Synthesis and single-crystal characterization of novel 2-ferrocenyl-4H-pyrazolo[5,1-c][1,4]oxazin-4-one derivatives

Article abstract of DOI:10.1016/j.molstruc.2009.04.042

A series of novel 2-ferrocenyl-6-substituted-4H-pyrazolo[5,1-c][1,4]oxazin-4-one derivatives were synthesized by the intra-esterification reaction of ethyl 1-(2-aryl-2-oxoethyl)-3-ferrocenyl-1H-pyrazole-5-carboxylate in the presence of magnesium bromide a

Full text of DOI:10.1016/j.molstruc.2009.04.042

Journal of Molecular Structure 930 (2009) 83–87
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis and single-crystal characterization of novel
2-ferrocenyl-4H-pyrazolo[5,1-c][1,4]oxazin-4-one derivatives
a
b
a
c
Yong-Sheng Xie a, Bao-Xiang Zhao a, , Hong-Shui Lv , Ji-Kun Li , Bai-Shan Wang , Dong-Soo Shin
*
a Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, People’s Republic of China
b Department of Materials Science and Chemical Engineering, Taishan University, Taian 271021, Shandong, People’s Republic of China
c Department of Chemistry, Changwon National University, Changwon 641-773, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel 2-ferrocenyl-6-substituted-4H-pyrazolo[5,1-c][1,4]oxazin-4-one derivatives were syn-
thesized by the intra-esterification reaction of ethyl 1-(2-aryl-2-oxoethyl)-3-ferrocenyl-1H-pyrazole-5-
carboxylate in the presence of magnesium bromide and diisopropylethylamine in one-pot procedure.
The structures of compounds were characterized by 1H NMR, 13C NMR, IR, HRMS and X-ray diffraction
analysis.
Received 2 March 2009
Received in revised form 24 April 2009
Accepted 27 April 2009
Available online 6 May 2009
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Ferrocene
Pyrazole-fused oxazinone
Synthesis
X-ray structure
1. Introduction
As part of an ongoing program aimed at developing new anticancer
agents, we synthesized a series of novel fused-pyrazole derivatives
Ferrocene and its derivatives have been attracted much more
attention in wide fields such as organometallic chemistry, materi-
als science, catalysis and biological activities since the discovery of
ferrocene in 1951. Incorporation of a ferrocene fragment into a
molecule of an organic compound often obtained unexpected bio-
logical activity, which is rationalized as being due to their different
membrane permeation properties and anomalous metabolism.
Many ferrocenyl compounds display interesting cytotoxic, antitu-
mor, antimalarial, antifungal and DNA-cleaving activity [1–10].
Furthermore, the stability and non-toxicity of the ferrocenyl moi-
ety is of particular interest rendering such drugs compatible with
other treatment [11]. Therefore, the integration of one or more fer-
rocene units into a heterocyclic ring molecule has been recognized
as an attractive way to endow a novel molecule functionally [12–
18].
including 6-(aroxymethyl)-2-aryl-6,7-dihydropyrazolo[5,1-c][1,4]-
oxazin-4-one derivatives [28], 5-alkyl-2-ferrocenyl-6,7-dihydropy-
razolo[1,5-a]pyrazin-4(5H)-one [29,30] and 5-alkyl-2-aryl-6,
7- dihydropyrazolo[1,5-a]pyrazin-4(5H)-one [31]. Oxazinones con-
stitute an important class of heterocycles, which has attracted
much synthetic interest due to their wide range of biological activ-
ities [32–35]. However, a search of the literature revealed very few
reports concerning pyrazole fused oxazinone [36]. Therefore, the
synthesis of pyrazole-fused oxazinone derivatives directly linked
to a ferrocene unit is of considerable interest.
Herein, we would like to report the synthesis and structural
characterization of novel ferrocenyl pyrazole-fused oxazinone
derivatives.
2. Results and discussion
On the other hand, it is well known that pyrazole derivatives are
associated with various pharmaceutical activities such as cannab-
inoid hCB1 and hCB2 receptor, anti-inflammatory, inhibitors of
p38 Kinase, CB1 receptor antagonists, antimicrobial activity [19–
23]. The incorporation of heterocyclic rings into prospective phar-
maceutical candidates is a major strategy to obtain activity and
safety advantages. As a consequence, much attention has been paid
to the design and synthesis of fused-pyrazole derivatives [24–27].
2.1. Chemistry
The synthesis of 2-ferrocenyl-6-substituted-4H-pyrazolo[5,1-
c][1,4]oxazin-4-one
in Scheme 1. The key intermediate in the present study is the
ethyl 1-(2-aryl-2-oxoethyl)-3-ferrocenyl-1H-pyrazole-5-carboxyl-
4
has been accomplished as outlined
ate 3 that can be synthesized from
a-bromo-arylethanone 2 and
ethyl 3-ferrocenyl-1H-pyrazole-5-carboxylate 1, which can be ob-
tained from acetylferrocene and diethyl oxalate, with hydrazine
hydrate in the presence of acetic acid at room temperature as
* Corresponding author. Tel.: +86 531 88366425; fax: +86 531 88564464.
E-mail addresses: bxzhao@sdu.edu.cn, sduzhao@hotmail.com (B.-X. Zhao).
0022-2860/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2009.04.042

84
Y.-S. Xie et al. / Journal of Molecular Structure 930 (2009) 83–87
Scheme 1.
previous report [29]. The structure was determined by IR, 1H NMR,
13C NMR, HRMS and X-ray diffraction analysis. In the IR spectrum,
the carbonyl group absorptions were observed in the region of
1743–1748 cmꢀ1. The physical property and HRMS spectrum data
2.1.2. Synthesis of 2-ferrocenyl-6-substituted-4H-pyrazolo[5,1-
c][1,4]oxazin-4-one 4
Ethyl
1-(2-aryl-2-oxoethyl)-3-ferrocenyl-1H-pyrazole-5-car-
boxylate 3 undergo intramolecular esterification reaction via soft
enolate formation on treatment with MgBr2Et2O and i-Pr2NEt to
afford 2-ferrocenyl-6-substituted-4H-pyrazolo[5,1-c][1,4]oxazin-
4-one 4. It is reported that in soft enolization, a weak base and a
Lewis acid act in concert to effect deprotonation reversibly. Here,
the Lewis acid, MgBr2Et2O, interacts with the carbonyl oxygen to
polarize it beyond its normal state, resulting in a substantial in-
of compounds 4 are shown in Table 1. The data of 1H NMR and 13
NMR of the compounds 4 are given in Table 2.
C
2.1.1. Synthesis of ethyl 1-(2-aryl-2-oxoethyl)-3-ferrocenyl-1H-
pyrazole-5-carboxylate 3
It is known that nitrogen atom at N-1 position of a pyrazole
moiety possesses nucleophilic ability to react with alkyl halide
under a suitable condition [29]. Thus, according to our previous pa-
per, the N-alkylation reaction between ethyl 3-ferrocenyl-1H-pyr-
crease in the acidity of the a-proton, to the extent that it can be re-
moved appreciably by the weak base. Since enolization in this case
is reversible, it is conducted in a direct fashion in the presence of
the electrophilic species, further simplifying the procedure [37].
azole-5-carboxylate 1 and
a-bromo-arylethanone 2 was achieved
in the presence of potassium carbonate as the base in acetonitrile.
After flash chromatography on silica gel, the ethyl 1-(2-aryl-2-oxo-
ethyl)-3-ferrocenyl-1H-pyrazole-5-carboxylate 3 and the isomer,
1-(2-aryl-2-oxoethyl)-5-ferrocenyl-1H-pyrazole-3-carboxylate 30
were obtained (Scheme 1). Two isomers can be distinguished by
comparing the chemical shift, especially the signals of methylene
bonded to nitrogen of pyrazole moiety and protons of ferrocene
moiety in 1H NMR spectra as described in our previous paper
[29]. For example, the signals of two protons in methylene bonded
to nitrogen in 3d appear at 5.95 ppm while corresponding protons
in 30d appear at 5.71 ppm. Two protons in substituted Cp of Fc moi-
ety peaks in 3d are relatively downfield and appear around
4.70 ppm while corresponding protons in 30d are relatively upfield
and resonate around 4.38 ppm. In the case of 3b and 30b, the sig-
nals of two protons in methylene are 6.03 and 5.76, respectively.
Furthermore, two protons in substituted Cp of Fc moiety peaks in
3b and 30b are 4.72 and 4.34 ppm.
2.2. Single-crystal structure
The spatial structure of compound 4b was determined by using
X-ray diffraction analysis. Crystals suitable for X-ray diffraction
were obtained by slow evaporation of a solution of the solid in
ethyl acetate/dichloromethane at room temperature for 4 days.
The molecular view of 4b is shown in Fig. 1. A summary of crystal-
lographic data collection parameters and refinement parameters
for 4b are compiled in Table 3, meanwhile important bond lengths
and angles are depicted in Table 4.
The asymmetric unit of 4b contains two crystallographically
independent molecules A (containing O1) and B (containing O3).
Fig. 1 shows 4b contained a ferrocenyl bound to pyrazole ring
which fused with plane oxazinone connected benzene ring. The
corresponding bond lengths and angles of pyrazole rings in A and
B agree well with each other, but that of oxazinone rings in A
Table 1
Formula, melting points, HRMS and IR spectrum data of compounds 4.
4
Formula
M.p. °C
Required HRMS [M + H]+
Found HRMS [M + H]+
IR (KBr) m
(cmꢀ1) C@O,
4a
4b
4c
4d
4e
4f
C20H20FeN2O2
C22H16FeN2O2
C23H18FeN2O2
C23H18FeN2O3
C22H15ClFeN2O2
C22H15FeN3O4
161–163
240–241
277–279
218–220
220–222
246–248
377.0947
397.0634
411.0790
427.0740
431.0244
442.0485
377.0944
397.0627
411.0782
427.0747
431.0233
442.0471
1747.9
1747.5
1742.9
1743.8
1746.5
1745.3

Y.-S. Xie et al. / Journal of Molecular Structure 930 (2009) 83–87
85
Table 2
The data of 1H NMR and 13C NMR for compounds 4.
4
1H NMR (400 MHz, d, CDCl3) and 13C NMR (100 MHz, d, CDCl3)
4a 1H NMR: 7.28 (s, 1H, NCH@C), 7.04 (s, 1H, PyzH), 4.82 (s, 2H, C5H4), 4.43 (s, 2H, C5H4), 4.15 (s, 5H, C5H5), 1.32 (s, 9H, CH3);
13C NMR: 154.4, 153.8, 153.0, 127.1, 105.4, 104.8, 70.2, 69.8, 67.3, 34.4, 27.6.
4b 1H NMR: 7.90 (s, 1H, NCH@C), 7.76-7.40 (m, 5H, PhH), 7.16 (s, 1H, PyzH), 4.82 (s, 2H, C5H4), 4.42 (s, 2H, C5H4), 4.13 (s, 5H, C5H5);
13C NMR: 154.6, 153.7, 142.3, 129.9, 129.8, 129.1, 127.5, 124.4, 106.8, 105.6, 70.2, 69.9, 67.3.
4c 1H NMR: 7.85 (s, 1H, NCH@C), 7.63 (d, J = 7.8 Hz, 2H, PhH), 7.28 (d, J = 7.8 Hz, 2H, PhH), 7.15 (s, 1H, PyzH), 4.80 (s, 2H, C5H4), 4.39 (s, 2H, C5H4), 4.10 (s, 5H, C5H5), 2.41 (s,
3H, CH3);
13C NMR: 154.4, 153.8, 143.0, 140.2, 129.8, 127.4, 127.0, 124.4, 106.2, 105.4, 69.8, 69.5, 67.1, 21.4.
4d 1H NMR: 7.76 (s, 1H, NCH@C), 7.66 (d, J = 8.7 Hz, 2H, PhH), 7.10 (s, 1H, PyzH), 6.99 (d, J = 8.7 Hz, 2H, PhH), 4.88 (s, 2H, C5H4), 4.48 (s, 2H, C5H4), 4.18 (s, 5H, C5H5), 3.87 (s,
3H, OCH3);
13C NMR: 161.0, 154.3, 153.8, 143.1, 127.1, 126.0, 122.2, 114.6, 114.3, 105.4, 71.2, 70.9, 68.0, 55.5.
4e 1H NMR: 7.88 (s, 1H, NCH@C), 7.68 (d, J = 8.6 Hz, 2H, PhH), 7.46 (d, J = 8.6 Hz, 2H, PhH), 7.17 (s, 1H, PyzH), 4.79 (s, 2H, C5H4), 4.40 (s, 2H, C5H4), 4.10 (s, 5H, C5H5);
13C NMR: 154.9, 153.4, 141.8, 135.9, 129.4, 128.3, 127.4, 125.6, 106.9, 105.8, 69.8, 69.6, 67.1.
4f
1H NMR: 8.62-7.65 (m, 5H, PhH and NCH@C), 7.20 (s, 1H, PyzH), 4.81 (s, 2H, C5H4), 4.42 (s, 2H, C5H4), 4.11 (s, 5H, C5H5);
13C NMR: 155.5, 152.8, 148.9, 140.2, 131.7, 130.3, 129.7, 127.6, 124.2, 119.2, 108.3, 106.3, 69.9, 69.8, 67.2.
Fig. 1. The molecular structure of 4b, showing displacement ellipsoids drawn at the 50% probability level for non-H atoms.
and B have obvious differences (Table 1). In the ferrocenyl moiety,
the cyclopentadienyl (Cp) rings are perfectly planar but deviate
slightly from being parallel being 3.7(4)° in A and 2.4(4)° in B,
twisted from the eclipsed conformation by 1.11–2.70° in A and
15.11–18.37° in B, respectively. The distances Cg1–Fe1, Cg2–Fe1
in A and Cg3–Fe2, Cg4–Fe2 in B are 1.638(3) Å, 1.652(3) Å,
1.642(3) Å and 1.655(4) Å, respectively. The angles Cg1–Fe–Cg2
and Cg3–Fe2–Cg4 are 177.87(16)° and 178.59(17)°. The dihedral
angles between the substituted Cp ring and the pyrazole ring are
8.3(3)° in A and 8.4(3)° in B which are less than that of ferrocenyl
substituted pyrazole pyrazinone we have reported (16.08°). The
distances C1–C11 and C23–C33 [1.457(8) and 1.454(8) Å] are
slightly shorter than that of ferrocenyl substituted pyrazole pyraz-
inone (1.464(3) Å) [29]. In the crystal structure, the pyrazole, oxaz-
inone and benzene rings are almost planar.
hydrogen bond symmetry code of ‘1–X, 2–Y, 1–Z’ between a Cp
ring hydrogen (C26–H26) and Cg2, which may be attributed to a
CAHꢁ ꢁ ꢁ
p interaction, and contact distance being C26–H26 0.98 Å,
H26ꢁ ꢁ ꢁCg1 2.88 Å, C26ꢁ ꢁ ꢁCg1 3.714(7) Å and C26–H26 ꢁꢁꢁ Cg1 144°.
3. Summary
In summary, we have elaborated the facile synthesis of a
series of novel 2-ferrocenyl-6-substituted-4H-pyrazolo[5,1-
c][1,4]oxazin-4-one derivatives from ethyl 1-(2-aryl-2-oxoeth-
yl)-3-ferrocenyl-1H-pyrazole-5-carboxylate via intramolecular
esterification in one-pot procedure in the presence of magne-
sium bromide ethyl etherate and N,N-diisopropylethylamine.
This strategy could open new entries for the preparation of pyr-
azole fused oxazinone derivatives owing to the ready availability
of the starting materials. These novel compounds were charac-
terized by 1H NMR, IR, HRMS and single-crystal of compound
4b as representative has been determined by X-ray diffraction
analysis.
The dihedral angles of oxazinone with the pyrazole plane are
2.6(3)° in A and 3.0(3)° in B. However, the dihedral angles of ben-
zene rings with the pyrazole plane are 1.5(3)° in A and B.
The crystal packing is mainly stabilized by van der Waals inter-
actions. However, there is a significant intermolecular contact with

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Y.-S. Xie et al. / Journal of Molecular Structure 930 (2009) 83–87
Table 3
4.2. The following procedure is representative of the synthesis
of (3a-3f)
Summary of crystallographic data and structure refinement details for 4b.
4b
4.2.1. Ethyl 1-(3,3-dimethyl-2-oxobutyl)-3-ferrocenyl-1H-pyrazole-5-
carboxylate (3a)
Empirical formula
Formula weight
Temperature
Wavelength
Crystal system
Space group
C22 H16 Fe1 N2 O2
396.22
293(2) K
0.71069 Å
Triclinic
To a stirred solution of ethyl 3-ferrocenyl-1H-pyrazole-5-car-
boxylate (1.62 g, 5.0 mmol) and 1-bromo-3,3-dimethylbutan-2-
one (1.34 g, 7.5 mmol) in dry acetonitrile (30 mL) was added
potassium carbonate (2.07 g, 15 mmol) and potassium iodide
(166 mg, 1.0 mmol) under N2. After refluxed for 4 h, the reaction
mixture was cooled to room temperature, filtered and evaporated
under reduced pressure. The residue was purified by column chro-
matography on silica gel with the eluent system of ethyl acetate/
petroleum ether (v/v = 1:4). The product 3a was obtained as yellow
crystal in 62% yield (1.31 g). M.p. 124–126 °C. 1H NMR (400 MHz,
CDCl3): 6.88 (s, 1H, PyzH), 5.55 (s, 2H, NCH2), 4.67 (s, 2H, C5H4),
4.30 (q, J = 7.2 Hz, 2H, CH2CH3), 4.27 (s, 2H, C5H4), 4.08 (s, 5H,
C5H5), 1.38 (t, J = 7.2 Hz, 3H, CH2CH3), 1.29 (s, 9H, CCH3).
P-1
Unit cell dimensions
a = 7.634(4) Å,
a = 80.33(1)°
b = 11.188(6) Å, b = 88.62(1)°
c = 20.62(1) Å,
1736.0(17) A3
4
c = 89.48(1)°
Volume
Z
Calculated density
Absorption coefficient
F(000)
Crystal size
h range for data collection
Limiting indices
Reflections collected/unique
Completeness to h = 25.05°
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
1.516 Mg/m3
0.89 mmꢀ1
816
0.12 ꢂ 0.10 ꢂ 0.06 mm
2.5–23.6°
ꢀ8 ꢃ h ꢃ 9, ꢀ11 ꢃ k ꢃ 13, ꢀ23 ꢃ l ꢃ 24
8889/6078 [R(int) = 0.036]
99.0%
Multi-scan
4.2.2. Ethyl 1-(2-phenyl)-2-oxoethyl)-3-ferrocenyl-1H-pyrazole-5-
carboxylate (3b)
0.901 and 0.949
Full-matrix least-squares on F2
6078/0/487
Starting from the corresponding 2-bromo-1-phenylethanone:
Flash column chromatography over silica gel using ethyl acetate/
petroleum ether (v/v = 1:4) give the product (3b) in 40% yield.
M.p. 144–146 °C. 1H NMR (400 MHz, CDCl3): 8.02 (d, J = 7.7 Hz,
2H, PhH), 7.65 (t, J = 7.5 Hz, 1H, PhH), 7.54 (t, J = 7.5 Hz, 2H, PhH),
6.97 (s, 1H, PyzH), 6.03 (s, 2H, NCH2), 4.72 (s, 2H, C5H4), 4.32–
4.29 (m, 4H, CH2CH3 and C5H4), 4.12 (s, 5H, C5H5), 1.36 (t,
J = 7.1 Hz, 3H, CH2CH3). The compound 30b was obtained as a yel-
low crystal in 58% yield. M.p. 142–144 °C; 1H NMR (400 MHz,
CDCl3): 7.96 (d, J = 7.5 Hz, 2H, PhH), 7.65 (t, J = 7.2 Hz, 1H, PhH),
7.53 (t, J = 7.4 Hz, 2H, PhH), 6.97 (s, 1H, PyzH), 5.76 (s, 2H, NCH2),
4.43 (q, J = 7.0 Hz, 2H, CH2CH3), 4.34 (s, 2H, C5H4), 4.28 (s, 2H,
C5H4), 4.19 (s, 5H, C5H5), 1.42 (t, J = 7.0 Hz, 3H, CH2CH3).
1.03
Final R indices [I > 2
R indices (all data)
Largest diff. peak and hole
r
(I)]
R1 = 0.0637, wR2 = 0.1454
R1 = 0.1134, wR2 = 0.1691
0.753 and ꢀ0.669 e.Åꢀ3
Table 4
Selected bond lengths (Å) and angles (°) for 4b.
Cg1–Fe1
1.638(3)
Cg2–Fe1
1.652(3)
Cg3–Fe2
Cg1–Fe–Cg2
O1–C14
O2–C14
O2–C15
N1–N2
N2–C13
N2–C16
C15–C17
C17–C18
C17–C22
C18–C19
C19–C20
C20–C21
C1–Fe1–C2
C3–Fe1–C6
N2–N1–C11
O1–C14–O2
N4–C35–C36–O4
1.642(3)
177.87(16)
1.219(7)
1.361(7)
1.387(7)
1.349(6)
1.353(7)
1.371(7)
1.468(9)
1.398(8)
1.395(8)
1.378(9)
1.381(8)
1.364(9)
41.4(2)
Cg4–Fe2
Cg3–Fe2–Cg4
O3–C36
O4–C36
O4–C37
N1–C11
C11–C12
N4–C38
C37–C39
C39–C44
C39–C40
C44–C43
C43–C42
1.655(4)
178.59(17)
1.193(7)
1.380(7)
1.385(7)
1.347(7)
1.408(8)
1.390(7)
1.484(9)
1.386(8)
1.383(8)
1.387(9)
1.375(8)
1.364(8)
41.0(2)
4.2.3. Ethyl 1-(2-oxo-2-p-tolylethyl)-3-ferrocenyl-1H-pyrazole-5-
carboxylate (3c)
Starting from the corresponding 2-bromo-1-p-tolylethanone:
Flash column chromatography over silica gel using ethyl acetate/
petroleum ether (v/v = 1:4) give the product (3c) in 32% yield.
M.p. 122–124 °C. 1H NMR (400 MHz, CDCl3): 7.89 (d, J = 8.1 Hz,
2H, PhH), 7.30 (d, J = 8.1 Hz, 2H, PhH), 6.94 (s, 1H, PyzH), 5.98 (s,
2H, NCH2), 4.70 (s, 2H, C5H4), 4.30 (s, 2H, C5H4), 4.28 (q,
J = 7.2 Hz, 2H, CH2CH3), 4.10 (s, 5H, C5H5), 2.44 (s, 3H, CH3), 1.33
(t, J = 7.2 Hz, 3H, CH2CH3).
C42–C41
C23–Fe2–C24
C25–Fe2–C28
C14–O2–C15
O3–C36–O4
C37–O4–C36–O3
158.7(3)
104.1(4)
117.7(5)
1.1(7)
168.9(3)
122.0(4)
118.6(5)
ꢀ179.2(5)
4.2.4. Ethyl 1-(2-(4-methoxyphenyl)-2-oxoethyl)-3-phenyl-1H-
pyrazole-5-carboxylate (3d)
Where Cg1/Cg3 and Cg2/Cg4 are the centroids of substituted and unsubstituted
cyclopentadienyl rings, respectively.
Starting from the corresponding 2-bromo-1-(4-methoxy-
phenyl)ethanone: Flash column chromatography over silica gel
using ethyl acetate/petroleum ether (v/v = 1:4) give the product
(3d) in 43% yield. M.p. 131–133 °C. 1H NMR (400 MHz, CDCl3):
7.96 (d, J = 8.8 Hz, 2H, PhH), 6.98 (d, J = 8.8 Hz, 2H, PhH), 6.94 (s,
1H, PyzH), 5.95 (s, 2H, NCH2), 4.70 (s, 2H, C5H4), 4.30–4.25 (m,
4H, CH2CH3 and C5H4), 4.10 (s, 5H, C5H5), 3.89 (s, 3H, OCH3), 1.33
(t, J = 7.1 Hz, 3H, CH2CH3). The compound 30d was obtained as a
yellow crystal in 51% yield. M.p. 135–137 °C; 1H NMR (400 MHz,
CDCl3): 7.94 (d, J = 7.6 Hz, 2H, PhH), 6.98 (d, J = 7.6 Hz, 2H, PhH),
6.92 (s, 1H, PyzH), 5.71 (s, 2H, NCH2), 4.42 (q, J = 6.8 Hz, 2H,
CH2CH3), 4.38 (s, 2H, C5H4), 4.30 (s, 2H, C5H4), 4.21 (s, 5H, C5H5),
3.90 (s, 3H, OCH3), 1.41 (t, J = 6.7 Hz, 3H, CH2CH3).
4. Experimental
4.1. General consideration
All solvents were pre-dried and distilled prior to use. All reac-
tions were carried out under nitrogen and monitored by TLC on sil-
ica gel 60 F254 plates (Merck KGaA). 1H NMR and 13C NMR spectra
were recorded on a Bruker Avance 400 spectrometer, using CDCl3
as solvents and tetramethylsilane (TMS) as internal standard. Melt-
ing points were determined on an XD-4 digital micro melting point
apparatus. IR spectra were recorded with an IR spectrophotometer
Avtar 370 FT-IR (Termo Nicolet). HRMS spectra were recorded on a
LTQ Orbitrap Hybrid mass spectrograph. X-ray diffraction data
were recorded on a Bruker Smart CCD diffractometer.
4.2.5. Ethyl 1-(2-(4-chlorophenyl)-2-oxoethyl)-3-phenyl-1H-
pyrazole-5-carboxylate (3e)
Starting from the corresponding 2-bromo-1-(4-chloro-
phenyl)ethanone: Flash column chromatography over silica gel

Y.-S. Xie et al. / Journal of Molecular Structure 930 (2009) 83–87
87
using ethyl acetate/petroleum ether (v/v = 1:4) give the product
Acknowledgment
(3e) in 61% yield. M.p. 148–149 °C. 1H NMR (400 MHz, CDCl3):
7.93 (d, J = 8.5 Hz, 2H, PhH), 7.49 (d, J = 8.5 Hz, 2H, PhH), 6.95 (s,
1H, PyzH), 5.96 (s, 2H, NCH2), 4.69 (s, 2H, C5H4), 4.31–4.25 (m,
4H, CH2CH3 and C5H4), 4.09 (s, 5H, C5H5), 1.34 (t, J = 7.1 Hz, 3H,
CH2CH3). The compound 30e was obtained as a yellow crystal in
32% yield. M.p. 168–170 °C; 1H NMR (400 MHz, CDCl3): 7.88 (d,
J = 8.5 Hz, 2H, PhH), 7.50 (d, J = 8.5 Hz, 2H, PhH), 6.96 (s, 1H, PyzH),
5.70 (s, 2H, NCH2), 4.43 (q, J = 7.1 Hz, 2H, CH2CH3), 4.31 (s, 2H,
C5H4), 4.28 (s, 2H, C5H4), 4.18 (s, 5H, C5H5), 1.42 (t, J = 7.1 Hz, 3H,
CH2CH3).
This study was supported by the Natural Science Foundation of
Shandong Province (Z2008B10).
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4.3. The following procedure is representative of the synthesis
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Yellow solid, 37% yield.
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Yellow solid, 14% yield.
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Yellow solid, 11% yield.