Reusable Ce-V Loaded Alumina Catalyst for Multicomponent Synthesis of Substituted Pyridines in Green Media

Article abstract of DOI:10.1002/jhet.2430

Ce-V/Al2O3 as an effective heterogeneous catalyst is synthesized by a simple technique. The catalyst was identified by powder X-ray diffraction, SEM, TEM, and BET surface area analysis. The catalyst is fully recyclable and reusable for several runs preser

Full text of DOI:10.1002/jhet.2430

Month 2015 Reusable Ce-V Loaded Alumina Catalyst for Multicomponent Synthesis of
Substituted Pyridines in Green Media
a
a
a
b
*
Suresh Maddila, Surya N. Maddila, Sreekantha B. Jonnalagadda, and Palakondu Lavanya
aSchool of Chemistry, University of KwaZulu-Natal, West Ville Campus, Chilten Hills, Durban 4000, South Africa
bDepartment of Chemistry, Annamacharya Institute of Technology & Sciences, J.N.T. University, Tirupati 517 502,
Andhra Pradesh, India
*
E-mail: gajulapallilavanya@gmail.com
Received December 27, 2014
DOI 10.1002/jhet.2430
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
Ce-V/Al2O3 as an effective heterogeneous catalyst is synthesized by a simple technique. The catalyst was
identified by powder X-ray diffraction, SEM, TEM, and BET surface area analysis. The catalyst is fully re-
cyclable and reusable for several runs preserving its high activity. The catalytic activity of Ce-V/Al2O3 is
described by synthesis of a series of multisubstituted pyridines in good to excellent yields via a facile
one-pot multicomponent reaction within shorter reaction time.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
heterogeneous catalysts for the synthesis of heterocyclic
compound is a topic of present interest.
Multicomponent reactions (MCRs) have been developed
as an efficient and powerful implements in modern syn-
thetic organic [1], bioactive medicinal [2], pharmaceutical
[3], agro [4], and combinatorial chemistry [5], because of
the synthesis of these complex molecules from simple
and readily available substrates that can be accomplished
in a very fast and efficient manner without use of chro-
matograms for any intermediates. Advantages of MCRs
are wide, including simple protocols, low-cost reactants,
and green principles. Therefore, developing new MCRs
and improving known MCRs are widespread areas of re-
search in current heterocyclic synthesis. Thus, such envi-
ronmentally benign protocols are suitable and well desired.
Heterogeneous catalysts have attracted much consider-
ation in heterocyclic synthesis because of several benefits
which include reusability, cost effectiveness, non-
environmental compatibility, non-harsh, and ease of sepa-
ration [6–8]. Among the various solid catalysts, metal
doped with silica has attracted widespread attention
because of its unique properties, including high surface
area, excellent thermal stability, large pore volume, and
tunable pore diameter [9,10]. For these reasons, develop-
ment of metal-functionalized alumina as recoverable
Synthesis of polysubstituted pyridines and its derivatives
have recently fascinated much interest because of their
biological and pharmacological activities [11]. They are
constituents of many pharmaceuticals and natural products,
which reveal wide range of biological activity [12]. Within
a long-term research program aimed at developing pharma-
ceutically active materials, synthesis of substituted pyridines
are of special implication because of varied biological
activities [13] such as anticancer [14], antimicrobial [15],
antibacterial [16], antifungal [17], anti-inflammatory [18],
antioxidant activity [19], cytotoxicity [20], and anti-HIV
[21]. Thus, the synthesis of polysubstituted pyridine
derivatives have fascinated many researchers, and several
approaches have been pursued using catalysts, such as
K2CO3 [22], NaH [23], Et3N [24], [bmIm]OH [25], ZnCl2
[26], DBU [27], MgO [28], KF/Al2O3 [29], H3BO3 [30],
and NaOH [31].
In continuation of our research work in the domains of
MCRs [32–35] herein, we report a novel, environmentally
benign, a facile and efficient method for the first time of the
use of Ce-V/Al2O3 as heterogeneous catalyst to promote a
fast MCR protocol for the synthesis of polysubstituted pyr-
idines at room temperature (R.T.) in eco-friendly in aque-
ous ethanol media (Scheme 1).
© 2015 HeteroCorporation

S. Maddila, S. N. Maddila, S. B. Jonnalagadda, and P. Lavanya
Vol 000
Scheme 1. Synthesis of multisubstituted pyridines (4a-k).
4a in various solvents was examined. It was found that
only a trace of the target molecule was obtained in H2O
or Dichloromethane (DCM) for 10h (Table 1, entries 1
and 2) and in MeOH, EtOH, or MeCN, the cyclization
reaction was slow, and the yield of product was minor after
6 h (25–38%, Table 1, entries 3–5), while the addition of
equal ratio of water to them could efficiently accelerate
the reaction and increase its yield (65–90%, Table 1,
entries 6–8), the reason is that the addition of water is
favorable to excited state intramolecular proton transfer.
From the economic and environmental point of view,
EtOH :H2O (1:1) was finally chosen as the reaction
medium for all further reactions. Further, the reaction was
investigated under various catalysts. Low amount of the
anticipated product was achieved, when K2CO3 and NaOH
were used as catalysts (Table 1, entries 9 and 10). With
Ce/Al2O3, V/Al2O3, and simple alumina as catalyst, a
61%, 58%, and 48% yield was obtained (Table 1, entries
11–13), respectively. Then, we tried to synthesize the het-
erocyclic framework using Ce-V/Al2O3 as catalyst with
aqueous ethanol as solvent. To our delight, MCR was ac-
complished successfully, just in 1 h at R.T. and obtained
the expected substituted pyridines selectively and in good
yield. The heterogeneous catalyzed reaction was found to
proceed almost instantaneously, although it took about
1 h for completion of reaction. In the proposed MCR, Ce-
V/Al2O3 displayed greater efficiency compared with the
other catalysts investigated because of its synergetic effect
of the metals. The surface properties of this catalyst can be
modified by loading cations of varied properties. Inclusion
of Ce3+, V3+ into the place of Al3+ provides acidity and
acidic sites on the catalyst surface. An optimal distribution
of the acidic and basic sites due to loading of Ce-V/Al2O3
mixed oxides possibly contributed to its enhanced catalytic
efficiency, which is evident from the high yield, selectivity,
and speed of the reaction achieved in the title reaction.
Consequently, to find the optimal quantity of catalyst
needed, the reaction was carried out using various amounts
of catalyst at R.T. It was found that 30mg of catalyst gave
maximum yield of 94% in 1 h. Using more than 30mg of
catalyst for the reaction had no significant improvement
on the yield or the reaction time. However, the decrease
in amount of the catalyst from 20 to 10mg, affected the
product yield by reducing to 70% and 66%, respectively
(Table 1, entries 14–17).
RESULTS AND DISCUSSION
To determine the optimum conditions, reaction of benz-
aldehyde, malononitrile, and ethanol for the synthesis of
polysubstituted pyridines, in the presence of Ce-V/Al2O3
as catalyst, was preferred as ideal reaction (Table 1). In
the first example, benzaldehyde (1 mmol), malononitrile
(2.2 mmol), aqueous ethanol (1:1 ratio), and catalyst
(30 mg) were stirred at R.T. The condensation reaction of
Table 1
Optimization condition for the synthesis of multisubstituted pyridines by
Ce-V/Al2O3 catalysta.
Time Yield
Entry
1
Catalyst
Solvent
H2O
Condition
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
R.T.
(h)
(%)b
21
18
30
38
25
76
94
61
48
40
61
58
39
94
95
70
66
Ce-V/Al2O3
(30 mg)
Ce-V/Al2O3
(30 mg)
Ce-V/Al2O3
(30 mg)
Ce-V/Al2O3
(30 mg)
Ce-V/Al2O3
(30 mg)
Ce-V/Al2O3
(30 mg)
Ce-V/Al2O3
(30 mg)
Ce-V/Al2O3
(30 mg)
10
2
DCM
MeOH
EtOH
MeCN
10
6
3
4
6
5
6
6
MeOH :
H2O
EtOH :
H2O
MeCN :
H2O
EtOH :
H2O
EtOH :
H2O
EtOH :
H2O
EtOH :
H2O
EtOH :
H2O
EtOH :
H2O
EtOH :
H2O
EtOH :
H2O
EtOH :
H2O
3
7
1
8
4
9
K2CO3
3
10
11
12
13
14
15
16
17
NaOH
5
Ce/Al2O3
V/Al2O3
Al2O3
3.5
4
4.5
1
Ce-V/Al2O3
(40 mg)
Ce-V/Al2O3
(50 mg)
Ce-V/Al2O3
(20 mg)
Ce-V/Al2O3
(10 mg)
The scope of the Ce-V/Al2O3 catalyzed MCR was fur-
ther explored. Choosing the conditions optimal for the syn-
thesis of 4a, that is, 30mg of Ce-V/Al2O3 at R.T. and
EtOH :H2O as solvent (Scheme 1), we employed varied
structurally different aldehydes (1a–k) for the MCR. To
our delight, most of the reactions afforded desired pyridine
derivatives (4a–k) in good yields (86–94%) with good se-
lectivity and with no byproducts. The results are depicted
in Table 2. The MCRs with substrates bearing electron-
1
2
2.5
aAll product were characterized by 1H NMR, 13C NMR, and 15N NMR
(GHSQC) spectral analysis.
bIsolated yields.
No reaction.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Reusable Ce-V Loaded Alumina Catalyst for Multicomponent Synthesis of
Substituted Pyridines in Green Media
Table 2
Synthesis of multisubstituted pyridines catalyzed by Ce-V/Al2O3 catalyst.
donating or electron-withdrawing groups on the aromatic
ring proceeded smoothly and formed the corresponding
multisubstituted pyridines in good yields under the chosen
conditions. Structures of the multisubstituted pyridines
Yield
(%)
Mp
°C
Entry
R
Product
4a
Lit mp °C
1
(4a–k) were established and confirmed on the basis of H
NMR, 13C NMR, 15N NMR (GHSQC), and HR-MS spec-
tral analysis.
1
H
94
92
89
91
88
86
92
90
87
94
93
179–
180
185–
187
255–
256
208–
210
169–
171
223–
224
205–
206
190–
192
—
2
2-MeO
3-MeO
2-Cl
4b
4c
185–186 [31]
Powder X-ray diffractogram. The powder diffraction
patterns (Fig. 1) of 1%, 2.5%, and 5 wt% Ce-V/Al2O3
catalyst reveals that different phases of metal oxides are
present with alumina support (Joint Committee on
Powder Diffraction Standards [JCPDS] file 10–425). The
presence of V2O5 phase and CeO2 phase are evident and
in agreement with the JCPDS 41–1426 and JCPDS 34–
0394, respectively. Sharp diffraction peaks of V2O5 were
observed at 2θ value of 17.4°, 26°, 42.2°, 49°, and 62.4°
as well as CeO2 peaks were also observed at 29.8°,
32.5°, 37.2°, 46.2°, 49.1°, 67.1°, and 72.4° 2θ value.
Diffractogram shows the intense and sharp characteristic
peaks of both the metal oxides with support, it means that
there may be less agglomeration of metals on the support,
and this is a very important factor to improve in catalytic
activity under reaction.
3
—
—
—
—
—
—
—
4
4d
4e
5
2-NO2
2-Br
6
4f
7
4-
4g
N(CH3)2
2-Br
8
4h
4i
9
Furyl
4-F
214–
215
10
11
4j
162– 163—164 [31]
163
214–
4-CF3
4k
—
215
aReaction conditions: aromatic aldehyde (1.0 mmol), malononitrile
(2.2 mmol), and EtOH (1 mmol), EtOH : water (1:1 v/v, 10 mL), R.T.
bAll synthesized compounds are identified, and their structures were
conformed with 1H NMR, 13C NMR spectral data, and melting points as
compared with literature values.
SEM and TEM analysis. Figure 2a is the SEM images of
the 2.5wt% Ce-V/Al2O3 catalyst, and it shows that CeO2 and
V2O5 particles are dispersed on the alumina support, and they
are in nanodimension but varying in size. During microscopy,
New compounds/no literature available.
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0
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2-Theta - Scale
CVA1 - File: CVA1.raw - Type: 2Th/Th locked - Start: 15.000 ° - End: 89.589 ° - Step: 0.014 ° - Step time: 189.5 s - Temp.: 25 °C (Room) - Time Started: 18 s - 2-Theta: 15.000 ° - Theta: 7.500 ° - Chi: 0.00 ° - Phi: 0.0
Operations: Smooth 0.150 | Background 1.000,1.000 | Smooth 0.150 | Background 1.000,1.000 | Import
Y + 20.0 mm - CVA25 - File: CVA25.raw - Type: 2Th/Th locked - Start: 15.000 ° - End: 89.589 ° - Step: 0.014 ° - Step time: 189.5 s - Temp.: 25 °C (Room) - Time Started: 17 s - 2-Theta: 15.000 ° - Theta: 7.500 ° - Ch
Operations: Smooth 0.150 | Background 1.000,1.000 | Import
Y + 40.0 mm - CVA5 - File: CVA5.raw - Type: 2Th/Th locked - Start: 15.000 ° - End: 89.589 ° - Step: 0.014 ° - Step time: 189.5 s - Temp.: 25 °C (Room) - Time Started: 17 s - 2-Theta: 15.000 ° - Theta: 7.500 ° - Chi:
Operations: Smooth 0.150 | Background 1.000,1.000 | Import
Figure 1. Powder X-ray diffraction spectra of Ce-V/Al2O3 catalyst. [Color figure can be viewed in the online issue, which is available at www.
wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Maddila, S. N. Maddila, S. B. Jonnalagadda, and P. Lavanya
Vol 000
Figure 2. (a) SEM images and (b) SEM–EDX mapping of 2.5 wt% Ce-V/Al2O3 catalyst. [Color figure can be viewed in the online issue, which is avail-
able at www.wileyonlinelibrary.com.]
BET surface area analysis. The surface characteristics
of the catalyst depend on the metal loadings of the
catalyst and type of metal particles present with the
support. It can be seen from the results, with the addition
of total 2.5 wt% Ce and V on alumina is responsible to
decrease the total surface area, pore volume, and pore size
gradually of the sample. Major change was found in the
surface properties of catalyst after impregnation of metals
on alumina, it means metals are well dispersed on the
support, and there might be possibility of blocking the
pores of the support. The isotherm (Fig. 4) shows IUPAC
type IV patterns with sharp inflections of nitrogen
adsorbed at P/P0 of about 0.60, and indicating the
presence of mesopores. BET analysis study also shows
the sharp decrease in pore volume from 0.98 to 0.49cm3/g
samples were found with similar morphology throughout the
surface. We can clearly see from images that micron size
alumina support agglomerates are present with different
morphologies and shapes. SEM–EDX image (Fig. 2b)
reveals the distribution and dispersion of both CeO2 and
V2O5 on alumina surface. Total 2.5 wt% loading of both
the metal oxides cover the maximum surface of alumina.
No agglomeration of oxide particles on support was
observed during SEM–EDX mapping. Less agglomeration
plays a very important role in catalysis, and it also helps
to provide good metal–support interaction. TEM images
of catalyst show the metal oxides present on the alumina
support with different shapes and sizes. Elongated rod
shape particles are mostly of alumina support, and the
other irregular shape particles are of metal oxides. The
size of all particles was found less than 20 nm during
random scanning under TEM (Fig. 3).
Figure 4. Nitrogen adsorption–desorption isotherm of 2.5 wt% Ce-V/
Al2O3 catalyst. [Color figure can be viewed in the online issue, which is
available at www.wileyonlinelibrary.com.]
Figure 3. TEM image of 2.5 wt% Ce-V/Al2O3 catalyst.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Reusable Ce-V Loaded Alumina Catalyst for Multicomponent Synthesis of
Substituted Pyridines in Green Media
and pore size from 12.5 to 9.3 nm in the case of bimetallic
catalyst of Ce and V with 2.5 wt% total metal loadings on
alumina in comparison with alumina only.
CHARACTERIZATION OF CATALYSTS
Micromeritics Tristar-II porosity and surface area ana-
lyzer was used for estimation of pore size, pore volume,
and surface area of the catalysts. Barret–Joyner–Halenda
adsorption–desorption curves were obtained at À196°C,
to assess the particulate properties of the catalyst. All the
catalyst materials were degassed by passing nitrogen over-
night at 200°C. Bruker D8 advance instrument with a Cu K
radiation source by λ =1.5406 was used for the X-ray dif-
fraction data for the catalyst. JEOL JEM-1010 electron mi-
croscope and JEOL JSM-6100 microscope (JEOL
Solutions for Innovation, Peabody, MA) were used for
TEM and SEM analyses, respectively. In TEM analysis
for particles distribution, size of 40–60 particles were aver-
aged and with standard deviation. An emission current
(100 μA) by a Tungsten (W) filament with 12kV accelera-
tor voltage was employed for EDX analysis of the SEM
images. Elemental composition of the catalyst materials
was established by using Inductively Coupled Plasma Op-
tical Emission Spectrometer (Optima 5300 DV Perkin-
Elmer, San Diego, CA).
Reusability of Ce-V/Al2O3.
The facile heterogeneous
character of the catalyst, recycling experiment was employed
using model reaction. After completion of reaction, the
catalyst was recovered by filtration, washed with ethanol,
and dried under vacuum. The recovered catalyst was reused
five times with a slight loss in catalytic activity. The minor
loss observed in the catalytic activity after fifth run could be
due to temporary poisoning by organic impurities or due to
minor changes in the structure and morphology of the
catalyst under the operating conditions.
CONCLUSION
In conclusion, we report an efficient and environmentally
benign one-pot multicomponent protocol for synthesis of
multisubstituted pyridines with good atom efficiency. We
have developed simple, highly efficient, and recyclable
heterogeneous catalyst Ce-V/Al2O3 for MCR protocol at
R.T., which be put into practice for the selective synthesis
of multisubstituted pyridines using eco-friendly water and
ethanol solvent. Main objectives of mild reaction condi-
tions, use of recyclable catalyst, cost-effectiveness, and
eco-friendly simple method are achieved.
General procedure for the synthesis of pyridines.
A
mixture of benzaldehyde (1mmol), malononitrile (2.2 mmol),
and ethanol (1mmol) were dissolved in water (5 mL) and
added Ce-V/Al2O3 (30 mg) catalyst at R.T. and stirred
continuously for 1 h. TLC was performed to notice the
complete consumption of starting material in the reaction
mixture. A crude product was afforded upon filtering the
reaction mass and subsequent evaporation under reduced
pressure. Further, this crude was recrystallized by EtOH
solvent to obtain pure product (4a–k). The filtered catalyst
is washed with ethanol and dried, reused for successive
EXPERIMENTAL
All chemicals and reagents required for the reaction were
of analytical grade and were used without any further
purification. Bruker AMX 400MHz NMR spectrometer
was used to record the 1H NMR, 13C NMR, and 15N NMR
Gradient Heteronuclear Single Quantum Coherence
(GHSQC) spectral values. HRMS data were obtained using
a Bruker microTOF-Q II ESI instrument operating at ambi-
ent temperature. The DMSO-d6 solution was utilized for this,
while TMS served as the internal standard. TMS was further
used as an internal standard for reporting all the chemical
shifts in δ (parts per million). Purity of all the reaction prod-
ucts was confirmed by TLC using aluminum plates coated
with silica gel (Merck Kieselgel 60 F254).
five runs.
2-Amino-6-ethoxy-4-phenylpyridine-3,5-dicarbinitrile (4a).
1H NMR (400 MHz, CDCl3, 25°C): δ= 1.46 (t, 3H,
J = 7.06 MHz, CH3), 4.58 (q, 2H, J = 7.08 MHz, CH2),
7.29 (d, 2H, J = 7.81 MHz, Ar-H), 7.43 (t, 3H,
J = 7.86 MHz, Ar-H), 7.86 (s, 2H, NH2) ppm. 15N NMR-
GHSQC (400 MHz, CDCl3, 25°C): δ= 7.86 (s, 2H, NH2)
ppm. 13C NMR (100 MHz, CDCl3, 25°C): δ= 14.9, 64.5,
82.8, 83.9, 114.2, 115.6, 127.8, 128.3, 130.4, 134.2,
159.5, 162.0, 164.9. HRMS of [C15H12N4O + H]+ (m/z):
Preparation of catalyst. The wet impregnation method
was used in the preparation of metal oxide supported
catalysts [36,37]. The catalysts were prepared by wet
impregnation method by dissolving appropriate amount
of Ce (cerium nitrate, Aldrich-99%) and V (vanadyl
sulfate, Aldrich-99%) with a ratio of 1:1 in distilled water
(50.0 mL) and adding it to 5 g of Alumina (Al2O3,
Aldrich). The mixture is stirred for 3 h using a magnetic
stirrer at room temperature and left at R.T. overnight. All
the catalysts are dried in an oven at 110–120°C for 12h
and calcined in the presence of air, at 450°C for 3 h to
obtain the 2.5% w/w of Ce-V supported catalysts.
Calcd for: 265.0125 Found: 265.0120.
2-Amino-4-(2-methoxyphenyl)-6-ethoxypyridine-3,5-dicarbinitrile
(4b). MP: 189–190°C; 1H NMR (400MHz, CDCl3, 25°C):
δ=1.30 (t, 3H, J=7.08MHz, CH3), 3.85 (s, 3H, OCH3),
4.56 (q, 2H, J=7.04MHz, CH2), 7.03–7.09 (m, 3H, Ar-H),
7.36 (d, 1H, J=7.84MHz, Ar-H), 7.84 (s, 2H, NH2) ppm.
15N NMR-GHSQC (400MHz, CDCl3, 25°C): δ=7.84
(s, 2H, NH2) ppm. 13C NMR (100MHz, CDCl3, 25°C):
δ=15.2, 56.2, 64.2, 83.1, 83.8, 114.4, 115.5, 120.2, 121.9,
128.1, 129.7, 130.8, 155.0, 160.8, 162.3, 165.4. HRMS of
[C16H14N4O2 +H]+ (m/z): Calcd for: 295.1105 Found:
295.1101.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Maddila, S. N. Maddila, S. B. Jonnalagadda, and P. Lavanya
Vol 000
2-Amino-4-(3-methoxyphenyl)-6-ethoxypyridine-3,5-dicarbinitrile
(d, 2H, J=7.64MHz, Ar-H), 7.65 (d, 2H, J=7.80MHz,
Ar-H), 7.80 (s, 2H, NH2) ppm. 15N NMR-GHSQC
(400 MHz, CDCl3, 25°C): δ=7.80 (s, 2H, NH2) ppm. 13C
NMR (100MHz, CDCl3, 25°C): δ =15.3, 64.4, 83.0, 83.7,
113.8, 114.9, 121.6, 127.5, 129.7, 130.2, 132.6, 135.5,
159.8, 162.8, 165.2. HRMS of [C15H11BrN4O+2H]+ (m/z):
(4c). 1H NMR (400 MHz, CDCl3, 25°C): δ=1.38 (t, 3H,
J= 7.06 MHz), 3.76 (s, 3H, OCH3), 4.56 (q, 2H,
J=7.06MHz, CH2), 7.05 (d, 2H, J=7.71MHz, Ar-H), 7.52
(d, 2H, J= 7.66 MHz, Ar-H), 7.79 (s, 2H, NH2) ppm. 15N
NMR-GHSQC (400MHz, CDCl3, 25°C): δ =7.79 (s, 2H,
NH2) ppm. 13C NMR (100MHz, CDCl3, 25°C): δ= 15.1,
56.4, 63.8, 82.7, 83.9, 113.7, 114.6, 115.8, 128.5, 130.8,
159.8, 160.4, 163.2, 165.1ppm. HRMS of [C16H14N4O2
Calcd for: 344.0838 Found: 344.0844.
2-Amino-4-(furan-2-yl)pyridine-6-ethoxy-3,5-dicarbinitrile (4i).
1H NMR (400MHz, CDCl3, 25°C): δ=1.46 (t, 3H,
J=7.08MHz, CH3), 4.55 (q, 2H, J=7.08MHz, CH2), 6.54
(t, 1H, Ar-H), 7.12 (d, 1H, J= 7.66 MHz, Ar-H), 7.78
(d, 1H, Ar-H), 7.85 (s, 2H, NH2) ppm. 15N NMR-GHSQC
(400MHz, CDCl3, 25°C): δ=7.85 (s, 2H, NH2) ppm. 13C
NMR (100MHz, CDCl3, 25°C): δ= 14.6, 63.6, 83.0, 83.8,
108.5, 111.2, 114.1, 115.2, 141.5, 150.2, 159.3, 163.4,
165.7 ppm. HRMS of [C13H10N4O2 +H]+ (m/z): Calcd for:
+H]+ (m/z): Calcd for: 295.0560 Found: 295.0562.
2-Amino-4-(2-chlorophenyl)-6-ethoxypyridine-3,5-dicarbinitrile
(4d). 1H NMR (400MHz, CDCl3, 25°C): δ =1.47 (t, 3H,
J=7.06MHz, CH3), 4.58 (q, 2H, J=7.10MHz, CH2), 7.22
(d, 2H, J= 7.78 MHz, Ar-H), 7.65 (d, 2H, J=7.70MHz,
Ar-H), 7.81 (s, 2H, NH2) ppm. 15N NMR-GHSQC
(400MHz, CDCl3, 25°C): δ =7.81 (s, 2H, NH2) ppm. 13C
NMR (100 MHz, CDCl3, 25°C): δ= 15.3, 64.7, 83.3, 83.9,
113.8, 114.6, 126.6, 128.3, 129.5, 130.1, 132.8, 137.1,
160.7, 163.4, 165.3. HRMS of [C15H11ClN4O+H]+ (m/z):
255.0093 Found: 255.0103.
2-Amino-4-(4-fluorophenyl)-6-ethoxypyridine-3,5-dicarbinitrile
(4j). 1H NMR (400MHz, CDCl3, 25°C): δ=1.47 (t, 3H,
J=7.06MHz, CH3), 4.57 (q, 2H, J=7.07MHz, CH2), 7.17
(d, 2H, J= 6.98 MHz, Ar-H), 7.51 (d, 2H, J=7.48MHz,
Ar-H), 7.88 (s, 2H, NH2) ppm. 15N NMR-GHSQC (400 MHz,
CDCl3, 25°C): δ=7.88 (s, 2H, NH2) ppm. 13C NMR
(100MHz, CDCl3, 25°C): δ= 15.4, 64.5, 83.5, 84.5, 114.1,
115.8, 117.6, 130.7, 132.2, 142.9, 161.5, 163.6, 165.7ppm.
HRMS of [C15H11FN4O+H]+ (m/z): Calcd for: 283.1083
Calcd for: 298.1015 Found: 298.1018.
2-Amino-4-(2-nirtophenyl)-6-ethoxypyridine-3,5-dicarbinitrile
(4e). 1H NMR (400MHz, CDCl3, 25°C): δ=1.55 (t, 3H,
J=7.02MHz, CH3), 4.54 (q, 2H, J=7.12MHz, CH2), 7.54
(d, 1H, J=7.56MHz, Ar-H), 7.80 (d, 2H, J=7.94MHz,
Ar-H), 7.88 (s, 2H, NH2), 8.10 (d, 1H, J=8.22MHz, Ar-H)
ppm. 15N NMR-GHSQC (400MHz, CDCl3, 25°C): δ =7.88
(s, 2H, NH2) ppm. 13C NMR (100MHz, CDCl3, 25°C):
δ=15.5, 64.9, 83.5, 83.9, 114.3, 115.3, 123.6, 128.2,
128.8, 129.8, 132.8, 143.8, 160.7, 163.6, 165.4. HRMS of
[C15H11N5O3 +H]+ (m/z): Calcd for: 310.1141 Found:
Found: 283.1079.
2-Amino-4-(4-(trifluoromethyl)phenyl)-6-ethoxypyridine-3,5-
dicarbinitrile (4k).
1H NMR (400MHz, CDCl3, 25°C):
δ=1.47 (t, 3H, J=7.06MHz, CH3), 4.59 (q, 2H,
J=7.08MHz, CH2), 7.54 (d, 2H, J=7.7MHz, Ar-H), 7.62
(d, 2H, J=8.1 MHz, Ar-H), 7.85 (s, 2H, NH2) ppm. 15N
NMR-GHSQC (400MHz, CDCl3, 25°C): δ=7.85 (s, 2H,
NH2) ppm. 13C NMR (100MHz, CDCl3, 25°C): δ=15.5,
63.8, 83.4, 84.2, 114.5, 115.3, 123.7, 124.8, 126.7, 130.3,
139.6, 159.8, 163.5, 165.6ppm. HRMS of [C16H11F3N4O
+H]+ (m/z): Calcd for: 333.1162 Found: 333.1166.
310.1141.
2-Amino-4-(4-bromophenyl)-6-ethoxypyridine-3,5-dicarbinitrile
(4f). 1H NMR (400 MHz, CDCl3, 25°C): δ=1.45 (t, 3H,
J=7.08MHz, CH3), 4.57 (q, 2H, J=7.04MHz, CH2), 7.53
(d, 2H, J= 7.64 MHz, Ar-H), 7.59 (d, 2H, J=7.64MHz,
Ar-H), 7.86 (s, 2H, NH2) ppm. 15N NMR-GHSQC
(400MHz, CDCl3, 25°C): δ =7.86 (s, 2H, NH2) ppm. 13C
NMR (100MHz, CDCl3, 25°C): δ= 14.8, 63.9, 83.4, 83.9,
114.2, 115.2, 121.0, 122.6, 128.6, 139.1, 159.8, 163.2,
165.8ppm. HRMS of [C15H11BrN4O+2H]+ (m/z): Calcd
for: 344.0893 Found: 344.0889.
Acknowledgments. The authors are thankful to the National
Research Foundation of South Africa, University of KwaZulu-
Natal, Durban, South Africa, and Department of Chemistry,
Annamacharya Institute of Technology and Sciences, Tirupati,
India, for the providing facilities.
2-Amino-4-(4-dimethylaminophenyl)-6-ethoxypyridine-3,5-
dicarbinitrile (4g).
1H NMR (400MHz, CDCl3, 25°C):
δ=1.46 (t, 3H, J=7.06MHz, CH3), 3.08 (s, 6H, N(CH3)2),
4.54 (q, 2H, J =7.05 MHz, CH2), 7.20 (d, 2H,
J =7.24 MHz, Ar-H), 7.74 (d, 2H, J=7.80MHz, Ar-H),
7.86 (s, 2H, NH2) ppm. 15N NMR-GHSQC (400MHz,
CDCl3, 25°C): δ= 7.86 (s, 2H, NH2) ppm. 13C NMR
(100 MHz, CDCl3, 25°C): δ=14.8, 39.6, 63.7, 111.8, 113.9,
115.6, 126.4, 127.8, 154.6, 160.1, 163.2, 165.7ppm. HRMS
of [C17H17N5O+H]+ (m/z): Calcd for 308.0988 Found:
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Reusable Ce-V Loaded Alumina Catalyst for Multicomponent Synthesis of
Substituted Pyridines in Green Media
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet