Synthesis, experimental, and DFT studies on FT-IR, 1H, and 13C NMR spectra of azo-linked dihydropyridines

Article abstract of DOI:10.1134/S1070363213120347

An efficient one-pot synthesis of dihydropyridines by solid state three-component condensation reactions of aldehydes, dimedone, and ammonium acetate in the presence of HY-Zeolite has been achieved. The conversion took short time to form the products in e

Full text of DOI:10.1134/S1070363213120347

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 12, pp. 2395–2401. © Pleiades Publishing, Ltd., 2013.
Synthesis, Experimental, and DFT Studies
on FT–IR, 1H, and 13C NMR Spectra
of Azo-Linked Dihydropyridines1
L. Zare Fekria and M. Nikpassandb
a Department of Chemistry, Payame Noor University, PO Box 19395-3697 Tehran, Iran
email: chem_zare@pnu.ac.ir; chem_zare@yahoo.com
b Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
Received August 8, 2013
Abstract—An efficient one-pot synthesis of dihydropyridines by solid state three-component condensation
reactions of aldehydes, dimedone, and ammonium acetate in the presence of HY-Zeolite has been achieved.
The conversion took short time to form the products in excellent yields. HY-Zeolite can be recovered and
reused. Density Functional Theory (DFT) calculations at the B3LYP level is used to optimize the geometry and
1
calculate FT–IR, H, and 13C NMR spectra of the compounds. We found that the calculated values are in
accordance with the experimental data.
DOI: 10.1134/S1070363213120347
INTRODUCTION
EXPERIMENTAL
1,4-Dihydropyridine is a common feature of various
biological compounds such as antibacterial, anti-
inflammatory, calcium antagonist and anti tyrosine
kinase inhibiting agents [1–4].
Materials and measurements. Chemicals were
purchased from Merck and Fluka and used as
purchased. Melting points were measured on an
Electro-thermal 9100 apparatus and were uncorrected.
1H NMR spectra were obtained on a Bruker DRX 500
in DMSO as solvent and with TMS as internal
reference. FT–IR spectra were recorded on a Shimadzu
FT–IR-8400S spectrometer. Elemental analyses were
carried out on a Carlo-Erba EA1110CNNO-S analyzer.
The classical method for the synthesis of dihydro-
pyridines involves the three-component condensation
of an aldehyde with ethyl acetoacetate and ammonia in
acetic acid or refluxing alcohol [5]. However, these
methods suffer from drawbacks like long reaction
time, use of an excess of organic solvent, and low yields
of the products. Yet a number of modified methods
under improved conditions by using microwave
irradiation [6], ionic liquids [7], molecular iodine [8],
cerium ammonium nitrate [9], polymers [10], and
organo-catalyst [11] was developed. However, the use
of high temperatures, expensive metal precursors,
catalysts that are harmful to environment, unsatis-
factory yields and long reaction time limit the use of
these methods. Moreover, the main disadvantage of
almost all existing methods is that the catalysts are
destroyed in the work-up procedure and cannot be
recovered or reused. Therefore, the search continues
for the synthesis of dihydropyridines in terms of
operational simplicity, reusability, economic viability,
and greater selectivity.
In recent years, HY-Zeolite has received
considerable attention as a mild Lewis acid for a
number of organic transformations because the catalyst
is green and reusable. As a part of the continuing effort
in our laboratory toward the development of new
methods in organic synthesis for the synthesis of
heterocyclic and pharmaceutical compounds, [12–14]
we became interested in the possibility of developing a
one-pot synthesis of dihydropyridines derivatives
through the Hantzsch reaction of aldehydes, dimedone,
and ammonium acetate in the presence of a reusable
HY-Zeolite catalyst under solid state condition
(Scheme 1).
We have examined other Lewis acids such as KSF,
bentonite, MCM-41, and K10 for this reaction (Table 1),
and HY-Zeolite was found to be the most effective
catalyst in terms of conversion and reaction rates. To
1
The text was submitted by the authors in English.
2395

2396
ZARE FEKRI, NIKPASSAND
H
N
R2
R3
R2
R3
O
O
CHO
OH +
O
O
NH4OAc
R1
N=N
OH
R1
N=N
HY-Zeolite
Ia−Ii
II
IIIa−IIIi
Scheme 1. Synthetic route to azo-linked dihydropyridines.
achieve suitable conditions for the synthesis of fused
heterocyclic dihydropyridines, we investigated the reac-
tion of azo-linked benzaldehyde I, dimedone II, and
ammonium acetate in the presence of HY-Zeolite in
different conditions. In refluxing alcohol the reaction
was very slow and the yield of product was very low.
We found that the best results were obtained in the
presence of HY-Zeolite under solid state conditions.
separate the organic compound and HY-Zeolite. The
organic compound was purified by column chromato-
graphy to produce 1,4-dihydropyridine derivatives
IIIa–IIIi as pure crystalline products.
Computational details. The geometries were
optimized at the B3LYP level of theory along with
standard 6-31G(d) basis set as shown in Fig. 1. The
harmonic vibrational frequencies and their relative in-
tensities were calculated by this method and the results
were compared with experimental FT–IR spectrum.
The most widely used technique for calculating NMR
shielding tensors is the GIAO (Gauge Including
Atomic Orbital) method. This method was used for
Apart from the mild conditions of the process and
its excellent results, the simplicity of product isolation,
replacement of carcinogenic solvent with solvent-free
process and the possibility to recycle HY-zeolite offer
a significant advantage.
1
calculating H and 13C NMR chemical shifts at the
General procedure for the synthesis of Va–Vi in
the presence of HY-Zeolite under solid state
condition. A mixture of aldehyde (1 mmol), dimedone
(2 mmol), NH4OAc (1 mmol), and HY-Zeolite (0.1 g)
without solvent was heated at 60°C for the required
reaction time (Table 1). When the reaction was
stopped, the mixture was washed with CHCl3 to
B3LYP/6-31G(d) level. All the calculations were
carried out with the Gaussian03 software.
The structure and the scheme of atoms numbering
in IIIa, IIIc, and IIId are shown in Fig. 2.
The observed and calculated frequencies using DFT
B3LYP/6-31G and their probable assignments for IIIa,
Table 1. Synthesis of azo-linked dihydropyridines under solid state condition
mp, °C
(observed)
mp, °C
(publ.)
Run no.
R1
R2
R3
Product
Time, min
Yield, %a,b
1
2
3
4
5
6
7
8
9
H
H
H
8
10
10
5
82
85
81
95
94
85
87
84
87
180–182
159–160
130–132
250–251
166–167
267–268
170–171
166–167
145–147
186–188
160–162
129–131
248–250
165–167
265–267
171–173
167–169
148–150
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
Me
Et
NO2
Cl
H
H
H
H
H
Cl
H
H
H
H
H
H
H
H
H
Cl
H
5
5
Br
H
3
5
I
4
a Isolated yields. b All products were characterized by comparison of their mp, IR, and NMR spectra with those of authentic samples [11].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

SYNTHESIS, EXPERIMENTAL, AND DFT STUDIES ON FT–IR, 1H, AND 13C NMR SPECTRA
2397
IIIa
IIIb
IIId
X = H
X = CH3
X = NO2
Fig. 1. The geometry optimization of the selected synthesized compounds.
H53
H54
H52
H51 C23
H55
H56
H45
N35
C18
H50
H49
H48
C22 C19
C20
H57
C24
H58
C25
H61
H60
C15
C17
C16
C
C29 H59
H62
C14
C21
O30
H47
H43
C13
H46
C28
C26
H63
65H64
C27
H
H37
C4
H36
C1
C12 C11
B
H66
O31
C3 C2
A
C7
C10 O32 H44
N33 N34
X38
C8 C9
C5 C6
H41
H42
H39
H40
Fig. 2. Structure, atom, and ring numbering scheme of IIIa, IIIb, and IIId.
IIIb, and IIId are summarized in Table 3. The C=C
stretching vibration bands appeared in the infrared
spectrum at 1600–1425 cm–1. The bands occurring at
1375 in IIIa, 1313 in IIIb, and 1340 in IIId in the IR
spectra are assigned to the ring C–N stretching
vibrations. The C=O stretching vibration bands are
calculated at 1645 in IIIa, 1654 in IIIb, and 1645 in
IIId. The bands observed in the infrared spectra of
IIIa at 3342, 3394 in IIIb, and 3272 in IIId are
assigned to the N–H stretching vibrations. The
asymmetric and symmetric stretching vibrations of the
nitro group are the most intense bands of the spectrum.
The frequencies observed at 1519 cm–1 in the infrared
spectrum are assigned to the –NO2 asymmetric
stretching modes of IIId. The very strong symmetric
stretching vibration of nitro group of the compound is
assigned to the wave number 1371 cm–1 in the infrared
spectrum. The correction factors used to correlate the
experimentally observed and theoretically computed
frequencies for each vibrational mode of IIIa, IIIb,
and IIId under DFT-B3LYP method are similar. The
linear regression between the experimental and
theoretical wave number of IIIa, IIIb, and IIId is
shown in Fig. 3. Thus, vibrational frequencies
calculated by using the B3LYP functional with 6-31G
basis sets can be utilized to eliminate the uncertainties
in the fundamental assignments in infrared vibrational
spectra.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

2398
ZARE FEKRI, NIKPASSAND
(b)
(a)
Experimental wave number
Experimental wave number
(c)
Experimental wave number
Fig. 3. Correlation plot of experimental and theoretical IR of (a) IIIa, (b) IIIb, and (c) IIId at the B3LYP/6-31G(d) level.
The 1H and 13C theoretical and experimental
chemical shifts, isotropic shielding tensors and the
assignments ofsignals in the spectra of IIIa, IIIb, and
IIId are presented in Table 4 and Table 5, respectively.
Aromatic carbons give signals in overlapped areas of
the spectrum with chemical shift values from 100 to
1
150 ppm in 13C NMR and 6–8.5 ppm in H NMR
spectra of IIIa, IIIb, and IIId.
Table 2. The observed FT–IR and frequencies calculated using B3LYP/6-31G(d) force field
IIIa
IIIb
IIIc
Assignment
calculated
3365.2147
3254.3697
3079.3158
2936.8913
1645.3821
–
experimental
3342
3456
3255
2952
1641
–
calculated
3412.1010
3214.5891
3175.3584
2910.3248
1654.2559
–
experimental
3394
3250
3103
2999
1649
–
calculated
3257.1465
3250.1023
3017.8657
2965.6522
1645.2154
1385.6578
1555.3248
1475.2189
1610.9521
1465.2147
1229.3165
1359.7831
1024.7898
1141.6524
1175.4562
875.4352
experimental
3272
3197
3064
2927
1612
1371
1519
1481
1600
1479
1228
1340
1014
1141
1150
852
ν(N–H)
ν(O–H)
ν(C–H) aromatic
ν(C–H) aliphatic
ν(C=O)
ν(NO2)
ν(NO2)
–
–
–
–
ν(N=N)
1465.2139
1601.9812
1543.8745
1254.3125
1359.6544
1140.3654
1006.2126
1240.3555
850.5454
1481
1591
1558
1249
1375
1151
1020
1220
829
1445.3695
1610.6875
1414.3225
1220.3212
1330.2549
1076.3651
1042.5954
963.2544
836.3214
1431
1600
1425
1228
1313
1020
1000
962
ν(C=C)
ν(C=C)
ν(C–O)
ν( C–N)
β(HCC)
β(HCC)
β(HCC)
γ(C–H)
823
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

SYNTHESIS, EXPERIMENTAL, AND DFT STUDIES ON FT–IR, 1H, AND 13C NMR SPECTRA
2399
Table 3. The experimental and calculated 1H isotropic chemical shifts (ppm) with respect to TMS of IIIa–IIIc
IIIa
experimental
IIIb
experimental calculated
IIIc
experimental
Assignment
calculated
1.07
calculated
0.6
H51,H50,H49
H52, H53,H54
1.04
1.14
0.94
0.84
0.59
0.6
0.89
1.00
1.34
0.5
H61, H60,H59
H62, H63,H64
1.03
1.34
1.04
1.14
0.43
0.58
0.84
0.94
0.44
0.52
0.89
1.00
H47,H48
H55, H56
2.34
1.81
2.29
1.92
1.68
1.51
2.50
2.07
1.79
1.54
2.50
2.10
H58, H57
H65, H66
H46
1.99
2.27
4.62
7.65
2.05
2.12
4.70
7.15
1.46
1.56
3.88
7.91
1.93
2.35
5.1
1.45
1.58
3.73
7.93
1.99
2.15
4.8
H36
7.68
7.90
H40
H37
X38
H39
H41
H42
H43
6.06
7.56
6.51
6.59
7.12
7.85
7.01
7.15
7.47
7.44
7.47
7.77
7.83
7.62
7.84
7.18
1.21
6.85
7.79
6.55
7.34
7.68
7.32
2.23
7.32
7.6
7.14
6.68
–
7.90
8.35
–
8.7
8.35
7.64
6.87
7.62
6.84
6.65
7.84
7.09
7.46
The downfield chemical shift of C15 rather than C14
is observed in IIIa, IIIb, and IIId. That is due to the
mesomeric effect between C15–C14–C21–O30. The
benzylic and allylic C–H carbon atom (C13) is
calculated at 26.7 in IIIa, 27.24 in IIIb, and 31.2 in
IIId in relatively good accordance with experimental
results. Similarly, the benzylic and allylic C–H proton
atom (H46) appeared at 4.7 in IIIa, 5.1 in IIIb, and 4.8
in IIId in according to their resonated chemical shift in
the experimental results. The calculated and experi-
mental chemical shift values given in Tables 4 and 5
show a good agreement with each other. The linear
regression between the experimental and theoretical 1H
and 13C NMR chemical shifts of IIIa, IIIb, and IIId
are presented in Figs. 4–6.
CONCLUSIONS
Consequently, we have developed an efficient,
green, fast, and convenient procedure for the synthesis
of 1,4-dihydropyridines through the three component
(b)
(a)
Experimental wave number
Experimental wave number
1
Fig. 4. Correlation plots of experimental and theoretical (a) H and (b) 13C NMR chemical shifts of IIIa at the B3LYP/6-31G(d)
level.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

2400
ZARE FEKRI, NIKPASSAND
compound have been precisely assigned and analyzed
and the theoretical results were compared with the
condensation of aldehydes, dimedone and ammonium
acetate over K10 Zeolite under solid state conditions.
The geometries of IIIa, IIIb, and IIId were optimized
with DFT-B3LYP using 6-31G basis sets. The
vibration frequencies of the fundamental modes of the
1
experimental vibrations. H and 13C NMR isotropic
chemical shifts were calculated and the assignments
made were compared with the experimental values.
Table 4. The experimental and calculated 13C isotropic chemical shifts (ppm) with respect to TMS of IIIa–IIIc
IIIa
experimental
IIIb
experimental calculated
IIIc
experimental
Assignment
calculated
111.05
calculated
120.48
C4
C3
C5
C2
121.6
130.0
130.0
126.2
128.7
140.7
140.7
124.0
149.7
133.4
146.8
123.8
135.88
117.29
135.93
121.26
131.29
123.85
115.46
127.73
126.99
114.39
C6
C1
116.86
153.5
126.2
157.3
119.02
150.92
124.0
160.2
121.2
157.9
125.71
146.25
C7
141.52
122.73
119.55
139.54
112.42
105.19
26.7
150.8
129.5
127.0
149.3
143.61
122.97
119.84
142.36
112.96
115.72
27.24
156.2
131.2
125.5
153.3
121.2
113.5
31.1
144.86
129.9
129.8
152.9
123.8
114.9
31.2
144.86
122.21
122.01
141.44
114.03
120.23
27.73
105.14
181.62
44.85
29.9
C8
C9
C10
C11
C12
C13
C14
C21
C20
C19
C18
C15
C22
C23
C16
C27
C26
C25
C24
C17
C29
C28
123.5
111.5
27.9
105.3
182.45
47.56
28.86
43.95
135.83
25.66
33.21
106.23
186.92
48.17
24.45
38.86
130.58
33.76
30.13
119.2
196.3
51.7
105.26
180.93
45.37
118.2
198.2
52.5
123.5
198.8
42.7
30.0
30.39
32.3
50.2
40.1
37.45
41.8
33.6
37.19
134.12
26.92
20.3
147.6
34.4
133.75
26.95
146.4
26.6
132.0
28.0
34.4
20.46
26.6
28.0
119.2
196.3
51.7
105.75
180.38
44.74
118.2
198.2
52.5
123.5
198.8
42.7
105.32
181.21
44.69
29.73
36.9
30.0
29.54
32.3
50.2
40.1
37.04
41.8
33.6
147.6
34.4
132.88
26.89
146.4
23.0
132.0
28.0
134.1
20.26
26.81
34.4
20.25
23.0
28.0
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

SYNTHESIS, EXPERIMENTAL, AND DFT STUDIES ON FT–IR, 1H, AND 13C NMR SPECTRA
2401
(a)
(b)
Experimental wave number
Experimental wave number
1
Fig. 5. Correlation plots of experimental and theoretical (a) H and (b) 13C NMR chemical shifts of IIIb at the B3LYP/6-31G(d)
level.
(b)
(a)
Experimental wave number
Experimental wave number
1
Fig. 6. Correlation plots of experimental and theoretical (a) H and (b) 13C NMR chemical shifts of IIId at the B3LYP/6-31G(d)
level.
berto, M., Margaria, Q., Carlos, S., Jose, S., Hector, L.N.,
Norbert, B., Oswald, M., and Camiel, D., J. Heterocycl.
Chem., 2000, vol. 37, pp. 735–742.
Thus the present investigation provides complete
vibration assignments, structural information, and
chemical shifts of the compounds under study.
6. Agarwal, A. and Chauhan, P.M.S., Tetrahedron Lett.,
ACKNOWLEDGMENTS
2005, vol. 46, pp. 1345–1348;
7. Ji, S.J., Jiang, Z.Q., Lu, J., and Loh, T.P., Synlett, 2004,
We thank the Research Committee of Islamic Azad
University of Rasht Branch for partial support given to
this study.
pp. 831–835.
8. Ko, S., Sastry, M.N.V., Lin, C., and Yao, C.F.,
Tetrahedron Lett., 2005, vol. 46, pp. 5771–5774.
9. Ko, S. and Yao, C.F., Tetrahedron, 2006, vol. 62,
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