 268.4 Hz),
111.0, 150.4 (q, J = 3.8 Hz), 76.9, 21.5. 19F NMR (376 MHz, CDCl3) δ -
57.4.
N-Cyclohexyl-N-(2-(2-oxo-2-phenylethyl)phenyl)benzamide
(2p’):
This compound can be obtained as a byproduct during 2p synthesis after
the column chromatography step as yellow crystals. Yield: 1.071 g (54%).
MP 112-114 °C. HRMS (APCI) calcd for C27H27NO2 [M+H+]: 398.2120,
found: 398.2118. IR (KBr) 3064, 3031, 2934, 2856, 1693, 1630, 1599,
1578, 1494, 1446, 1377, 1364, 1326, 1263, 1214, 989, 893, 750, 738,
728, 709, 695, 686, 669, 652, 638, 583, 569 cm-1. 1H NMR (600 MHz,
DMSO-d6) δ 7.98 (d, J = 7.5 Hz, 2H), 7.67 (t, J = 7.2 Hz, 1H), 7.56 (t, J =
7.2 Hz, 2H), 7.39 – 7.01 (m, 9H), 4.38 (d, J = 17.5 Hz, 1H), 4.23 (d, J =
15.7 Hz, 1H), 4.08 (s, 1H), 1.99 (d, J = 11.7 Hz, 1H), 1.72 – 1.54 (m, 4H),
1.51 (d, J = 11.8 Hz, 1H), 1.17 (s, 3H), 1.01 – 0.88 (m, 1H). 1H NMR (600
MHz, Chloroform-d) δ 7.84 (s, 2H), 7.58 (t, J = 7.3 Hz, 1H), 7.46 (t, J =
7.6 Hz, 2H), 7.33 – 7.16 (m, 6H), 7.08 (s, 3H), 4.54 (s, 1H), 4.20 (d, J =
17.6 Hz, 1H), 3.99 (d, J = 16.3 Hz, 1H), 2.16 (s, 1H), 1.79 (d, J = 10.6 Hz,
1H), 1.73 – 1.52 (m, 4H), 1.46 – 1.27 (m, 2H), 1.15 (d, J = 11.8 Hz, 1H),
1.02 (d, J = 11.5 Hz, 1H). 13C{1H} NMR (151 MHz, Chloroform-d) δ 196.1 ,
170.3 , 139.7 , 137.0 , 136.8 , 133.5 , 132.2 , 130.9 , 129.5 , 128.8 ,
128.4 , 128.2 , 127.9 , 127.7 , 127.2 , 57.9 , 40.4 , 32.4 , 30.1 , 26.1 ,
26.0 , 25.5 .
6-tert-Butyl-1-phenyl-2-(trifluoromethyl)-1H-indole (2m): Following
the general procedure A, 2m was obtained as a yellowish solid from
3.352 g
of
N-(5-tert-butyl-2-methylphenyl)-2,2,2-trifluoro-N-
phenylacetamide (1m). Yield: 1.982 g (62%). MP 60-62 °C. HRMS
(APPI) calcd for C19H18F3N [M+]: 317.1391, found: 317.1389. IR (KBr)
3051, 2960, 2903, 2867, 1598, 1546, 1500, 1411, 1280, 1184, 1157,
1099, 828, 696 cm-1. 1H NMR (600 MHz, Chloroform-d) δ 7.68 (d, J = 8.5
Hz, 1H), 7.59 – 7.53 (m, 3H), 7.45 (d, J = 7.2 Hz, 2H), 7.36 – 7.33 (m,
1H), 7.08 (s, 1H), 7.04 (s, 1H), 1.33 (s, 9H). 13C{1H} NMR (151 MHz,
CDCl3) δ 148.8, 140.1, 136.9, 129.5, 129.0, 128.7, 127.1 (q, J = 37.1 Hz),
123.3, 121.6, 121.4 (q, J = 268.3 Hz), 120.0, 107.1, 105.5 (q, J = 3.7 Hz),
35.2, 31.7. 19F NMR (376 MHz, CDCl3) δ -57.4.
1-Phenyl-2-(1-adamantyl)-1H-indole (2n): Following the general
procedure A, 2n was obtained as a white crystalline solid from 3.455 g of
N-phenyl-N-o-tolyladamantane-1-carboxamide (1n). Yield: 3.253 g (99%).
MP 143-144 °C. HRMS (APPI) calcd for C24H25N [M+]: 327.1987, found:
327.1981. IR (KBr) 3043, 2905, 2850, 1595, 1495, 1455, 1355, 1304,
781, 749, 699, 669, 608 cm-1. 1H NMR (600 MHz, Chloroform-d) δ 7.60
(d, J = 7.7 Hz, 1H), 7.56 – 7.48 (m, 3H), 7.42 – 7.37 (m, 2H), 7.10 (t, J =
7.3 Hz, 1H), 7.04 (t, J = 7.6 Hz, 1H), 6.65 (d, J = 8.1 Hz, 1H), 6.48 (s, 1H),
2.02 – 1.92 (m, 9H), 1.68 (d, J = 11.9 Hz, 3H), 1.58 (d, J = 12.0 Hz, 3H).
13C{1H} NMR (151 MHz, Chloroform-d) δ 151.2 , 140.9 , 140.7 , 130.8 ,
129.1 , 128.7 , 127.0 , 121.2 , 119.8 , 119.7 , 110.3 , 99.3 , 42.3 , 36.7 ,
35.9 , 28.6 . When the reaction mixture was quenched with water instead
1-Methyl-2-phenyl-1H-indole (2q): Following the general procedure A,
2q was obtained as a white crystalline solid from 2.253 g of N-methyl-N-
o-tolylbenzamide (1q). Yield: 1.277 g (62%). MP 99-100 °C (lit. 99-
100 °C).[35] 1H NMR (400 MHz, Chloroform-d) δ 7.70 (d, J = 7.8 Hz, 1H),
7.57 (dd, J = 8.1, 1.2 Hz, 2H), 7.52 (t, J = 7.5 Hz, 2H), 7.48 – 7.39 (m,
2H), 7.31 (t, J = 7.6 Hz, 1H), 7.20 (t, J = 7.4 Hz, 1H), 6.62 (s, 1H), 3.79 (s,
3H). 13C{1H} NMR (151 MHz, Chloroform-d) δ 141.7 , 138.5 , 133.0 ,
129.5 , 128.6 , 128.1 , 128.0 , 121.8 , 120.6 , 120.0 , 109.7 , 101.8 , 31.3 .
The 1H, 13C NMR spectra were identical to the previously reported in the
This article is protected by copyright. All rights reserved.