NO2-Fe(III)PcCl@C -catalyzed one-pot synthesis of tetrahydropyridine derivatives

Article abstract of DOI:10.1134/S1070363217040259

A highly efficient, one-pot synthesis of functionalized tetrahydropyridines by multicomponent condensation of ethyl acetoacetate, two equivalents of aromatic aldehyde, and aromatic amine in the presence of a catalytic amount of NO₂-Fe(III)PcCl@

Full text of DOI:10.1134/S1070363217040259

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 4, pp. 821–828. © Pleiades Publishing, Ltd., 2017.
NO2-Fe(III)PcCl@C -Catalyzed One-Pot Synthesis
of Tetrahydropyridine Derivatives1
Jiao-dan Wang, Qiao-li Lin, Jun Qiu, Xiao-feng Gou, Cheng-wen Hua,
Jun-long Zhao, and Bang Chen*
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry
and Materials Science, Northwest University, Xi’an 710069, Shaanxi, China
*e-mail: chenbang@china.com.cn
Received February 22, 2016
Abstract—A highly efficient, one-pot synthesis of functionalized tetrahydropyridines by multicomponent
condensation of ethyl acetoacetate, two equivalents of aromatic aldehyde, and aromatic amine in the presence
of a catalytic amount of NO2-Fe(III)PcCl@C is reported. In this way, a series of pharmacologically interesting
substituted pyridine derivatives were obtained in moderate to good yields.
Keywords: multicomponent reactions, one-pot synthesis, NO2-Fe(III)PcCl@C, tetrahydropyridines
DOI: 10.1134/S1070363217040259
Metal phthalocyanines are stable and nontoxic
compounds. Due to the ease of their modification,
resistance to heat, acids, and alkalies, excellent
performance in terms of electrical conductivity,
chemical catalysis, and photoelectric effect, and
nonlinear optical properties, they have found
widespread applications in various technological
fields, as well as in light therapy. Six-membered
heterocyclic structural units containing a nitrogen atom
exist in a number of biologically active drug molecules
[1]. Tetrahydropyridine derivatives are very important
in organic synthesis and medical research field, and
applications of these compounds are very extensive.
For example, a tetrahydropyrido[1,2-a]indole deri-
vative (Eburnamonine) isolated from the ornamental
plant Vinca minor and called “brain oxygen supply
device” has obvious cerebral vasodilation effect [2]
and is used in the treatment of cerebrovascular diseases.
Thiophene and tetrahydropyridine derivatives are com-
monly used as antithrombotic drugs (Prasugrel,
Clopidogrel). These basic structural units are res-
ponsible for efficient platelet aggregation inhibition
[3], as well as for antibacterial, antiviral, and her-
bicidal activities [4, 5].
much attention in organic synthesis [6–8] because of
various advantages such as simple reaction procedures,
environmental safety, and atom economy. At present,
MCRs are widely used in the synthesis of some natural
products [9], asymmetric syntheses [10], drug
discovery [11], and a few other applications.
Herein we report one-pot three-component syn-
thesis of functionalized tetrahydropyridines using 5–
6 mol % of NO2-Fe(III)PcCl@C as catalyst (Scheme 1).
The procedure is characterized by simple operation, zero
pollution, high yields, and easy purification technique.
Various reaction conditions were tested for the
direct synthesis of tetrahydropyridines by the model
reaction of benzaldehyde (2.0 mmol) with aniline
(2.0 mmol) and ethyl acetoacetate (1.0 mmol). The
results are listed in Table 1. A wide range of catalysts
were tested under the same reaction conditions (Table 1,
run nos. 1–8), and we found the catalyst NO2-Fe(III)
PcCl@C to be superior, providing the best yield (run
no. 8). A blank reaction was performed with the same
reactants but in the absence of NO2-Fe(III)PcCl@C,
and no product was isolated in this case (run no. 9).
The solvent was also varied (run nos. 8, 10–16);
satisfactory results were obtained in ethanol (run
no. 8). We also tried to optimize the temperature
conditions and found decrease in the reaction rate as
the temperature decreases (run nos. 17, 18).
Multicomponent reactions (MCRs) are chemical
reactions (generally one-pot) in which three or more
substrates react to form a single product containing
fragments of each substrate. MCRs have received
The scope and limitations of the three-component
one-pot synthesis of tetrahydropyridines under the opti-
1 The text was submitted by the authors in English.
821

822
JIAO-DAN WANG et al.
Scheme 1.
NO2
O2N
N
R1
O
R2
R1
N
N
N
N
NO2-Fe(III)PcCl@C,
HOAC
N
O
O
O
N
N
Fe
2R2NH2
2R1CHO
+
+
EtOH, reflux
NH
R2
O
Cl
N
1−30
NO2
O2N
NO2-Fe(III)PcCl
R1 = Ph, 4-ClC6H4, 4-MeC6H4, 3-NO2C6H4, 4-NO2C6H4, 2-FC6H4, 3-BrC6H4, 2,4-Cl2C6H3; R2 = Ph, 4-MeOC6H4, 4-BrC6H4,
4-ClC6H4.
mized conditions were explored using a variety of al-
dehydes and amines; the results are summarized in
Table 2. The reactions of ethyl acetoacetate with various
aromatic amines and aldehydes afforded desired products
1–30 in 78–90% yield. The nature and position of substi-
tuents on the aromatic ring has little effect on the yield
(Table 2).
A probable mechanism [12–14] for the described
three-component condensation is outlined in Scheme 2.
Table 1. Three-component condensation of ethyl acetoacetate with benzaldehyde and anilinea
Run no.
Catalyst
Solvent
EtOH
Temperature, °C
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
50
Time, h
Yield,b %
1
2
NO2-Cu(II)Pc
4
4
4
4
4
4
2
2
8
2
2
2
2
2
2
2
2
2
0
NO2-Zn(II)Pc
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeCN
THF
0
3
NO2-Co(II)Pc
0
4
NO2-Ni(II)Pc
41
0
5
NO2-Mn(II)Pc
6
NO2-Fe(III)Pc
63
60
88
0
7
NO2-Ni(II)PcCl@C
NO2-Fe(III)PcCl@C
No catalyst
8
9
10
11
12
13
14
15
16
17
18
NO2-Fe(III)PcCl@C
NO2-Fe(III)PcCl@C
NO2-Fe(III)PcCl@C
NO2-Fe(III)PcCl@C
NO2-Fe(III)PcCl@C
NO2-Fe(III)PcCl@C
NO2-Fe(III) PcCl@C
NO2-Fe(III) PcCl@C
NO2-Fe(III)PcCl@C
58
67
43
50
38
40
45
75
35
CH2Cl2
Acetone
Toluene
n-Hexane
Et2O
EtOH
EtOH
25
a
Benzaldehyde (2.0 mmol), aniline (2.0 mmol), ethyl acetoacetate (1.0 mmol); solvent, 20 mL, containing 5–6 drops of acetic acid.
Isolated yield.
b
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NO2-Fe(III)PcCl@C -CATALYZED ONE-POT SYNTHESIS
823
Scheme 2.
R2
O
O
R2
H
N
O
N
O
R1CHO
O
R2NH2
O
H+
O
R1
31
32
R2
R2
H
N
O
N
O
Cat.
O
O
R1
R1
33
32
R1
R1CHO
R2NH2
R2
+
N
34
R2
H
R2
N
O
NH
N
O
O
O
Cat.
R1
R1
R1
R1
N
R2
33
R2
34
Initially, acid-catalyzed reaction of aromatic amine
with ethyl acetoacetate gave enamino ester 31 which
reacted with aromatic aldehyde to generate inter-
mediate 32 via aldol-type condensation. Tautomeriza-
tion of 32 in presence of NO2-Fe(III)PcCl@C led to
structure 33 stabilized by intramolecular hydrogen
bond. Concurrently, the reaction of aromatic amine
with aromatic aldehyde produced Schiff base 34. The
subsequent [4 + 2]-Diels–Alder reaction of 33with34
in presence of NO2-Fe(III)PcCl@C afforded the final
product (Scheme 2).
ranged from 86 to 88% in 8 cycles. Experimental
results showed that NO2-Fe(III)PcCl@C can be used
as a heterogeneous catalyst and is easy to recycle.
After completion of the reaction, the mixture was
filtered to remove the catalyst, and the product preci-
pitated from the filtrate. Thus, NO2-Fe(III)PcCl@C as
catalyst is advantageous due to its high activity and
recyclability without appreciable loss of activity, which
makes it the best catalyst for this kind of reactions.
In summary, we have developed an efficient
method of synthesis of functionalized tetrahydropyri-
dines, which is suitable for combinatorial synthesis,
through a one-pot three-component reaction catalyzed
by NO2-Fe(III)PcCl@C in ethanol under reflux.
Attractive features of the proposed procedure are
environmental safety, high efficiency, high yield,
simple operation, wide application range, and low cost
and recyclability of the catalyst.
The reaction of benzaldehyde with aniline and ethyl
acetoacetate was also performed using recovered
catalyst. The catalyst was regenerated by filtration of
the reaction mixture at the reaction temperature,
washing with ethanol, and drying in air. The recycled
catalyst showed the same activity as that of a fresh
catalyst. The yield of 1 under the general conditions
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

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JIAO-DAN WANG et al.
Table 2. NO2Fe(III)PcCl@C-catalyzed synthesis of tetrahydropyridines 1–30a
Comp.
no.
Comp.
no.
R1
R2
Yield,b %
R1
R2
Yield,b %
1
2
3-BrC6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
89
88
81
83
85
79
88
84
86
78
81
89
83
86
84
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
2,4-Cl2C6H3
3-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
Ph
90
89
86
85
84
82
87
88
81
83
85
86
82
87
89
3
4-ClC6H4
4-MeC6H4
2,4-Cl2C6H3
3-NO2C6H4
4-NO2C6H4
4-MeC6H4
4-ClC6H4
2-FC6H4
3-BrC6H4
3-NO2C6H4
4-ClC6H4
4-MeC6H4
Ph
4-NO2C6H4
3-NO2C6H4
4-MeC6H4
4-ClC6H4
4
5
6
7
2,4-Cl2C6H3
3-NO2C6H4
Ph
8
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-BrC6H4
9
10
11
12
13
14
15
3-BrC6H4
4-NO2C6H4
2-FC6H4
Thiophen-2-yl
Thiophen-2-yl
Thiophen-2-yl
4-BrC6H4
4-BrC6H4
4-ClC6H4
4-BrC6H4
a
Aldehyde (2.0 mmol), amine (2.0 mmol), ethyl acetoacetate (1.0 mmol), NO2Fe(III)PcCl@C (5–6 mol %), acetic acid (5–6 drops),
ethanol (20 mL); reflux, 2 h.
Isolated yield.
b
EXPERIMENTAL
The H and 13C NMR spectra were recorded in
(5–6 mol %) in 20 mL of anhydrous ethanol containing
5–6 drops of glacial acetic acid was refluxed for 2 h.
When the reaction was complete (TLC), the
transparent reaction mixture was filtered while hot to
remove the catalyst. The filtrate was allowed to cool
down without external cooling and kept for 30 min,
and product was filtered off and recrystallized from
THF–EtOH (1 : 1 by volume).
1
CDCl3 -on a Varian INOVA spectrometer (400 and 100
MHz, respectively). The mass spectra (electrospray
ionization) were obtained with an Agilent AXIMA-
CFR-plus MALDI-TOF mass spectrometer. The IR
spectra were taken on a Bruker EQUINOX 55 FT-IR
spectrometer. The melting points were determined by
means of an XT-4 melting point microscope without
correction. The progress of reactions and the purity of
the final products were monitored by TLC on silica gel
using petroleum ether–ethyl acetate (4 : 1) as eluent.
All reagents and solvents were commercial products
and were used without further purification. The
catalyst NO2Fe(III)PcCl@C was prepared according to
the procedure described in [15].
Ethyl 4-anilino-2,6-bis(3-bromophenyl)-1-phenyl-
1,2,5,6-tetrahydropyridine-3-carboxylate (1). Yield
89%, mp 179–180°C. IR spectrum, ν, cm–1: 3430,
1
1651, 1586. H NMR spectrum, δ, ppm: 1.47 t (3H,
CH3 J = 7.2 Hz), 2.76–2.87 d.d (2H, CH2, J = 15.2,
13.2 Hz), 4.33–4.46 m (2H, CH2), 5.15 d (1H, CH, J =
4.4 Hz), 6.46 s (1H, CH), 6.52–7.31 m (18H, Harom),
10.29 s (1H, NH). Mass spectrum: m/z 653.0416 [M +
Na]+. C32H28Br2N2O2. Calculated: [M + Na]+. 653.0415.
Typical procedure for the synthesis of tetrahyd-
ropyridine derivatives 1–30. A mixture of ethyl aceto-
acetate (1.0 mmol), aromatic aldehyde (2.0 mmol),
aromatic amine (2 mmol), and NO2-Fe(III)PcCl@C
Ethyl 4-anilino-1,2,6-triphenyl-1,2,5,6-tetrahyd-
ropyridine-3-carboxylate (2). Yield 88%, mp 175–
1
176°C. IR spectrum, ν, cm–1: 3430, 1651, 1585. H
NMR spectrum, δ, ppm: 1.48 m (3H, CH3), 2.74–2.83
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

NO2-Fe(III)PcCl@C -CATALYZED ONE-POT SYNTHESIS
825
1
d.d (2H, CH2, J = 15.2, 13.2 Hz), 4.32–4.49 m (2H,
CH2), 5.10 d (1H, CH, J = 4.4 Hz), 6.37 s (1H, CH),
6.35–7.54 m (20H, Harom), 10.29 s (1H, NH). 13C NMR
spectrum, δC, ppm: 14.8, 33.6, 55.1, 58.2, 59.7, 98.2,
113.0, 116.2, 125.7, 125.8, 126.3, 126.4, 126.7, 127.2,
128.3, 128.7, 128.8, 128.9, 137.9, 142.8, 144.0, 147.0,
156.1, 168.2. Mass spectrum: m/z 497.2206 [M + Na]+.
C32H30N2O2. Calculated: [M + Na]+ 497.2205.
1658, 1600. H NMR spectrum, δ, ppm: 1.47 t (3H,
CH3, J = 7.1 Hz), 2.76–2.82 m (2H, CH2), 4.33–4.44 m
(2H, CH2), 5.11 s (1H, CH), 6.33 s (1H, CH), 6.45–
7.30 m (18H, Harom), 10.28 s (1H, NH). Mass spectrum:
m/z 587.1911 [M + Na]+. C32H28N4O6. Calculated:
[M + Na]+ 587.1907.
Ethyl 4-(4-methoxyanilino)-1-(4-methoxyphenyl)-
2,6-bis(4-methylphenyl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (8). Yield 84%, mp 221–224°C. IR
spectrum, ν, cm–1: 3419, 1660, 1510. 1H NMR
spectrum, δ, ppm: 1.38 t (3H, CH3, J = 6.9 Hz), 2.32 s
(6H, CH3), 2.76–2.87 m (2H, CH2), 3.8 s (6H, OCH3),
4.32–4.49 m (2H, OCH2), 5.01 s (1H, CH), 6.28 s (1H,
CH), 6.22–7.19 m (16H, Harom), 10.13 s (1H, NH).
Mass spectrum: m/z 585.2703 [M + Na]+. C36H38N2O4.
Calculated: [M + Na]+ 585.2729.
Ethyl 4-anilino-2,6-bis(4-chlorophenyl)-1-phenyl-
1,2,5,6-tetrahydropyridine-3-carboxylate (3). Yield
81%, mp 225–226°C. IR spectrum, ν, cm–1: 3420,
1
1651, 1594. H NMR spectrum, δ, ppm: 1.45 t (3H,
CH3, J = 7.1 Hz), 2.75–2.83 d.d (2H, CH2, J = 15.2,
15.2 Hz,), 4.32–4.45 m (2H, CH2), 5.10 s (1H , CH),
6.36 s (1H, CH), 6.43–7.25 m (18H, Harom), 10.29 s
(1H, NH). Mass spectrum: m/z 565.1423 [M + Na]+.
C32H28Cl2N2O2. Calculated: [M + Na]+ 565.1425.
Ethyl 2,6-bis(4-chlorophenyl)-4-(4-methoxy-
anilino)-1-(4-methoxyphenyl)-1,2,5,6-tetrahydro-
pyridine-3-carboxylate (9). Yield 86%, mp 213–214°
Ethyl 4-anilino-2,6-bis(4-methylphenyl)-1-
phenyl-1,2,5,6-tetrahydropyridine-3-carboxylate
(4). Yield 83%, mp 230–231°C. IR spectrum, ν, cm–1:
C. IR spectrum, ν, cm–1: 3423, 1622, 1515. H NMR
1
1
3420, 1651, 1594. H NMR spectrum, δ, ppm: 1.46 t
spectrum, δ, ppm: 1.37 t (3H, CH3, J = 6.8 Hz), 2.74–
2.83 d.d (2H, CH2, J = 15.2,13.2 Hz), 3.77 s (6H,
OCH3), 4.32–4.49 m (2H, CH2), 5.10 d (1H, CH, J =
4.4 Hz), 6.37 s (1H, CH), 6.35–7.54 m (16H, Harom),
10.29 s (1H, NH). Mass spectrum: m/z 625.1460 [M +
Na]+. C34H32Cl2N2O4. Calculated: [M + Na]+ 625.1637.
(3H, CH3, J = 6.9 Hz), 2.32 s (6H, CH3), 2.76–2.86 d.d
(2H, CH2-, J = 13.6, 15.2 Hz), 4.31–4.45 m (2H, CH2),
5.11 d (1H, CH, J = 3.2 Hz), 6.40 s (1H, CH), 6.30–
6.66 m (18H, Harom), 10.29 s (1H, NH). Mass spectrum:
m/z 525.2558 [M + Na]+. C34H34N2O2. Calculated:
[M + Na]+ 525.2518.
Ethyl 2,6-bis(2-fluorophenyl)-4-(4-methoxy-
anilino)-1-(4-methoxyphenyl)-1,2,5,6-tetrahydro-
pyridine-3-carboxylate (10). Yield 78%, mp 204–
Ethyl 4-anilino-2,6-bis(2,4-dichlorophenyl)-1-
phenyl-1,2,5,6-tetrahydropyridine-3-carboxylate
(5). Yield 85%, mp 285–286°C. IR spectrum, ν, cm–1:
205°C. IR spectrum, ν, cm–1: 3438, 1651, 1500. H
1
1
3430, 1660, 1595. H NMR spectrum, δ, ppm: 1.32 t
NMR spectrum, δ, ppm: 1.32 t (3H, CH, J = 7.2 Hz),
2.76–2.79 m (2H, CH2), 3.75 s (6H, OCH3), 4.20–4.32
m (2H, CH2), 5.19 s (1H, CH), 6.35 s (1H, CH), 6.43–
7.18 m (16H, Harom), 10.12 s (1H, NH). Mass
spectrum: m/z 593.2261 [M + Na]+. C34H32F2N2O4.
Calculated: [M + Na]+ 593.2228.
(3H, CH3, J = 7.2 Hz), 2.77–2.97 d.d (2H, CH2, J =
15.2, 13.2 Hz), 4.27 q (2H, CH2), 5.26 t (1H, CH, J =
5.2 Hz), 6.32 s (1H, CH), 6.38–7.40 m (16H, Harom),
10.21 s (1H, NH). Mass spectrum: m/z 633.0632 [M +
Na]+. C32H26Cl4N2O2. Calculated: [M + Na]+ 633.0646.
Ethyl 4-anilino-2,6-bis(3-nitrophenyl)-1-phenyl-
1,2,5,6-tetrahydropyridine-3-carboxylate (6). Yield
79%, mp 181–182°C. IR spectrum, ν, cm–1: 3422,
Ethyl 2,6-bis(3-bromophenyl)-4-(4-methoxy-
anilino)-1-(4-methoxyphenyl)-1,2,5,6-tetrahydro-
pyridine-3-carboxylate (11). Yield 81%, mp 179–
1
1
1659, 1558. H NMR spectrum, δ, ppm: 1.49 s (3H,
180°C. IR spectrum, ν, cm–1: 3430, 1642, 1510. H
CH3), 2.77–2.84 m (2H, CH2), 4.32–4.44 m (2H, CH2),
5.12 s (1H, CH), 6.35 s (1H, CH), 6.42–7.28 m (18H,
NMR spectrum, δ, ppm: 1.44 t (3H, CH3, J = 7.1 Hz),
2.62–2.74 m (2H, CH2), 3.77 s (6H, OCH3), 4.29–4.46
m (2H, CH2), 5.00 t (1H, CH, J = 5.1 Hz), 6.38 s (1H,
CH), 6.27–7.51 m (16H, Harom), 10.12 s (1H, NH).
Mass spectrum: m/z 713.0627 [M + Na]+. C34H32Br2N2O4.
Calculated: [M + Na]+ 713.0626.
H
arom), 10.27 s (1H, NH). Mass spec-trum: m/z
587.1909 [M + Na]+. C32H28N4O6. Cal-culated: M + Na
587.1907.
Ethyl 4-anilino-2,6-bis(4-nitrophenyl)-1-phenyl-
1,2,5,6-tetrahydropyridine-3-carboxylate (7). Yield
88%, mp 247–250°C. IR spectrum, ν, cm–1: 3428,
Ethyl 4-(4-methoxyanilino)-1-(4-methoxyphenyl)-
2,6-bis(3-nitrophenyl)-1,2,5,6-tetrahydropyridine-
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JIAO-DAN WANG et al.
3-carboxylate (12). Yield 89%, mp 240–241°C. IR
Ethyl 4-(4-bromoanilino)-2,6-bis(3-bromo-
phenyl)-1-(4-bromophenyl)-1,2,5,6-tetrahydro-
pyridine-3-carboxylate (17). Yield 89%, mp 165–
1
spectrum, ν, cm–1: 3428, 1644, 1511. H NMR spec-
trum, δ, ppm: 1.44 t (3H, CH3, J = 7.1 Hz), 2.77–2.82
d.d (2H, CH2, J = 13.6, 15.2 Hz), 3.80 s (6H, OCH3),
4.31–4.49 m (2H, CH2), 5.11 s (1H, CH), 6.35 s (1H,
CH), 6.31–7.43 m (16H, Harom), 10.20 s (1H, NH).
Mass spectrum: m/z 647.2125 [M + Na]+. C34H32N4O8.
Calculated: [M + Na]+ 647.2118.
1
166°C. IR spectrum, ν, cm–1: 3420, 1642, 1594. H
NMR spectrum, δ, ppm: 1.41 t (3H, CH3, J = 7.1 Hz),
2.70–2.80 m (2H, CH2), 4.32–4.49 m (2H, CH2), 5.06 s
(1H, CH), 6.34 s (1H, CH), 7.02–7.49 m (16H, Harom),
10.24 s (1H, NH). Mass spectrum: m/z 808.8621 [M +
Na]+. C32H26Br2N2O2. Calculated: [M + Na]+ 808.8625.
Ethyl 4-(4-bromoanilino)-1-(4-bromophenyl)-2,6-
bis(4-chlorophenyl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (13). Yield 89%, mp 159–160°C. IR
spectrum, ν, cm–1: 3439, 1651, 1613. 1H NMR
spectrum, δ, ppm: 1.46 t (3H, CH3, J = 7.0 Hz), 2.70–
2.84 m (2H, CH2), 4.32–4.46 m (2H, CH2), 5.06 s (1H,
CH), 6.38 s (1H, CH), 6.12–7.12 m (16H, Harom), 10.23
s (1H, NH). Mass spectrum: m/z 720.9643 [M + Na]+.
C32H26Br2Cl2N2O2. Calculated: [M + Na]+ 720.9636.
Ethyl 4-(4-bromoanilino)-1-(4-bromophenyl)-2,6-
bis(4-nitrophenyl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (18). Yield 86%, mp 240–241°C. IR
spectrum, ν, cm–1: 3422, 1650, 1588. 1H NMR
spectrum, δ, ppm: 1.45 t (3H, CH3, J = 7.1 Hz), 2.75–
2.85 m (2H, CH2), 4.33–4.47 m (2H, CH2), 5.10 s (1H,
CH), 6.39 s (1H, CH), 6.28–7.20 m (18H, Harom), 10.23
s (1H, NH). Mass spectrum: m/z 743.0118 [M + Na]+.
C32H26Br2N4O6. Calculated: [M + Na]+ 743.0117.
Ethyl 4-(4-bromoanilino)-1-(4-bromophenyl)-2,6-
bis(4-methylphenyl)-1,2,5,6-tetrahydropyridne-
3-carboxylate (14). Yield 86%, mp 253–254°C. IR
Ethyl 4-(4-bromoanilino)-1-(4-bromophenyl)-2,6-
bis(3-nitrophenyl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (19). Yield 85%, mp 194–195°C. IR
1
spectrum, ν, cm–1: 3422, 1655, 1600. H NMR spec-
1
spectrum, ν, cm–1: 3415, 1666, 1590. H NMR spec-
trum, δ, ppm: 1.47 t (3H, CH3, J = 7.2 Hz), 2.33 s (6H,
CH3), 2.70–2.85 d.d (2H, CH2, J = 15.2, 15.2 Hz), 4.33–
4.47 m (2H, CH2), 5.17 d (1H, CH, J = 4.9 Hz), 6.40 s
(1H, CH), 6.10–7.23 m (16H, Harom), 10.23 s (1H,
NH). Mass spectrum: m/z 681.0411 [M + Na]+.
C34H32Br2N2O2. Calculated: [M + Na]+ 681.0415.
trum, δ, ppm: 1.45 t (3H, CH3, J = 7.1 Hz), 2.75–2.86
m (2H, CH2), 4.32–4.46 m (2H, CH2), 5.11 s (1H,
CH), 6.41 s (1H, CH), 6.28–7.31 m (16H, Harom), 10.23
s (1H, NH). Mass spectrum: m/z 743.0120 [M + Na]+.
C32H26Br2N4O6. Calculated: [M + Na]+ 743.0117.
Ethyl 4-(4-chloroanilino)-1-(4-chlorophenyl)-2,6-
bis(4-methylphenyl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (20). Yield 84%, mp 221–222°C. IR
Ethyl 4-(4-bromoanilino)-1-(4-bromophenyl)-2,6-
diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate
(15). Yield 84%, mp 197–198°C. IR spectrum, ν, cm–1:
1
spectrum, ν, cm–1: 3430, 1642, 1604. H NMR spec-
1
3428, 1658, 1600. H NMR spectrum, δ, ppm: 1.47 t
trum, δ, ppm: 1.47 t (3H, CH3, J = 7.2 Hz), 2.33 s (6H,
CH3), 2.70–2.85 d.d (2H, CH2, J = 15.2, 15.2 Hz), 4.33–
4.47 m (2H, CH2), 5.17 s (1H, CH), 6.40 s (1H, CH),
6.10–7.23 m (16H, Harom), 10.23 s (1H, NH). Mass
spectrum: m/z 593.1722 [M + Na]+. C34H32Cl2N2O2.
Calculated: M + Na 593.1738.
(3H, CH3, J = 7.1 Hz), 2.76–2.82 m (2H, CH2), 4.33–
4.44 m (2H, CH2), 5.11 s (1H, CH), 6.33 s (1H, CH),
6.45–7.30 m (18H, Harom), 10.28 s (1H, NH). 13C NMR
spectrum, δC, ppm: 14.8, 33.4, 55.2, 58.3, 59.9, 98.7,
114.0, 121.2, 128.5, 128.6, 128.8, 129.0, 131.4, 136.4,
142.3, 143.3, 145.5, 155.3, 168.2. Mass spectrum: m/z
653.0411 [M + Na]+. C32H28Br2N2O2. Calculated: [M +
Na]+ 653.0415.
Ethyl 4-(4-chloroanilino)-1,2,6-tris(4-chloro-
phenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate
(21). Yield 82%, mp 181–182°C. IR spectrum, ν, cm–1:
Ethyl 4-(4-bromoanilino)-1-(4-bromophenyl)-2,6-
bis(2,4-dichlorophenyl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (16). Yield 90%, mp 258–259°C. IR
spectrum, ν, cm–1: 3433, 1640, 1583. 1H NMR
spectrum, δ, ppm: 1.46 t (3H, CH3, J = 6.9 Hz), 2.69–
2.85 m (2H, CH2), 4.31–4.47 m (2H, CH2), 5.11 s (1H,
CH), 6.35 s (1H, CH), 6.12–7.19 m (14H, Harom), 10.23
s (1H, NH). Mass spectrum: m/z 788.8863 [M + Na]+.
C32H24Br2Cl4N2O2. Calculated: [M + Na]+ 788.8856.
1
3411, 1653, 1587. H NMR spectrum, δ, ppm: 1.47 t
(3H, CH3, J = 7.1 Hz), 2.69–2.83 m (2H, CH2), 4.32–
4.46 m (2H, CH2), 5.08 s (1H, CH), 6.32 s (1H, CH),
6.17–7.09 m (16H, Harom), 10.23 s (1H, NH). Mass
spectrum: m/z 633.0642 [M + Na]+. C32H26Cl4N2O2.
Calculated: M + Na 633.0646.
Ethyl 4-(4-chloroanilino)-1-(4-chlorophenyl)-2,6-
bis(2,4-dichlorophenyl)-1,2,5,6-tetrahydropyridine-
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NO2-Fe(III)PcCl@C -CATALYZED ONE-POT SYNTHESIS
827
3-carboxylate (22). Yield 87%, mp 231–232°C. IR
3-carboxylate (27). Yield 86%, mp 161–162°C. IR
spectrum, ν, cm–1: 3410, 1648, 1539. 1H NMR
spectrum, δ, ppm: 1.46 t (3H, CH3, J = 7.1 Hz), 2.35–
2.93 m (2H, CH2), 4.32–4.45 m (2H, CH2), 5.28 s (1H,
CH), 6.37 s (1H, CH), 6.32–7.18 m (16H, Harom), 10.35
s (1H, NH). Mass spectrum: m/z 601.1237 [M + Na]+.
C32H26F2Cl2N2O2. Calculated: [M + Na]+ 601.1236.
1
spectrum, ν, cm–1: 3422, 1655, 1613. H NMR spec-
trum, δ, ppm: 1.46 t (3H, CH3, J = 7.2 Hz), 2.70–2.84
m (2H, CH2), 4.31–4.48 m (2H, CH2), 5.11 s (1H,
CH), 6.34 s (1H, CH), 6.15–7.22 m (14H, Harom), 10.23
13
s (1H, NH). C NMR spectrum, δC, ppm: 14.8, 33.4,
55.3, 58.3, 59.9, 98.7, 114.0, 121.2, 128.4, 128.7,
128.8, 129.0, 131.4, 136.4, 142.3, 143.2, 145.5, 155.4,
168.2. Mass spectrum: m/z 700.9860 [M + Na]+.
C32H24Cl6N2O2. Calculated: [M + Na]+ 700.9867.
Ethyl 4-anilino-1-phenyl-2,6-di(thiophen-2-yl)-
1,2,5,6-tetrahydropyridine-3-carboxylate (28). Yield
82%, mp 255–256°C. IR spectrum, ν, cm–1: 3425,
1
Ethyl 4-(4-chloroanilino)-1-(4-chlorophenyl)-2,6-
bis(3-nitrophenyl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (23). Yield 88%, mp 161–162°C. IR
1650, 1593. H NMR spectrum, δ, ppm: 1.45 t (3H,
CH3, J = 7.2 Hz), 2.70–2.85 d.d (2H, CH2, J = 15.2,
13.2 Hz), 4.23–4.45 m (2H, CH2), 5.10 s (1H, CH),
6.35 s (1H, CH), 6.32–7.46 m (16H, Harom), 10.24 s
(1H, NH). Mass spectrum: m/z 509.1334 [M + Na]+.
C28H26N2O2S2. Calculated: [M + Na]+ 509.1333.
1
spectrum, ν, cm–1: 3390, 1638, 1589. H NMR spec-
trum, δ, ppm: 1.45 t (3H, CH3, J = 7.2 Hz), 2.69–2.85
m (2H, CH2), 4.33–4.46 m (2H, CH2), 5.12 s (1H,
CH), 6.40 s (1H, CH), 6.17–7.22 m (16H, Harom), 10.24
s (1H, NH). Mass spectrum: m/z 655.1127 [M + Na]+.
C32H26Cl2N4O6. Calculated: [M + Na]+ 655.1130.
Ethyl 4-(4-bromoanilino)-1-(4-bromophenyl)-2,6-
di(thiophen-2-yl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (29). Yield 87%, mp 277–278°C. IR
Ethyl 4-(4-chloroanilino)-1-(4-chlorophenyl)-2,6-
diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate
(24). Yield 81%, mp 201–202°C. IR spectrum, ν, cm–1:
1
spectrum, ν, cm–1: 3425, 1644, 1600. H NMR spec-
trum, δ, ppm: 1.45 t (3H, CH3, J = 7.1 Hz), 2.69–2.86
m (2H, CH2), 4.25–4.46 m (2H, CH2), 5.10 s (1H, CH),
6.37 s (1H, CH), 6.31–7.48 m (14H, Harom), 10.23 s
(1H, NH). Mass spectrum: m/z 664.9551. C28H24Br2N2O2S2
[M + Na]+. Calculated: [M + Na]+ 664.9544.
1
3421, 1651, 1604. H NMR spectrum, δ, ppm: 1.47 t
(3H, CH3, J = 7.0 Hz), 2.70–2.85 m (2H, CH2), 4.33–
4.47 m (2H, CH2), 5.10 s (1H, CH), 6.40 s (1H, CH),
6.10–7.30 m (18H, Harom), 10.24 s (1H, NH). Mass
spectrum: m/z 565.1408 [M + Na]+. C32H28Cl2N2O2.
Calculated: [M + Na]+ 565.1425.
Ethyl 4-(4-chloroanilino)-1-(4-chlorophenyl)-2,6-
di(thiophen-2-yl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (30). Yield 89%, mp 234–235°C. IR
spectrum, ν, cm–1: 3433, 1651, 1604. 1H NMR
spectrum, δ, ppm: 1.46 t (3H, CH3, J = 6.8 Hz), 2.69–
2.82 m (2H, CH2), 4.26–4.47 m (2H, CH2), 5.07 s (1H,
CH), 6.33 s (1H, CH), 6.28–7.48 m (14H, Harom), 10.24
s (1H, NH). Mass spectrum: m/z 577.0561 [M + Na]+.
C28H24Cl2N2O2S2. Calculated: [M + Na]+ 577.0554.
Ethyl 2,6-bis(3-bromophenyl)-4-(4-chloro-
anilino)-1-(4-chlorophenyl)-1,2,5,6-tetrahydro-
pyridine-3-carboxylate (25). Yield 83%, mp 239–
1
241°C. IR spectrum, ν, cm–1: 3430, 1651, 1604. H
NMR spectrum, δ, ppm: 1.45 t (3H, CH3, J = 7.0 Hz),
2.36–3.08 d.d (2H, CH2, J = 15.2, 13.6 Hz), 4.31–4.44
m (2H, CH2), 5.33 s (1H, CH), 6.36 s (1H, CH), 6.47–
7.10 m (16H, Harom), 10.41 s (1H, NH). Mass
spectrum: m/z 720.9689 [M + Na]+. C32H26Br2Cl2N2O2.
Calculated: [M + Na]+ 720.9636.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from
the Industrial Research Project of Shaanxi Science and
Technology Department (2014K08-29), Science and
Technology Plan Project of Xi’an [CXY1511(7)], and
the Scientific Research Foundation of Northwestern
University.
Ethyl 4-(4-chloroanilino)-1-(4-chlorophenyl)-2,6-
bis(4-nitrophenyl)-1,2,5,6-tetrahydropyridine-
3-carboxylate (26). Yield 85%, mp 204–205°C. IR
1
spectrum, ν, cm–1: 3433, 1655, 1580. H NMR spec-
trum, δ, ppm: 1.46 t (3H, CH3, J = 7.1 Hz), 2.70–2.85
d.d (2H, CH2, J = 15.2, 13.2 Hz), 4.32–4.45 m (2H,
CH2), 5.11 s (1H, CH), 6.40 s (1H, CH), 6.17–7.20 m
(16H, Harom), 10.24 s (1H, NH). Mass spectrum: m/z
655.1127 [M + Na]+. C32H26Cl2N4O6. Calculated: [M +
Na]+ 655.1129.
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