The Journal of Organic Chemistry
Article
v), mp 118−120 °C; 1H NMR (CDCl3, 300 MHz) δH 7.76 (d, J = 8.1
Hz, 2H), 7.65 (d, J = 8.7 Hz, 2H), 7.46−7.43 (m, 2H), 7.40−7.31 (m,
2H), 7.19 (d, J = 8.1 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 6.62 (s, 1H),
5.25−5.23 (m, 1H), 3.91 (d, J = 6.3 Hz, 2H), 3.82 (s, 3H), 3.80 (s, 2H),
2.33 (s, 3H); 13C{1H} NMR (CDCl3, 75 MHz) δC 160.0, 143.4, 137.5,
137.1, 132.6, 131.6, 130.2, 129.6, 129.3, 128.4, 128.2, 128.1, 127.2,
122.5, 117.7, 113.9, 113.7, 93.6, 92.8, 55.3, 50.1, 22.9, 21.5; HRMS
(ESI) m/z calcd for C27H24N2NaO3S [M + Na]+ 479.1405, found
479.1409.
(E)-N-(4-(2-(Cyanomethyl)phenyl)-2-(3-methoxybenzylidene)-
but-3-yn-1-yl)-4-methylbenzene-sulfonamide (8ah). Pale yellow
solid (163 mg, 87%), Rf = 0.29 (25% ethyl acetate in petroleum
ether, v/v), mp 124−126 °C; 1H NMR (CDCl3, 300 MHz) δH 7.77 (d,
J = 8.1 Hz, 2H), 7.48−7.28 (m, 6H), 7.26−7.15 (m, 3H), 6.87 (dd, J =
8.1, 1.8 Hz, 1H), 6.67 (s, 1H), 5.13 (t, J = 6.4 Hz, 1H), 3.95 (d, J = 6.3
Hz, 2H), 3.83 (s, 2H), 3.80 (s, 3H), 2.35 (s, 3H); 13C{1H} NMR
(CDCl3, 75 MHz) δC 159.3, 143.4, 137.4, 137.1, 136.6, 132.6, 131.8,
129.6, 129.5, 129.3, 128.2, 128.1, 127.1, 122.2, 121.4, 117.7, 117.0,
114.2, 113.9, 93.5, 93.0, 55.2, 49.9, 22.9, 21.4; HRMS (ESI) m/z calcd
for C27H25N2O3S [M + H]+ 457.1586, found 457.1590.
petroleum ether, v/v), mp 196−198 °C; 1H NMR (CDCl3, 600 MHz)
δH 8.97 (d, J = 9 Hz, 1H), 7.84−7.82 (m, 1H), 7.80 (d, J = 9 Hz, 1H),
7.69 (s, 1H), 7.66−7.64 (m, 1H), 7.56−7.54 (m, 3H), 7.49−7.46 (m,
3H), 7.34−7.28 (m, 3H), 7.14 (d, J = 8.4 Hz, 2H), 6.68 (s, 1H), 4.45 (s,
2H), 3.76 (brs, 2H), 2.33 (s, 3H); 13C{1H} NMR (CDCl3, 150 MHz)
δC 144.8, 139.0, 137.0, 135.0, 133.8, 133.7, 133.6, 132.4, 129.7, 128.8,
128.5, 127.7, 127.6, 126.9, 126.6, 126.5, 126.4, 126.3, 125.9, 125.3,
124.3, 122.8, 122.1, 120.7, 118.9, 107.6, 32.9, 21.6; HRMS (ESI) m/z
calcd for C30H25N2O2S [M + H]+ 477.1637, found 477.1639.
3-(Furan-2-ylmethyl)-1-tosyl-1H-benzo[g]indol-4-amine (2ac).
Brown solid (65.1 mg, 68%), Rf = 0.20 (15% ethyl acetate in petroleum
ether, v/v), mp 134−136 °C; 1H NMR (CDCl3, 600 MHz) δH 8.90 (d,
J = 8.4 Hz, 1H), 7.70 (s, 1H), 7.57 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 8.4
Hz, 2H), 7.39−7.38 (m, 1H), 7.33−7.30 (m, 1H), 7.27−7.25 (m, 1H),
7.09 (d, J = 8.4 Hz, 2H), 6.76 (s, 1H), 6.30−6.29 (m, 1H), 5.86−5.85
(m, 1H), 4.27 (s, 2H), 3.96 (brs, 2H), 2.28 (s, 3H); 13C{1H} NMR
(CDCl3, 150 MHz) δC 153.7, 144.8, 142.1, 138.9, 134.9, 133.7, 133.3,
129.7, 128.2, 126.9, 126.3, 125.2, 124.1, 122.8, 121.8, 118.9, 118.5,
110.6, 107.9, 106.7, 26.3, 21.6; HRMS (ESI) m/z calcd for
C24H21N2O3S [M + H]+ 417.1273, found 417.1304.
3-(Thiophen-2-ylmethyl)-1-tosyl-1H-benzo[g]indol-4-amine
(2ad). Brown solid (75.5 mg, 76%), Rf = 0.21 (15% ethyl acetate in
petroleum ether, v/v), mp 174−176 °C; 1H NMR (CDCl3, 600 MHz)
δH 8.94 (d, J = 8.4 Hz, 1H), 7.73 (s, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.52
(d, J = 8.4 Hz, 2H), 7.31 (t, J = 7.5 Hz, 1H), 7.28−7.26 (m, 1H), 7.21
(d, J = 4.8 Hz, 1H), 7.11 (d, J = 8.4 Hz, 2H), 6.93−6.92 (m, 1H), 6.73
(s, 1H), 6.70−6.69 (m, 1H), 4.43 (s, 2H), 3.86 (brs, 2H), 2.29 (s, 3H);
13C{1H} NMR (CDCl3, 150 MHz) δC 144.9, 143.4, 138.9, 134.9, 133.8,
(E)-N-(2-Benzylidene-4-(2-(cyanomethyl)-4,5-dimethoxyphenyl)-
but-3-yn-1-yl)-4-methylbenzene-sulfonamide (8ai). Yellow solid
(162 mg, 81%), Rf = 0.13 (25% ethyl acetate in petroleum ether, v/
v), mp 140−142 °C; 1H NMR (CDCl3, 300 MHz) δH 7.78 (d, J = 8.1
Hz, 2H), 7.67 (d, J = 6.9 Hz, 2H), 7.39−7.31 (m, 3H), 7.26−7.23 (m,
2H), 6.95 (s, 1H), 6.90 (s, 1H), 6.65 (s, 1H), 5.05 (t, J = 6.4 Hz, 1H),
3.95−3.94 (m, 5H), 3.90 (s, 3H), 3.75 (s, 2H), 2.36 (s, 3H); 13C{1H}
NMR (CDCl3, 100 MHz) δC 150.3, 148.6, 143.5, 137.6, 136.6, 135.6,
129.7, 128.8, 128.6, 128.3, 127.2, 125.1, 118.0, 117.1, 114.9, 114.4,
111.2, 93.7, 91.6, 56.3, 56.2, 50.0, 22.4, 21.5; HRMS (ESI) m/z calcd
for C28H26N2NaO4S [M + Na]+ 509.1511, found 509.1514.
133.6, 129.8, 128.1, 127.2, 126.9, 126.3, 125.3, 125.2, 125.1, 124.2,
122.8, 121.7, 120.7, 118.9, 107.7, 27.7, 21.6; HRMS (ESI) m/z calcd for
C24H21N2O2S2 [M + H]+ 433.1044, found 433.1046.
3-(4-Chlorobenzyl)-1-tosyl-1H-benzo[g]indol-4-amine (2ae).
Brown solid (86.7 mg, 82%), Rf = 0.22 (15% ethyl acetate in petroleum
ether, v/v), mp 158−160 °C; 1H NMR (CDCl3, 600 MHz) δH 8.92 (d,
J = 8.4 Hz, 1H), 7.58−7.56 (m, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.32 (t, J =
7.2 Hz, 1H), 7.29−7.25 (m, 3H), 7.11 (d, J = 7.8 Hz, 2H), 7.03 (d, J =
8.4 Hz, 2H), 6.72 (s, 1H), 4.24 (s, 2H), 3.71 (brs, 2H), 2.31 (s, 3H);
13C{1H} NMR (CDCl3, 150 MHz) δC 144.9, 138.7, 137.7, 134.9, 133.8,
133.7, 132.7, 129.7, 129.6, 129.1, 128.4, 126.9, 126.3, 125.4, 124.3,
122.9, 121.8, 120.5, 118.9, 107.7, 32.2, 21.6; HRMS (ESI) m/z calcd for
C26H22ClN2O2S [M + H]+ 461.1091, found 461.1097.
3-(4-Methylbenzyl)-1-tosyl-1H-benzo[g]indol-4-amine (2af).
Brown solid (78.9 mg, 78%), Rf = 0.27 (15% ethyl acetate in petroleum
ether, v/v), mp 178−180 °C; 1H NMR (CDCl3, 600 MHz) δH 8.92 (d,
J = 9 Hz, 1H), 7.59 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 8.4 Hz,
2H), 7.33−7.30 (m, 1H), 7.28−7.25 (m, 1H), 7.11 (d, J = 8.4 Hz, 2H),
7.08 (d, J = 7.8 Hz, 2H), 6.97 (d, J = 7.8 Hz, 2H), 6.70 (s, 1H), 4.23 (s,
2H), 3.77 (brs, 2H), 2.33 (s, 3H), 2.31 (s, 3H); 13C{1H} NMR (CDCl3,
150 MHz) δC 144.7, 139.0, 136.5, 136.1, 134.9, 133.8, 129.7, 129.6,
128.4, 128.1, 126.9, 126.2, 125.3, 124.3, 122.7, 122.1, 121.4, 119.0,
107.5, 32.3, 21.6, 21.1; HRMS (ESI) m/z calcd for C27H25N2O2S [M +
H]+ 441.1637, found 441.1640.
3-(4-Methoxybenzyl)-1-tosyl-1H-benzo[g]indol-4-amine (2ag).
Pale brown solid (25.2 mg, 24%), Rf = 0.18 (15% ethyl acetate in
petroleum ether, v/v), mp 190−192 °C; 1H NMR (CDCl3, 600 MHz)
δH 8.92 (d, J = 8.4 Hz, 1H), 7.58 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.49
(d, J = 8.4 Hz, 2H), 7.31 (td, J = 7.5, 0.8 Hz, 1H), 7.28−7.26 (m, 1H),
7.11 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 9 Hz, 2H),
6.70 (s, 1H), 4.21 (s, 2H), 3.79−3.77 (m, 5H), 2.31 (s, 3H); 13C{1H}
NMR (CDCl3, 150 MHz) δC 158.5, 144.6, 138.9, 134.9, 133.81, 133.80,
131.0, 129.6, 129.2, 128.3, 126.9, 126.2, 125.2, 124.3, 122.7, 122.0,
121.6, 118.9, 114.3, 107.4, 55.2, 31.8, 21.5; HRMS (ESI) m/z calcd for
C27H25N2O3S [M + H]+ 457.1586, found 457.1592.
3-(3-Methoxybenzyl)-1-tosyl-1H-benzo[g]indol-4-amine (2ah).
Pale yellow solid (83.9 mg, 80%), Rf = 0.16 (15% ethyl acetate in
petroleum ether, v/v), mp 142−144 °C; 1H NMR (CDCl3, 600 MHz)
δH 8.95 (d, J = 9 Hz, 1H), 7.63 (s, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.51 (d,
J = 8.4 Hz, 2H), 7.31 (t, J = 7.5 Hz, 1H), 7.29−7.27 (m, 1H), 7.20 (t, J =
7.8 Hz, 1H), 7.10 (d, J = 8.4 Hz, 2H), 6.79 (dd, J = 8.1, 2.1 Hz, 1H), 6.72
(s, 1H), 6.69−6.67 (m, 2H), 4.25 (s, 2H), 3.76 (s, 5H), 2.29 (s, 3H);
( E ) - M e t h y l 3 - ( C y a n o m e t h y l ) - 4 - ( 3 - ( ( 4 -
methylphenylsulfonamido)methyl)-4-phenylbut-3-en-1-yn-1-yl)-
benzoate (8aj). Light yellow solid (175 mg, 88%), Rf = 0.22 (25% ethyl
acetate in petroleum ether, v/v), mp 128−130 °C; 1H NMR (CDCl3,
300 MHz) δH 8.09 (s, 1H), 7.98 (dd, J = 8.1, 1.2 Hz, 1H), 7.76 (d, J =
8.1 Hz, 2H), 7.66−7.63 (m, 2H), 7.50 (d, J = 7.8 Hz, 1H), 7.37−7.32
(m, 3H), 7.21 (d, J = 8.1 Hz, 2H), 6.75 (s, 1H), 5.33 (t, J = 6.4 Hz, 1H),
3.96−3.94 (m, 5H), 3.83 (s, 2H), 2.34 (s, 3H); 13C{1H} NMR (CDCl3,
75 MHz) δC 165.8, 143.5, 138.5, 137.4, 135.1, 132.7, 132.0, 130.5,
129.6, 129.5, 129.3, 129.1, 128.7, 128.4, 127.1, 126.8, 117.2, 116.4, 96.0,
92.2, 52.5, 49.8, 22.8, 21.4; HRMS (ESI) m/z calcd for C28H25N2O4S
[M + H]+ 485.1535, found 485.1539.
General Procedure for the Synthesis of Products 2a. To a
well-stirred solution of Pd(OAc)2 (2.58 mg, 0.011 mmol, 5 mol %) and
bpy (3.59 mg, 0.023 mmol, 10 mol %) in dry THF (1.5 mL), p-TsOH·
H2O (87.4 mg, 0.46 mmol, 2 equiv) was added and the mixture was
heated to reflux under argon atmosphere. Next, 8a (0.23 mmol, 1
equiv) dissolved in dry THF (1.5 mL) was added dropwise and heating
was continued for another 4−12 h. Upon completion of reaction
(TLC), the reaction mixture was neutralized by adding 10% aqueous
sodium bicarbonate solution (to pH ∼ 7) dropwise. It was then
extracted with ethyl acetate (3 × 20 mL) and the combined organic
extracts were washed with brine (10 mL), dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The
resulting residue was purified through silica gel (100−200 mesh)
column chromatography using 10−18% ethyl acetate in petroleum
ether to afford the pure products (2aa−aj) in 24−82% yields.
Spectral Data of Products 2aa−aj. 3-Benzyl-1-tosyl-1H-benzo-
[g]indol-4-amine (2aa). Brown solid (73.5 mg, 75%), Rf = 0.24 (15%
1
ethyl acetate in petroleum ether, v/v), mp 146−148 °C; H NMR
(CDCl3, 300 MHz) δH 8.93 (d, J = 8.1 Hz, 1H), 7.60−7.54 (m, 2H),
7.50 (d, J = 8.1 Hz, 2H), 7.34−7.26 (m, 5H), 7.12−7.08 (m, 4H), 6.70
(s, 1H), 4.28 (s, 2H), 3.73 (brs, 2H), 2.31 (s, 3H); 13C{1H} NMR
(CDCl3, 100 MHz) δC 144.8, 139.3, 139.0, 135.0, 133.92, 133.90,
129.7, 129.0, 128.5, 128.3, 127.0, 126.9, 126.3, 125.3, 124.4, 122.8,
122.1, 121.2, 119.1, 107.6, 32.8, 21.6; HRMS (ESI) m/z calcd for
C26H22N2NaO2S [M + Na]+ 449.1300, found 449.1300.
3-(Naphthalen-2-ylmethyl)-1-tosyl-1H-benzo[g]indol-4-amine
(2ab). Brown solid (85.4 mg, 78%), Rf = 0.25 (15% ethyl acetate in
M
J. Org. Chem. XXXX, XXX, XXX−XXX