The Journal of Organic Chemistry
Article
δ −62.6; HRMS (ESI+): m/z [M]+ calcd for C16H12NF3, 275.0922;
found 275.0912.
3-(3,5-Dimethoxyphenyl)-2-(4-methoxyphenyl)propanenitrile
1
(3u). Pale yellow oil; 68 mg (92%); H NMR (CDCl3, 500 MHz): δ
7.18(d, 2H, J = 8.7 Hz), 6.88 (d, 2H, J = 8.6 Hz), 6.36 (t, 2H, J = 2.2
Hz), 6.28 (d, 2H, J = 2.3 Hz), 3.94 (dd, 1H, J = 8.3, 6.5 Hz), 3.81 (s,
3H), 3.74 (s, 6H), and 3.13−3.01 (m, 2H); 13C{1H} NMR (CDCl3,
125 MHz): δ 160.9, 159.5, 138.7, 128.7, 127.3, 120.7, 114.4, 107.3,
99.49, 55.4, 55.3, 42.6, and 38.8; HRMS (ESI+): m/z [M + Na]+
calcd for C18H19NNaO3, 320.1257; found 320.1256.
4-(Benzyl-cyano-methyl)-benzonitrile (3l). White solid; 33 mg
(57%); m.p. 84 °C; 1H NMR (CDCl3, 500 MHz) δ 7.65 (d, 2H, J =
8.4 Hz), 7.34 (d, 2H, J = 8.4 Hz), 7.30-7.27 (m, 3H,), 7.07 (dd, 2H, J
= 7.0, 2.3 Hz), 4.08 (t, 1H, J = 7.2 Hz), and 3.19 (ddd, 2H, J = 20.3,
13.6, 7.2 Hz); 13C{1H} NMR (CDCl3, 125 MHz): 140.2, 135.2,
132.8, 129.2, 128.8, 128.5, 127.8, 119.2, 118.1, 112.6, 41.8, and 39.7;
HRMS (ESI+): m/z [M]+ calcd for C16H13N2, 233.1073; found
233.1077.
2-(4-Methoxyphenyl)-3-(naphthal-en-2-yl)propanenitrile8d (3v).
Pale yellow oil; 63 mg (88%); 1H NMR (CDCl3, 500 MHz): δ 7.84−
7.80 (m, 1H), 7.77 (d, 2H, J = 8.0 Hz), 7.60 (s, 1H), 7.49−7.43 (m,
2H), 7.23 (dd, 1H, J = 8.3, 1.8 Hz), 7.18 (d, 2H, J = 8.7 Hz), 6.86 (d,
2H, J = 8.6 Hz), 4.05 (dd, 1H, J = 8.1, 6.7 Hz), 3.80 (s, 3H), and
3.36−3.24 (m, 2H); and 13C{1H} NMR (CDCl3, 125 MHz): δ 159.5,
133.9, 133.4, 132.6, 128.7, 128.3, 128.2, 127.8, 127.7, 127.2, 126.2,
125.9, 120.7, 114.4, 55.4, 42.5, and 39.0.
3-Phenyl-2-(o-tolyl)propanenitrile6l (3m). Colorless oil; 39 mg
1
(70%); H NMR (CDCl3, 500 MHz): δ 7.44−7.42 (m, 1H), 7.33−
7.27 (m, 3H), 7.25−7.22 (m, 2H), 7.18−7.16 (m, 3H), 4.15 (dd, 1H,
J = 8.9, 6.0 Hz), 3.18−3.06 (m, 2H), and 2.26 (s, 3H); and 13C{1H}
NMR (CDCl3, 125 MHz): δ 136.6, 135.1, 133.7, 131.0, 129.1, 128.7,
128.3, 127.7, 127.4, 126.9, 120.7, 41.0, 36.6, and 19.0.
3-Phenyl-2-(pyridin-3-yl)propanenitrile6c (3n). Colorless solid; 31
mg (60%); 1H NMR (CDCl3, 500 MHz): δ 8.59 (dd, 1H, J = 4.9, 1.5
Hz), 8.46 (d, 1H, J = 2.4 Hz), 7.61−7.55 (m, 1H), 7.35−7.27 (m,
4H), 7.11 (dd, 2H, J = 7.4, 1.8 Hz), 4.06 (t, 1H, J = 7.2 Hz), and
3.26−3.13 (m, 2H); 13C{1H} NMR (CDCl3, 125 MHz): δ 149.7,
148.9, 135.4, 135.0, 131.0, 129.3, 128.8, 127.8, 123.7, 119.4, 41.9, and
37.3.
2-(4-Methoxyphenyl)-3-(4-(trifluoromethyl)phenyl)-
propanenitrile8d (3w). Colorless oil; 55 mg (72%); 1H NMR
(CDCl3, 500 MHz): δ 7.55 (d, 2H, J = 8.1 Hz), 7.23 (d, 2H, J = 8.1
Hz), 7.15 (d, 2H, J = 8.7 Hz), 6.88 (d, 2H, J = 8.6 Hz), 3.9 (t, 1H, J =
7.5 Hz), 3.81 (s, 3H), and 3.24−3.15 (m, 2H); 13C{1H} NMR
(CDCl3, 125 MHz): δ 159.6, 140.2, 129.7, 128.6, 126.5, 125.6 (q,
JC−F = 3.7 Hz), 124.1 (q, JC−F = 270.0 Hz), 120.2, 114.5, 55.4, 41.9,
and 38.6; and 19F NMR (283 MHz, CDCl3): δ −62.4.
2-(4-Methoxyphenyl)hept-6-enenitrile (3x). Colorless oil; 44 mg
(82%); 1H NMR (CDCl3, 500 MHz) δ 7.23 (d, 2H, J = 8.6 Hz), 6.90
(d, 2H, J = 8.6 Hz), 5.75 (ddt, 1H, J = 16.9, 10.1, 6.7 Hz), 5.07−4.89
(m, 2H), 3.81 (s, 3H) 3.73 (dd, 1H, J = 8.2, 6.5 Hz), 2.09 (q, 2H, J =
7.1 Hz), 1.96−1.76 (m, 2H), and 1.63−1.45 (m, 2H); 13C{1H} NMR
(CDCl3, 125 MHz): 159.4, 137.6, 128.4, 127.9, 121.1, 115.4, 114.5,
55.4, 36.5, 35.3, 33.0, and 26.1; HRMS (ESI+): m/z [M]+ calcd for
C14H18NO, 216.1383; found 216.1388.
2-(4-Methoxyphenyl)tetradecanenitrile (3y). Colorless oil; 75 mg
(95%); 1H NMR (CDCl3, 500 MHz): δ 7.23 (d, 2H, J = 8.7 Hz), 6.90
(d, 2H, J = 8.6 Hz), 3.81 (s, 3H), 3.71 (dd, 1H, J = 8.5, 6.3 Hz),
1.93−1.78 (m, 2H), 1.50−1.37 (m, 2H), 1.30−1.25 (m, 18H), and
0.88 (t, 3H, J = 6.9 Hz); 13C{1H} NMR (CDCl3, 125 MHz): δ 158.4,
127.5, 127.3, 120.3, 113.5, 54.5, 35.7, 35.1, 31.0, 28.8, 28.7, 28.6, 28.5,
28.5, 28.1, 26.1, 21.8, and 13.2; HRMS (ESI+): m/z [M + H]+ calcd
for C21H34NO, 316.2635; found 316.2631.
2-(Naphthalen-2-yl)-3-phenylpropanenitrile (3o). White solid; 46
1
mg (71%); m.p. 95−96 °C; H NMR (CDCl3, 500 MHz): δ 7.86−
7.83 (m, 2H), 7.81−7.79 (m, 1H), 7.73 (d, 1H, J = 1.3 Hz), 7.51 (dd,
2H, J = 6.1, 3.2 Hz), 7.35 (dd, 1H, J = 8.5, 1.8 Hz), 7.31-7.26 (m,
3H), 7.16 (dd, 2H, J = 7.6, 1.8 Hz), 4.17 (dd, 1H, J = 8.2, 6.5 Hz),
and 3.30−3.21 (m, 2H); 13C{1H} NMR (CDCl3, 125 MHz): δ 136.3,
133.3, 132.9, 132.5, 129.3, 129.0, 128.7, 127.9, 127.8, 127.5, 126.7,
126.7, 126.6, 125.0, 120.4, 42.2, and 40.0; HRMS (ESI+): m/z [M]+
calcd for C19H15N, 257.1204; found 257.1212.
2,3-bis(Benzo[d][1,3]dioxol-5-yl)propanenitrile (3p). Colorless
1
oil; 44 mg (60%); m.p. 64−66 °C; H NMR (CDCl3, 500 MHz):
δ 6.69 (dd, 3H), 6.62−6.58 (m, 2H), 5.98 (s, 2H), 5.95 (s, 2H), 3.85
(dd, 1H, J = 8.2, 6.6 Hz), and 3.09−2.99 (m, 2H); 13C{1H} NMR
(CDCl3, 125 MHz): δ 148.2, 147.8, 147.6, 146.9, 129.9, 128.8, 122.5,
121.0, 120.4, 109.5, 108.6, 108.4, 107.9, 101.4, 101.1, 42.0, and 39.7;
HRMS (ESI+): m/z [M + Na]+ calcd for C17H13NNaO4, 318.0737;
found 318.0735.
2-(4-Methoxyphenyl)-3-(p-tolyl)propanenitrile8d (3q). Colorless
2-(4-Methoxyphenyl)tridecanenitrile (3z). Colorless oil; 64 mg
(85%); 1H NMR (CDCl3, 500 MHz): δ 7.23 (d, 2H, J = 8.7 Hz), 6.90
(d, 2H, J = 8.8 Hz), 3.81 (s, 3H), 3.71 (dd, 1H, J = 8.5, 6.4 Hz),
1.93−1.78 (m, 2H), 1.50−1.37 (m, 2H), 1.31−1.25 (m, 16H), and
0.88 (t, 3H, J = 6.9 Hz); 13C{1H} NMR (CDCl3, 125 MHz): δ 159.4,
128.4, 128.2, 121.3, 114.5, 55.4, 36.7, 36.0, 32.0, 29.7, 29.7, 29.6, 29.4,
29.0, 29.0, 27.1, 22.8, and 14.2; HRMS (ESI+): m/z [M + Na]+ calcd
for C20H31NNaO, 324.2297; found 324.2289.
1
oil; 50 mg (80%); H NMR (CDCl3, 500 MHz): δ 7.17 (d, 2H, J =
8.7 Hz), 7.10 (d, 2H, J = 7.9 Hz), 7.02 (d, 2H, J = 8.0 Hz), 6.87 (d,
2H, J = 8.6 Hz), 3.92 (dd, 1H, J = 8.3, 6.5 Hz), 3.81 (s, 3H), 3.15−
3.04 (m, 2H), and 2.32 (s, 3H); and 13C{1H} NMR (CDCl3, 125
MHz): δ 159.4, 137.0, 133.4, 129.3, 129.1, 128.7, 127.4, 120.7, 114.4,
55.4, 41.9, 39.2, and 21.1.
2-(4-Methoxyphenyl)-3-(o-tolyl)propanenitrile (3r). Colorless oil;
1
36 mg (57%); H NMR (CDCl3, 500 MHz): δ 7.22−7.08 (m, 6H),
2-(4-Methoxyphenyl)undecanenitrile8d (3aa). Colorless oil; 62
mg (91%); 1H NMR (CDCl3, 500 MHz): δ 7.23 (d, 2H, J = 8.7 Hz),
6.90 (d, 2H, J = 8.8 Hz), 3.81 (s, 3H), 3.71 (dd, 1H, J = 8.5, 6.3 Hz),
1.93−1.78 (m, 2H), 1.50−1.37 (m, 2H), 1.30−1.25 (m, 12H), and
0.88 (t, 3H, J = 6.9 Hz); and 13C{1H} NMR (CDCl3, 125 MHz): δ
159.3, 128.4, 128.1, 121.2, 114.4, 55.4, 36.6, 36.0, 31.9, 29.5, 29.3,
29.3, 29.0, 27.0, 22.7, and 14.1.
6.87 (d, 2H, J = 8.6 Hz), 3.91 (dd, 1H, J = 8.5, 6.6 Hz), 3.81 (s, 3H),
3.23−3.07 (m, 2H), and 2.22 (s, 3H); 13C{1H} NMR (CDCl3, 125
MHz): δ 159.5, 136.3, 134.8, 130.6, 130.1, 128.6, 127.5, 126.3, 120.8,
114.4, 55.4, 39.6, 38.0, and 19.3; HRMS (ESI+): m/z [M + H]+ calcd
for C17H18NO, 252.1382; found 252.1374.
3 - ( 4 - I s o p r o p y l p h e n y l ) - 2 - ( 4 - m e t h o x y p h e n y l ) -
phenylpropanenitrile8d (3s). White solid; 55 mg (79%); m.p. 67−69
°C; 1H NMR (CDCl3, 500 MHz): δ 7.19 (d, 2H, J = 8.7 Hz), 7.16 (d,
2H, J = 8.1 Hz), 7.08 (d, 2H, J = 8.1 Hz), 6.88 (d, 2H, J = 8.7 Hz),
3.92 (dd, 1H, J = 8.7, 6.2 Hz), 3.81 (s, 3H), 3.15−3.04 (m, 2H),
2.93−2.84 (m, 1H), and 1.24 (d, 6H, J = 6.9 Hz); and 13C{1H} NMR
(CDCl3, 125 MHz): δ 159.4, 148.0, 133.8, 129.1, 128.6, 127.5, 126.7,
120.8, 114.4, 55.4, 42.0, 39.2, 33.8, and 24.0.
3-(Furan-2-yl)-2-(4-methoxyphen-yl)propanenitrile (3t). Color-
less oil; 28 mg (50%); 1H NMR (CDCl3, 500 MHz): δ 7.38−7.32 (m,
1H), 7.19 (d, 2H, J = 8.7 Hz), 6.88 (d, 2H, J = 8.6 Hz), 6.29 (dd, 1H,
J = 3.1, 1.9 Hz), 6.11 (d, 1H, J = 3.7 Hz), 4.09 (dd, 1H, J = 8.3, 6.7
Hz), 3.81 (s, 3H), and 3.27−3.10 (m, 2H); 13C{1H} NMR (CDCl3,
125 MHz): δ 159.6, 150.1, 142.1, 128.4, 126.9, 120.4, 114.5, 110.5,
108.2, 55.4, 36.3, and 34.8; HRMS (ESI+): m/z [M + Na]+ calcd for
C14H13NNaO2, 250.0838; found 250.0840.
2-(4-Methoxyphenyl)decanenitrile (3ab). Colorless oil; 58 mg
(90%); 1H NMR (CDCl3, 500 MHz): δ 7.23 (d, 2H, J = 8.7 Hz), 6.90
(d, 2H, J = 8.7 Hz), 3.81 (s, 3H), 3.71 (dd, 1H, J = 8.3, 6.5 Hz),
1.93−1.78 (m, 2H), 1.51−1.38 (m, 2H), 1.30−1.25 (m, 10H), and
0.87 (t, 3H, J = 6.8 Hz); 13C{1H} NMR (CDCl3, 125 MHz): δ 159.3,
128.4, 128.1, 121.2, 114.4, 55.4, 36.6, 36.0, 31.8, 29.3, 29.2, 29.0, 27.0,
22.6, and 14.1; HRMS (ESI+): m/z [M + Na]+ calcd for
C17H25NNaO, 282.1828; found 282.1824.
2-(4-Methoxyphenyl)hexanenitrile8d (3ac). Colorless oil; 45 mg
(88%); 1H NMR (CDCl3, 500 MHz): δ 7.24 (d, 2H, J = 8.7 Hz), 6.90
(d, 2H, J = 8.8 Hz), 3.81 (s, 3H), 3.71 (dd, 1H, J = 8.5, 6.4 Hz),
1.94−1.79 (m, 2H), 1.47−1.31 (m, 4H), and 0.90 (t, 3H, J = 7.2 Hz);
and 13C{1H} NMR (CDCl3, 125 MHz): δ 158.2, 127.3, 127.0, 120.1,
113.3, 54.3, 35.5, 34.6, 28.0, 21.0, and 12.7.
G
J. Org. Chem. XXXX, XXX, XXX−XXX