Crystal structure and synthesis of 4-(4-hydroxybenzylideneamino)-1-methyl- 3-propyl-1H-pyrazole-5-carboxamide

Article abstract of DOI:10.1016/j.molstruc.2011.03.045

The title compound C₁₅H₁₈N₄O₂ (I), was prepared from the reaction of 4-amino-1-methyl-3-propyl-1H-pyrazole-5- carboxamide and 4-hydroxybenzaldehyde; and was analyzed by analytical data from ¹H NMR,

Full text of DOI:10.1016/j.molstruc.2011.03.045

Journal of Molecular Structure 994 (2011) 332–334
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Crystal structure and synthesis of 4-(4-hydroxybenzylideneamino)-1-
methyl-3-propyl-1H-pyrazole-5-carboxamide
a,
D. Rambabu a, G. Rama Krishna b, Srinivas Basavoju c, C. Malla Reddy b, , Manojit Pal
⇑
⇑
a Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500 046, Andhra Pradesh, India
b Department of Chemical Sciences, Indian Institute of Science Education and Research, Kolkata, West Bengal 741 252, India
c Department of Chemistry, National Institute of Technology (NIT), Warangal 506 004, Andhra Pradesh, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The title compound C15H18N4O2 (I), was prepared from the reaction of 4-amino-1-methyl-3-propyl-1H-
pyrazole-5-carboxamide and 4-hydroxybenzaldehyde; and was analyzed by analytical data from 1H
NMR, 13C NMR, IR and Mass spectra. The crystal structure was determined by single crystal X-ray diffrac-
tion. The molecules in the crystal structure form cyclic centrosymmetric supramolecular tetramer syn-
thons [graph-set R44ð12Þ] through amide N–Hꢀ ꢀ ꢀO(hydroxy) and hydroxy O–Hꢀ ꢀ ꢀO(amide) hydrogen
bonds to form perpendicular tapes.
Received 31 January 2011
Received in revised form 21 March 2011
Accepted 21 March 2011
Available online 24 March 2011
Keywords:
Pyrazole derivative
Ó 2011 Elsevier B.V. All rights reserved.
Single crystal X-ray crystallography
Supramolecular tetramer synthon
Hydrogen bond
1. Introduction
evaluated for antibacterial and anthelmentic properties [15]. In
our effort to identify pyrazole-based novel antibacterial agents
Many natural products have the pyrazole unit as the core struc-
ture [1]. Pyrazole derivatives exhibit important biological proper-
ties such as antitumour [2], anticoagulant [3], anti-
hyperglycemic, analgesic, anti-inflammatory, anti-pyretic, anti-
bacterial, hypoglycemic and sedative–hypnotic activity [4–6].
These derivatives have attracted significant attention because of
the application in drug development [7]. Particularly, arylpyrazoles
are important in medicinal and pesticidal chemistry [8]; a number
of herbicides with pyrazole moieties have been commercialized
[9]. Recent literature shows that, some arylpyrazoles were re-
ported to have non-nucleoside HIV-1 reverse transcriptase inhibi-
tory activity [10]. Recently Tang et al. reported the synthesis and
crystal structure of a pyrazole derivative [11]. It is also reported
that novel five-substituted pyrazole analogs, which have CB1 bind-
ing affinities similar to SR 141716A have been synthesized [12].
Wei et al. investigated effects of pyrazole-5-carboxylate deriva-
tives on A549 cell growth and suppress this growth [13].
we prepared a series of 4-benzylideneamino-pyrazole-5-carbox-
amide for our in house in vitro screen. Among the compounds syn-
thesized 4-(4-hydroxybenzylideneamino)-1-methyl-3-propyl-1H-
pyrazole-5-carboxamide (I) was identified as a key compound in
this series. In this paper we describe the synthesis and crystal
structure analysis of this compound.
2. Results and discussion
The title compound was prepared (Scheme 1) by the reaction of
a mixture of 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carbox-
amide (1) (1.0 mmol), 4-hydroxybenzaldehyde (2) (1.0 mmol)
and Amberlist (10 mg). The reaction mixture was stirred in aceto-
nitrile (10 mL) at room temperature for 2 h. After completion of the
reaction, the solid product was filtered and dried. The crude prod-
uct was crystallized from methanol and colorless needle shaped
crystals were obtained on slow evaporation (yield: 80%). The ana-
lytical data (1H NMR, 13C NMR, IR and Mass spectra) of this com-
pound are available in supplementary information as Figs. S1–S4.
The X-ray data for crystals of the compound (I) were collected
on a Bruker Kappa APEX-II CCD DUO diffractometer at 296(2) K
Compounds containing carboxamide and benzylideneamino
group at the adjacent positions of a five-membered heterocyclic
ring are of considerable interest due to their interesting pharmaco-
logical properties [14,15]. For example Schiff bases derived from
benzaldehydes with 3-amino-2-benzofurancarboxamide were
using graphite-monochromated Mo K
a radiation (k = 0.71073 Å).
No absorption correction was applied. The lattice parameters were
determined from least-squares analysis, and reflection data were
integrated using the program SHELXTL [16a]. The structure was
solved by direct methods using SHELXS-97 and refined by full-ma-
⇑
Corresponding authors. Mobile: +91 9000015358 (M. Pal).
E-mail addresses: cmallareddy@rediffmail.com (C.M. Reddy), manojitpal@rediff-
mail.com (M. Pal).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.03.045

D. Rambabu et al. / Journal of Molecular Structure 994 (2011) 332–334
333
Scheme 1. Synthesis of 4-(4-hydroxybenzylideneamino)-1-methyl-3-propyl-1H-
pyrazole-5-carboxamide (I).
Table 1
Crystallographic data and refinement parameters of compound (I).
Empirical formula
Formula weight
Crystal system
Space group
T (K)
C15H18N4O2
286.33
Monoclinic
P21/n
296(2)
a (Å)
b (Å)
c (Å)
8.0008(6)
10.1498(7)
17.9367(13)
90.00
a
(°)
b (°)
98.534(3)
90.00
c
(°)
Z
4
Fig. 1. ORTEP representation of compound (I). Thermal ellipsoids are drawn at 50%
probability.
V (Å3)
1440.45(18)
1.320
Mo Ka (k = 0.71073 Å)
Dx (g/cm3)
Radiation
l
(Mo K
a
)/mm–1
0.091
F(0 0 0)
608.0
Crystal size/mm
h range for data collection (°)
Limiting indices
Reflections collected
Data/restraints/parameters
Unique reflections
0.28 ꢁ 0.20 ꢁ 0.18
2.36–26.99
ꢂ8 6 h 6 9, ꢂ12 6 k 6 11, ꢂ20 6 l 6 19
25,563
2575/0/202
2575
Observed reflections
1937
1.081
Goodness-of-fit on F2
R indices I > 2
R indices (all data)
r
(I)
R1 = 0.0470, wR2 = 0.1153
R1 = 0.0565, wR2 = 0.1236
0.011
(
(
D
D
/
/
r
q
)
)
max
(e Åꢂ3
)
0.30
max
Measurement
Programs system
Structure determination
CCDC deposition number
Bruker APEX-II CCD
SHELXTL-97
SHELXS-97
804,566
Table 2
Hydrogen bond parameters in compound (I).
Interaction
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D–Hꢀ ꢀ ꢀA
(°)a
Symmetry code
–
(Å)
(Å)
Intra N(4)–
2.07(2)
2.15(3)
1.68(3)
2.808(2) 138.2(19)
3.007(2) 164(2)
2.634(2) 171(2)
H(4B)ꢀ ꢀ ꢀN(3)
N(4)–H(4A)ꢀ ꢀ ꢀO(2)
1/2 ꢂ x, 1/2 + y, 1/
2 ꢂ z
O(2)–H(2)ꢀ ꢀ ꢀO(1)
1/2 + x, 3/2 ꢂ y, ꢂ1/
2 + z
a
All the N–H and O–H distances are neutron-normalized to 1.009 and 0.983 Å,
respectively.
trix least squares on F2 with anisotropic displacement parameters
for non-H atoms, using SHELXL-97 [16b]. The positions of all aro-
matic and aliphatic C–H hydrogen atoms were calculated geomet-
rically, and a riding model was used in the refinement, with C–H
distances in the range of 0.93–0.98 Å and Uiso(H) = 1.2Ueq(C). All
the N–H and O–H hydrogens were refined from difference Fourier
maps. The software used to prepare material for publication was
Mercury 2.3 (Build RC4), ORTEP-3 and X-Seed [17]. Table 1 sum-
Fig. 2. (a) A tetramer synthon is formed via N–Hꢀ ꢀ ꢀO and O–Hꢀ ꢀ ꢀO hydrogen bonds
in the crystal structure of compound (I). (b) Molecules forming perpendicular tapes
in compound (I).
marizes the pertinent crystallographic data and Table 2 gives the
hydrogen-bond geometries.

334
D. Rambabu et al. / Journal of Molecular Structure 994 (2011) 332–334
The compound (I) crystallizes in the monoclinic P21/n space
References
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h = 171(2)°) hydrogen bonds to form perpendicular tapes (Fig. 2b).
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D.R.B. thanks Professor Javed Iqbal, Director of ILS for his con-
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Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molstruc.2011.03.045.