Dimethyl 4-[3-(4-meth-oxy-phen-yl)-1-phenyl-1H-pyrazol-4-yl]-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxyl-ate dihydrate.

Abstract

In the title compound, C(27)H(27)N(3)O(5)·2H(2)O, the dihydro-pyridine ring adopts a flattened boat conformation. The central pyrazole ring is essentially planar [maximum deviation of 0.003 (1) Å] and makes dihedral angles of 50.42 (6) and 26.44 (6)° with the benzene rings. In the crystal, mol-ecules are linked via N-H⋯O, O-H⋯O, O-H⋯N and C-H⋯O hydrogen bonds into two-dimensional networks parallel to the bc plane. The crystal structure is further consolidated by weak C-H⋯π inter-actions.

Full text

Page 1

Dimethyl 4-[3-(4-methoxyphenyl)-1-
phenyl-1H-pyrazol-4-yl]-2,6-dimethyl-
1,4-dihydropyridine-3,5-dicarboxylate
dihydrate
Hoong-Kun Fun,a*‡ Chin Wei Ooi,aB. Garudachari,b
Kammasandra Nanjunda Shivanandacand Arun M. Isloorb
aX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800
USM, Penang, Malaysia,bMedicinal Chemistry Laboratory, Department of
Chemistry, National Institute of Technology Karnataka, Surathkal, Mangalore
575 025, India, andcSchulich Faculty of Chemistry, Technion Israel Institute of
Technology, Haifa 32000, Israel
Correspondence e-mail: hkfun@usm.my
Received 18 June 2012; accepted 20 June 2012
Key indicators: single-crystal X-ray study; T = 100 K; mean ?(C–C) = 0.002 A ˚;
R factor = 0.042; wR factor = 0.131; data-to-parameter ratio = 20.5.
In the title compound, C27H27N3O5?2H2O, the dihydropyridine
ring adopts a flattened boat conformation. The central
pyrazole ring is essentially planar [maximum deviation of
0.003 (1) A˚] and makes dihedral angles of 50.42 (6) and
26.44 (6)?with the benzene rings. In the crystal, molecules are
linked via N—H???O, O—H???O, O—H???N and C—H???O
hydrogen bonds into two-dimensional networks parallel to the
bc plane. The crystal structure is further consolidated by weak
C—H???? interactions.
Related literature
For details and applications of pyrazoles, see: Buhler &
Kiowski (1987); Isloor et al. (2000, 2009); Isloor (2011); Vijesh
et al. (2011); Vo et al. (1995). For the preparation of the
compound, see: Trivedi et al. (2011). For ring conformations,
see: Cremer & Pople (1975). For related structures, see: Fun et
al. (2011, 2012). For bond-length data, see: Allen et al. (1987).
For the stability of the temperature controller used in the data
collection, see: Cosier & Glazer (1986).
Experimental
Crystal data
C27H27N3O5?2H2O
Mr= 509.55
Monoclinic, P21=c
a = 14.1279 (9) A˚
b = 11.6313 (7) A˚
c = 15.3780 (9) A˚
? = 93.358 (1)?
V = 2522.7 (3) A˚3
Z = 4
Mo K? radiation
? = 0.10 mm?1
T = 100 K
0.34 ? 0.17 ? 0.14 mm
Data collection
Bruker APEX DUO CCD area-
detector diffractometer
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
Tmin= 0.968, Tmax= 0.987
28375 measured reflections
7347 independent reflections
5683 reflections with I > 2?(I)
Rint= 0.036
Refinement
R[F2> 2?(F2)] = 0.042
wR(F2) = 0.131
S = 1.04
7347 reflections
359 parameters
H atoms treated by a mixture of
independent and constrained
refinement
??max= 0.43 e A˚?3
??min= ?0.24 e A˚?3
Table 1
Hydrogen-bond geometry (A˚,?).
Cg1 and Cg2 are the centroids of the pyrazole (N2/N3/C6–C8) and benzene
(C15–C20) rings, respectively.
D—H???A
N1—H1N1???O2W
O1W—H2W1???N3
O2W—H2W2???O1Wi
O2W—H1W2???O3ii
O1W—H1W1???O2Wiii
C20—H20A???O1Wiv
C13—H13A???Cg2v
C18—H18A???Cg1vi
C25—H25A???Cg2i
C27—H27C???Cg1v
Symmetry codes: (i) ?x þ 1;y ?1
x;?y þ3
D—HH???AD???AD—H???A
0.904 (18)
0.90 (2)
0.98 (3)
0.90 (3)
0.87 (3)
0.95
0.95
0.95
0.98
0.98
2.001 (18)
2.05 (2)
1.84 (3)
1.91 (3)
2.06 (3)
2.44
2.90
2.63
2.87
2.62
2.9020 (14)
2.9449 (14)
2.7986 (15)
2.8074 (14)
2.9274 (15)
3.2980 (16)
3.6957 (14)
3.3682 (15)
3.7231 (14)
3.5720 (17)
175.2 (15)
174 (2)
166 (2)
174 (2)
178 (2)
151
142
135
146
164
2;?z þ1
2; (vi) ?x þ 1;y þ1
2; (ii) x;?y þ1
2;z þ1
2;?z þ1
2; (iii) x;?y þ3
2.
2;z ?1
2; (iv)
2;z þ1
2; (v) x;?y þ1
2;z ?3
Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT
(Bruker, 2009); data reduction: SAINT; program(s) used to solve
structure: SHELXTL (Sheldrick, 2008); program(s) used to refine
structure: SHELXTL; molecular graphics: SHELXTL; software used
to prepare material for publication: SHELXTL and PLATON (Spek,
2009).
organic compounds
o2210
Fun et al.
doi:10.1107/S1600536812027936
Acta Cryst. (2012). E68, o2210–o2211
Acta Crystallographica Section E
Structure Reports
Online
ISSN 1600-5368
‡ Thomson Reuters ResearcherID: A-3561-2009.

Page 2

HKFand CWO thank Universiti Sains Malaysia (USM) for
the Research University Grant (1001/PFIZIK/811160). CWO
also thanks the Malaysian Goverment and USM for the award
of the post of Research Officer under Research University
Grant No. 1001/PFIZIK/811160. AMI is thankful to the Board
of Research in Nuclear Sciences, Government of India, for a
Young Scientist award. AMI also thanks the Vision Group on
Science & Technology, Government of Karnataka, India, for
the best research paper award.
Supplementary data and figures for this paper are available from the
IUCr electronic archives (Reference: SJ5244).
References
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor,
R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
Bruker (2009). SADABS, APEX2 and SAINT. Bruker AXS Inc., Madison,
Wisconsin, USA.
Buhler, F. R. & Kiowski, W. (1987). J. Hypertens. 5, S3–S10.
Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107.
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.
Fun, H.-K., Hemamalini, M., Vijesh, A. M., Isloor, A. M. & Malladi, S. (2011).
Acta Cryst. E67, o1417–o1418.
Fun, H.-K., Ooi, C. W., Malladi, S., Shivananda, K. N. & Isloor, A. M. (2012).
Acta Cryst. E68, o892–o893.
Isloor, N. A. (2011). Eur. J. Med. Chem. 46, 5591–5597.
Isloor, A. M., Kalluraya, B. & Rao, M. (2000). J. Saudi Chem. Soc. 4, 265–270.
Isloor, A. M., Kalluraya, B. & Shetty, P. (2009). Eur. J. Med. Chem. 44, 3784–
3787.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Spek, A. L. (2009). Acta Cryst. D65, 148–155.
Trivedi,A., Dodiya, D., Dholariya, B., Kataria, V., Bhuva, V. & Shah, V. (2011).
Chem. Biol. Drug Des. 78, 881–886.
Vijesh, A.M., Isloor, A. M.,Peethambar, S. K., Shivananda, K. N., Arulmoli,T.
& Isloor, N. A. (2011). Eur. J. Med. Chem. 46, 5591–5597.
Vo, D., Matowe, W. C., Ramesh, M., Iqbal, N., Wolowyk, M. W., Howlett, S. E.
& Knaus, E. E. (1995). J. Med. Chem. 38, 2851–2859.
organic compounds
Acta Cryst. (2012). E68, o2210–o2211 Fun et al.
? C27H27N3O5?2H2O
o2211

Page 3

supplementary materials
sup-1
Acta Cryst. (2012). E68, o2210–o2211
supplementary materials
Acta Cryst. (2012). E68, o2210–o2211 [doi:10.1107/S1600536812027936]
Dimethyl 4-[3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl]-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate dihydrate
Hoong-Kun Fun, Chin Wei Ooi, B. Garudachari, Kammasandra Nanjunda Shivananda and Arun
M. Isloor
Comment
In the recent years, pyrazoles and their derivatives have attracted medicinal chemists because of their varied biological
properties such as anti-microbial (Isloor et al., 2009), analgesic (Isloor et al., 2000; Isloor, 2011) and anti-inflammatory
(Vijesh et al., 2011) activities. They are used most frequently as cardiovascular agents for the treatment of hypertension
(Buhler & Kiowski, 1987). A number of dihydropyridine (DHP) derivatives are employed as potential drug candidates for
the treatment of congestive heart failure (Vo et al., 1995). In view of this potential biological importance, we have
synthesised the title DHP compound and report its structure here.
The asymmetric unit of the title compound (Fig. 1), contains one dimethyl 4-[3-(4-methoxyphenyl)-1-phenyl-1H-
pyrazol-4-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate molecule and two water molecules. The dihydro-
pyridine (N1/C1–C5) ring adopts a flattened boat conformation with puckering parameters (Cremer & Pople, 1975) Q =
0.3369 (12) Å, θ = 107.1 (2)°, and φ = 1.5 (2)°. The central pyrazole ring (N2/N3/C6–C8) is essentially planar [maximum
deviation of 0.003 (1) Å at atoms N2 and C8] and makes dihedral angles of 50.42 (6)° and 26.44 (6)°, respectively, with
the benzene rings (C9–C14 & C15–C20). The bond lengths (Allen et al., 1987) and angles are within normal ranges and
are comparable to those found in related structures (Fun et al., 2011, 2012).
In the crystal structure (Fig. 2), the molecules are linked via intermolecular N1—H1N1···O2W, O1W—H1W1···O2W,
O1W—H2W1···N3, O2W—H1W2···O3, O2W—H2W2···O1W and C20—H20A···O1W hydrogen bonds (Table 1) into
two-dimensional networks parallel to the bc plane. The crystal structure is further consolidated by weak C—H···π
interactions (Table 1), involving the centroids of the pyrazole ring (N2/N3/C6–C8; Cg1) and benzene ring (C15–C20;
Cg2).
Experimental
3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (0.20 g, 0.0007 mol), acetyl acetone (0.17 g, 0.0015 mol)
and ammonium acetate (0.064 g, 0.00084 mol) in ethanol (10 ml) were refluxed for 5 h. After the completion of the
reaction, the reaction mixture was concentrated and poured into crushed ice. The precipitated product was filtered and
washed with water. The resulting solid was recrystallized from ethanol. Yield: 0.28 g, 82.3%; M.p. 393–395 K. (Trivedi et
al., 2011).
Refinement
All N and O bound H atoms were located from the difference map and were refined freely [N–H = 0.904 (18) Å and O–H
= 0.87 (3)–0.98 (2) Å]. The remaining H atoms were positioned geometrically and refined using a riding model with
Uiso(H) = 1.2 or 1.5Ueq(C) (C–H = 0.9500, 0.9800 and 1.0000 Å). A rotating group model was applied to the methyl

Page 4

supplementary materials
sup-2
Acta Cryst. (2012). E68, o2210–o2211
groups.
Computing details
Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009);
program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL
(Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication:
SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).
Figure 1
The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering
scheme.

Page 5

supplementary materials
sup-3
Acta Cryst. (2012). E68, o2210–o2211
Figure 2
The crystal packing of the title compound, viewed along the c axis. H atoms not involved in the intermolecular
interactions (dashed lines) have been omitted for clarity.
Dimethyl 4-[3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl]- 2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylate dihydrate
Crystal data
C27H27N3O5·2H2O
Mr = 509.55
Monoclinic, P21/c
Hall symbol: -P 2ybc
a = 14.1279 (9) Å
b = 11.6313 (7) Å
c = 15.3780 (9) Å
β = 93.358 (1)°
V = 2522.7 (3) Å3
Z = 4
F(000) = 1080
Dx = 1.342 Mg m−3
Mo Kα radiation, λ = 0.71073 Å
Cell parameters from 7658 reflections
θ = 2.3–30.0°
µ = 0.10 mm−1
T = 100 K
Block, yellow
0.34 × 0.17 × 0.14 mm
Data collection
Bruker APEX DUO CCD area-detector
diffractometer
Radiation source: fine-focus sealed tube
Graphite monochromator
φ and ω scans
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
Tmin = 0.968, Tmax = 0.987
28375 measured reflections
7347 independent reflections
5683 reflections with I > 2σ(I)
Rint = 0.036
θmax = 30.1°, θmin = 1.4°
h = −19→19
k = −16→13
l = −21→21
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.042
wR(F2) = 0.131
S = 1.04
7347 reflections
359 parameters
0 restraints
Primary atom site location: structure-invariant
direct methods
Secondary atom site location: difference Fourier
map
Hydrogen site location: inferred from
neighbouring sites
H atoms treated by a mixture of independent
and constrained refinement
w = 1/[σ2(Fo2) + (0.0713P)2 + 0.6924P]
where P = (Fo2 + 2Fc2)/3
(Δ/σ)max < 0.001
Δρmax = 0.43 e Å−3
Δρmin = −0.24 e Å−3