The Journal of Organic Chemistry
Article
Na SO , filtered through SiO , and concentrated under reduced
pressure. Yield: 131.3 g, 85%, yellow oil. H NMR of both amide
117.0, 51.8, 49.5, 47.0, 46.8, 33.8, 32.3 ppm. HRMS (ESI-TOF) m/z:
2
4
2
1
+
[M + H] calcd for C H N O, 293.1654; found, 293.1658.
1
9
21
2
rotamers (400 MHz, CDCl ): δ 7.74, 7.69 (2 × d, J = 15.7 Hz, 1H),
(E)-N-Benzyl-N-(but-3-en-1-yl)-3-(5-methylpyridin-3-yl)-
3
1
7
6
5
.53−7.44 (m, 1H), 7.42−7.15 (m, 6H), 7.05 (t, J = 8.3 Hz, 1H),
.98 (t, J = 8.0 Hz, 1H), 6.81, 6.70 (2 × d, J = 15.4 Hz, 1H), 5.90−
.63 (m, 1H), 5.17−4.96 (m, 2H), 4.71 (s, 1H), 4.67 (s, 1H), 3.53 (t,
acrylamide (29). Yield: 26.9 g, 88%, yellow oil. H NMR of both
amide rotamers (400 MHz, CDCl ): δ 8.56, 8.44 (2 × s, 1H), 8.39,
3
8.34 (2 × s, 1H), 7.72, 7.67 (2 × d, J = 15.6 Hz, 1H), 7.57, 7.47 (2 ×
s, 1H), 7.41−7.09 (m, 5H), 6.93, 6.82 (2 × d, J = 15.4 Hz, 1H),
1
3
J = 7.1 Hz, 1H), 3.44 (t, J = 8.0 Hz, 1H), 2.35 (br s, 2H) ppm.
C
1
5
3
.90−5.62 (m, 1H), 5.12−4.93 (m, 2H), 4.71 (s, 1H), 4.67 (s, 1H),
.54 (t, J = 7.3 Hz, 1H), 3.44 (t, J = 7.3 Hz, 1H), 2.37−2.22 (m, 5H)
{
1
1
1
1
H} of both amide rotamers NMR (126 MHz, CDCl ): δ 166.9,
3
66.5, 163.6 (d, J = 250 Hz), 163.6 (d, J = 250 Hz), 142.1, 142.0,
1
3
ppm. C NMR of both amide rotamers (126 MHz, CDCl ): δ 166.5,
37.8, 137.3, 135.5, 134.4, 131.6, 129.8, 129.7, 129.1, 128.7, 128.2,
27.8, 127.5, 126.5, 117.8, 117.5, 117.2, 116.9, 116.1 (d, J = 14 Hz),
15.9 (d, J = 14 Hz), 51.7, 49.5, 46.9, 46.6, 33.8, 32.3 ppm. LCMS
3
1
1
66.1, 151.13, 151.08, 146.7, 146.6, 139.9, 139.8, 137.6, 137.1, 135.4,
35.0, 134.8, 134.3, 133.4, 133.3, 130.7, 130.6, 129.1, 128.8, 128.2,
+
+
127.9, 127.6, 126.5, 119.6, 119.3, 117.9, 117.0, 51.8, 49.5, 47.0, 46.7,
(m/z): 310 (M + H ). HRMS (ESI-TOF) m/z: [M + H] calcd for
+
3
3.8, 32.3, 18.5, 18.4 ppm. HRMS (ESI-TOF) m/z: [M + H] calcd
C H FNO, 310.1607; found, 310.1602.
20
21
for C H N O, 307.1810; found, 307.1807.
(
E)-N-Benzyl-N-(but-3-en-1-yl)-3-(p-tolyl)acrylamide (24). Yield:
20 23
2
1
(E)-N-Benzyl-N-(but-3-en-1-yl)-3-(pyridin-2-yl)acrylamide (30).
2
4.4 g, 80%, yellow oil. H NMR of both amide rotamers (400 MHz,
1
Yield: 26.6 g, 91%, yellow oil. H NMR of both amide rotamers
CDCl ): δ 7.76, 7.72 (2 × d, J = 15.79 Hz, 1H), 7.47−7.03 (m, 9H),
3
(
(
500 MHz, CDCl ): δ 8.64, 8.57 (2 × d, J = 4.1 Hz, 1H), 7.79−7.65
6
2
7
.85, 6.75 (2 × d, 15.3 Hz, 1H), 5.90−5.63 (m, 1H), 5.16−4.97 (m,
3
m, 2H), 7.56, 7.50 (2 × d, J = 14.9 Hz, 1H), 7.40−7.19 (m, 7H),
H), 4.71 (s, 1H), 4.66 (s, 1H), 3.52 (t, J = 7.2 Hz, 1H), 3.43 (t, J =
1
3
1
5.88−5.69 (m, 1H), 5.16−5.01 (m, 2H), 4.76 (br s, 2H), 3.57−3.47
.3 Hz, 1H), 2.46−2.21 (m, 5H) ppm. C { H} NMR of both amide
13 1
(
m, 2H), 2.45−2.31 (m, 2H) ppm. C { H} NMR of both amide
rotamers (126 MHz, CDCl ): δ 167.2, 166.8, 143.2, 143.2, 140.0,
3
rotamers (126 MHz, CDCl ): δ 166.9, 166.6, 153.7, 153.6, 150.1,
1
1
5
39.9, 137.8, 137.3, 135.5, 134.4, 132.6, 132.5, 129.6, 129.5, 128.9,
28.6, 128.1, 127.8, 127.7, 127.4, 126.5, 117.6, 116.7, 116.5, 116.3,
3
1
1
41.8, 136.9, 136.9, 135.5, 134.4, 129.0, 128.7, 128.2, 127.8, 127.5,
26.9, 125.0, 124.9, 124.0, 123.9, 121.8, 121.6, 117.8, 116.9, 51.7,
1.6, 49.4, 46.8, 46.5, 33.7, 32.3, 21.4 ppm. HRMS (ESI-TOF) m/z:
+
+
49.5, 46.9, 46.1, 33.8, 32.2 ppm. HRMS (ESI-TOF) m/z: [M + H]
[
M + H] calcd for C H NO, 306.1858; found, 306.1852.
2
1
24
calcd for C H N O, 293.1654; found, 293.1652.
(
E)-N-Benzyl-N-(but-3-en-1-yl)cinnamamide (25). Yield: 27.1 g,
19 21
2
1
(E)-N-Benzyl-N-(but-3-en-1-yl)-3-(pyrimidin-5-yl)acrylamide
9
3%, yellow oil. H NMR of both amide rotamers (400 MHz,
1
(
(
1
31). Yield: 26.9 g, 92%, yellow oil. H NMR of both amide rotamers
CDCl ): δ 7.81, 7.76 (2 × d, J = 15.6 Hz, 1H), 7.57−7.16 (m, 10H),
3
400 MHz, CDCl ): δ 9.13, 9.07 (2 × s, 1H), 8.83 (s, 1H), 8.70 (s,
3
6
.91, 6.81 (2 × d, J = 15.4 Hz, 1H), 5.93−5.65 (m, 1H), 5.13−5.00
H), 7.69−7.53 (m, 1H), 7.36−7.15 (m, 5H), 7.01, 6.87 (2 × d, J =
(m, 2H), 4.73, 4.67 (2 × s, 2H), 3.55 (t, J = 7.2 Hz, 1H), 3.44 (t, J =
1
3
15.6 Hz, 1H), 5.84−5.62 (m, 1H), 5.15−4.94 (m, 2H), 4.69 (s, 1H),
7
.3 Hz, 1H), 2.43−2.28 (m, 2H) ppm. C NMR of both amide
4
2
.66 (s, 1H), 3.55 (t, J = 7.3 Hz, 1H), 3.43 (t, J = 7.3 Hz, 1H), 2.42−
rotamers (101 MHz, CDCl ): δ 166.9, 166.5, 143.1, 143.0, 137.7,
3
13
.27 (m, 2H) ppm. C NMR of both amide rotamers (151 MHz,
1
1
5
37.1, 135.4, 135.2, 135.1, 134.2, 129.6, 129.5, 128.9, 128.8, 128.7,
28.5, 128.0, 127.8, 127.6, 127.3, 126.4, 117.6, 117.5, 117.3, 116.7,
CDCl ): δ 165.8, 165.4, 158.7, 158.6, 155.5, 155.4, 137.2, 136.7,
3
1
1
35.8, 135.6, 135.1, 134.0, 129.2, 128.8, 128.2, 128.0, 127.7, 126.3,
1.5, 49.3, 46.7, 46.4, 33.6, 32.2 ppm. HRMS (ESI-TOF) m/z: [M +
21.9, 121.6, 118.5, 118.1, 117.1, 110.3, 51.8, 49.6, 46.9, 33.6, 32.2
+
H] calcd for C H NO, 292.1701; found, 292.1704.
+
20
22
ppm. LCMS (m/z): 294 (M + H ). HRMS (ESI-TOF) m/z: [M +
(
E)-N-Benzyl-N-(but-3-en-1-yl)-3-(pyridin-4-yl)acrylamide (26).
+
H] calcd for C H N O, 294.1606; found, 294.1609.
1
18 20
3
Yield: 27.1 g, 73%, yellow oil. H NMR of both amide rotamers
(
E)-N-Benzyl-N-(but-3-en-1-yl)-3-(1-methyl-1H-pyrazol-5-yl)-
(
(
1
4
(
500 MHz, CDCl ): δ 8.64, 8.57 (2 × d, J = 4.6 Hz, 1H), 7.69, 7.63
1
3
acrylamide (32). Yield: 23.9 g, 81%, yellow oil. H NMR of both
2 × d, J = 15.4 Hz, 1H), 7.41−7.20 (m, 8H), 7.07, 7.65 (2 × d, J =
amide rotamers (500 MHz, CDCl ): δ 7.71, 7.66 (2 × d, J = 15.1 Hz,
3
5.4 Hz, 1H), 5.91−5.66 (m, 1H), 5.19−5.00 (m, 2H), 4.74 (s, 1H),
1
6
1
H), 7.50−7.17 (m, 6H), 6.82, 6.70 (2 × d, J = 15.1 Hz, 1 H), 6.54,
.38 (2 × s, 1H), 5.87−5.66 (m, 1H), 5.17−5.00 (m, 2H), 4.73 (s,
H), 4.67 (s, 1H), 3.97, 3.91 (2 × s, 3H), 3.56 (t, J = 7.1 Hz, 1H),
.69 (s, 1H), 3.57 (t, J = 7.3 Hz, 1H), 3.46 (t, J = 7.2 Hz, 1H), 2.37
m, 2H) ppm. 13C { H} NMR of both amide rotamers (126 MHz,
1
CDCl ): δ 166.2, 150.7, 150.6, 140.5, 140.3, 135.3, 134.2, 129.2,
13
1
3
3.44 (t, J = 7.2 Hz, 1H), 2.46−2.25 (m, 2H) ppm. C { H} NMR of
1
5
28.8, 128.3, 128.0, 127.7, 126.4, 122.4, 122.1, 121.8, 118.1, 117.1,
both amide rotamers (126 MHz, CDCl ): δ 166.4, 166.0, 139.0,
3
1.8, 49.6, 47.0, 46.8, 33.8, 32.3 ppm. HRMS (ESI-TOF) m/z: [M +
1
38.9, 138.8, 138.7, 137.6, 137.1, 135.4, 134.2, 129.1, 128.8, 128.7,
128.6, 128.2, 127.9, 127.6, 126.5, 119.8, 119.6, 118.0, 117.0, 105.0,
04.8, 51.7, 49.7, 47.0, 46.8, 37.0, 33.8, 32.3 ppm. LCMS (m/z): 296
+
H] calcd for C H N O, 293.1654; found, 293.1650.
19
21
2
(
E)-N-Benzyl-N-(but-3-en-1-yl)-3-(3-methylpyridin-4-yl)-
1
(
2
1
acrylamide (27). Yield: 27.1 g, 82%, yellow oil. H NMR of both
+
+
M + H ). HRMS (ESI-TOF) m/z: [M + H] calcd for C H N O,
18 22 3
amide rotamers (400 MHz, DMSO-d ): δ 8.50−8.24 (m, 2H), 7.70
6
96.1763; found, 296.1765.
(
(
(
(
t, J = 14.2 Hz, 1H), 7.62, 7.47 (2 × d, J = 4.8 Hz, 1H), 7.38−7.08
m, 6H), 5.90−5.69 (m, 1H), 5.12−4.98 (m, 2H), 4.79 (s, 1H), 4.64
s, 1H), 3.53 (t, J = 7.1 Hz, 1H), 3.44 (t, J = 7.3 Hz, 1H), 2.60−2.23
(
E)-N-Benzyl-N-(but-3-en-1-yl)-3-(1-methyl-1H-pyrazol-4-yl)-
1
acrylamide (33). Yield 27 g, 92%, yellow oil. H NMR of both amide
rotamers (500 MHz, CDCl ): δ 8.01 (s, 1H), 7.71−7.19 (m, 5H),
3
m, 5H) ppm. 13C NMR of both amide rotamers (101 MHz, CDCl ):
3
6.63, 6.52 (2 × d, J = 15.3 Hz, 1H), 5.86−5.69 (m, 1H), 5.15−4.96
δ 166.9, 166.3, 151.9, 151.8, 147.9, 147.8, 138.5, 138.3, 137.5, 137.0,
(
(
2
m, 2H), 4.71 (s, 1H), 4.65 (s, 1H), 3.91 (s, 1H), 3.86 (s, 1H), 3.52
1
1
1
35.3, 134.1, 131.8, 131.7, 129.2, 128.8, 128.3, 128.0, 127.7, 126.4,
23.0, 122.6, 119.8, 118.1, 117.1, 51.8, 49.6, 47.0, 46.8, 33.7, 32.3,
6.69, 16.65 ppm. HRMS (ESI-TOF) m/z: [M + H] calcd for
t, J = 7.3 Hz, 1H), 3.41 (t, J = 7.4 Hz, 1H), 2.95, 2.88 (2 × s, 3H),
13
1
.42−2.22 (m, 2H) ppm. C { H} NMR of both amide rotamers
+
(
126 MHz, CDCl ): δ 167.3, 167.0, 162.6, 138.4, 138.3, 137.9, 137.4,
3
C H N O, 307.1810; found, 307.1812.
20
23
2
135.6, 134.5, 133.7, 133.6, 130.3, 130.2, 129.0, 128.7, 128.2, 127.7,
(
E)-N-Benzyl-N-(but-3-en-1-yl)-3-(pyridin-3-yl)acrylamide (28).
1
4
27.4, 126.5, 119.3, 119.2, 117.6, 116.8, 115.2, 114.9, 51.6, 49.4, 46.8,
1
+
Yield: 26.3 g, 90%, yellow oil. H NMR of both amide rotamers
500 MHz, CDCl ): δ 8.77, 8.65 (2 × s, 1H), 8.58, 8.52 (2 × d, J =
6.5, 39.2, 36.6, 33.8, 32.4, 31.6 ppm. LCMS (m/z): 296 (M + H ).
+
(
3
3
HRMS (ESI-TOF) m/z: [M + H] calcd for C H N O, 296.1763;
1
8
22
3
.8 Hz, 1H), 7.83−7.63 (m, 2H), 7.42−7.21 (m, 6H), 6.98, 6.85 (2 ×
found, 296.1766.
d, J = 15.5 Hz, 1H), 5.90−5.67 (m, 1H), 5.17−4.98 (m, 2H), 4.74 (s,
(E)-N-Benzyl-N-(but-3-en-1-yl)-3-(1-methyl-1H-imidazole-2-yl)-
1
1
2
(
H), 4.69 (s, 1H), 3.57 (t, J = 7.3 Hz, 1H), 3.46 (t, J = 7.3 Hz, 1H),
acrylamide (34). Yield 26.3 g, 89%, yellow oil. H NMR of both
1
3
1
.47−2.27 (m, 2H) ppm. C { H} NMR of both amide rotamers
126 MHz, CDCl ): δ 166.4, 166.0, 150.5, 150.4, 149.4, 149.4, 139.7,
amide rotamers (500 MHz, CDCl ): δ 7.65, 7.60 (2 × d, J = 15.2 Hz,
3
1H), 7.54−7.17 (m, 7H), 6.77, 6.64 (2 × d, J = 15.3 Hz, 1H), 5.88−
5.68 (m, 1H), 5.14−4.98 (m, 2H), 4.72 (s, 1H), 4.67 (s, 1H), 3.72,
3.63 (2 × s, 3H), 3.57 (t, J = 7.2 Hz, 1H), 3.44 (t, J = 7.5 Hz, 1H),
3
1
1
39.5, 137.6, 137.1, 135.4, 134.5, 134.4, 134.2, 131.2, 131.1, 129.2,
28.8, 128.2, 127.9, 127.6, 126.4, 123.8, 123.7, 119.9, 119.6, 118.0,
E
J. Org. Chem. XXXX, XXX, XXX−XXX