The Journal of Organic Chemistry
Article
247.5 Hz), 137.7 (d, JC−F = 6.2 Hz), 130.6 (d, JC−F = 7.5 Hz), 123.8 (d,
2H); 13C{1H} NMR (100 MHz, CDCl3) δ 198.0, 135.7, 133.8, 132.5,
129.8, 129.6, 128.7, 128.6, 127.8, 126.9, 123.6, 119.5, 36.5, 19.9, 16.8.
5-(Naphthalen-1-yl)-5-oxopentanenitrile (6i). Yellow oil13i (30.8
mg, 69%). 1H NMR (400 MHz, CDCl3) δ 8.63 (d, J = 8.6 Hz, 1H), 7.99
(d, J = 8.2 Hz, 1H), 7.88 (dd appear t, J1 = 6.9 Hz, J2= 6.9 Hz, 2H),
7.62−7.58 (m, 1H), 7.55−7.47 (m, 2H), 3.23−3.20 (m, 2H), 2.54−
2.51 (m, 2H), 2.17−2.10 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3)
δ 202.1, 135.1, 134.0, 133.2, 130.1, 128.6, 128.2, 127.9, 126.6, 125.6,
124.4, 119.4, 39.6, 20.2, 16.6.
JC−F = 2.5 Hz), 120.9 (d, JC−F = 21.2 Hz), 119.0, 114.8 (d, JC−F = 22.5
Hz), 34.4, 11.7.
4-(4-Methoxyphenyl)-4-oxobutanenitrile (5m). White solid (56.0
mg, 74%), mp 88−89 °C (lit.13g 90−91 °C). H NMR (500 MHz,
1
CDCl3) δ 7.95−7.92 (m, 2H), 6.97−6.95 (m, 2H), 3.89 (s, 3H), 3.33
(t, J = 9.0 Hz, 2H), 2.76 (t, J = 9.0 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 193.7, 164.1, 130.3, 128.8, 119.3, 114.0, 55.5, 33.8, 11.8.
4-Oxo-4-(4-phenoxyphenyl)butanenitrile (5n). White solid (44.2
mg, 44%), mp 66−67 °C. 1H NMR (500 MHz, CDCl3) δ 7.93 (d, J =
8.5 Hz, 2H), 7.43−7.40 (m, 2H), 7.24−7.21 (m, 1H), 7.08 (d, J = 8.5
Hz, 2H), 7.02 (d, J = 8.5 Hz, 2H), 3.34 (t, J = 7.0 Hz, 2H), 2.77 (t, J =
7.0 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 193.8, 162.7, 155.2,
130.3, 130.2, 130.1, 124.9, 120.3, 119.2, 117.4, 34.0, 11.8. HRMS calcd
for C16H14NO2+ [M + H]+: 252.1019, found 252.1020.
5-(4-Methoxyphenyl)-5-oxopentanenitrile (6j). Yellow solid (34.5
mg, 85%) mp 69−71 °C (lit.13i 70−71 °C). H NMR (400 MHz,
1
CDCl3) δ 7.92 (d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 3.84 (d, J =
4.8 Hz, 3H), 3.10 (t, J = 6.8 Hz, 2H), 2.49 (t, J = 7.0 Hz, 2H), 2.11−2.04
(m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.6, 163.8, 130.3,
129.6, 119.5, 113.9, 55.5, 36.0, 19.9, 16.7.
5-(3-Methoxyphenyl)-5-oxopentanenitrile (6k). Yellow solid (34.1
Ethyl 4-(3-Cyanopropanoyl)benzoate (5o). White solid (50.1 mg,
54%), mp 82−83 °C. 1H NMR (500 MHz, CDCl3) δ 8.27−8.08 (m,
2H), 8.05−7.95 (m, 2H), 4.42 (q, J = 7.5 Hz, 2H), 3.42 (t, J = 7.5 Hz,
2H), 2.80 (t, J = 7.5 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 194.9, 165.5, 138.6, 135.1, 130.0, 127.9, 118.9,
mg, 84%) mp 52−53 °C (lit.13i 52−53 °C). H NMR (400 MHz,
1
CDCl3) δ 8.59 (s, 1H), 8.26−8.24 (m, 1H), 8.17−8.15 (m, 1H), 7.58
(dd appear t, J1 = 7.8 Hz, J2 = 7.8 Hz, 1H), 3.96 (s, 3H), 3.23 (t, J = 6.8
Hz, 2H), 2.54 (t, J = 7.0 Hz, 2H), 2.17−2.10 (m, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ 197.3, 166.1, 136.7, 134.2, 132.0, 130.9, 129.1,
119.2, 52.4, 36.5, 19.6, 16.6.
+
61.6, 34.7, 14.3, 11.8. HRMS calcd for C13H14NO3 [M + H]+:
232.0974, found 232.0977.
2-Phenyl-4-(p-tolyl)quinazoline (6l). White solid (65.8 mg, 80%)
mp 117−119 °C. 1H NMR (400 MHz, CDCl3) δ 7.95−7.92 (m, 2H),
7.41−7.37 (m, 2H), 7.20 (dd appear t, J1 = 7.4 Hz, J2 = 7.4 Hz, 1H),
7.07−7.05 (m, 2H), 7.01−6.98 (m, 2H), 3.12 (t, J = 6.8 Hz, 2H), 2.50
(t, J = 7.0 Hz, 2H), 2.12−2.05 (m, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 196.7, 162.3, 155.4, 131.2, 130.3, 130.1, 124.7, 120.2, 119.4,
5-Oxo-5-phenylpentanenitrile (6a). Colorless oil (30.0 mg, 86%)
(lit.13i 32−33 °C). 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 7.7 Hz,
2H), 7.59 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 3.18 (t, J = 6.8 Hz,
2H), 2.53 (t, J = 7.0 Hz, 2H), 2.15−1.09 (m, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ 198.2, 136.5, 133.5, 128.8, 128.0, 119.4, 36.3, 19.7,
16.7.
5-Oxo-5-(p-tolyl)pentanenitrile (6b). Yellow solid (31.4 mg, 84%)
mp 58−59 °C (lit.13i 58−59 °C). 1H NMR (400 MHz, CDCl3) δ 7.81
(d, J = 8.0 Hz, 2H), 7.21 (d, J = 7.8 Hz, 2H), 3.08 (t, J = 6.8 Hz, 2H),
2.45 (t, J = 7.0 Hz, 2H), 2.36 (s, 3H), 2.06−1.98 (m, 2H); 13C{1H}
NMR (100 MHz, CDCl3) δ 197.8, 144.2, 134.1, 129.4, 128.1, 119.5,
36.3, 21.6, 19.9, 16.6.
+
117.4, 36.1, 19.9, 16.6. HRMS calcd for C17H16NO2 [M + H]+:
266.1181, found 266.1185.
5-(4-Fluorophenyl)-5-oxopentanenitrile (6m). Yellow solid (22.5
mg, 59%) mp 71−73 °C (lit.13i 72−73 °C). H NMR (400 MHz,
1
CDCl3) δ 7.99−7.97 (m, 2H), 7.13 (dd appear t, J1 = 8.1 Hz, J2 = 8.1
Hz, 2H), 3.14 (t, J = 6.7 Hz, 2H), 2.51 (t, J = 6.9 Hz, 2H), 2.12−2.07
(m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.5, 165.9 (d, JC−F
=
5-Oxo-5-(m-tolyl)pentanenitrile (6c). Yellow solid (30.3 mg, 81%)
255.4 Hz), 133.0 (d, JC−F = 2.9 Hz), 130.6 (d, JC−F = 9.4 Hz), 119.2,
115.8 (d, JC−F = 21.9 Hz), 36.24, 19.73, 16.60.
mp 59−61 °C (lit.13j 164−170 °C). H NMR (400 MHz, CDCl3) δ
1
7.71 (d, J = 10.3 Hz, 2H), 7.35−7.29 (m, 2H), 3.09 (t, J = 6.8 Hz, 2H),
2.45 (t, J = 7.0 Hz, 2H), 2.36 (s, 3H), 2.07−2.01 (m, 2H); 13C{1H}
NMR (100 MHz, CDCl3) δ 198.3, 138.5, 136.6, 134.1, 128.6, 128.5,
125.2, 119.4, 36.4, 21.3, 19.8, 16.6.
5-(4-Chlorophenyl)-5-oxopentanenitrile (6n). Yellow solid (29.0
mg, 70%) mp 63−65 °C (lit.13i 61−62 °C). H NMR (400 MHz,
1
CDCl3) δ 7.90 (d, J = 8.2 Hz, 2H), 7.45 (dd appear t, J1 = 9.5 Hz, J2 = 9.5
Hz, 2H), 3.15 (t, J = 6.6 Hz, 2H), 2.53 (t, J = 6.8 Hz, 2H), 2.13−2.10
(m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.9, 140.1, 134.9,
129.4, 129.1, 119.2, 36.3, 19.7, 16.7.
5-Oxo-5-(o-tolyl)pentanenitrile (6d). Colorless oil13k (26.9 mg,
1
1
72%). H NMR (400 MHz, CDCl3) H NMR (400 MHz, CDCl3) δ
7.64−7.62 (m, 1H), 7.36−7.32 (m, 1H), 7.25−7.20 (m, 2H), 3.03 (t, J
= 6.9 Hz, 2H), 2.46−2.43 (m, 5H), 2.05−1.98 (m, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ 201.9, 138.2, 137.2, 132.1, 131.7, 128.6, 125.8,
119.4, 39.1, 21.4, 19.9, 16.5.
5-(4-Bromophenyl)-5-oxopentanenitrile (6o). Yellow solid (26.1
mg, 52%) mp 57−58 °C (lit.13i 53−54 °C). H NMR (400 MHz,
1
CDCl3) δ 7.76 (dd appear t, J1 = 7.1 Hz, J2 = 7.1 Hz, 2H), 7.53 (dd
appear t, J1 = 7.3 Hz, J2 = 7.3 Hz, 2H), 3.07 (t, J = 6.8 Hz, 2H), 2.46 (t, J
= 7.0 Hz, 2H), 2.03 (p, J = 6.9 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 197.1, 135.2, 132.0, 129.5, 128.5, 119.3, 36.4, 19.7, 16.6.
5-(4-Iodophenyl)-5-oxopentanenitrile (6p). White solid (28.7 mg,
48%) mp 68−69 °C. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.1 Hz,
2H), 7.59 (d, J = 8.2 Hz, 2H), 3.06 (t, J = 6.8 Hz, 2H), 2.46 (t, J = 7.0
Hz, 2H), 2.06−2.00 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ
197.4, 138.0, 135.7, 129.3, 119.3, 101.4, 36.3, 19.7, 16.6. HRMS calcd
for C11H11INO+ [M + H]+: 299.9885, found 299.9883.
5-(4-(Tert-butyl)phenyl)-5-oxopentanenitrile (6e). Yellow solid
(39.9 mg, 87%) mp 53−55 °C (lit.13i 55−57 °C). H NMR (400
1
MHz, CDCl3) δ 7.86 (d, J = 7.9 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 3.09
(t, J = 6.7 Hz, 2H), 2.45 (t, J = 6.9 Hz, 2H), 2.05−2.01 (m, 2H), 1.28 (d,
J = 11.9 Hz, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.7, 157.1,
134.0, 127.9, 125.6, 119.4, 36.3, 35.1, 31.0, 19.9, 16.6.
5-(3,5-Dimethylphenyl)-5-oxopentanenitrile (6f). Colorless oil
(33.4 mg, 83%) (lit.13i 35−36 °C). H NMR (400 MHz, CDCl3) δ
1
7.55 (s, 2H), 7.20 (s, 1H), 3.12 (t, J = 6.8 Hz, 2H), 2.49 (t, J = 7.0 Hz,
2H), 2.35 (s, 6H), 2.11−2.04 (m, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 198.5, 138.4, 136.6, 135.0, 125.8, 119.4, 36.5, 21.2, 19.9, 16.6.
5-([1,1′-Biphenyl]-4-yl)-5-oxopentanenitrile (6g). Yellow solid
5-Oxo-5-(4-(trifluoromethyl)phenyl)pentanenitrile (6q). Yellow
oil13i (20.7 mg, 43%). H NMR (400 MHz, CDCl3) δ 8.05 (d, J =
1
8.3 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 3.19 (t, J = 6.8 Hz, 2H), 2.53 (t, J
= 7.0 Hz, 2H), 2.11 (p, J = 6.9 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 197.2, 139.1, 134.7 (q, JC−F = 32.7 Hz), 128.3, 125.8 (q, JC−F
= 3.7 Hz), 123.5 (q, JC−F = 272.8 Hz), 119.2, 36.7, 19.5, 16.5.
(39.4 mg, 79%) mp 113−114 °C (lit.13i 116−117 °C). H NMR
1
(400 MHz, CDCl3) δ 8.03 (d, J = 8.3 Hz, 2H), 7.69 (d, J = 8.3 Hz, 2H),
7.63 (d, J = 7.3 Hz, 2H), 7.48 (dd appear t, J1 = 7.4 Hz, J2 = 7.4 Hz, 2H),
7.41 (dd appear t, J1 = 7.3 Hz, J2 = 7.3 Hz, 1H), 3.20 (t, J = 6.8 Hz, 2H),
2.53 (t, J = 6.9 Hz, 2H), 2.17−2.10 (m, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 197.7, 146.1, 139.7, 135.2, 129.0, 128.6, 128.4, 127.3, 127.3,
119.4, 36.4, 19.8, 16.7.
6-Oxo-6-phenylhexanenitrile (7). Colorless oil13l (32.6 mg, 87%).
1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 7.9 Hz, 2H), 7.53 (dd
appear t, J1 = 7.1 Hz, J2 = 7.1 Hz, 1H), 7.43 (dd appear t, J1 = 7.6 Hz, J2 =
7.6 Hz, 2H), 3.00 (t, J = 7.0 Hz, 2H), 2.36 (t, J = 7.1 Hz, 2H), 1.89−1.83
(m, 2H), 1.75−1.69 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ
199.1, 136.8, 133.2, 128.7, 128.0, 119.5, 37.4, 25.0, 23.1, 17.1.
5-(Naphthalen-2-yl)-5-oxopentanenitrile (6h). Yellow solid (33.9
7-Oxo-7-phenylheptanenitrile (8). Colorless oil13l (35.8 mg, 89%).
1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.7 Hz, 2H), 7.53 (dd
appear t, J1 = 7.3 Hz, J2 = 7.3 Hz, 1H), 7.43 (dd appear t, J1 = 7.6 Hz, J2 =
mg, 76%) mp 60−61 °C (lit.13i 60−62 °C). H NMR (400 MHz,
1
CDCl3) δ 8.43 (s, 1H), 7.99−7.92 (m, 2H), 7.87−7.84 (m, 2H), 7.61−
7.52 (m, 2H), 3.27−3.23 (m, 2H), 2.54−2.50 (m, 2H), 2.16−2.08 (m,
J
J. Org. Chem. XXXX, XXX, XXX−XXX