RETRACTED ARTICLE: One-pot synthesis of Hantzsch dihydropyridines using a highly efficient and stable PdRuNi@GO catalyst

Article abstract of DOI:10.1039/c6ra13142e

Addressed herein, highly monodispersed PdRuNi nanoparticles furnished with graphene oxide (PdRuNi@GO NPs) were prepared as novel, stable, efficient and exceptionally reusable heterogeneous catalysts for 1,4-dihydropyridine synthesis via multicomponent con

Full text of DOI:10.1039/c6ra13142e

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One-Pot Synthesis of Hantzsch Dihydropyridines Using Highly
Efficient and Stable PdRuNi@GO Catalyst
Received 00th January
20xx,
Accepted 00th January
20xx
Tuna Demirci,‡a Betül Çelik,‡b Yunus Yıldız,b Sinan Eriş,b Mustafa Arslan,c Fatih Sen*b and Benan Kilbas*d
DOI: 10.1039/x0xx00000x
Addressed herein, highly monodisperse PdRuNi nanoparticles furnished with graphene oxide (PdRuNi@GO
NPs) have been prepared as novel, stable, efficient and exceptional reusable heterogeneous catalyst for 1,4-
Dihydropyridine synthesis via multicomponent condensation reactions of various aldehydes with dimedone,
ammonium acetate and ethyl acetoacetate at 70°C in DMF with efficient catalytic performance. These
synthesized novel materials were characterized by transmission electron microscopy (TEM), the high
resolution electron micrograph (HRTEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS).
This presented one pot catalytic process was described as a new methodology of Hantzsch synthesis which
can be assessed as a quite simple and efficient as well as exceptional reusable. At the end of the reaction,
one of the highest yield and the shortest time has been obtained for the model reaction in the presence of
novel monodisperse PdRuNi@GO NPs.
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Introduction
1,4-dihydropyridine compounds are also acted as catalysts in
The six-membered heterocyclic compounds are very important
components in organic chemistry. Recently, chemists have devoted
considerable attention to 1,4-dihydropyridine compounds, due to
their important roles such as medical,1,2 biological3 and
pharmacological activities.4 They are also used as key compounds of
drugs.5,6 For instance, 1,4-dihydropyridine is the common feature
for various pharmacological activities such as cyclooxygenase-2
inhibitors,3 inhibitors against α-glucosidase,7 anti-inflammatory
activity,8 myorelaxant activity of gastric fundus,9 antimicrobial10 and
antihypertensive.11,12 Nifedipine, nicardipine and amlodipine like
dihydropyridine derivatives are also known in pharmacology as
calcium channel blockers, used in the treatment of hypertension13
(Scheme 1).
different types of organic reactions. For instance, those compounds
are used as H2 surrogate for hydrogenation of α,β-epoxy ketones,14
alkenes,15 enamides16 and they are key compounds both in
cyclization reactions of 1,6-diynes with ruthenium17 and in
asymmetric aza-pinacol cyclization.18
Hantzsch dihydropyridine synthesis is a multi-component organic
reaction of an aldehyde with α,β-keto ester and nitrogen surrogate
such as ammonium acetate19 (Scheme 2).
Scheme 2 Synthesis of 1, 4-dihydropyridines
In recent years, various catalysts are well established for Hantzsch
Scheme 1 Examples of 1,4-dihydropyridine derivatives
dihydropyridine formations in literature such as chitosan
21
nanoparticles,20 Yb(OTf)3
,
Sc(OTf)3,22 ceric ammonium nitrate
(CAN),23 bismuth nitrate,24 La2O3,25 Zn-VCO3 hydrotalcite,26 sodium
perchlorate,27 triton X-100,28 samarium chloride,29 Zr(H2PO4)2,30
ASA(alumina sulfuric acid)31 and PtNPs@GO.32 Presently,
heterogenous catalysts are particularly attractive features because
of using minimum catalytic amount, reusability, recoverability and
tolerable metal leaching to the solution.33
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Herein,
a
novel monodispersed heterogeneous catalyst Particle size distribution and bulk structure were portrayed by TEM
PdRuNi@GO NPs was used for dihydropyridine formation. The and HR-TEM which are appeared in Fig. 2. TEM picture of
reaction was carried out at mild condition and product yields are PdRuNi@GO (Fig. 2a) demonstrates that fine particles are
quite high (Scheme 3).
homogeneously distributed on graphene oxide support. Moreover,
HR-TEM picture for monodisperse PdRuNi@GO have additionally
been used to analyse the atomic lattice fringes in Fig. 2b. As an
effect of these edges, Pd (111) plane were seen with separating of
0.22 nm on the prepared catalyst, which is exactly same with
nominal Pd (111) dividing of 0.22 nm, respectively.42 A particle size
histogram was performed for a distribution test of 100 particles and
the it was shown that the distribution is Gaussian and the most
plausible size of the particles was around 3.72 ± 0.41 nm (Fig. 2c).
Particle size got from TEM results coordinate well with XRD results.
As induced from ICP-OES, the atomic composition of PdRuNi@GO in
aqua regia solution are 70 : 20 : 10, individually which coordinated
well with those by EDX investigation.
Scheme 3 PdRuNi@GO NPs assisted 1, 4 -dihydropyridine synthesis
Results and discussion
Graphene oxide (GO) (Fig. S1-S4) and monodisperse PdRuNi@GO
NPs have been characterized by using XRD, TEM, HRTEM and XPS
techniques. For example, Fig.
1 shows the XRD pattern of
Figure 2. (a) TEM, (b) HR-TEM image and (c) particle size histogram
PdRuNi@GO NPs which show similar diffraction pattern as that of
Pd@GO but with a slight shift to higher 2Ɵ values due to formation
of alloy. The diffraction pattern at around 2Ɵ = 40.20, 46.72, 68.36
can be related to (111), (200) and (220) planes of Pd (JCPDS card
numbers 87-0637 of Pd). The diffraction peak at around 2Ɵ= 25.50
corresponds to the characteristic hexagonal structure of the
graphene oxide. The inset in Fig. 1 represents the extended (111)
and (200) peaks showing a slight shift in peak position and there is
no evidence any peaks relating to the metal oxides. The average
crystallite size of PdRuNi@GO NPs was calculated from the related
XRD patterns by the help of Scherrer equation and it was found to
be 3.64 nm as crystalline particle size.34-41
of PdRuNi@GO NPs
XPS investigations have been performed in order to analyse the
electronic structure and surface organization of PdRuNi@GO. Fig.
3a-c demonstrates the Pd (3d), Ru (3p) and Ni (2p) XPS spectra of
PdRuNi@GO NPs. The Pd 3d region consists of two spin–orbit part
peaks of Pd 3d5/2 and Pd 3d3/2 states43
. Every peak was
deconvoluted with various Pd oxidation conditions of metallic Pd (0)
and PdO (+2) (Fig. 3a). The ratios of the metallic state and oxidized
Pd species were ascertained on the premise of the coordination of
their individual parts. It was found that the ratio of metallic Pd
species to the oxidized Pd species have been found to be 2.1.
Furthermore, as shown in Fig. 3b, Ru(3p) XPS range of PdRuNi@GO
NPs have been investigated rather than Ru(3d) owing to the
overlapping peaks between C (1s) and Ru (3d). For the situation of
the Ru 3p state, two recognizable peaks of various intensities at
463.1 and 483.2 eV are likely ascribed to Ru-C and RuO2·xH2O,
44-48
respectively.
Another two recognizable peaks of Ni(2p) spectra
(2p1/2, 2p3/2) are situated at binding energies of 855.3 and 873.3 eV,
individually, which are directly related to Ni(0) and Ni(II) as
appeared in Fig. 3c. The noises in the Ni 2p spectra are relatively
high due to the low nickel contents in the catalyst, they are not
obstructing the effective information.
Figure 1. XRD pattern of PdRuNi@GO NPs
2 | J. Name., 2012, 00, 1-3
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Adsorption-desorption N2 experiments have been carried out and
BET method has been used for the calculation of the specific
surface area which was found at 136.2 m2/g. The comparison of 1,4-
dihydropyridine formation was examined with previous published
works. PdRuNi@GO assisted 1,4-dihydropyridine formation was
accomplished with high yields. In addition, the reaction was
performed in a short time respect to the previous works as seen
Table 1. Morover, PdRuNi@GO was a monodispersed heterogenous
catalyst, therefore it can be successfully reused more than five
times with the same strong effect.
Table
2 The effect of temperature for 1,4-dihydropyridine
formation
Figure 3 (a)Pd 3d, (b)Ru 3p, (c) Ni 2p XPS spectra of PdRuNi@GO
nanoparticles.
Table 1 Comparisons of catalytic efficiency for 1, 4-dihydropyridine
formation
Catalyst
Reaction Condition
Time Yield
Amonnium acetate (2 mmol), ethylaceto
acetate (2 mmol),benzaldehyde (1 mmol),
EtOH (5 ml), 70 °C
Amonnium acetate (4.5 mmol),
ethylaceto acetate (6 mmol),
benzaldehyde (3 mmol), catalyst (0.6
mmol ), water (2 ml), 70 °C
None19
5h
50
87
ASA30
5 h
Reaction Conditions: Amonnium acetate (2 mmol), ethylacetoacetate (1
mmol), dimedone (1 mmol), 4-nitrobenzaldehyde (1 mmol) and mg
PdRuNi@GO catalyst (%9.3 wt metal content) were added in 2 ml DMF.
6
Amonnium acetate (1.5 mmol),
ethylaceto acetate (2 mmol),
27
NaOCl3
3 h
5 h
4 h
3 h
89
90
93
85
benzaldehyde (10 mmol), catalyst (%10
mmol), AcCN (10 ml), 70°C
Amonnium acetate (2 mmol), dimedone
(2 mmol), ethylacetoacetate (2 mmol),
benzaldehyde (2 mmol), catalyst (%5
mmol ), EtOH (5 ml), RT
Amonnium acetate (1 mmol),dimedone
(1 mmol), ethylacetoacetate (1 mmol),
benzaldehyde (1 mmol), catalyst (%5
mmol), EtOH (5 ml), RT
Amonnium acetate (2.2 mmol), ethyl
acetoacetate (4.4 mmol), benzaldehyde (2
mmol), catalyst (0.2 mmol), AcCN (10 ml),
70 °C
In the present work, optimization process was dealed with
adjustment amount of catalyst, type of solvent system and ambient
temperature. DMF was chosen as solvent because facilitates
reactions that follow polar mechanisms such as nucleophilic
reactions. The present synthesis is a nucleophilic reaction to the
21
Yb(OTf)3
Sc(OTf)3
aldehyde carbonyl carbon. DMF’s boiling point 152 to 154 oC49
.
22
Next, the effect of temperature was studied. While the reaction was
kept 1 day at room temperature, the reaction was not completed.
Even elevated temperature up to 50 °C was applied, starting
material was still observed (%70 conversion). 1,4-Dihydropyridine
derivative was succesfully obtained around 90% yield when the
reaction was carried out at 70 °C with only 45 min using
PdNiRu@GO catalyst (Table 2) .
29
SmCl3
Amonnium acetate (2 mmol), ethylaceto
acetate (1 mmol), dimedone (1 mmol),
benzaldehyde (1 mmol), catalyst (6 mg),
DMF (2 ml), 70 °C
Amonnium acetate (2 mmol), ethyl aceto
acetate (2 mmol), benzaldehyde (1
mmol), catalyst (6 mg), DMF (2 mL), 70 °C
45
min
88
93
PdNiRu@G
O
45
min
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Table 3 The result of Hantzsch dihydropyridine synthesis using PdNiRu@GO catalysta
Entry Substrate
Product
TON/TOF(h-1)
Yieldb (%)
Entry Substrate Product
TON/TOF( h-1)
Yieldb (%)
1
153.1/204.1
88
10
160.1/213.4
92
94
95
2
149.6/199.5
86
11
163.5/218.1
3
160.1/213.4
92
12
165.3/220.4
4
158.3/211.1
91
13
161.8/215.7
93
5
158.3/211.1
91
14
156.6/208.8
90
6
7
8
156.6/208.8
161.8/215.7
160.1/213.4
90
93
92
15
16
17
153.1/204.1
154.8/206.4
161.8/215.7
88
89
93
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167.0/222.7
96
18
158.3/211.1
91
aReaction Conditions: Amonnium acetate (2 mmol), ethylacetoacetate (2 mmol) or ethylacetoacetate (1 mmol)-dimedone (1mmol) , aldehyde (1 mmol) and
b
6 mg PdRuNi@GO NPs (%9.3 wt metal content) were added in 2 ml DMF for 45 minutes at 70 °C. Isolated yield determined by 1H NMR. All
characterizations are given in Supporting Info.
O
As a result, the reaction condition was well established by using 6
O
mg of corresponding catalyst, 2 ml of DMF for 45 minutes at 70 °C
O
O
(Table 3).
O
OH
O
NH
O
EtO
Table 4 The efficiency of catalytic amount over 1, 4-dihydropyridine
-H2O
formation
-H2O
O
O
O
HN
O
O
OEt
OEt
-H2O
O
O
O
O
NH3
OH
O
O
O
O
O
O
O
OEt
EtO
OEt
EtO
OEt
OEt
Scheme 4 Suggested mechanistic pathway of 1,4-dihydropyridine
synthesis
Reuse of the heterogeneous catalyst was tested as shown in Table
5. After completion of the reaction, PdRuNi@GO was easily
separated from reaction medium by using centrifuge, washed with
methanol, water and dried under vacuum and reused again. As a
consequence, PdRuNi@GO catalyst was able to be reused more
than five times without any decrease about catalytic function.
Palladium, ruthenium and nickel content was approximately 0.6
ppm in solution after 5 times uses occured by ICP-OES analyses.
Furthermore, SEM and EDX image of PdRuNi@GO have been
analyzed before and after the 5th usage as shown in Fig. S5 and S6
and it was observed that there is not much change in the metal
content of PdRuNi@GO as shown in EDX spectra..
Reaction Conditions: Amonnium acetate (2 mmol), ethylacetoacetate
(1mmol), dimedone (1 mmol), 4-nitrobenzaldehyde (1 mmol) and 6 mg
PdRuNi@GO catalyst were added in 2 ml DMF for 45 minutes at 70 °C.
The reaction performance was also monitored by different amount
of PdRuNi@GO catalyst. 6 mg of catalyst is sufficient when 1 mmol
of reactants were used as seen in Table 4.
According to the plausible mechanism, PdRuNi@GO NPs provide
more positive carbonyl group of dimedone as illustrated in scheme
4. For this reason, elimination of methylenic proton adjacent to the
carbonyl groups becomes easier which affords easy and fast
nucleophilic addition to the aldehyde carbonyl carbon.
Table 5 Reusability Analysis of PdRuNi@GO NPs
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Reaction Conditions: Amonium acetate (2 mmol), ethylacetoacetate (2 m
mol), benzaldehyde (1mmol) and 6 mg PdRuNi@GO catalyst in 2 ml DMF for
45 minutes at 70 °C.
Diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylate (2) 31 1H NMR (CDCl3, 300 MHz): δ 1.22 (6H, t, J =
:
7.10 Hz, –CH3), 2.33 (6H, s, –CH3), 4.06 (4H, q, J = 6.70 Hz, –OCH2),
4.95 (1H, s, –CH), 5.61 (NH, s), 7.16 (2H, d, J = 8.80 Hz, Ar-H), 7.26
(2H, d, J= 8.80 Hz, Ar-H). 13C NMR (CDCl3, 75 MHz): δ 14.5, 19.9,
39.5, 60.0, 104.0, 120.11, 130.0, 131.11, 144.1, 147.0, 167.6.
Conclusions
Diethyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dic
In conclusion, traditional 1,4-dihydropyridine synthetic methods
have several disadvantages such as long reaction time, tedious
work-up procedure, low yield, and hard refluxing conditions.
However, a novel monodisperse PdRuNi@GO NPs provided one of
the highest yield and the shortest time as novel, stable, long-lived,
efficient and exceptional reusable heterogeneous catalyst for 1,4-
dihydropyridine synthesis via multicomponent condensation
reactions of various aldehydes with dimedone, ammonium acetate
and ethyl acetoacetate at 70°C in DMF with efficient catalytic
performance. The current catalytic process was described as an
easy, effective, practical and exceptional reusable synthetic method
for Hantzsch synthesis. This nano sized heterogeneous catalyst
showed excellent catalytic activity for model reaction in mild
condition most likely due to high monodispersity, low crystalline
particle size and high % metal (0) contents of the prepared
PdRuNi@GO NPs. Since the given methodology is efficient and
practical, this method would be a rather attractive synthetic
method in near future.
arboxylate (3)31 1H NMR (CDCl3, 300 MHz): δ 1.27 (6H, t, J = 7.20
:
Hz, –CH3 ), 2.37 (6H, s, –CH3), 4.21 (4H, q, J = 6.70 Hz, –OCH2), 5.31
(1H, s, –CH), 6.05 (NH, s), 7.43 (2H, d, J = 9.01 Hz, Ar-H), 8.09 (2H, d,
J = 9.01 Hz, Ar-H). 13C NMR (CDCl3, 75 MHz): δ 20.81, 30.77, 39.83,
113.48, 124.04, 128.72, 144.17, 146.88, 153.32, 197.27.
Diethyl 4-(3-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dic
arboxylate (4): 1H NMR (CDCl3, 300 MHz): δ 1.10 (6H, t, J = 7.20 Hz,
–CH3), 2.25 (6H, s, –CH3), 4.07 (4H, q, J = 6.75 Hz, –OCH2), 5.06 (1H,
s, –CH), 5.80 (1H, NH), 7.08 (1H, t, –CH), 7.11(2H, d, J = 9.01 Hz, Ar–
H), 8.10 (1H, s, Ar–H). 13C NMR (CDCl3, 75 MHz): δ 14.41, 19.87,
40.12, 60.21, 103.65, 121.53, 123.38, 128.81, 134.73, 144.81,
148.32, 150.11, 167.37.
Diethyl 4-(4-cyanophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-di
carboxylate (5): 1H NMR (CDCl3, 300 MHz): δ= 1.17 (6H, t, J = 7.2 Hz,
–CH3), 2.39 (6H, s, –CH3), 4,05 (4H, q, J = 6.70 Hz, –OCH2), 5.06 (H, s,
–CH), 5,92 (NH, s), 7.43 (2H, d, J = 7.80 Hz, Ar-H), 7.52 (2H, d, J =
7.71 Hz, Ar-H), 13C NMR (CDCl3, 75 MHz): δ= 14.12, 50.87, 115.42,
109.71, 111.49, 119.52, 129.17, 132.13, 144.29, 148. 64, 152.62,
167.14.
Experimental
Diethyl 4-(4-(dimethylamino)phenyl)-2,6-dimethyl-1,4-dihydropyri
dine-3,5-dicarboxylate (6)49: 1H NMR (CDCl3, 300 MHz): δ 1.26 (6H,
t, J = 7.21 Hz, –CH3), 2.32 (6H, s, –CH3), 2.90 (6H, s, –CH3), 4.15 (4H,
q, J = 6.70 Hz, –OCH2), 4.81(1H, s, –CH), 5.51 (NH, s), 6.70 (2H, d, J
= 8.60 Hz, Ar-H), 7.10 (2H, d, J = 8.60 Hz, Ar-H). 13C NMR (CDCl3, 75
MHz): δ 14.23, 21.36, 40.32, 43.21, 62.78, 103. 62, 114.25, 129. 82,
135.26, 146. 73, 150.76, 168. 22.
The preparation of monodisperse Pd-Ni-Ru@GO NPs
Monodisperse PdRuNi@GO NPs have been prepared by using
sonochemical double solvent reduction method. Summarizing this
process, superhydride and ethanol were used to reduce the mixture
of 0.25 mmol of precursor of Pd, Ni and Ru lysed in small amount of
dehydrated tetrahydrofuran and 0.25 mmol of octanethiol (OT)
ligand in an ultrasonic conditions. The brown-black color solution
indicates the formation of PdRuNi NPs.39-41 Finally, in the room
temperature, the solid Pd-Ni-Ru NPs were dried under vacuum. The
prepared PdNiRu NPs were mixed in a 1:1 (moles) ratio with GO by
Ethyl 2,7,7-trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoli
:
ne-3-carboxylate (7)31 1H NMR (CDCl3, 300 MHz): δ 0.92 (3H, s,–
CH3), 1.04 (3H, s,–CH3), 1.21 (3H, t, J = 7.20 Hz, –CH3), 2.10 – 2.26
using tip sonicator in order to get PdRuNi@GO NPs. The (4H, m, –CH2), 2.30 (3H, s,–CH3), 4.06 (2H, q, J = 7.20 Hz, –OCH2),
4.66 (1H,s,–CH) 5.05 (NH, s), 7.11-7.31 (5H, m, Ar-H). 13C NMR
ultrasonication method was employed to increase PdRuNi@GO NPs
dispersion on GO. The data show that the route is very effective for
uniform distribution of PdRuNi@GO NPs on GO and for
agglomeration problem of NPs.
(CDCl3, 75 MHz): δ 14.42, 19.55, 27.33, 29.77, 32.93, 36.88, 41.02,
51.04, 60.03, 106.17, 112.13, 126.22, 128.18, 128.23, 144.08,
147.33, 149.26, 167.73, 196.09.
Ethyl 4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahy
1
droquinoline-3-carboxylate (8)31: H NMR (CDCl3, 300 MHz): δ0.91
General procedure of 1,4-dihydropyridine synthesis
(3H, s, –CH3), 1.06 (3H, s, –CH3), 1.19 (3H, t, J = 7.10 Hz, –CH3), 2.14
– 2.32 (4H, m, –CH2), 2.35 (3H, s, –CH3), 4.05(2H, q, J = 7.10 Hz, –
OCH2), 5.00 (1H, s, –CH), 6.58 (NH, s), 7.19 (2H, d, J = 7.60 Hz, Ar-H),
7.30 (2H, d, J = 7.70 Hz, Ar-H). 13C NMR (CDCl3, 75 MHz): δ 14.44,
19.63, 27.35, 29.74, 32.98, 36.54, 41.18, 50.98, 60.14, 105.89,
111.84, 120.09, 130.04, 131.10, 144.14, 146.46, 149.06, 167.54,
195.98.
Amonnium acetate
(2 mmol), ethylacetoacetate (2 mmol),
aldehyde (1 mmol) and 6 mg PdRuNi@GO catalyst were added in 2
ml DMF. The reaction was kept 45 min at 70 °C. After completion of
the reaction, catalyst was removed by centrifugation (6000 rpm)
and PdRuNi@GO catalyst was washed with methanol, water and
dried. DMF solution was poured into 20 ml of ice-cold water. The
resulting precipitate was filtered off and solid was allowed to dry.
Ethyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydr
oquinoline-3-carboxylate (9): 1H NMR (CDCl3, 300 MHz): δ 0.90 (3H,
s, –CH3), 1.08 (3H, s, –CH3), 1.82 (3H, t, J = 7.10 Hz, –CH3), 2.16 –
2.36 (4H, m, –CH2), 2.40 (3H, s, –CH3), 4.04 (2H, q, J = 7.80 Hz, –
OCH2), 5.15 (1H, s, –CH), 6.31 (NH, s), 7.50 (2H, d, J = 7.80 Hz, Ar-H),
8.09 (2H, d, J = 7.8 Hz, Ar-H). 13C NMR (CDCl3, 75 MHz): δ 14.33,
Diethyl 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxyla
te (1)31: 1H NMR (CDCl3, 300 MHz): δ 1.22 (6H, t, J = 7.05 Hz, –CH3),
2.31 (6H, s, –CH3), 4.09 (4H, q, J = 6.80 Hz, –OCH2), 4.99 (1H, s, –
CH), 5.81 (NH, s), 7.14-7.25 (5H, m, Ar-H). 13C NMR (CDCl3, 75 MHz):
δ 14.52, 19.81, 39.84, 60.02, 104.12, 126.31, 128.06, 128.21,
144.45, 148.02, 168.09.
6 | J. Name., 2012, 00, 1-3
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148.30, 108.36, 103.22, 59.99 51.23, 36.55, 31.04, 30.03, 29.18,
29.16, 26.38, 23.56, 22.15, 18.99, 13.88, 13.65.
18.97, 27.03, 29.57, 32.54, 37.29, 50.74, 59.79, 103.47, 110.27,
123.14, 129.03, 145.99, 146.04, 150.294, 155.23, 167.14, 195.47.
Ethyl 2,7,7-trimethyl-5-oxo-4-p-tolyl-1,4,5,6,7,8-hexahydroquinoli
:
ne-3-carboxylate (10)31 1H NMR (CDCl3, 300 MHz): δ 0.94 (3H, s, –
Ethyl 2,7,7-trimethyl-4-(naphthalen-2-yl)-5-oxo-1,4,5,6,7,8-hexa
hydroquinoline-3-carboxylate (17)51 1H NMR (CDCl3, 300 MHz): δ
:
0.88 (3H, s, –CH3), 0.92 (3H, t, J = 7.10 Hz, –CH3), 0.99 (3H, s, –CH3),
2.14( 4H, m, -CH2), 2.31 (3H, s, –CH3), 4.06 (2H, m, -OCH2), 5.02 (1H,
s, CH), 6.86 (NH, s), 7.90-7.22(6H, m, Ar-H), 8.68 (1H, m, Ar-H). 13C
NMR (CDCl3, 75 MHz): δ 195.38, 167.56, 150.05, 148.21, 143.99,
134.12, 130.93, 127.61, 126.56, 126.47, 126.26, 126.11, 125.58,
125.32, 112.09, 106.99, 60.24, 50.87, 32.85, 31.12, 28.25, 27.08,
18.97, 14.53.
CH3), 1.06 (3H, s, –CH3), 1.22 (3H, t, J = 6.40 Hz, –CH3), 2.11 – 2.21
(4H, m,–CH2), 2.25 (3H, s,–CH3), 2.33 (3H, s,–CH3), 4.07 (2H, q, J =
6.40 Hz, –OCH2), 5.00 (1H, s,–CH), 6.49 (NH, s), 7.00 (2H, d, J = 7.60
Hz, Ar-H), 7.19 (2H, d, J = 8.0 Hz Ar-H). 13C NMR (CDCl3, 75 MHz): δ
14.51, 19.52, 21.36, 27.43, 29.79, 32.93, 36.39, 41.14, 51.09, 60.04,
106.36, 112.39, 128.13, 128.80, 135.63, 143.82, 144.51, 148.94,
167.87, 195.92.
Ethyl 4-(furan-2-yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroqu
inoline-3-carboxylate (18)52 1H NMR (CDCl3, 300 MHz): δ 0.92 (3H,
:
Ethyl 4-(2,4-dimethoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (11)31
:
1H NMR (CDCl3, 300
s,–CH3), 0.99 (3H, s,–CH3), 1.11 (3H, t, J = 6.90 Hz), 2.18-2.10 (2H, m,
–CH2), 2.24 (3H, s, –CH3), 2.40-2.28 (2H, m, –CH2), 4.08 (2H, t, J =
6.40 Hz, –OCH2), 5.00 (1H, s), 5.77 (NH, s), 5.90 (1H, s), 6.20 (1H, s,
Ar-H), 7.28 (1H, s, Ar-H), 9.13 (1H, s, Ar-H). 13CNMR (CDCl3, 75 MHz):
δ 192.61, 168.32, 159.24, 151.25, 146.87, 140.99, 110.46, 107.57,
103.99, 101.86, 61.64, 51.73, 30.99, 30.86, 29.24, 26.23, 19.86,
16.72.
MHz): δ 0.91 (3H, s, –CH3), 1.03 (3H, s, –CH3), 1.20 (3H, t, J = 7.20
Hz, –CH3), 2.06 – 2.22 (4H, m, –CH2), 2.27 (3H, s, –CH3), 3.73 (3H, s,
–OCH3), 3.76 (3H, s, –OCH3), 3.99 – 4.06 (2H, q, J = 7.20 Hz, –OCH2),
5.16 (1H, s, –CH), 6.35 (2H, d, J = 7.20 Hz, Ar-H), 6.52 (NH, s, Ar-H),
7.19 (1H, s, Ar-H). 13C NMR (CDCl3, 75 MHz): δ 14.43, 19.41, 26.92,
29.86, 32.72, 33.26, 41.13, 51.03, 55.47, 55.52, 59.86, 98.53,
104.25, 105.24, 110.93, 127.72, 131.81, 143.43, 149.35, 158.62,
159.27, 168.32, 195.87.
Ethyl 4-(4-cyanophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahyd
roquinoline-3-carboxylate (12): 1H NMR (CDCl3, 300 MHz): δ 0.90
(3H, s, –CH3), 1.08 (3H, s, –CH3), 1.17 (3H, t, J = 7.20 Hz, –CH3), 2.18
(2H, s, –CH2), 2.23 (2H, s, –CH2), 2.39 (3H, s, –CH3), 4.05 (2H, q, J =
7.20 Hz, –OCH2), 5.09 (H, s, –CH), 6.22 (NH, s ) , 7.42 (2H, d, J = 7.80
Hz, Ar–H), 7.51 (2H, d, J = 7.8 Hz, Ar–H), 13C NMR (CDCl3, 75 MHz): δ
14.11, 19.72, 27.37, 29.52, 32.94, 37.42, 41.25, 50.72, 100.29,
115.14, 109.86, 111.42, 119.55, 129.12, 132.11, 144.21, 148.63,
152.52, 167.01, 195.92.
Ethyl 4-(4-(dimethylamino)phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,
8-hexahydroquinoline-3-carboxylate(13)22: 1H NMR (CDCl3, 300
MHz): δ 0.98 (3H, s, –CH3), 1.09 (3H, s, –CH3), 1.24 (3H, t, J = 7.20
Hz, –CH3), 2.29–2.36 (4H, m, –CH2), 2.88 (6H, s, –NCH3), 4.09 (2H, q,
J = 7.20 Hz, –OCH2), 4.96 (1H, s, –CH), 5.88 (NH, s), 6.62 (2H, d, J =
7.60 Hz, Ar–H), 7.16 (2H, d, J = 7.60 Hz, Ar–H). 13C NMR (CDCl3, 75
MHz): δ 14.62, 20.11, 27.95, 33.21, 41.36, 41.62, 42.81, 52.42,
63.25, 110.91, 11.35, 129.21, 135.68, 147.83, 148.25, 150.92,
168.18, 192.02.
Acknowledgements
This research was supported by Dumlupinar (2014-05, 2015-35 and
2015-50) and Duzce University Research Fund (Grant no.
2016.05.03.410). The partial supports by Science Academy and
FABED are gratefully acknowledged.
Notes and references
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Table of contents entry
One-Pot Synthesis Of Hantzsch Dihydropyridines Using Highly Efficient and Stable
PdNiRu@GO Catalyst
Tuna Demirci‡a, Betül Çelik‡b, Yunus Yıldızb, Sinan Eriꢀb, Mustafa Arslanc, Fatih Sen*b and
Benan Kilbas*d
The method for the synthesis of 1,4 dihydropyridine compounds has been developed in the
presence of PdꢁNiꢁRu@GO which is simple, effective and productive.