Synthesis and molecular crystal structure of 4-(4,5-dimethoxy-2- nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1,4-dihydropyridine (C 19H 22N 2O 8)

Article abstract of DOI:10.1080/15421406.2012.752308

A novel three-component one-pot synthesis of 4-(4,5-dimethoxy-2- nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1,4-dihydropyridine from methyl 3-oxobutanoate, ammonium carbonate, and 4,5-dimethoxy-2-nitrobenzaldehyde has been carried out by typical Hantzsch synthesis. The single crystal was obtained by crystallization from methanol in 0.30 × 0.20 × 0.20 mm dimensional of 4-(4,5-dimethoxy-2-nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1, 4-dihydropyridine (C₁₉H₂₂N₂O₈), which was investigated by X-ray diffraction. The compound crystallizes in the monoclinic P₂₁/c space group with unit cell dimensions a = 14.4830(3) A, b = 8.66000(10) A, c = 15.1036(3) A, α = 90°, β = 90.0870(10)°, γ = 90°. ¹H NMR (hydrogen-1 nuclear magnetic resonance), mass, and IR (infrared) spectroscopic methods of the compound are also described.

Full text of DOI:10.1080/15421406.2012.752308

This article was downloaded by: [Ball State University]
On: 07 May 2013, At: 13:05
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Molecular Crystals and Liquid Crystals
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gmcl20
Synthesis and Molecular Crystal
Structure of 4-(4,5-Dimethoxy-2-
nitrophenyl)-2,6-dimethyl-3,5-
dicarbmethoxy-1,4-dihydropyridine
(C19H22N2O8)
Minaxi S. Maru a & Manish K. Shah a
a Department of Chemistry, Saurashtra University, Rajkot, Gujarat,
India
Published online: 02 Apr 2013.
To cite this article: Minaxi S. Maru & Manish K. Shah (2013): Synthesis and Molecular Crystal Structure
of 4-(4,5-Dimethoxy-2-nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1,4-dihydropyridine (C19H22N2O8),
Molecular Crystals and Liquid Crystals, 574:1, 117-128
To link to this article: http://dx.doi.org/10.1080/15421406.2012.752308
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Mol. Cryst. Liq. Cryst., Vol. 574: pp. 117–128, 2013
Copyright © Taylor & Francis Group, LLC
ISSN: 1542-1406 print/1563-5287 online
DOI: 10.1080/15421406.2012.752308
Synthesis and Molecular Crystal Structure of
4-(4,5-Dimethoxy-2-nitrophenyl)-2,6-dimethyl-3,5-
dicarbmethoxy-1,4-dihydropyridine
(C19H22N2O8)
MINAXI S. MARU AND MANISH K. SHAH∗
Department of Chemistry, Saurashtra University, Rajkot, Gujarat, India
A novel three-component one-pot synthesis of 4-(4,5-dimethoxy-2-nitrophenyl)-2,6-
dimethyl-3,5-dicarbmethoxy-1,4-dihydropyridine from methyl 3-oxobutanoate, ammo-
nium carbonate, and 4,5-dimethoxy-2-nitrobenzaldehyde has been carried out by typical
Hantzsch synthesis. The single crystal was obtained by crystallization from methanol in
0.30 × 0.20 × 0.20 mm dimensional of 4-(4,5-dimethoxy-2-nitrophenyl)-2,6-dimethyl-
3,5-dicarbmethoxy-1,4-dihydropyridine (C19H22N2O8), which was investigated by X-ray
diffraction. The compound crystallizes in the monoclinic P21/c space group with unit
cell dimensions a = 14.4830(3) Å, b = 8.66000(10) Å, c = 15.1036(3) Å, α = 90◦, β =
90.0870(10)◦, γ = 90◦. 1H NMR (hydrogen-1 nuclear magnetic resonance), mass, and
IR (infrared) spectroscopic methods of the compound are also described.
Keywords Crystal structure; Hantzsch synthesis; symmetric 1,4-DHP; X-ray diffrac-
tion study
Introduction
1,4-Dihydropyridines (DHPs) are one of the most interesting and extensively investigated
molecules by chemists worldwide because of their large existence in biological and medic-
inal area [1–3]. 1,4-DHP drugs having substitution of o/m-nitrophenyl at C(9) position are
generally used for the treatment of cardiovascular disorder as calcium channel antagonists
(i.e., nifedipine, nimodipine, manidipine, nicardipine, etc.) together with cardiac arrhyth-
mias, hypertension, angina, etc. [4]. Some new research exposes several other more medic-
inal applications of 1,4-DHPs, including as a cerebral anti-ischemic agent in the treatment
of Alzheimer’s disease [5a], platelet antiaggregratory activity [5b], and neuroprotectant [6]
and as a chemosensitizer in tumor therapy [7].
The symmetric and asymmetric structures with respect to the C(10) and C(13)
positions of 1,4-DHP drugs are well known [8]. The structure activity relationship studies
reveal that substitutions present at the C(10), C(9), and C(13) atoms of the nifedipine vary
the tissue selectivity and activity [9,10]. The selectivity and activity of 1,4-DHP derivatives
is depending on the design of DHP-calcium channel modulators. Because of the selectivity
and activity study, it is proved that 1,4-DHPs are the most potent molecules as calcium
channel transformers and has impelled the studies for the investigation of geometrical and
∗Address correspondence to Manish K. Shah, Department of Chemistry, Saurashtra Uni-
versity, Rajkot 360005, Gujarat, India. Tel.: +91-281-2583984; Fax: +91-281-2576802. E-mail:
drmks2000@hotmail.com
117

118
M. S. Maru and M. K. Shah
Table 1. Crystal data and structure refinement for C19H22N2O8
Identification code
Shelxl
Empirical formula
Formula weight
Temperature
C19H22N2O8
406.39 gm · mole−1
293(2) K
Wavelength
0.71073 Å
Crystal system
Space group
Unit cell dimensions
Monoclinic
P21/c
a = 14.4830(3) Å α = 90◦
b = 8.66000(10) Å β = 90.0870(10)◦
C = 15.1036(3) Å γ = 90◦
1894.33(6) A3
Volume
Z
4
Calculated density
Absorption coefficient
F(000)
1.425 mg · m−3
0.112 mm−1
856
Crystal size
Theta range for data collection
Limiting indices
0.30 × 0.20 × 0.20 mm
2.70◦ to 25.00◦
−17 ≤ h ≤ 12
−10 ≤ k ≤ 9
−17 ≤ l ≤ 17
Reflections collected/unique
Completeness to theta = 25.00
Absorption correction
Max. and min. transmission
Refinement method
16674/3335 [R(int) = 0.0290]
100.0%
Semiempirical from equivalents
0.9836 and 0.9325
Full-matrix least-squares on F2
3335/0/272
Data/restraints/parameters
Goodness-of-fit on F2
1.034
Final R indices [I > 2 sigma(I)]
R indices (all data)
Extinction coefficient
R1 = 0.0374, wR2 = 0.0973
R1 = 0.0492, wR2 = 0.1060
0.0090(9)
0.226 e · Å−3 and −0.166 e · Å−3
Largest diff. peak and hole
functional requirements at the DHP binding site [11]. Namely, the activity of 1,4-DHP
calcium channel antagonists is highly dependent on the nature, size, and position of the
C(9) phenyl ring substitutions, which were key of voltage-dependent calcium channel
antagonist activity [12,13]. The substitutions, such as ester, acyl, sulphonyl, or nitrile
groups, present at C(10) and C(13) positions of 1,4-DHP ring have established to be a
vital necessities for the pharmacological activity [14,15]. Earlier crystallographic studies
of several 2,6-dimethyl-3,5-dicarbmethoxy-1,4-dihydropyridines show that substitution
present on the phenyl ring confine the free rotation of the phenyl ring due to the repulsion
effect of the carbmethoxy groups at the C(10) and C(13) positions and also could influence
the possibility of puckering of the 1,4-DHP ring, which cause a more suitable conformation
for drug receptor interaction [16,17].

Molecular Crystal Structure of Novel 1,4-Dihydropyridine
119
Table 2. Atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2
× 103) for C19H22N2O8
No.
Atom
x
y
z
U(eq)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
8116(1)
8978(1)
9432(1)
9041(1)
8192(1)
7692(1)
10641(1)
9264(2)
6767(1)
6925(1)
6798(1)
6046(1)
6144(1)
5693(1)
5608(2)
7267(1)
7997(2)
5536(2)
6971(1)
7715(1)
6442(1)
8248(1)
6879(1)
10253(1)
9559(1)
7360(1)
7512(1)
5122(1)
6003(1)
1729(2)
1939(2)
718(2)
−761(2)
−935(2)
298(2)
2296(2)
−3461(2)
−81(2)
5236(1)
5634(1)
6002(1)
5936(1)
5539(1)
5184(1)
6541(1)
6153(2)
4738(1)
3884(1)
3848(1)
5285(1)
5364(1)
6093(1)
6858(1)
3110(1)
2639(2)
5894(1)
3090(1)
4875(1)
4575(1)
4614(1)
4838(1)
6439(1)
6281(1)
2369(1)
3314(1)
6593(1)
6163(1)
33(1)
37(1)
37(1)
36(1)
34(1)
30(1)
53(1)
56(1)
30(1)
33(1)
36(1)
37(1)
32(1)
35(1)
55(1)
39(1)
65(1)
52(1)
49(1)
40(1)
42(1)
66(1)
52(1)
53(1)
51(1)
64(1)
48(1)
54(1)
48(1)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
N(1)
N(2)
O(1)
O(2)
O(3)
O(4)
O(5)
O(6)
O(7)
O(8)
−981(2)
−2524(2)
−2528(2)
−983(2)
−168(2)
2199(2)
−147(2)
2147(3)
−3589(2)
−3593(2)
3142(2)
−3269(2)
4149(2)
3302(1)
810(2)
−1914(2)
−641(2)
1308(2)
−682(2)
1284(2)
U(eq) = 1/3 of the trace of the orthogonalized Uij tensor.
With view of the wide pharmacological importance of 1,4-DHPs,
a
a
novel symmetric 4-(4,5-dimethoxy-2-nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1,4-
dihydropyridine (C19H22N2O8) compound has been synthesized by the Hantzsch synthetic
1
method and characterized by single crystal X-ray diffraction crystallography, H NMR
(hydrogen-1 nuclear magnetic resonance), mass, and IR (infrared) spectroscopy.
Experimental
General Methods
All the chemicals and solvents were commercially available and used as purchased without
further purification. Analytical thin layer chromatography (TLC) was performed on silica
gel-G, using ethyl acetate:hexane (1:4) solvent system. Melting point was determined
in open capillaries on a melting point apparatus purchased from Jain Scientific Glass

120
M. S. Maru and M. K. Shah
Table 3. Bond lengths [Å] and angles [◦]
No.
Atoms
C(1)–C(6)
Lengths [Å]
No.
Atoms
Lengths [Å]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
1.386(2)
1.396(2)
1.460(2)
1.363(2)
0.9300
1.362(2)
1.404(2)
1.354(2)
1.375(2)
1.396(2)
0.9300
1.534(2)
1.412(2)
0.9600
0.9600
0.9600
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
C(11)–C(19)
C(12)–C(13)
C(12)–N(2)
C(12)–C(18)
C(13)–C(14)
C(14)–O(7)
C(14)–O(8)
C(15)–O(8)
C(15)–H(15A)
C(15)–H(15B)
C(15)–H(15C)
C(16)–O(5)
1.493(2)
1.351(2)
1.375(2)
1.496(3)
1.463(2)
1.206(2)
1.339(2)
1.434(2)
0.9600
0.9600
0.9600
1.207(2)
1.344(2)
1.436(2)
0.9600
0.9600
0.9600
0.9600
0.9600
0.9600
0.9600
0.9600
0.9600
C(1)–C(2)
C(1)–N(1)
C(2)–C(3)
C(2)–H(2)
C(3)–O(3)
C(3)–C(4)
C(4)–O(4)
C(4)–C(5)
C(5)–C(6)
C(5)–H(5)
C(6)–C(9)
C(7)–O(3)
C(7)–H(7A)
C(7)–H(7B)
C(7)–H(7C)
C(8)–O(4)
C(8)–H(8A)
C(8)–H(8B)
C(8)–H(8C)
C(9)–C(13)
C(9)–C(10)
C(9)–H(9)
C(10)–C(11)
C(10)–C(16)
C(11)–N(2)
C(16)–O(6)
C(17)–O(6)
C(17)–H(17A)
C(17)–H(17B)
C(17)–H(17C)
C(18)–H(18A)
C(18)–H(18B)
C(18)–H(18C)
C(19)–H(19A)
C(19)–H(19B)
C(19)–H(19C)
N(1)–O(2)
1.419(2)
0.9600
0.9600
0.9600
1.523(2)
1.524(2)
0.927(17)
1.350(2)
1.461(2)
1.375(2)
1.2193(19)
1.2298(19)
0.88(2)
N(1)–O(1)
N(2)–H(2A)
No.
1
2
3
4
5
6
7
8
Atoms
Angle [◦]
122.52(15)
123.47(14)
114.00(14)
120.25(16)
119.9
No.
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
Atoms
Angle [◦]
113.52(16)
119.82(15)
121.01(15)
119.07(14)
121.81(16)
126.93(17)
111.26(14)
109.5
109.5
109.5
109.5
109.5
C(6)–C(1)–C(2)
C(6)–C(1)–N(1)
C(2)–C(1)–N(1)
C(3)–C(2)–C(1)
C(3)–C(2)–H(2)
C(1)–C(2)–H(2)
O(3)–C(3)–C(2)
O(3)–C(3)–C(4)
C(2)–C(3)–C(4)
O(4)–C(4)–C(5)
O(4)–C(4)–C(3)
C(5)–C(4)–C(3)
C(4)–C(5)–C(6)
C(4)–C(5)–H(5)
C(6)–C(5)–H(5)
C(1)–C(6)–C(5)
C(1)–C(6)–C(9)
C(5)–C(6)–C(9)
O(3)–C(7)–H(7A)
O(3)–C(7)–H(7B)
H(7A)–C(7)–H(7B)
O(3)–C(7)–H(7C)
N(2)–C(12)–C(18)
C(12)–C(13)–C(14)
C(12)–C(13)–C(9)
C(14)–C(13)–C(9)
O(7)–C(14)–O(8)
O(7)–C(14)–C(13)
O(8)–C(14)–C(13)
O(8)–C(15)–H(15A)
O(8)–C(15)–H(15B)
H(15A)–C(15)–H(15B)
O(8)–C(15)–H(15C)
H(15A)-C(15)-H(15C)
H(15B)–C(15)–H(15C)
O(5)–C(16)–O(6)
O(5)–C(16)–C(10)
O(6)–C(16)–C(10)
O(6)–C(17)–H(17A)
O(6)–C(17)–H(17B)
H(17A)–C(17)–H(17B)
O(6)–C(17)–H(17C)
H(17A)–C(17)–H(17C)
H(17B)–C(17)–H(17C)
119.9
124.90(16)
116.12(15)
118.98(15)
125.59(16)
114.94(15)
119.46(15)
123.08(15)
118.5
9
10
11
12
13
14
15
16
17
18
19
20
21
22
109.5
120.95(17)
127.29(18)
111.73(15)
109.5
109.5
109.5
109.5
109.5
109.5
118.5
115.62(14)
127.11(14)
117.19(14)
109.5
109.5
109.5
109.5
(Continued on next page)

Molecular Crystal Structure of Novel 1,4-Dihydropyridine
121
Table 3. Bond lengths [Å] and angles [◦] (Continued)
No.
Atoms
Lengths [Å]
No.
Atoms
Lengths [Å]
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
H(7A)–C(7)–H(7C)
H(7B)–C(7)–H(7C)
O(4)–C(8)–H(8A)
O(4)–C(8)–H(8B)
H(8A)–C(8)–H(8B)
O(4)–C(8)–H(8C)
H(8A)–C(8)–H(8C)
H(8B)–C(8)–H(8C)
C(13)–C(9)–C(10)
C(13)–C(9)–C(6)
C(10)–C(9)–C(6)
C(13)–C(9)–H(9)
C(10)–C(9)–H(9)
C(6)–C(9)–H(9)
C(11)–C(10)–C(16)
C(11)–C(10)–C(9)
C(16)–C(10)–C(9)
C(10)–C(11)–N(2)
C(10)–C(11)–C(19)
N(2)–C(11)–C(19)
C(13)–C(12)–N(2)
C(13)–C(12)–C(18)
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
110.69(13)
110.79(13)
110.36(13)
107.3(10)
109.6(10)
108.0(10)
120.21(16)
121.30(15)
118.41(15)
118.89(16)
128.45(17)
112.64(16)
119.18(16)
127.30(17)
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
C(12)–C(18)–H(18A)
C(12)–C(18)–H(18B)
H(18A)–C(18)–H(18B)
C(12)–C(18)–H(18C)
H(18A)–C(18)–H(18C)
H(18B)–C(18)–H(18C)
C(11)–C(19)–H(19A)
C(11)–C(19)–H(19B)
H(19A)–C(19)–H(19B)
C(11)–C(19)–H(19C)
H(19A)–C(19)–H(19C)
H(19B)–C(19)–H(19C)
O(2)–N(1)–O(1)
O(2)–N(1)–C(1)
O(1)–N(1)–C(1)
C(12)–N(2)–C(11)
C(12)–N(2)–H(2A)
C(11)–N(2)–H(2A)
C(3)–O(3)–C(7)
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
121.88(15)
120.46(14)
117.65(15)
124.12(15)
116.9(13)
118.9(13)
116.94(14)
118.51(14)
116.18(15)
116.26(15)
C(4)–O(4)–C(8)
C(16)–O(6)–C(17)
C(14)–O(8)–C(15)
Works, Ambala Cantt, Haryana, India and is uncorrected. The IR spectra were recorded on
Shimadzu FT-IR 8400 spectrophotometer, using KBr discs. The mass spectra were recorded
on the Shimadzu GC-MS QP-2010 gas chromatograph. 1H NMR spectra were recorded in
dimethyl sulfoxide-d6 (DMSO-d6) on a Bruker AV 400 spectrophotometer. The chemical
shifts are reported in parts per million (ppm) on the δ scale, using the Tetramethylsilane
(TMS) peak as a reference value. The single crystal X-ray diffraction analyzed on Enraf
Nonius CAD4-MV31 diffractometer.
Synthesis of 4-(4,5-Dimethoxy-2-nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1,4-
dihydropyridine
A mixture of methyl 3-oxobutanoate (0.025 mole) and 4,5-dimethoxy-2-nitrobenzaldehyde
(0.01 mole) was dissolve in 30 mL of methanol and then ammonium carbonate (0.015 mole)
was added to the mixture and allowed to refluxed on water bath for 48 hours. The progress
of reaction was monitored by TLC. After completion of reaction, the resulting reaction
mixture was poured into the crushed ice, filtered, and then dried over suction to get yellow
colored compound by several washes of water (Scheme 1). Melting point 180◦C–183◦C,
yield 95%. Elemental analysis: Calcd. for C19H22N2O8: C, 56.15; H, 5.46; N, 6.89; O,
31.50. Found: C, 56.10; H, 5.40; N, 6.83; O, 31.44. Mass: m/z = 406, IR (KBr, ν cm−1):
3367 (N–H stretching), 3088 and 3010 (C–H stretching of aromatic), 2982 and 2926 (C–H
asymmetric stretching of –CH3), 2872 and 2845 (C–H symmetric stretching of –CH3),
1735 and 1693 (C = O stretching of ester). 1H NMR (δ ppm, DMSO-d6 + 400 MHz): 2.25
(s, 6H, –CH3), 3.45 (s, 6H, –OCH3 of 1,4-DHP ring), 3.71 and 3.78 (2s, 6H, –OCH3 of
phenyl ring), 5.57 (s, 1H, –CH), 6.85 (s, 1H, Ar–H), 7.29 (s, 1H, Ar–H), and 8.95 (s, 1H,
–NH).

122
M. S. Maru and M. K. Shah
H3C
O
H3C
O
O
O
CH3
O
CH3
O
O
Ammonium carbonate
O2N
O
H3C
+
O2N
O
CH3
a
H
H3C
CH3
O
O
H
O
H3C
N
H
CH3
aReagents and conditions:Methanol; reflux; 48hr
Scheme 1. Reaction scheme for the synthesis of C19H22N2O8.
Method for Single Crystal Development
The dried pure product of 1 g of quantity was taken in a small beaker with sufficient amount
of methanol and heated on hot plate to dissolve the solid product and then 1 g of charcoal
was added to it and filtered the hot solution in 50-mL stopper flask through Whatman 42
filter paper. The collected filtrate was allowed to stand at room temperature for few weeks
to obtained yellow colored crystals. Figure 1 shows a prospective view of a molecule with
an atomic number scheme.
Figure 1. The molecular structure of the title compound showing the atom-labeling scheme (ORTEP).

Molecular Crystal Structure of Novel 1,4-Dihydropyridine
Results and Discussion
123
The crystal data of the title compound was collected at 293(2) K. Intensity data were
collected in the ω-2θ scan mode, using graphite monochromated Mo Kα radiation (0.71073
Å). The title compound crystallizes in the monoclinic P21/c space group with unit cell
dimensions a = 14.4830(3) Å, b = 8.66000(10) Å, c = 15.1036(3) Å, α = 90◦, β =
90.0870(10)◦, γ = 90◦. The crystal data solved by direct method and resolve by full-
matrix least-squares on F2 with program system SHELXS-97 [18] and SHELXL-97 [19],
respectively. The crystal data and structure refinement parameters of the title compound are
summarized in Table 1.
The atomic coordinates and equivalent isotropic displacement parameters for title
compound (C19H22N2O8) are listed in Table 2. The list of bond lengths and bond angles
Table 4. Anisotropic displacement parameters (Å2 × 103) for C19H22N2O8
No.
Atom
U11
U22
U33
U23
U13
U12
2(1)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
35(1)
37(1)
32(1)
37(1)
37(1)
32(1)
40(1)
62(1)
31(1)
29(1)
31(1)
33(1)
29(1)
31(1)
60(1)
37(1)
78(2)
60(1)
53(1)
43(1)
50(1)
58(1)
41(1)
42(1)
49(1)
89(1)
63(1)
52(1)
54(1)
31(1)
35(1)
45(1)
38(1)
31(1)
32(1)
61(1)
39(1)
27(1)
36(1)
38(1)
37(1)
34(1)
39(1)
52(1)
45(1)
63(1)
40(1)
44(1)
31(1)
28(1)
45(1)
35(1)
53(1)
43(1)
68(1)
44(1)
55(1)
41(1)
32(1)
37(1)
35(1)
33(1)
34(1)
26(1)
59(1)
66(1)
34(1)
32(1)
39(1)
40(1)
35(1)
36(1)
52(1)
35(1)
54(1)
58(1)
51(1)
47(1)
48(1)
96(1)
80(1)
65(1)
62(1)
34(1)
39(1)
56(1)
49(1)
0(1)
0(1)
−3(1)
−2(1)
2(1)
−1(1)
−2(1)
−4(1)
9(1)
−1(1)
−3(1)
−1(1)
−1(1)
2(1)
−13(1)
−8(1)
−1(1)
−3(1)
−6(1)
−5(1)
−1(1)
−2(1)
12(1)
−5(1)
0(1)
5(1)
−1(1)
2(1)
−9(1)
6(1)
3(1)
4(1)
5(1)
C(9)
1(1)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
N(1)
N(2)
O(1)
O(2)
O(3)
O(4)
O(5)
O(6)
O(7)
O(8)
−2(1)
−5(1)
2(1)
2(1)
5(1)
−13(1)
−1(1)
13(1)
7(1)
−1(1)
1(1)
2(1)
11(1)
7(1)
−9(1)
−11(1)
3(1)
−2(1)
23(1)
3(1)
−15(1)
−6(1)
−6(1)
−2(1)
−15(1)
−3(1)
−20(1)
−16(1)
8(1)
1(1)
−2(1)
−2(1)
27(1)
3(1)
1(1)
9(1)
0(1)
−14(1)
7(1)
−3(1)
5(1)
−8(1)
−2(1)
−6(1)
−2(1)
−4(1)
4(1)
11(1)
21(1)
17(1)
5(1)
−10(1)
The anisotropic displacement factor exponent takes the form: −2π2 [h2a∗2U11 + · · · + 2 hk
a∗b∗U12].

124
M. S. Maru and M. K. Shah
between the atoms of title compound are given in Table 3. The atoms rather than hydrogen
were defined by anisotropic displacement parameters as shown in Table 4, and the hydrogen
atoms were refined riding on their bonded atoms with a global isotropic temperature factor
(Table 5). The torsion angles between anisotropic atoms are given in Table 6, and the
hydrogen bonding geometry summarized in Table 7. The bond angles and bond lengths are
in good agreement with the previously reported symmetric 1,4-DHP crystal structures [20].
The N(1) atom show an sp2 hybridization [21], which can be seen from the observed val-
ues of the bond angles of the title compound about at 120◦, O(2)–N(1)–O(1) at 121.88(15)◦,
O(2)–N(1)–C(1) at 120.46(14)◦, and O(1)–N(1)–C(1) at 117.65(15)◦. The same trend is
observed for the N(2) atom in the pyridyl ring C(12)–N(2)–C(11) at 124.12(15)◦ (Table 3).
The C(11)–C(10)–C(16)–O(5) and C(9)–C(13)–C(14)–O(7) torsion angles are 9.6(3)◦ and
10.8(3)◦, respectively, showing that both carbonyl groups are sp/cis (synperiplanar) to the
respective endocyclic double bonds of the 1,4-DHP ring [22]. It was stated in past literature
that the carbonyl groups, which are not involved in the hydrogen bonding, exist in sp/cis
(synperiplanar) conformation, and if the carbonyl groups are involved in hydrogen bonding,
it would be considered as an ap/trans (antiperiplanar) conformation [23,24]. The degree
of distortions N(2) and C(9) is directly reflected in the magnitude of the torsion angles
originating from these two atoms. The torsion angle value of C(10)–C(9)–C(13)–C(12) is
higher, showing 21.3(2)◦ angle in DHP ring, which indicates the puckering is grater at C(9)
than at N(2) (Table 6).
Table 5. Hydrogen coordinates (×104) and isotropic displacement parameters (Å2 × 103)
No.
Atom
x
Y
z
U(eq)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
H(2)
H(5)
9245
7939
11215
10222
10749
9694
9234
8664
5877
5729
4953
8138
7617
8560
5578
4899
5803
6398
2917
−1921
2217
2939
2741
−4152
−3681
−3597
3212
1718
2279
5646
5505
6856
6867
5968
6431
5531
6412
6850
7419
6770
2850
2119
2497
5676
5921
6475
2794
3307
2682
4611(10)
4585(13)
44
41
80
80
80
83
83
83
82
82
82
98
98
98
79
79
79
H(7A)
H(7B)
H(7C)
H(8A)
H(8B)
H(8C)
H(15A)
H(15B)
H(15C)
H(17A)
H(17B)
H(17C)
H(18A)
H(18B)
H(18C)
H(19A)
H(19B)
H(19C)
H(9)
3165
2218
1616
−4628
−3285
−3534
−3811
−4538
−3118
840(20)
−4280(30)
74
74
74
26(4)
53(6)
7234
7391
6471(11)
6439(13)
H(2A)

Molecular Crystal Structure of Novel 1,4-Dihydropyridine
125
Table 6. Torsion angles [◦]
No.
Atom
Angle [◦]
No.
Atom
Angle [◦]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
C(6)–C(1)–C(2)–C(3)
N(1)-C(1)–C(2)–C(3)
C(1)-C(2)–C(3)–O(3)
C(1)-C(2)–C(3)–C(4)
O(3)-C(3)–C(4)–O(4)
C(2)-C(3)–C(4)–O(4)
O(3)-C(3)–C(4)–C(5)
C(2)–C(3)–C(4)–C(5)
O(4)–C(4)–C(5)–C(6)
C(3)–C(4)–C(5)–C(6)
C(2)–C(1)–C(6)–C(5)
N(1)–C(1)–C(6)–C(5)
C(2)–C(1)–C(6)–C(9)
N(1)–C(1)–C(6)–C(9)
C(4)–C(5)–C(6)–C(1)
C(4)–C(5)–C(6)–C(9)
C(1)–C(6)–C(9)–C(13)
C(5)–C(6)–C(9)–C(13)
C(1)–C(6)–C(9)–C(10)
C(5)–C(6)–C(9)–C(10)
C(13)–C(9)–C(10)–C(11)
C(6)–C(9)–C(10)–C(11)
C(13)–C(9)–C(10)–C(16)
C(6)–C(9)–C(10)–C(16)
C(16)–C(10)–C(11)–N(2)
C(9)–C(10)–C(11)–N(2)
C(16)–C(10)–C(11)–C(19)
C(9)–C(10)–C(11)–C(19)
N(2)–C(12)–C(13)–C(14)
C(18)–C(12)–C(13)–C(14)
1.1(3)
179.76(15)
176.90(16)
3.2(3)
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N(2)–C(12)–C(13)–C(9)
C(18)–C(12)–C(13)–C(9) 173.80(17)
C(10)–C(9)–C(13)–C(12)
C(6)–C(9)–C(13)–C(12)
C(10)–C(9)–C(13)–C(14) 162.49(14)
C(6)–C(9)–C(13)–C(14)
C(12)–C(13)–C(14)–O(7)
C(9)–C(13)–C(14)–O(7)
6.5(2)
21.3(2)
101.47(17)
3.1(2)
176.81(16)
177.12(15)
3.0(3)
179.17(16)
0.6(3)
74.75(18)
10.8(3)
172.94(17)
C(12)–C(13)–C(14)–O(8) 168.37(15)
C(9)–C(13)–C(14)–O(8)
C(11)–C(10)–C(16)–O(5)
C(9)–C(10)–C(16)–O(5)
7.9(2)
9.6(3)
173.58(18)
1.2(2)
177.81(15)
177.76(15)
1.3(3)
C(11)–C(10)–C(16)–O(6) 168.51(15)
C(9)–C(10)–C(16)–O(6)
C(6)–C(1)–N(1)–O(2)
C(2)–C(1)–N(1)–O(2)
C(6)–C(1)–N(1)–O(1)
C(2)–C(1)–N(1)–O(1)
C(13)–C(12)–N(2)–C(11)
C(18)–C(12)–N(2)–C(11) 167.69(16)
C(10)–C(11)–N(2)–C(12) 12.4(3)
C(19)–C(11)–N(2)–C(12) 165.95(16)
C(2)–C(3)–O(3)–C(7)
C(4)–C(3)–O(3)–C(7)
C(5)–C(4)–O(4)–C(8)
C(3)–C(4)–O(4)–C(8)
O(5)–C(16)–O(6)–C(17)
C(10)–C(16)–O(6)–C(17) 170.08(16)
O(7)–C(14)–O(8)–C(15) 0.8(2)
C(13)–C(14)–O(8)–C(15) 179.96(15)
8.3(2)
30.4(2)
150.47(16)
149.76(17)
29.4(2)
1.5(2)
178.34(15)
129.22(17)
54.30(19)
107.83(18)
68.66(18)
20.9(2)
102.09(17)
162.25(14)
74.73(18)
177.51(15)
5.7(2)
12.0(3)
2.4(3)
177.77(16)
6.8(3)
173.05(17)
8.1(3)
0.6(3)
176.19(16)
177.28(15)
2.4(3)
The torsion angles observed for the title compound specify that the atoms C(9) and
N(2) are displaced from the ring in the same direction, conflicting to that of the substituted
phenyl ring orientated in a pseudoaxial confirmation, this pseudoaxial phenyl ring C(6),
C(1), C(2), C(3), C(4), C(5) being perpendicular to dihydropyridine ring (Figs 2(a) and
(b)). The distance between C(9) and N(2) atoms and the perpendicular orientation of phenyl
ring on C(9) atom allows more quantification about a flattened boat-type conformation of
the dihydropyridine ring. The perpendicular orientation of the phenyl ring with respect to
Table 7. Hydrogen bonds [Å] and [◦]
D–H . . . A
d(D–H)
0.88(2)
d(H . . . A)
2.22(2)
d(D . . . A)
3.062(2)
<(DHA)
160.8(18)
N(2)–H(2A) . . . O(2)a
a
= symmetry transformations used to generate equivalent atoms: x, y − 1, z.

126
M. S. Maru and M. K. Shah
Figure 2. (a) The unit cell content of C19H22N2O8 showing hydrogen bonding interactions. (b) The
unit cell content of C19H22N2O8 showing hydrogen bonding interactions.
the dihydropyridine ring and the flattened boat-type conformation of 1,4-DHP is the highly
active position as well as conformation for the antagonist activity [25,26].
The carbonyl group substituted at C(10) and C(13) (sp) is not involved in hydrogen
bonding; consequently, the structure exhibits only one intermolecular hydrogen bond in-
volving the O(2) atom of C(1) substituted nitro group to the H(2A) atom substituted at
N(2) atom of 1,4-DHP ring (Figs 2(a) and (b)). The presence of hydrogen bonding in
the crystal structure shows the major role of calcium antagonist effect [27–29]. The inter-
molecular hydrogen bond observed in the crystal structure of title compound is the type
of N(2)–H(2A) . . . O(2) having (x, y − 1, z) symmetry code with 2.22(2) Å length and
160.8(18)◦ angle (Table 7).

Molecular Crystal Structure of Novel 1,4-Dihydropyridine
Supplementary data
127
Crystallographic data for the structure reported in this paper have been deposited
in the Cambridge Crystallographic Data Centre as supplementary publications no.
CCDC-896984 for 4-(4,5-dimethoxy-2-nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1,4-
dihydropyridine. Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: (+44)1223–336-033; e-mail:
deposit@ccdc.cam.ac.uk, www: http://www.ccdc.cam.ac.uk).
Supplemental materials are available for this article. Go to the publisher’s online edition
of Molecular Cyrstals and Liquid Crystals to view the free supplemental file.
Acknowledgments
The authors would like to thank the Department of Chemistry, Saurashtra University, Rajkot,
Gujarat, India, for providing necessary facilities for this research. M.S.M. would like to
express her genuine gratitude to the University Grant Commission, New Delhi, India, for
financial support under Rajiv Gandhi National Fellowship Scheme.
References
[1] Mauzeral, D., & Westheimer, F. H. (1955). J. Am. Chem. Soc., 77, 2261.
[2] Nakamichi, N., Kawashita, Y., & Hayashi, M. (2004). Synthesis, 7, 1015.
[3] Nakamichi, N., Kawashita, Y., & Hayashi, M. (2002). Org. Lett., 4, 3955.
[4] (a) Triggle, D. J. (1990). Drugs Acting On Ion Channels and Membranes. In: J. C. Emmet
(Eds.), Comprehensive Medicinal Chemistry, Vol. 3, Chapter 14.1, Pergamon: Oxford; (b) Rah-
way, N. J. (1996). The Merck Index, 12th ed., Merck Research Laboratories: New York, p
1121; (c) Iwanami, M., Shibanuma, T., Fujimoto, M., Kawai, R., Tamazawa, K., Takenaka, T.,
Takahashi, K., & Murakami, M. (1979). Chem. Pharm. Bull., 27, 1426.
[5] (a) Bretzel, R. G., Bollen, C. C., Maeser, E., & Federlin, K. F. (1992). Drugs Fut., 17, 465;
(b) Bretzel, R. G., Bollen, C. C., Maeser, E., & Federlin, K. F. (1993). Am. J. Kidney Dis. 21,
53.
[6] Klusa, V. (1995). Drugs Fut., 20, 135.
[7] Boer, R., & Gekeler, V. (1995). Drugs Fut., 20, 499.
[8] Christiaans, J. A. M., & Timmerman, H. (1996). Euro. J. Pharma. Sci., 4, 1.
[9] Ferry, D. R., & Glossmann, H. (1982). Naunyn-Schmiedeberg’s Arch Pharmacol., 321, 80.
[10] Itil, T. M., Michael, S. T., Hoffmeister, F., Kunitz, A., & Eralp, E. (1984). Curr. Ther. Res., 35,
405.
[11] Murphy, K. M. M., Gould, R. J., Largent, B. L., & Synder, S. H. (1983). Proc. Matl. Acad. Sci.
USA, 80, 860.
[12] Langs, D. A., & Triggle, D. J. (1985). Mol. Pharm., 27, 544.
[13] Love, B., Goodman, M. M., Snader, K. M., Tedeschi, R., & Macko, E. (1974). J. Med. Chem.,
17, 956.
[14] (a) Goldmann, S., & Stoltefuss, J. (1991). Angew. Chem. Ed. Engl., 30, 1559; (b) Schramm,
M., Thomas, G., Towart, R., & Franckowiak, G. (1983). Nature, 303, 535; (c) Budriesi, R.,
Bisi, A., Ioan, P., Rampa, A., Gobbi, S., Bulleti, F., Piazzi, L., Valenti, P., & Chiarini, A. (2005).
Bioorg. Med. Chem., 13, 3423.
[15] (a) Cobum, R. A., Wierzba, M., Suto, M. J., Solo, A. J., Triggle, A. M., & Triggle, D. J. (1988).
J. Med. Chem., 31, 2103; (b) Triggle, A. M., Shefter, E., & Triggle, D. J. (1980). J. Med. Chem.,
23, 1442.
[16] Fossheim, R., Svarteng, K., Mostad, A., Romming, C., Shefter, E., & Triggle, D. J. (1982). J.
Med. Chem., 25, 126.

128
M. S. Maru and M. K. Shah
[17] Meyer, H., Bossert, F., Wehinger, E., Stoepel, K., & Vater, W. (1981). Arzneim-Forsch., 31, 407.
[18] Sheldrick, G. M. (1990). Acta Crystallogr., A46, 467.
[19] Sheldrick, G. M. (1997). SHELXL-1997, Program for Refinement of Crystal Structures, Uni-
versity of Gottingen: Germany.
[20] Caignan, A. G., & Holt, M. E. (2000). J. Chem. Cryst., 30(10), 677.
[21] Suarez, M., De Armas, M., Ramirez, O., Alvarez, A., Martinez-Alvarez, R., Molero, D., Seoane,
C., Liz, R., De Rmas, H. N., Blaton, N. M., Peeters, O. M., & Martın, N. (2005). New. J. Chem.,
29, 1567.
[22] (a) Triggle, A. M., Scheffer, E., & Trigle, D. J. (1980). J. Med. Chem., 23, 1442; (b) Fosseheim,
R. (1986). J. Med. Chem., 29, 305.
[23] Mahendra, M., Doreswamy, B. H., Sridhar, M. A., Prasad, J. S., Patel, G. R., Patel, J. A., &
Shah, A. (2004). J. Chem. Crystallogr., 34(7), 441.
[24] (a) Caignan, G. A., & Holt, E. M. (2000). Z. Kristallogr., 215(2), 122; (b) Metcalf, S. K., &
Holt, E. M. (2000). Acta Crystallogr., C56, 1228.
[25] Triggle, D. J., Langs, D. A., & Janis, R. A. (1989). Med. Res. Rev., 9, 123.
[26] Allen, F. H., Kennard, O., Watson, D. G., Brummer, L., Orpen, A. G., & Taylor, R. (1987). J.
Chem. Soc. Perkin Trans, II, S1.
[27] Triggle, D. J., Langs, D. A., & Janis, R. A. (1989). Med. Res. Rev., 9, 123.
[28] Fossheim, R. (1986). Acta. Chem. Scand., B41. 581.
[29] Fossheim, R. (1986). J. Med. Chem., 29, 305.