Month 2014
One-pot Synthesis of Highly Functionalized Tetrahydropyridines:
A Camphoresulfonic acid Catalyzed Multicomponent Reaction
13
J2 = 15.3 Hz, 1H), 3.93 (s, 3H), 5.04–5.07 (m, 1H), 6.18
7.26–7.29 (m, 5H), 7.33 (d, J = 7.6 Hz, 2H), 10.32 (s, 1H);
C
(
(
d, J = 8.5 Hz, 2H), 6.32 (s, 1H), 6.42 (d, J = 8.8 Hz, 2H), 6.98
d, J = 8.8 Hz, 2H), 7.01 (d, J = 7.6 Hz, 2H), 7.05 (d, J = 8.2 Hz,
NMR (CDCl , 125 MHz): δ = 14.7, 33.5, 55.1, 58.1, 59.5, 98.4,
113.3, 116.5, 125.6, 125.8, 126.5, 126.6, 126.8, 127.4, 128.4,
3
2
H), 7.08 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 7.15
128.6, 128.8, 129.2, 138.1, 142.9, 144.2, 147.2, 156.4, 168.4;
Anal. Calcd for C32H N O (474.59): C, 80.98; H, 6.37; N,
30 2 2
1
3
(
d, J = 7.9 Hz, 2H), 10.19 (s, 1H); C NMR (CDCl
3
, 125 MHz):
δ = 21.2, 21.4, 33.8, 51.3, 55.1, 58.3, 98.9, 114.3, 121.0, 126.5,
5.90. Found: C, 80.88; H, 6.42; N, 6.05.
Ethyl 2,6-bis(4-chlorophenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-
tetrahydropyridine -3-carboxylate (1k).
1
1
26.7, 127.3, 128.6, 129.1, 129.3, 129.6, 131.5, 136.3, 136.6,
37.2, 139.4, 140.3, 145.5, 155.6, 168.7; Anal. Calcd for
White solid; 80%; mp:
33 2 2 2
C H30Cl N O (557.51): C, 71.09; H, 5.42; N, 5.02. Found: C,
199–201°C; IR (KBr): 3250, 2940, 1653, 1598, 1495, 1250,
À1
1
7
1.16; H, 5.48; N, 5.15.
1076 cm ; H NMR (CDCl , 500 MHz): δ =1.45 (t, J=7.3Hz,
3
Methyl 1,2,6-tri-p-tolyl-4-(p-tolylamino)-1,2,5,6-tetrahydro-
3H), 2.75 (dd, J =2.4Hz, J = 15.1 Hz, 1H), 2.82 (dd, J =6.0Hz,
1
2
1
pyridine-3-carboxylate (1g).
White crystalline solid; 73%;
2
J = 15.1 Hz, 1H), 4.30–4.32 (m, 1H), 4.43–4.46 (m, 1H), 5.06–5.09
mp: 168–171°C; IR (KBr): 3432, 2928, 1656, 1594, 1505,
(m, 1H), 6.34 (s, 1H), 6.37 (d, J= 7.3 Hz, 2H), 6.47 (d, J=8.2Hz,
2H), 6.65 (t, J= 6.8 Hz, 1H), 7.05–7.15 (m, 5H), 7.22–7.26 (m, 8H),
À1
1
1
254, 1076 cm
;
3
H NMR (CDCl , 500 MHz): δ = 2.15
13
(
(
s, 3H), 2.24 (s, 3H), 2.30 (s, 3H), 2.35 (s, 3H), 2.71
dd, J1 = 2.4 Hz, J2 = 15.3 Hz, 1H), 2.82 (dd, J1 = 5.8 Hz,
10.30 (s, 1H), C NMR (CDCl , 125 MHz): δ = 14.7, 33.9, 54.9,
3
57.6, 59.7, 97.9, 113.2, 116.9, 125.9, 126.1, 127.8, 128.2, 128.6,
2
J = 15.3 Hz, 1H), 3.92 (s, 3H), 5.05–5.08 (m, 1H), 6.18
128.8, 129.1, 129.3, 132.4, 132.7, 137.8, 141.1, 142.7, 146.5, 155.8,
(
(
d, J = 8.2 Hz, 2H), 6.32 (s, 1H), 6.44 (d, J = 8.8 Hz, 2H), 6.87
d, J = 8.5 Hz, 2H), 6.89 (d, J = 7.9 Hz, 2H), 7.04 (d, J = 7.9 Hz,
2 2 2
168.2; Anal. Calcd for C32H28Cl N O (543.49): C, 70.72; H, 5.19;
N, 5.15. Found: C, 70.82; H, 5.13; N, 5.28.
2
H), 7.05–7.07 (m, 4H), 7.20 (d, J = 8.2 Hz, 2H), 10.18 (s, 1H);
Ethyl 1-phenyl-4-(phenylamino)-2,6-di-p-tolyl-1,2,5,6-tetra-
1
3
C NMR (CDCl , 125 MHz): δ = 20.4, 21.1, 21.2, 21.3, 33.9,
hydropyridine-3-carboxy late (1l).
White crystalline solid;
3
5
1
1
1.1, 55.2, 58.3, 97.5, 112.7, 124.7, 126.1, 126.5, 126.8, 129.2,
29.5, 129.8, 135.2, 135.5, 135.9, 136.7, 140.2, 141.5, 145.2,
72%; mp: 227–230°C; IR (KBr): 3240, 2980, 1651, 1594,
1501, 1248, 1068 cm ; H NMR (CDCl , 500 MHz): δ = 1.45
3
À1
1
56.8, 168.9. Anal. Calcd for C35
H
36
N
2
O
2
(516.67): C, 81.36;
(t, J = 7.3 Hz, 3H), 2.32 (s, 3H), 2.34 (s, 3H), 2.76 (dd,
J1 = 2.4 Hz, J2 = 15.1 Hz, 1H), 2.87 (dd, J1 = 5.5 Hz,
J2 = 15.1 Hz, 1H), 4.30–4.32 (m, 1H), 4.41–4.45 (m, 1H), 5.08–
5.11 (m, 1H), 6.27 (d, J = 6.8 Hz, 2H), 6.41 (s, 1H), 6.53
(d, J = 8.2 Hz, 2H), 6.57 (t, J = 7.3 Hz, 1H), 7.05–7.08 (m, 11H),
H, 7.02; N, 5.42. Found: C, 81.43; H, 7.07; N, 5.55.
Methyl 1-(4-nitrophenyl)-4-(4-nitrophenyl amino)2,6-di-p-
tolyl-1,2,5,6-tetrahydropyridine-3-carboxylate (1h).
solid; 80%; mp: 167–171°C; IR (KBr): 3354, 2951, 1657, 1588,
1
Yellow
À1
1
13
516, 1342, 1255, 1071 cm
;
H NMR (CDCl , 400 MHz):
7.22 (d, J = 7.8 Hz, 2H), 10.30 (s,1H); C NMR (CDCl3,
3
δ = 2.34 (s, 6H), 2.94 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H), 3.07
100 MHz): δ = 15.2, 21.4, 21.5, 33.9, 55.1, 58.3, 59.6, 98.8,
113.2, 116.2, 125.5, 125.8, 126.4, 126.8, 128.7, 129.1, 129.3,
129.6, 135.7, 136.9, 138.5, 139.7, 141.3, 147.1, 156.4, 168.5;
Anal. Calcd for C34H N O (502.65): C, 81.24; H, 6.82; N,
34 2 2
5.57. Found: C, 81.35; H, 6.89; N, 5.70.
1
2
(
(
(
(
1 2
dd, J = 5.6 Hz, J = 15.2 Hz, 1H), 3.99 (s, 3H), 5.28
d, J = 3.2 Hz, 1H), 6.43 (d, J = 9.2 Hz, 2H), 6.48 (s, 1H), 6.54
d, J = 9.6 Hz, 2H),7.02 (d, J = 8.0 Hz, 2H), 7.13 (s, 6H), 7.97
13
d, J = 9.6 Hz, 2H), 8.00 (d, J = 9.2 Hz, 2H), 10.56 (s, 1H);
C
NMR (CDCl , 100 MHz): δ = 21.1, 21.3, 33.8, 52.0, 55.8, 58.5,
Ethyl 1,2,5,6-tetrahydro-2,6-bis(4-meth oxyphenyl)-1-phenyl-
3
1
02.0, 112.3, 123.2, 125.1, 125.9, 126.1, 126.2, 129.7, 130.0,
4-(phenylamino)pyr idine-3-carboxylate (1m).
White solid;
1
37.2, 137.5, 137.9, 138.1, 138.3, 144.1, 151.9, 153.4, 168.3;
75%; mp: 177–179°C; IR (KBr): 3256, 2942, 1656, 1590,
À1
1
Anal. Calcd for C33
.68. Found: C, 68.39; H, 5.15; N, 9.84.
Methyl 1-(4-bromophenyl)-4-(4-bromo phenylamino)2,6-di-
p-tolyl-1,2,5,6-tetra hydropyridine-3-carboxylate (1i). White
solid; 68%; mp: 229–230 °C; IR (KBr): 3240, 2949, 2917,
H
30
N
4
O
6
(578.62): C, 68.50; H, 5.23; N,
1500, 1240, 1060 cm ; H NMR (CDCl
3
, 400 MHz): δ = 1.50
9
(t, J = 7.2 Hz, 3H), 2.80 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H), 2.90
1
2
(dd, J = 5.6 Hz, J = 15.2 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H),
1
2
4.39 (dq, J
1
2 1
= 7.2 Hz, J = 10.8 Hz, 1H), 4.50 (dq, J = 7.0 Hz,
J
2
= 10.8 Hz, 1H), 5.15 (d, J = 2.8 Hz, 1H), 6.41 (d, J = 6.8 Hz,
À1
1
1
4
656, 1607, 1587, 1492, 1255, 1071 cm ; H NMR (CDCl
3
,
2H), 6.42 (s, 1H), 6.58 (d, J = 8.4 Hz, 2H), 6.67 (t, J = 7.2 Hz,
13
00 MHz): δ = 2.31 (s, 3H), 2.34 (s, 3H), 2.68 (dd, J = 2.4 Hz,
1H), 6.84–6.88 (m, 4H), 7.09–7.28 (m, 9H), 10.36 (s, 1H);
C
1
J = 15.2 Hz, 1H), 2.82 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H), 3.91
NMR (CDCl , 100 MHz): δ = 14.7, 33.8, 54.5, 55.2, 55.3, 57.5,
2
1
2
3
(
s, 3H), 5.03–5.05 (m, 1H), 6.10 (d, J = 8.4 Hz, 2H), 6.29
59.6, 98.4, 113.0, 113.6, 114.0, 116.0, 125.6, 125.7, 127.5,
127.7, 128.9, 134.7, 136.1, 138.0, 147.1, 156.2, 158.2, 158.7,
168.3; Anal. Calcd for C H N O (534.25): C, 76.38; H, 6.41;
(
s, 1H), 6.36 (d, J = 9.2 Hz, 2H), 7.00 (d, J = 8.0 Hz, 2H),7.06–
13
7
.13 (m, 8H), 7.18 (d, J = 8.8 Hz, 2H), 10.16 (s, 1H); C NMR
34 34 2 4
(
CDCl , 100 MHz): δ = 21.2, 21.3, 33.5, 51.4, 55.3, 58.2, 98.9,
N, 5.24. Found: C, 76.48; H, 6.46; N, 5.11.
3
1
1
08.5, 114.7, 119.3, 126.4, 126.6, 127.5, 129.4, 129.6, 131.7,
32.1, 136.3, 137.2, 137.3, 139.2, 140.2, 146.1, 155.6, 168.8;
Allyl 2,6-bis(4-methylphenyl)-1-Phenyl-4-(phenylamino)-1,2,5,6-
tetrahydropyridine -3-carboxylate (1n). Light yellow solid; 73%;
mp: 183–185°C; IR (KBr): 3241, 3022, 2922, 1655, 1594, 1501,
Anal. Calcd for C33
.33. Found: C, 61.40; H, 4.63; N, 4.46.
Ethyl 1,2,6-triphenyl-4-(phenylamino)-1,2,5,6-tetrahydropy-
ridine-3-carboxylate (1j). White crystalline solid; 76%; mp:
68–171°C; IR (KBr): 3242, 3059, 2979, 1651, 1594, 1500,
2 2 2
H30Br N O (646.43): C, 61.32; H, 4.68; N,
À1
1
4
1372, 1246, 1063 cm ; H NMR (CDCl , 400MHz): δ =2.31 (s,
3
3H), 2.32 (s, 3H), 2.74 (dd, J =2.4Hz, J = 15.2 Hz, 1H), 2.86 (dd,
1
2
J
J
3
1
=5.6Hz, J
=13.6 Hz, 1H), 4.86 (ddt, J
1H), 5.07–5.10 (m, 1H), 5.30 (dq, J
5.44 (dq, J =1.6Hz, J = 17.2 Hz, 1H), 6.08–6.14 (m, 1H), 6.26–
2
= 15.2 Hz, 1H), 4.78 (ddt, J
=1.6Hz, J
=1.6Hz, J
1
=1.6Hz, J
=5.6Hz, J =13.6 Hz,
= 10.4 Hz, 1H),
2
=5.6Hz,
1
1
1
2
3
À1
1
251, 1068 cm
;
H NMR (CDCl
3
, 500 MHz): δ = 1.50 (t,
1
2
J = 7.0 Hz, 3H), 2.77 (dd, J = 2.4 Hz, J = 15.0 Hz, 1H), 2.90
1
2
1
2
(
4
dd, J = 5.8 Hz, J = 15.0 Hz, 1H), 4.32–4.38 (m, 1H), 4.41–
.49 (m, 1H), 5.14–5.17 (m, 1H), 6.26–6.30 (m, 2H), 6.45
6.30 (m, 2H), 6.42 (s, 1H), 6.51 (d, J=8.0Hz, 2H), 6.58 (t,
J=7.2Hz, 1H), 7.0–7.07 (m, 11H),7.20 (d, J=8.0Hz, 2H), 10.25
1
2
13
(
7
s, 1H), 6.51 (d, J = 8.5 Hz, 2H), 6.63 (t, J = 7.0 Hz, 1H), 7.05–
.11 (m, 5H), 7.18–7.21 (m, 2H), 7.24 (d, J = 7.0 Hz, 1H),
3
(s, 1H); C NMR (CDCl , 100 MHz): δ = 21.2, 21.3, 33.9, 55.0,
58.1, 64.5, 98.1, 113.1, 116.2, 117.8, 125.9, 126.0, 126.5, 126.8,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet