Synthesis, experimental and DFT studies on the crystal structure, FTIR, 1H NMR and 13C NMR spectra of drivatives of dihydropyridines

Article abstract of DOI:10.4067/S0717-97072012000400017

Several derivatives of dihydropyridines are prepared through the condensation of aldehydes, dimedone and NH₄OAc in H₂O, in the presence of a catalytic amount of nano-Fe₃O₄. The crystalline products were characte

Full text of DOI:10.4067/S0717-97072012000400017

J. Chil. Chem. Soc., 57, Nº 4 (2012)
SYNTHESIS, EXPERIMENTAL AND DFT STUDIES ON THE CRYSTAL STRUCTURE, FTIR, 1H NMR AND 13C
NMR SPECTRA OF DRIVATIVES OF DIHYDROPYRIDINES
LEILA ZARE FEKRIa , MOHAMMAD NIKPASSAND*,b
aDepartment of Chemistry, Payame Noor University, PO Box 19395-3697 Tehran, Iran
bDepartment of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
(Received: November 30, 2011 - Accepted: August 6, 2012)
ABSTRACT
Several derivatives of dihydropyridines are prepared through the condensation of aldehydes, dimedone and NH4OAc in H2O, in the presence of a catalytic
amount of nano-Fe3O4. The crystalline products were characterized by FTIR, 1H NMR and 13C NMR. Density Functional Theory (DFT) calculations at the B3LYP
level is used to optimize the geometries of isolated molecules, and to calculate the, FTIR, 1H NMR and 13C NMR spectra of selected synthesized compounds. We
found that the DFT B3LYP calculated FTIR, 1H NMR and 13C NMR spectra are in accordance with the experimental data.
Keywords: dihydropyridines, nano-Fe3O4, FTIR, DFT, B3LYP, NMR.
Yellow-orange solid, mp 282-283 °C. IR (KBr): ν 3450, 3080, 2980,
1650, 1540, 1520, 1480, 1360, 1345, 1220 Cm-1. 1H NMR (500 MHz, CDCl3):
δ = 0.96 (s, 6H), 1.06 (s, 6H), 2.23-2.46 (m, 8H), 5.80 (s, 1H), 7.21 (t, J = 6.99
Hz, 1H), 7.39-7.35 (d, J = 6.81Hz, 1H) , 7.41-7.48 (m, 2H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 27.8, 29.5, 32.9, 41.2, 51.1, 112.9, 124.5, 127.0, 132.5,
134.2, 141.2, 149.6, 149.8, 195.9 ppm. Anal. Calcd. for C23H26N2O4: C, 70.03;
H, 6.63; N, 7.10. Found: C, 70.25; H, 6.48; N, 7.02.
INTRODUCTION
1, 4- dihydropyridines (1, 4- DHPs) and their derivatives are an important
class of bioactive molecules in the field of drugs and pharmaceutical
The heterocyclic ring in DHP is a common feature of various bioactive
compounds such as anticonvulsant, antidiabetic, antianxiety, antidepressive,
antitumor, analgesic, sedative, vasodilator, bronchodilator, hypnotic and
1
.
2
3,3,6,6-tetramethyl-9-(3-nitrophenyl)-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione (3c)
anti-inflammatory agents . DHPs are commercially used as calcium channel
blockers for the treatment of cardiovascular diseases including hypertension 3.
Starting from Hantzsch more than a century ago, there are several
efficient methods developed for the synthesis of 1, 4-dihydropyridines 4, which
comprise the use of microwave 5, ionic liquid 6, high temperature in refluxing
Off white solid, mp 273-275 °C. IR (KBr): ν 3380, 3060, 1645, 1610,
1480, 1520, 1360, 1340 Cm-1. 1H NMR (500 MHz, CDCl3): δ = 0.86 (s, 6H),
1.01 (s, 6H), 2.0 (d, J = 16.3Hz, 2H), 2.10 (d, J = 16.3Hz, 2H), 2.28 (d, J =
17.1Hz, 2H), 2.35 (d, J = 17.1Hz, 2H), 5.01 (s, 1H), 7.29 (t, J = 7.86 Hz, 1H),
7.65 (d, J = 6.9Hz, 1H) , 7.83 (d, J = 8.1Hz, 1H), 8.02 (s, 1H), 8.90 (s, br, 1H)
ppm. 13C NMR (125 MHz, CDCl ): δ = 27.4, 30.0, 33.0, 34.5, 51.1, 112.2,
121.2, 123.1, 130.0, 135.2, 148.4,3149.6, 150.2, 195.6 ppm. Anal. Calcd. for
C23H26N O4: C, 70.03; H, 6.63; N, 7.10. Found: C, 69.88; H, 6.52; N, 7.28.
3,3,26,6-tetramethyl-9-(4-nitrophenyl)-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione (3d)
7
8
9
10
solvent , TMSCl-NaI , metal triflates , I
and CAN 11. However, these
methods suffers several disadvantages such2as long reaction times, excess of
organic solvent, lower product yield, harsh refluxing condition, use of high
temperatures, extensive amounts of reagents, occurrence of several side
products and difficulty in the recovery and reusability of the catalyst. Thus, the
development of a simple, efficient and versatile method for the preparation of
dihydropyridines is an active area of research and there is a scope for further
improvement towards milder reaction condition and higher product yields.
In recent years, density functional theory (DFT) calculations have been
used extensively for calculating a wide variety of molecular properties such
as equilibrium structure, charge distribution, FTIR and NMR spectra, and
provide reliable results which are in agreement with experimental data 12. In
this research, Beck’s three-parameter exchange functional 13 with Lee, Yang
and Parr’s 14 correlation functional (B3LYP), developed by Truhlar et al., 15 are
Yellow-orange solid, mp 282-283 °C. IR (KBr): ν 3384, 3070, 2956,
1643, 1540, 1460, 1360, 1342, 1130, 840 Cm-1. 1H NMR (500 MHz, CDCl3):
δ = 0.87 (s, 6H), 1.02 (s, 6H), 2.04 (d, J = 16.3 Hz, 2H), 2.15 (d, J = 16.3 Hz,
2H), 2.26 (d, J = 17.0 Hz, 2H), 2.34 (d, J = 17.0 Hz, 2H), 5.05 (s, 1H), 7.44 (t, J
= 8.5 Hz, 2H), 7.98 (d, J = 6.9 Hz, 2H), 8.49 (s, 1H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 27.4, 29. 9, 32.9, 34.9, 51.0, 109.2, 112.3, 123.5, 129.3, 146.3,
149.8, 154.9, 195.6 ppm. Anal. Calcd. for C23H26N2O4: C, 70.03; H, 6.63; N,
7.10. Found: C, 69.93; H, 6.75; N, 7.32.
1
used to perform theoretical calculations on the structure, FTIR, H NMR and
13C NMR spectra and some additional properties of the title compounds.
9 - ( 2 - c h l o r o p h e n y l ) - 3 , 3 , 6 , 6 - t e t r a m e t h y l - 3 , 4 , 6 , 7 , 9 , 1 0 -
hexahydroacridine-1,8(2H,5H)-dione (3e): Off white solid, mp 217-219 oC,
1
IR (KBr): ν 3400, 2980,1660, 1620, 1465, 1350, 1200 Cm-1. H NMR (500
EXPERIMENTAL
MHz, CDCl3): δ = 1.05 (s, 6H), 1.14 (s, 6H), 2.10-2.30 (m, 4H), 2.45-2.62 (m,
4H), 5.04 (s, 1H), 7.09 (d, J = 7.2 Hz, 1H), 7.01-7.19 (m, 1H), 7.25 (d, J = 7.5
Hz, 1H), 7.47 (d, J = 6.4 Hz, 1H) ppm. 13C NMR (125 MHz, CDCl3): δ = 27.8,
29.7, 32.5, 41.2, 51.2, 114.2, 126.8, 127.6, 129.5, 128.2, 130.6, 130.2, 133.9,
163.5, 197.0 ppm. Anal. Calcd. for C23H26ClNO2: C, 71.96; H, 6.82; N, 3.65.
Found: C, 71.72; H, 6.55; N, 3.81.
Materials and measurements
IR spectra were determined on a Shimadzu IR-470 spectrometer. 1H NMR
spectra were obtained on a Bruker DRX 500, and 250 and 13C NMR spectra
on a Bruker DRX 125 Avance spectrometer, in CDCl as solvent and with
TMS as internal standard. Chemicals were purchased fr3om Merck and Fluka.
Elemental analyses were done on a Carlo-Erba EA1110CNNO-S analyzer and
agreed with the calculated values. All used solvents were dried and distilled
according to standard procedures.
9 - ( 4 - c h l o r o p h e n y l ) - 3 , 3 , 6 , 6 - t e t r a m e t h y l - 3 , 4 , 6 , 7 , 9 , 1 0 -
hexahydroacridine-1,8(2H,5H)-dione (3f):Yellow solid, mp 228-229°C. IR
1
(KBr): 3440, 3178, 3020, 2958, 1641, 1606, 1488, 1020, 850 Cm-1. H NMR
(500 MHz, CDCl3): δ = 1.03 (s, 6H), 1.15 (s, 6H), 2.17-2.33 (m, 8H), 5.51 (s,
1H), 7.20 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.3 Hz, 2H), 8.06 (s, 1H) ppm.13C
NMR (125 MHz, CDCl3): δ = 27.5, 30.0, 33.0, 41.1, 51.2, 113.3, 128.5, 129.9,
132.0, 145.6, 149.7, 196.4 ppm. Anal. Calcd. for C23H26ClNO2 : C, 71.96; H,
6.82; N, 3.65. Found: C, 71.83; H, 6.71; N, 3.55.
Preparation of dihydropyridines 3a-3j
A mixture of aldehyde (1 mmol), dimedone (2 mmol), NH4OAc (1mmol)
and 0.05 g nano-Fe O in 10 mL H2O were refluxed for the required reaction
times (8-15 minute3s).4 The progress of the reaction was monitored by TLC
(EtOAc:petroleum ether 1:4). After completion of the reaction, the mixture
was filtered in the presence of an efficient magnetic bar to separate it from
the catalyst. The product was recrystallized from ethanol to produce 1,
4-dihydropyridine derivatives 3a-j as pure crystalline products.
3,3,6,6-tetramethyl-9-(2-nitrophenyl)-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione (3b)
9 - ( 3 - b r o m o p h e n y l ) - 3 , 3 , 6 , 6 - t e t r a m e t h y l - 3 , 4 , 6 , 7 , 9 , 1 0 -
hexahydroacridine-1,8(2H,5H)-dione (3g): Off white solid, mp 305-307 oC,
1
IR (KBr): ν 3280, 3080, 2970, 1640, 1555, 1250, 1220 Cm-1. H NMR (500
MHz, CDCl3): δ = 1.01 (s, 6H), 1.12 (s, 6H), 2.18-2.35 (m, 8H), 5.05 (s, 1H),
7.11 (t, J = 7.74 Hz, 1H), 7.35 (t, J = 7.59 Hz, 1H), 7.48 (s, 1H), 7.98 (s, 1H)
e-mail: Nikpassand@iaurasht.ac.ir
1415

J. Chil. Chem. Soc., 57, Nº 4 (2012)
ppm. 13C NMR (125 MHz, CDCl3): δ = 27.5, 30.0, 33.1, 41.1, 51.3, 113.1,
122.6, 127.5, 129.5, 130.0, 131.4, 149.3, 149.8, 196.3 ppm. Anal. Calcd. for
C23H26BrNO : C, 64.49; H, 6.11; N, 3.27. Found: C, 64.66; H, 6.32; N, 3.11.
9 - ( 4 - f2l u o r o p h e n y l ) - 3 , 3 , 6 , 6 - t e t r a m e t h y l - 3 , 4 , 6 , 7 , 9 , 1 0 -
hexahydroacridine-1,8(2H,5H)-dione (3h): Yellow solid, mp 215-218 °C.
IR (KBr): 3355, 3047, 2958, 1653, 1618, 1498, 1147, 891 cm-1. 1H NMR (500
MHz, CDCl3): δ = 0.98 (s, 6H), 1.10 (s, 6H), 2.04-2.38 (m, 8H), 5.09 (s, 1H),
6.90 (m, 2H), 7.30 (m, 2H), 8.30 (s, 1H) ppm.13C NMR (125 MHz, CDCl3): δ
With the best quantity of nano-Fe3O in hand, we were interested
to synthesis several dihydropyridines in t4he multicomponent reaction of
various aldehydes, dimedone and NH4OAc with this catalyst. The results are
summarized in Table 2.
Table 2. Synthesis of fused 1, 4-dihydropyridine derivatives (3a-j) using
nano-Fe3O4.
2
In the presence of
Nano-Fe3O4
= 27.4, 30.0, 33.0, 41.0, 51.3, 107.2, 113.3, 115.0 (d, JCF = 83.5 Hz), 129.7
Mp( °C)
3
1
(d, JCF = 31.0 Hz), 143.0, 149.9, 162.5 (d, JCF = 249.0 Hz), 196.5 ppm.Anal.
Calcd. for C23H26FNO : C, 75.18; H, 7.12; N, 3.81. Found: C, 75.32; H, 7.23;
N, 3.67. The detailed 2descriptions of FTIR and NMR spectra of the selected
synthesized compounds are given in the next sections.
Entry
aldehydes
Time Yield
(min)
10
14
12
8
(%)a
96
91
95
98
94
95
90
88
84
86
a
b
c
d
e
f
C6H4CHO
189-200
282-283
273-275
282-283
217-219
228-229
305-307
215-218
211-212
274-275
RESULTS AND DISCUSSION
2-NO2 C6H4CHO
3-NO2 C6H4CHO
4-NO2 C6H4CHO
2-ClC6H4CHO
4-ClC6H4CHO
3-BrC6H4CHO
4-FC6H4CHO
Recent development in the dihydropyridines chemistry and our continued
interest in the development of an efficient and environmentally friendly
procedure for the synthesis of pharmaceutical compounds [16-18] triggered
us to synthesize of derivatives of dihydropyridines and calculate the FT-IR,
1H NMR and 13C NMR spectra of selected compounds at the B3LYP level.
Nano-Fe3O4 was initially prepared (Figure 1) and used as a green catalyst for
the synthesis of diihydropyridines, as shown in (Scheme 1).
15
11
13
8
g
h
i
4-CH3OC6H4CHO
4-HOC6H4CHO
15
15
j
a isolated yield
Apart from the mild condition of the process and its excellent results, the
simplicity of product isolation, replacement of carcinogenic solvent by H2O
and the possibility to recycle nano-Fe O4 offer a significant advantage. After
the reaction was completed, the catalys3t could be easily attracted by an efficient
magnetic bar. After further treatments including washing with CHCl3 and
activation at 80°C, the recycled catalyst has been examined in following runs.
Studies on the synthesis of 3a as model substrate showed that the recovered
catalyst could be successively recycled in subsequent reactions without any
decrease of yields (Figure 2).
Figure 1. SEM image of synthesized nano-Fe3O4
Figure 2. Reusability of nano-Fe3O4 in the synthesis of 3a.
In the continuation of our study, we concentrated on the calculation of
the FT-IR, 1H NMR and 13C NMR spectra of these compounds at the B3LYP
level. The geometries were optimized at the B3LYP level of theory along with
standard 6-31G(d) basis set as shown in Figure 3. The harmonic vibrational
frequencies were calculated by this method and the results were compared with
experimental FTIR spectrum. The most widely used technique for calculating
NMR shielding tensors is the GIAO (Gauge Including Atomic Orbital) method.
Scheme 1. Shematic representation of the synthesis of DHPs
With the best catalyst in hand, we moved to study the effects of catalyst
amount on the model reaction and the results were listed in Table 1. 0.05g
of nano-Fe3O is sufficient to push the reaction forward completion. Higher
amount of cat4alyst did not lead to significant change in the reaction yields.
1
This method was used for calculating H NMR and 13C NMR chemical shifts
Table 1. The effect of amount of nano-Fe3O4 for the synthesis of 3a.
at the B3LYP/6-31G(d) level. All the calculations were carried out with the
Gaussian03 software 19
.
Catalyst
amount(%)
entry
catalyst
Time(min)
Yield(%)a
1
2
3
4
-
-
720
50
10
30
20
No reaction
Fe3O4
50mg
50mg
10mg
30mg
76
96
83
92
Nano- Fe3O4
Nano- Fe3O4
5
Nano- Fe3O4
a.
isolated yield.
Figure 3. The geometry optimization of 3d, 3f and 3h.
1416

J. Chil. Chem. Soc., 57, Nº 4 (2012)
The structure and the scheme of numbering the atoms of 3d, 3f and 3h are
shown in Figure 4.
The optimized structural parameters bond length and bond angle for the
thermodynamically preferred geometry (Figure 3) of 3d, 3f and 3h determined
at B3LYP/6-31G level are presented in Table 3 in accordance with the atom
numbering scheme of the molecule shown in Figure 4. From the structural
data, it is observed that the various C–C bond distances calculated between
the carbon atoms and the C–H and C-N bond length are found to be nearly
the same in 3d, 3f and 3h structures. The influence of the substituent on the
molecular parameters, particularly in the C–C bond distance of ring carbon
atoms seems to be negligibly small. The calculated bond angles are very close
to each other in these molecules. Investigation of bond angles between N1-
C2-C3 and N1-C8-C shows that these atoms were hibridized sp2 and they are
completely planar.1T3 his experimental data is indicative clearly that there is a
pronounced mesomeric intraction between NH and C=O group that is shown
in Scheme 2.
Figure 4. Structure and atom numbering scheme of 3d, 3f and 3h.
Scheme 2. Schematic mesomeric intraction in 3d
Table 3. The selected structural parameters calculated for 3d, 3f and 3h by DFT/B3LYP method with a 6-31G basis sets.
parameters
Bond length(A)
N1-C2
3d
3f
3h
3d
3f
3h
Bond angles(° )
N1-C2-C3
1.3853
1.0106
1.3590
1.5221
1.4685
1.5327
1.0941
1.4038
1.4005
1.3912
1.3939
1.3940
1.3911
1.3588
1.5209
1.4691
1.3863
1.3966
0.9934
1.3672
1.5021
1.4670
1.5059
1.1339
1.4015
1.3984
1.3927
1.3982
1.3973
1.3936
1.3673
1.5001
1.4681
1.3970
1.3872
1.01058
1.3585
1.5210
1.4689
1.5340
1.0943
1.3995
1.4016
1.3946
1.3894
1.3895
1.3956
1.3587
1.5218
1.4685
1.3870
120.04
119.99
118.46
122.04
120.04
110.14
111.88
108.48
106.32
120.52
120.71
120.07
121.76
118.54
121.16
118.0
120.68
120.66
118.52
119.23
121.28
110.81
111.80
108.03
107.63
119.00
121.81
121.81
120.48
119.54
120.60
119.48
120.71
119.94
119.94
118.32
121.91
119.89
109.97
111.51
108.49
106.47
121.02
120.55
119.87
121.86
118.72
121.18
118.50
121.30
N1-H30
N1-C8- C13
C2-N1-H30
C2-N1-C8
C2-C3
C3-C14
C3-C4
C2-C3-C4
C14-C15
C14-H31
C15-C20
C15-C16
C19-C20
C18-C19
C17-C18
C16-C17
C8-C13
C3-C14-C13
C13-C14-C15
C13-C14-H31
C15-C14-H31
C14-C15-C20
C14-C15-C16
C8-C13-C12
C17-C18-C19
C18-C19-C20
C15-C20-C19
C16-C17-C18
C15-C16-C17
C13-C14
C12-C13
N1-C8
120.99
The observed and calculated frequencies using DFT B3LYP/6-31G and
probable assignments of 3d, 3f and 3h are summarized in Table 4. The C=C
stretching bands appear at 1480-1640 cm-1in the infrared spectrum. The bands
occurring at 1360, 1370 and 1367 cm-1 in 3d, 3f and 3h, respectively in IR
are assigned to the C–N stretching vibrations. The C=O stretching bonds is
observed at 1643, 1651 and 1653 in 3d, 3f and 3h, respectively. The aromatic
C–H stretching vibrations in 3d, 3f and 3h are observed at 3070, 3020 and 3047
cm-1, respectively. The bands observed in the infrared spectra of 3d, 3f and 3h
at 3384, 3440 and 3355 cm-1 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 1540 cm-1 in
the infrared spectrum are assigned to the –NO2 asymmetric stretching modes
of 3d. The very strong symmetric stretching vibration of nitro group of the
compound is assigned to the wave number 1342 cm-1 in the infrared spectra.
The C-Cl absorption is observed in the broad region between 850 and 550 cm-1.
The very strong band in IR at 720 cm-1 and 650 cm-1 are to the C-Cl and C-F
stretching of 3f and 3h, respectively. The correction factors used to correlate
the experimentally observed and theoretically computed frequencies for each
vibrational modes of 3d, 3f and 3h under DFT-B3LYP method is similar. The
linear regression between the experimental and theoretical wave number of 3d,
3f and 3h are shown in Figures 5-7. 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 vibration spectra.
1417

J. Chil. Chem. Soc., 57, Nº 4 (2012)
Figure 5. A plot of experimental and theoretical IR of 3d at the B3LYP/6-31G(d) level.
Table 4. The observed FTIR, FT-Raman and calculated frequencies using B3LYP/6-31G(d) force field.
3d
3f
3h
Assignment
calcd.
Exp.
3384
3070
2956
1643
1342
1540
1640
1620
1500
1480
1360
-
Calcd.
3299.3526
3075.6049
3074.5208
1651.4347
-
Exp.
3440
3020
2975
1650
-
Calcd.
3341.8726
3098.8765
2987.6543
1657.8798
-
Exp.
3355
3047
2958
1653
-
ν N-H
ν C-H(aromatic)
ν C-H(aliphatic)
ν C=O
3326.1348
3086.6595
3077.0829
1643.9472
1347.3871
1540.8131
1643.9472
1622.4582
1499.3334
1479.6697
1359.7844
-
ν NO2
ν NO2
-
-
-
-
ν C=C
1622.4851
1618.6870
1596.1266
1479.5006
1359.8949
704.6949
-
1620
1612
1600
1480
1370
720
1633.3451
1610.4565
1609.6767
1501.8921
1359.9831
-
1625
1612
1594
1498
1367
-
ν C=C
ν C=C
ν C=C
ν C-N
ν
C-Cl
C-F
ν
-
-
-
661.2345
1034.9823
1141.5672
1230.5123
890.4352
650
β
HCC
HCC
HCC
C-H
1136.9538
1206.0126
1465.5443
850.4244
1130
1220
1460
840
1076.6673
1142.5954
1205.4971
851.5648
1080
1140
1210
850
1030
1147
1211
891
β
β
γ
a ν-stretching; β-in-plane bending; γ-out of plane bending, wave numbers (cm-1)
Figure 6. A plot of experimental and theoretical IR of 3f at the B3LYP/6-
31G(d) level.
Figure 7. A plot of experimental and theoretical IR of 3h at the B3LYP/6-
31G(d) level.
1418

J. Chil. Chem. Soc., 57, Nº 4 (2012)
The 1H and 13C theoretical and experimental chemical shifts, isotropic shielding tensors and assignments of 3d, 3f and 3h are presented in Table 5 and Table
6, respectively. Aromatic carbons give signals in overlapped areas of the spectrum, with chemical shift values from 100 to 150 ppm in 13C NMR, and 6-8.5 ppm
in 1H NMR spectra of 3d, 3f and 3h.
Table 5. The experimental and calculated 1H isotropic chemical shifts (ppm) with respect to TMS of 3d, 3f and 3h.
3d
3f
3h
Assignment
Calcd.
0.39
0.44
0.46
0.5
Exp.
0.87
0.87
1.02
1.02
2.04
2.15
2.26
2.34
5.05
7.44
7.44
7.98
7.98
Calcd.
0.88
0.96
1.08
1.34
2.02
2.14
2.18
2.18
5.41
6.48
6.59
6.74
7.61
Exp.
1.03
1.03
1.15
1.15
2.18
2.22
2.28
2.31
5.51
7.20
7.20
7.32
7.32
Calcd.
0.88
0.96
1.08
1.34
2.02
2.14
2.18
2.18
4.25
7.08
6.68
6.02
6.11
Exp.
0.98
0.98
1.10
1.10
2.16
2.22
2.28
2.34
5.09
6.90
6.90
7.30
7.30
H34,H35,H36
H37, H38,H39
H47, H48,H49
H44, H45,H46
H42,H43
H50, H51
H40, H41
H32, H33
H31
1.5
1.52
1.53
1.54
4.31
6.72
7.23
7.51
7.46
H54
H52
H55
H53
Table 6. The experimental and calculated 13C isotropic chemical shifts (ppm) with respect to TMS of 3d, 3f and 3h.
3d
3f
3h
Assignment
Calcd.
134.08
106.8
133.68
107.07
36.64
30.06
44.06
178.19
27.1
Exp.
146.3
109.25
146.3
109.25
32.9
Calcd.
136.75
106.78
134.63
108.32
39.56
Exp.
149.7
113.3
149.7
113.3
33.0
Calcd.
132.85
108.05
133.18
107.78
36.73
30.26
44.2
Exp.
143.0
113.3
143.0
113.3
33.0
C8
C13
C2
C3
C7
C6
29.9
27.16
30.0
30.0
C5
34.9
46.82
41.1
41.0
C4
195.6
27.4
180.86
33.8
196.4
27.5
177.99
27.18
20.91
32.76
132.73
116.57
104.55
150.25
104.34
123.31
178.12
44.2
196.5
27.4
C24
C23
C14
C15
C20
C19
C18
C17
C16
C12
C11
C10
C9
20.77
34.21
144.62
115.77
113.52
135.07
113.19
122.7
178.42
43.95
29.91
36.59
27.04
20.63
27.4
26.51
27.5
27.4
51.0
30.83
51.2
51.3
154.9
123.5
112.3
149.8
112.3
123.5
195.6
34.9
132.68
124.23
119.43
123.99
118.09
115.94
180.13
46.73
145.6
145.6
129.9
132.0
129.9
145.6
196.4
41.1
129.7
115.0
107.2
149.9
107.2
115.0
196.5
41.0
29.9
27.14
30.0
30.22
36.7
30.0
32.9
39.65
33.0
33.0
C21
C22
27.4
33.47
27.5
27.14
20.78
27.4
27.4
25.27
27.5
27.4
1419

J. Chil. Chem. Soc., 57, Nº 4 (2012)
Due to the influence of electronegative atom, the chemical shift value of
C2, C8 and C18 in 3d, 3f and 3h are differ significantly in the shift positions
in the range 123-150 ppm and the corresponding values of chemical shifts
related to C , C8 and C are 133.68, 134.08 and 135.07 in 3d, 134.63, 136.75
and 123.99 2in 3f and 11383.18, 132.85 and 150.25 ppm in 3h, respectively. The
higher chemical shift of C in 3d, 3f and 3h is due to the attachment of electron
withdrawing nitro, Cl and1F8 group at C18. A down field shift is observed for C2
compared with C3 in 3d, 3f and 3h. That is due to the mesomeric effect between
C2-C3-C4-O25. The benzilic and allylic C-H carbon atom is calculated at 34.21,
30.83 and 32.76 in relatively good accordance with experimental results in 3d,
3f and 3h. Similarly, the benzilic and allylic C-H proton appear at 4.31, 5.41
and 4.25ppm, in according to their resonated chemical shift. The down field
signals at 7.51 and 7.46 in 3d, 6.74 and 7.61 in 3f and 6.68 and 7.08 ppm in
3h are assigned to H53 and H55 protons, respectively. This strongly indicates
the electron withdrawing nature of NO2, Cl and F in their neibourhood. The
electron withdrawing nitro group cause deshielding of the aromatic protons H53
and H more than Cl and F. The calculated and experimental chemical shift
values55given in Table 5 and 6, show a good agreement. The linear regressions
of the experimental and theoretical 1H and 13C NMR Chemical shifts of 3a-c are
represented in Figures 8-10.
1
Figure 9. A plot of experimental and theoretical a) H NMR and b) 13C
NMR chemical shifts of 3f at the B3LYP/6-31G(d) level.
1
Figure 8. A plot of experimental and theoretical a) H NMR and b) 13C
NMR chemical shifts of 3d at the B3LYP/6-31G(d) level.
Figure 10. A plot of experimental and theoretical a) 1H NMR and b) 13
C
NMR chemical shifts of 3h at the B3LYP/6-31G(d) level.
5. ACKNOWLEDGEMENT
We thank the Research Committee of Islamic Azad University of Rasht
Branch for partial support given to this study.
6. CONCLUSIONS
Finally, we develop an efficient and convenient procedure for the synthesis
1420

J. Chil. Chem. Soc., 57, Nº 4 (2012)
of 1, 4- dihydropyridines through the three component synthesis of aldehydes,
dimedone and ammonium acetate over nano-Fe3O . This procedure offer
advantages such as reduced reaction time, and higher4yield, ease of execution
and economic viability of the catalyst. This simple process combined with easy
recovery and reuse of the catalyst make this procedure economic, benign and a
waste free chemical process for the synthesis of dihydropyridines.
Selected structural parameters of the optimized geometries of the
compounds have been obtained from DFT calculations. The vibration
frequencies of the fundamental modes of the compound have been precisely
assigned and analyzed and the theoretical results were compared with the
experimental vibrations. 1H and 13C NMR isotropic chemical shifts were
calculated and the assignments are compared with the experimental values.
The present investigation provides complete vibration assignments, structural
information and NMR chemical shifts of these compounds.
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