466 JOURNAL OF CHEMICAL RESEARCH 2012
Table 4 Comparation of [Hpyro][HSO4] with reported catalysts
Methyl-(2RS, 6SR)-4-(4-bromophenylamino)-1-(4-bromophenyl)-
2,6-di(4-methyphenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate (4l):
White solid; 1H NMR (400 MHz, CDCl3): δH 2.36 (3H, s, CH3), 2.38
(3H, s, CH3), 2.74 (1H, d, J = 15.2 Hz, H′-5), 2.88 (1H, dd, J = 15.2,
5.6 Hz, H″-5), 3.97 (3H, s, O CH3), 5.10 (1H, d, J = 3.6 Hz H-6), 6.17
(2H, d, J = 8.4 Hz, ArH), 6.35 (1H, s, H-2), 6.42 (2H, d, J = 9.2 Hz,
ArH), 7.05–7.25 (12H, m, ArH), 10.23 (1H, s, NH).
Methyl-(2RS, 6SR)-4-(4-methyphenylamino)-1,2,6-tri(4-methyphenyl)-
1,2,5,6-tetrahydropyridine-3-carboxylate (4n): Light yellow solid; 1H
NMR (400 MHz, CDCl3): 2.19 (3H, s, CH3), 2.30 (3H, s, CH3), 2.35
(3H, s, CH3), 2.37 (3H, s, CH3), 2.76 (1H, dd, J = 15.1, 2.4 Hz, H′-5),
2.87 (1H, dd, J = 15.2, 5.6 Hz, H″-5), 3.94 (3H, s, OCH3), 5.11 (1H,
d, J = 3.2 Hz, H-6), 6.21 (2H, d, J = 8.4 Hz, ArH), 6.39 (1H, s, H-2),
6.47 (2H, d, J = 8.8 Hz, ArH), 6.89–7.25 (12H, m, ArH), 10.21 (1H, s,
NH).
Ethyl-(2RS, 6SR)-2,6-bis(4-chlorophenyl)-1-(4-methylphenyl)-4-(4-
methylphenylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate (4p):
White solid; 1H NMR (400 MHz, CDCl3): δH 1.46 (3H, t, J = 7.0 Hz,
OCH2CH3), 2.19 (3H, s, CH3), 2.28 (3H, s, CH3), 2.74 (1H, dd,
J = 15.2, 2.4 Hz, H′-5), 2.86 (1H, dd, J = 15.2, 5.6 Hz, H″-5), 4.30–
4.36 (1H, m, OCHaHb), 4.39–4.45 (1H, m, OCHaHb), 5.10 (1H, d,
J = 2.8 Hz, H-6), 6.29 (2H, d, J = 8.0 Hz, ArH), 6.37 (1H, s, H-2), 6.46
(2H, d, J = 8.8 Hz,ArH), 6.97 (2H, d, J = 8.4 Hz,ArH), 7.05–7.27
(10H, m, ArH), 10.20 (1H, br s, NH).
Ethyl-(2RS, 6SR)-4-(3,4-dichlorophenylamino)-1-(3,4-dichlorophenyl)-
2,6-di(4-methyphenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate (4q):
White solid; 1H NMR (400 MHz, CDCl3): δH 1.50 (3H, t, J = 6.4 Hz,
OCH2CH3), 2.34 (3H, s, CH3), 2.35 (3H, s, CH3), 2.73 (1H, d, J =
15.2 Hz, H′-5), 2.90 (1H, dd, J = 15.2, 5.6 Hz, H″-5), 4.31–4.40 (1H,
m, OCHaHb), 4.46–4.54 (1H, m, OCHaHb), 5.08 (1H, br s, H-6), 6.15
(2H, d, J = 7.2 Hz, ArH), 6.36 (1H, s, H-2), 6.42 (2H, d, J = 7.6 Hz,
ArH), 6.95–7.25 (10H, m, ArH), 10.24 (1H, s, NH); 13C NMR
(100 MHz, CDCl3): δC 14.8 (OCH2CH3), 21.6 (CH3), 21.8 (CH3), 33.4
(C-5), 55.3 (C-2), 58.3 (C-6), 59.8 (OCH2CH3), 98.9 (C-3), 108.3,
114.6, 119.1, 123.5, 123.5, 126.9, 127.2, 127.4, 127.4, 128.2, 128.2,
128.7, 131.5, 131.9, 137.0, 138.0, 138.4, 142.2, 143.3, 146.0, 155.3
(C-4), 168.1 (C=O).
for the synthesis of highly substituted piperidine derivatives
Entry Compound
Catalyst
/Conditions
Time Yield Ref.
/h
/%
1
2
3
4b
4d
4h
InCl3/CH3CN, r.t.
BDMS/CH3CN, r.t.
TBATB/EtOH, r.t.
I2/MeOH, r.t.
CAN/CH3CN, r.t.
ZrOCl2·8H2O/EtOH, reflux
p-TsOH·H2O/EtOH, r.t.
BF3·SiO2/MeOH, 65 °C
Bi(NO3)3·5H2O/EtOH, r.t.
L-proline/TFA/CH3CN,
20–30 °C
[Hpyro][HSO4]/EtOH, reflux
InCl3/CH3CN, r.t.
BDMS/CH3CN, r.t.
TBATB/EtOH, r.t.
24
3
50 26
80 28
78 29
84 30
85 31
8
8
22
—
7
—
32
89 40
33
—
18
—
—
73 35
—
4
a
8
—
3
10
6
15
4
7
79
—
—
26
76 28
82 29
85 30
86 31
80 32
86 40
I2/MeOH, 55 °C
CAN/CH3CN, r.t.
ZrOCl2·8H2O/EtOH, reflux
p-TsOH·H2O/EtOH, r.t.
BF3·SiO2/MeOH, 65 °C
Bi(NO3)3·5H2O/EtOH, r.t.
L-proline/TFA/CH3CN,
20–30 °C
[Hpyro][HSO4]/EtOH, reflux
InCl3/CH3CN, r.t.
BDMS/CH3CN, r.t.
TBATB/EtOH, r.t.
—
18
17
—
33
76 35
70
80
4
a
9
24
3
24
8
20
—
60 26
75 28
74 29
81 30
82 31
I2/MeOH, r.t.
CAN/CH3CN, r.t.
ZrOCl2·8H2O/EtOH, reflux
p-TsOH·H2O/EtOH, r.t.
BF3·SiO2/MeOH, 65 °C
Bi(NO3)3·5H2O/EtOH, r.t.
L-proline/TFA/CH3CN,
20–30 °C
3.5 80 32
10
9
12
17
78 40
78 33
81 35
70
4
Ethyl-(2RS,6SR)-4-(4-methylphenylamino)-2,6-diphenyl-1-(4-methyl-
phenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate (4r): White solid;
1H NMR (400 MHz, CDCl3): δH 1.50 (3H, t, J = 7.0 Hz, OCH2CH3),
2.20 (3H, s, CH3), 2.30 (3H, s, CH3), 2.78 (1H, dd, J = 15.0, 2.0 Hz,
H′-5), 2.88 (1H, dd, J = 15.0, 5.6 Hz, H″-5), 4.37 (1H, dq, J = 10.4,
7.0 Hz, OCHaHb), 4.49 (1H, dq, J = 10.4, 7.0 Hz, OCHaHb), 5.16 (1H,
d, J = 3.6 Hz, H-6), 6.20 (2H, d, J = 8.0 Hz, ArH), 6.47 (1H, s, H-2),
6.48 (2H, d, J = 8.4 Hz, ArH), 6.92 (2H, d, J = 8.4 Hz, ArH), 6.93 (2H,
d, J = 8.0, Hz), 7.21–7.39 (10H, m, ArH), 10.26 (1H, s, NH). 13C NMR
(100 MHz, CDCl3): δc 14.9 (OCH2CH3), 20.2 (CH3), 20.9 (CH3), 33.6
(C-5), 55.2 (C-2), 58.3 (C-6), 59.6 (OCH2CH3), 97.8 (C-3), 112.9,
125.1, 125.9, 126.2, 126.5, 127.1, 127.2, 128.2, 128.6, 129.4, 129.5,
135.3, 135.5, 143.1, 144.4, 144.9, 156.4, (C-4), 168.3 (C=O).
Methyl-(2RS, 6SR)-4-(4-methylphenylamino)-2,6-bis(4-fluorophenyl)-
1-(4-methylphenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate (4t):
White solid; 1H NMR (400 MHz, CDCl3): δH 2.20 (3H, s, CH3), 2.31
(3H, s, CH3), 2.75 (1H, dd, J = 15.1, 2.4 Hz, H′-5), 2.83 (1H, dd,
J = 15.1, 5.6 Hz, H″-5), 3.95 (3H, s, OCH3), 5.11 (1H, br s, H-6), 6.31
(2H, d, J = 8.4 Hz, ArH), 6.37 (1H, s, H-2), 6.42 (2H, d, J = 8.8 Hz,
ArH), 6.92 (2H, d, J = 8.4 Hz, ArH), 6.97–7.02 (6H, m, ArH), 7.12–
7.15 (2H, m, ArH), 7.27–7.31 (2H, m, ArH), 10.22 (1H, s, NH); 13C
NMR (100 MHz, CDCl3): δC 20.1 (CH3), 20.9 (CH3), 33.7 (C-5),
51.0 (OCH3), 54.7 (C-2), 57.3 (C-6), 97.2 (C-3), 113.0, 114.9 (d, J =
21.0 Hz), 115.4 (d, J = 21.0 Hz), 125.6, 125.8, 127.9 (d, J = 8.0 Hz),
128.2 (d, J = 7.0 Hz), 129.6, 135.0, 135.9, 138.4, 139.7, 144.5, 156.4
a
[Hpyro][HSO4]/EtOH, reflux
8
77
—
a This work.
with EtOH (3 × 2 mL) to give the pure product. Spectral data of
selected products are represented below.
Ethyl-(2RS, 6SR)-1-phenyl-4-(phenylamino)-2,6-di(4-methyphenyl)-
1,2,5,6-tetrahydropyridine-3-carboxylate (4a): White solid; 1H NMR
(400 MHz, CDCl3): δH 1.50 (3H, t, J = 7.0 Hz, OCH2CH3), 2.36
(3H, s, CH3), 2.37 (3H, s, CH3), 2.80 (1H, dd, J = 15.2, 2.4 Hz, H′-5),
2.90 (1H, dd, J = 15.2, 5.6 Hz, H″-5), 4.33–4.38 (1H, m, OCHaHb),
4.47–4.51 (1H, m, OCHaHb), 5.15 (1H, d, J = 3.2 Hz, H-6), 6.33 (2H,
d, J = 7.6 Hz, ArH), 6.45 (1H, s, H-2), 6.57 (2H, d, J = 8.8 Hz, ArH),
6.63 (1H, t, J = 7.0 Hz, ArH), 7.06–7.31 (13H, m, ArH), 10.33 (1H, s,
NH).
Methyl-(2RS, 6SR)-1-phenyl-4-(phenylamino)-2,6-di(4-methyphenyl)-
1,2,5,6-tetrahydro-pyridine-3-carboxylate (4b): White solid; 1H NMR
(400 MHz, CDCl3): δH 2.25 (3H, s, CH3), 2.32 (3H, s, CH3), 2.72
(1H, dd, J = 15.2, 2.4 Hz, H’-5), 2.84 (1H, dd, J = 15.2, 5.6 Hz, H″-5),
3.93 (3H, s, OCH3), 5.12 (1H, d, J = 2.9 Hz, H-6), 6.30 (2H, d, J =
8.0 Hz, ArH), 6.42 (1H, s, H-2), 6.48 (2H, d, J = 8.8 Hz, ArH),
6.60 (1H, t, J = 7.2 Hz, ArH), 6.99–7.12 (11H, m, ArH), 7.20 (2H, d,
J = 8.0 Hz, ArH), 10.27 (1H, s, NH).
Methyl-(2RS, 6SR)-2,6-bis(4-chlorophenyl)-1-phenyl-4-(phenylamino)-
1,2,5,6-tetrahydropyridine-3-carboxylate (4d): White solid; 1H NMR
(400 MHz, CDCl3): δH 2.74 (1H, dd, J = 15.2, 2.4 Hz, H’-5), 2.86
(1H, dd, J = 15.2, 5.6 Hz, H″-5), 3.94 (3H, s, OMe), 5.09 (1H, br s,
H-6), 6.39 (2H, d, J = 7.5 Hz, ArH), 6.40(1H, s, H-2), 6.56 (2H, d,
J = 8.0 Hz, ArH), 6.64(1H, t, J = 7.0 Hz, ArH), 7.05–7.27 (13H, m,
ArH), 10.26 (1H, s, NH).
Methyl-(2RS, 6SR)-1,2,6-triphenyl-4-(phenylamino)-1,2,5,6-tetra-
hydropyridine-3-carboxylate (4h): Light yellow solid; 1H NMR
(400 MHz, CDCl3): δH 2.73 (1H, dd, J = 15.1, 2.6 Hz, H’-5), 2.84
(1H, dd, J = 15.1, 5.4 Hz, H″-5), 3.98 (3H, s, OCH3), 5.11 (1H, d,
J = 3.5 Hz, H-6), 6.34 (2H, d, J = 7.2 Hz, ArH), 6.42(1H, s, H-2), 6.53
(2H, d, J = 7.2 Hz, ArH), 6.63 (1H, t, J = 7.0 Hz, ArH), 7.05–7.28
(15H, m, ArH), 10.29 (1H, s, NH).
1
1
(C-4), 161.5 (d, JCF = 243.0 Hz), 161.9 (d, JCF = 244.0 Hz), 168.4
(C=O).
Ethyl-(2RS, 6SR)-4-(4-fluorophenylamino)-1-(4-fluorophenyl)-2,6-
di-4-methylphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate (4u):
White solid; 1H NMR (400 MHz, CDCl3): δH 1.49 (3H, t, J = 7.2 Hz,
OCH2CH3), 2.36 (3H, s, CH3), 2.39 (3H, s, CH3), 2.67 (1H, dd,
J = 15.2, 2.4 Hz, H′-5), 2.86 (1H, dd, J = 15.2, 5.8 Hz, H″-5), 4.36
(1H, dq, J = 10.5, 7.2 Hz, OCHaHb), 4.49 (1H, dq, J = 10.5, 6.8 Hz,
OCHaHb), 5.08 (1H, d, J = 3.6 Hz, H-6), 6.25–6.29 (2H, m, ArH), 6.35
(1H, s, H-2), 6.44–6.48 (2H, m, ArH), 6.77–6.84 (4H, m, ArH), 7.06–
7.23 (8H, m, ArH), 10.22 (1H, s, NH); 13C NMR (100 MHz, CDCl3):
δC 14.8 (OCH2CH3), 21.0 (CH3), 21.1 (CH3), 33.6 (C-5), 55.4 (C-2),
58.1 (C-6), 59.7 (OCH2CH3), 98.3 (C-3), 113.6 (d, J = 7.0 Hz), 115.2