Synthesis and crystal structure of 5-chloro-3-methyl-1-phenyl-1H-pyrazole- 4-carbaldehyde

Article abstract of DOI:10.1007/s10870-011-0178-4

The title compound, 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde 2, was prepared in a series of syntheses to produce new pyrazole derivatives, and its crystal structure was determined by X-ray diffraction method. The crystal belongs to monoclinic

Full text of DOI:10.1007/s10870-011-0178-4

J Chem Crystallogr (2011) 41:1816–1819
DOI 10.1007/s10870-011-0178-4
ORIGINAL PAPER
Synthesis and Crystal Structure of 5-Chloro-3-Methyl-1-Phenyl-
1H-Pyrazole-4-Carbaldehyde
•
Cun-Jin Xu Yan-Qin Shi
Received: 19 April 2009 / Accepted: 26 September 2011 / Published online: 5 October 2011
Ó Springer Science+Business Media, LLC 2011
Abstract The title compound, 5-chloro-3-methyl-1-phenyl-
1H-pyrazole-4-carbaldehyde 2, was prepared in a series of
syntheses to produce new pyrazole derivatives, and its crystal
structure was determined by X-ray diffraction method. The
crystal belongs to monoclinic, space group P21/c with unit
as potential new drugs [8, 9]. For example, the natural pyra-
zole C-glycoside, pyrazofurin, an antibiotic, was reported to
possess a broad spectrum of antimicrobial and antiviral
activities in addition to being active against several tumor cell
lines [10]. Motivated by the afore-mentioned findings, and as
a continuation of our on going program in the field of pyra-
zoles, the title compound, 2, which is a highly versatile
intermediate for the synthesis of thiolates [11], azides [12],
amines [13] and fused pyrazolo heterocycles via cyclocon-
densation reactions [14], was prepared under Vilsmeyer
conditions in which chlorination of C1 occurs in addition to
the expected formylation (Scheme 1), and its crystal structure
was determined by X-ray diffraction method.
˚
cell parameters a = 6.7637(4) A, b = 6.8712(3) A, c =
˚
3
˚
˚
22.4188(10) A, b = 93.8458(14)8, V = 1039.56(9) A and
Z = 4. X-Ray reveals that the aldehydic fragment is almost
coplanar with the adjacent pyrazole ring, but the two ring
planes are inclined at 72.8(1)8. The molecule is linked to its
neighbor by two directionally specific C–HÁÁÁO interactions.
Keywords Pyrazole Á Carbaldehyde Á Crystal structure
Introduction
Experimental
The pyrazole ring is an important structural motif found in
many biologically and pharmaceutically active compounds.
Over the past few years, both pyrazoles and their derivatives
have attracted much attention because they possess a wide
spectrum of biological activities, such as antimicrobial [1],
anti-inflammatory [2], antiviral [3], anticancer [4], insecti-
cidal [5], herbicidal [6] and plant growth regulatory [7]. Many
pyrazoles are currently being tested and clinically evaluated
General
All reagents were of reagent grade and were used without
further purification. Melting points were determined using
an electrothermal digital melting point apparatus and are
uncorrected. Element analysis (CHN) was performed with
a Flash-EA1112 elemental analyzer. 1H-NMR spectra were
collected on a Bruker-400 spectrometer. FT-IR spectra
were carried out from a KBr pellet on a Bruker Tensor 27
spectrophotometer. Mass spectra were measured on an
Aligent 5975 spectroscopy.
C.-J. Xu (&)
College of Material, Chemistry and Chemical Engineering,
Hangzhou Normal University, Hangzhou 310036,
People’s Republic of China
Synthesis
e-mail: xcj7215@yahoo.com.cn
3-Methyl-1-Phenyl-5-Pyrazolone (1) [15]
Y.-Q. Shi
College of Chemical Engineering and Material Science,
Zhejiang University of Technology, Hangzhou 310014,
People’s Republic of China
To a well stirred solution of the phenyl hydrazine
(21.6 g, 0.2 mol) in ethanol (30 mL) was added dropwise
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J Chem Crystallogr (2011) 41:1816–1819
1817
O
O
Table 1 Crystal data and structural refinement parameters of the title
compound
O
O
PhNHNH2
POCl3 / DMF
N
N
N
O
Cl
Cl
N
N
N
OEt
Ph
Ph
2
Ph
CCDC deposition
Formula
725344
11H9ClN2O
2a
1
C
Formula weight
Crystal size (mm)
Crystal colour
Crystal system
Space group
220.66
Scheme 1 Preparation of the title compound
0.33 9 0.25 9 0.20
Colorless
3-Oxo-butyric acid ethyl ester (26.0 g, 0.2 mol). The
reaction mixture was heated under reflux for 5 h. The
solvent was concentrated and the reaction product was
allowed to cool. The separated product was filtered off,
dried and recrystallized from ethanol (29.6 g, 85%). m.p.:
128–130 °C. IR: (KBr) t cm-1, 3128, 2612, 1806, 1600,
1521, 1497, 1153, 1028. 70 eV MS m/z(%): 174(M?), 153,
Monoclinic
P21/c
˚
a = 6.7637(4) A
Unit cell parameters
˚
b = 6.8712(3) A
˚
c = 22.4188(10) A
b = 93.8458(14)8
˚
1039.56 (9) A
1
3
Volume
132, 105, 91, 77(100%). H-NMR (400 MHz, CDCl3) d:
7.856 (d, J = 7.7 Hz, 2H, ArH), 7.388 (m, 2H, ArH), 7.174
(m, 1H, ArH), 3.420 (s, 2H, –CH2–), 2.189 (s, 3H, –CH3).
Anal. Calcd. for C10H10N2O C, 68.95; H, 5.79; N, 16.08.
Found: C, 68.99; H, 5.75; N, 16.13.
Z
4
Density
1.410 g cm-3
˚
0.71075 A
Wavelength
Temperature
296 K
Absorption correction type
Absorption coefficient (l)
F(000)
Multi-scan
0.339
5-Chloro-3-Methyl-1-Phenyl-1H-Pyrazole-4-
Carbaldehyde (2)
456
Theta range for data collection
Index ranges
3.0–27.4°
-8 B h B 8; -8 B k B 8;
-29 B l B 27
Phosphoryl chloride (0.7 mol, 64 mL) was added drop-
wise to ice-cold dimethylformamide (0.3 mol, 23 mL). To
this mixture was added 3-methyl-1-phenyl-5-pyrazolone
(17.5 g, 0.1 mol), and the reaction mixture was then heated
under reflux for 1 h. After cooling, the reaction mixture
was poured into ice-cold water (600 mL). The product was
filtered and recrystallized from ethanol to yield pale-yellow
Reflections collected/unique
Rint
9785/2363
0.019
Completeness to theta = 27.4
99.2%
Tmin, Tmax
0.887, 0.934
SHELXL
1944
Refinement method
Data with I [ 2.0 r(I)
Goodness of fit ref
R factor
plates (17.6 g, 80%). m.p.: 140–141 °C. IR: (KBr) t cm-1
,
1.004
3063, 1677, 1598, 1528, 1463, 1436, 1376, 1004, 763.
70 eV MS m/z(%): 220(M?, 100%), 155, 143, 128, 104,
0.0397
1
wR factor
0.1036
77. H-NMR (400 MHz, CDCl3) d: 9.983 (s, 1H, –CHO),
7.564–7.471 (m, 5H, ArH), 2.546 (s, 3H, –CH3). Anal.
Calcd. for C11H9ClN2O C, 59.88; H, 4.11; N, 12.70.
Found: C, 59.90; H, 4.09; N, 12.72.
Results and discussion
The results of the 1H NMR, IR, MS and elemental analysis
were in good agreement with the title compound. The
molecular structure of the compound 2, drawn with the
program ORTEP-3 [17], is given in Fig. 1. The bond dis-
tances and angles are listed in Table 2.
X-ray Crystallography
X-ray quality crystals were obtained by slow evaporation of
ethanol solution of 2. Crystallographic data was collected on
a Rigaku RAXIS RAPID diffractometer (graphite-mono-
˚
In the pyrazole ring, the atoms N(1), N(2), C(1), C(2),
and C(3) are coplanar with a mean plane deviation of
chromated Mo-Ka radiation with k = 0.71075 A). The
structure was solved by direct methods using the program
SIR97 [16] and refined by full-matrix least squares tech-
niques against F2 using the SHELXL. The non-hydrogen
atoms were located in a difference Fourier map and refined
anisotropically. All hydrogen atoms were placed in calcu-
6
˚
0.0014(1) A to form a p5 configurations (six p electrons,
three from carbon atoms, one from nitrogen atom N(2) and
two from N(1)). The aldehydic fragment is almost coplanar
with the adjacent pyrazole ring, but the two ring planes are
inclined at 72.8(1)°.
As can be seen in Table 2, the internal and external
angles of the pyrazole ring follow the set of empirical rules
given by Bonati and Bovio [18], such that (a) N(1)–N(2)–
3
2
˚
lated positions, with C–H = 0.96 (sp ) or 0.93 A (sp ), and
were refined using a riding model with Uiso(H) = 1.2Ueq of
the carrier atoms. The detailed crystal data and structural
refinement parameters of 2 are summarized in Table 1.
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J Chem Crystallogr (2011) 41:1816–1819
Fig. 2 ViewofC–HÁÁÁO interactions. Symmetrycode:(i) -x, 1 - y, -z
C(3) [105.10(13)°] is smaller than N(2)–N(1)–C(1)
[111.11(11)°]; (b) N(2)–C(3)–C(2) [111.81(14)°] is larger
than N(1)–N(2)–C(3) [105.10(13)°], C(3)–C(2)–C(1)
[103.63(13)°] and N(1)–C(1)–C(2) [108.35(13)°]; (c) C(3)–
C(2)–C(1) is not the largest internal angle; (d) N(2)–N(1)–
C(6) [120.27(12)°] is smaller than C(1)–N(1)–C(6)
[128.62(12)°]; (e) N(2)–C(3)–C(5) [119.62(15)°] is smaller
than C(2)–C(3)–C(5) [128.57(15)°]. Within the pyrazole-
carbaldehyde portion of the molecule, the bonds N(1)–C(1)
Fig. 1 Molecular structure of the title compound. Thermal ellipsoids
shown at 50% possibility
˚
Table 2 Selected bond distances (A) and angles (8) of the title
compound
Cl1–C1
1.7002(16)
1.214(2)
˚
[1.338(2) A] and C(2)–C(4) [1.451(2) A] are both short for
˚
O1–C4
˚
their types [1.359(12) and 1.462(18) A, respectively] [19],
˚
while bonds C(1)–C(2) [1.385(2) A] and C(4)–O(1)
˚
[1.214(2) A] are both long for their types [1.372(19) and
˚
1.192(5) A, respectively], suggesting some contribution to
N1–N2
1.3757(18)
1.338(2)
N1–C1
N1–C6
1.4396(19)
1.323(2)
N2–C3
the overall molecular–electronic structure from the charge-
separated form (2a) (Scheme 1) [20].
C1–C2
1.385(2)
C2–C3
1.417(2)
No interesting intramolecular hydrogen bonding is seen
within the molecule. However, intermolecular interactions
involving two directionally specific C–HÁÁÁO interactions
C2–C4
1.451(2)
C3–C5
1.497(2)
C6–C7
1.379(2)
i
˚
[C11–H11ÁÁÁO1 , CÁÁÁO distance being 3.425(2) A and
C6–C11
C7–C8
1.369(2)
C–HÁÁÁO angle being 153.7(2)°, Fig. 2] stabilize the
1.386(2)
packing.
C8–C9
1.375(3)
C9–C10
C10–C11
C4–H4
1.370(3)
1.390(2)
Supplementary Material
0.930
C5–H5
0.960
CCDC: 725344 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge at http://www.ccdc.cam.ac.uk/conts/retrieving.
html [or from the Cambridge Crystallographic Data Center
(CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax:
?44(0)1223-336033; e-mail: deposit@ccdc.cam.ac.uk].
N2–N1–C1
N2–N1–C6
C1–N1–C6
N1–N2–C3
Cl1–C1–N1
Cl1–C1–C2
N1–C1–C2
C1–C2–C3
C1–C2–C4
C3–C2–C4
N2–C3–C2
N2–C3–C5
C2–C3–C5
111.11(11)
120.27(12)
128.62(12)
105.10(13)
122.01(11)
129.62(12)
108.35(13)
103.63(13)
125.65(14)
130.72(14)
111.81(14)
119.62(15)
128.57(15)
Acknowledgments The authors thank the Opening Foundation of
Zhejing Provincial Top Key Discipline (No. 20110938), the Special
Funds for Key Innovation Team of Zhejing Province (No. 2010R50017).
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