Synthesis, structure characterization, and X-ray crystallography of novel 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate derivatives with a carbohydrate moiety

Article abstract of DOI:10.1080/07328303.2011.583371

A series of novel (2S,3R,4S,5R)-3,4,5-triacetoxy-tetrahydro-2H-pyran-2-yl 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate derivatives (3) were synthesized by the reaction of 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide (2) and 1-benzyl-3-phenyl-1H-pyrazole-5-

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Synthesis, Structure Characterization,
and X-ray Crystallography of Novel
1-Benzyl-3-phenyl-1H-pyrazole-5-
carboxylate Derivatives with a
Carbohydrate Moiety
Song Lian a , Jin-Ting Liu a , Liang-Wen Zheng a , Wei-Yong Liu a &
Bao-Xiang Zhao a
a Institute of Organic Chemistry, School of Chemistry and Chemical
Engineering , Shandong University , Jinan, 250100, P.R. China
Published online: 27 Jun 2011.
To cite this article: Song Lian , Jin-Ting Liu , Liang-Wen Zheng , Wei-Yong Liu & Bao-Xiang Zhao (2011)
Synthesis, Structure Characterization, and X-ray Crystallography of Novel 1-Benzyl-3-phenyl-1H-
pyrazole-5-carboxylate Derivatives with a Carbohydrate Moiety, Journal of Carbohydrate Chemistry,
30:1, 1-15, DOI: 10.1080/07328303.2011.583371
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Journal of Carbohydrate Chemistry, 30:1–15, 2011
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Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2011.583371
Synthesis, Structure
Characterization, and X-ray
Crystallography of Novel
1-Benzyl-3-phenyl-1H-
pyrazole-5-carboxylate
Derivatives with a
Carbohydrate Moiety
Song Lian, Jin-Ting Liu, Liang-Wen Zheng, Wei-Yong Liu,
and Bao-Xiang Zhao
Institute of Organic Chemistry, School of Chemistry and Chemical Engineering,
Shandong University, Jinan 250100, P.R. China
A series of novel (2S,3R,4S,5R)-3,4,5-triacetoxy-tetrahydro-2H-pyran-2-yl 1-benzyl-3-
phenyl-1H-pyrazole-5-carboxylate derivatives (3) were synthesized by the reaction of
2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide (2) and 1-benzyl-3-phenyl-1H-pyrazole-5-
carboxylic acid (1) in the presence of sodium bicarbonate and tetrabutylammonium bro-
mide in dichloromethane at reflux temperature. The structures of new compounds were
1
determined by IR and H NMR spectroscopy and HR mass spectrometry (HRMS), and
the configuration of the newly generated chiral carbon (C-1) in the xylose ring was ten-
tatively assigned based on the X-ray crystallographic structure of 3d and 3g.
Keywords Synthesis; Structure; Pyrazole; Xylose; X-ray
INTRODUCTION
Many pyrazole derivatives are known to exhibit a wide range of biological
properties such as cannabinoid hCB1 and hCB2 receptors, anti-inflammatory
Received June 14, 2010; accepted April 19, 2011.
Address correspondence to Jin-Ting Liu, Institute of Organic Chemistry, School of
Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P.R. China.
E-mail: jintliu@sdu.edu.cn; and Bao-Xiang Zhao, Institute of Organic Chemistry, School
of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P.R.
China. E-mail: bxzhao@sdu.edu.cn
1

S. Lian et al.
2
activity, inhibitors of p38 kinase, CB1 receptor antagonists, and antimicrobial
activity.[1–5] Extensive studies have been devoted to arylpyrazole derivatives
such as celecoxib, a well-known cyclooxygenase-2 inhibitor.[6–8] In our pre-
vious papers, we synthesized a series of novel multisubstituted pyrazole
derivatives such as ethyl 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate deriva-
tives,[9] ethyl 1-(2ꢁ-hydroxy-3ꢁ-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate
derivatives,[10] ethyl 3-(o-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-
carboxylate,[11] 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide,[12] 1-(2ꢁ-
hydroxy-3ꢁ-aroxypropyl)-3-aryl-1H-pyrazole-5-carbohydrazide derivatives,[13]
and 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide hydrazone deriva-
tives,[14,15] as well as fused-pyrazole derivatives including 6-(aroxymethyl)-
2-aryl-6,7-dihydropyrazolo[5,1-c][1,4]oxazin-4-one derivatives,[16] pyrazolo[1,
5-a]pyrazin-4(5H)-one,[17] and 5-alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-
a]pyrazin-4(5H)-one.[18,19] The evaluation of biological activity showed that
these compounds can inhibit A549 lung cancer cell growth.
It is accepted that incorporation of potential biologically active moieties
into body-friendly-type compounds should reduce toxic or other disadvan-
tageous side effects and, thus, obtain molecules with better chances for
pharmacological applications. The incorporation of sugar into prospective
pharmaceutical candidates is a major strategy to obtain activity and safety
advantages. Recently, some O-glucoside-containing compounds have been iso-
lated from natural plants[20,21] and the synthesis of O-glycosides has received
considerable attention due to their occurrence in a variety of natural products
endowed with numerous biological activities.[22,23] A search of the literature
revealed very few reports concerning pyrazole-glycoside[24,25]; however, there
were no reports about pyrazole-xyloside.
In our ongoing interest in the preparation of novel pyrazole deriva-
tives with sugar moiety,[26] herein, we would like to report the synthe-
sis and structure characterization of a series of novel (2S,3R,4S,5R)-3,4,5-
triacetoxy-tetrahydro-2H-pyran-2-yl 1-benzyl-3-phenyl-1H-pyrazole-5-carbo-
xylate derivatives.
RESULTS AND DISCUSSION
Synthesis of the Compounds
(2S,3R,4S,5R)-3,4,5-Triacetoxy-tetrahydro-2H-pyran-2-yl
1-benzyl-3-
phenyl-1H-pyrazole-5-carboxylate derivatives (3) were synthesized by the
reaction of 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide (2)[27,28] and 1-
benzyl-3-phenyl-1H-pyrazole-5-carboxylic acid (1), which can be easily
obtained by the alkali hydrolysis of corresponding ethyl 1-benzyl-3-phenyl-
1H-pyrazole-5-carboxylate[29] in the presence of sodium bicarbonate and
tetrabutylammonium bromide in dichloromethane at reflux for 2 to 4 h as
outlined in Figure 1.

Novel 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate Derivatives
3
Figure 1: Synthesis of compounds 3.
Structure Characterization of the Compounds
The structures of the compounds 3 were determined by the analyses of
1
their spectral data including H NMR, IR, and HRESIMS. Compound 3d, for
example, obtained as white crystals, gave a [M+H]-ion peak at m/z 517.1470 in
the HRESIMS, in accord with the molecular formula C28H28ClN2O9. In the IR
spectra, the carbonyl group absorptions were observed in the 1732–1757 cm−1
region. Two ortho-aromatic proton signals in 4-chlorophenyl moiety appear at
the range of δ = 7.76 and 7.39 ppm as doublet peaks (J = 8.5 Hz). The multiplet
peaks from 7.26 to 7.31 ppm are benzene proton signals. The singlet signal
appeared at δ = 7.15 ppm and is consistent with pyrazole moiety. The doublet
peaks at δ = 5.88 (J = 6.6 Hz) are consistent with the proton in the 1-position
of sugar moiety. Two doublet peaks at δ = 5.80 and 5.74 (J = 14.7 Hz) are
consistent with the protons of methylene in benzyl moiety. Two triplet peaks
at δ = 5.29 (J = 8.0 Hz) and 5.16 (J = 7.5 Hz) are consistent with the proton
of the 2- and 3-position in the sugar moiety, respectively. A multiplet peak at
δ = 4.98–5.03 (m, 1H, C4-H) is consistent with the proton in the 4-position of
sugar moiety. Finally, two double doublet peaks at δ = 4.18 (J = 4.8, 12.1 Hz)
and 3.59 (J = 8.0, 12.1 Hz) are consistent with the methylene protons in sugar
moiety. All other signals are consistent with the structure of 3d.
Single-Crystal Structure
The single crystals were grown from ethyl acetate at rt. The molecular
view of 3d and 3g is shown in Figures 2 and 3, respectively. A summary of
crystallographic data collection parameters and refinement parameters for 3d

S. Lian et al.
4
Figure 2: The molecular structure of 3d, showing displacement ellipsoids drawn at the 50%
probability level for non-H atoms.
Figure 3: The molecular structure of 3g, showing displacement ellipsoids drawn at the 50%
probability level. H atoms are omitted for clarity.

Novel 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate Derivatives
Table 1: Crystal data and structure refinement for 3d and 3g
3d
5
3g
Empirical formula
Formula weight
Temperature
C28 H27 Cl N2 O9
C29 H30 N2 O10
566.55
273(2) K
570.97
273(2) K
Wavelength
Crystal system
Space group
0.71073 Å
Triclinic
P1
0.71073 Å
Monoclinic
P21
Unit cell dimensions
a = 8.1078(10) Å, α =
a = 11.3169(13) Å
79.748(2)◦
b = 8.6406(10)Å, β =
b = 7.7734(9) Å, β =
82.991(2)◦
94.034(2)◦
c = 23.281(3)Å, γ =
c = 16.317(2) Å
63.334(2)◦
Volume
Z
Calculated density
1432.6(3) A3
2
1431.9(3) Å 3
2
1.324 mg/m3
0.188 mm−1
596
1.314 mg/m3
0.100 mm−1
596
Absorption coefficient
F(000)
Crystal size
0.16 × 0.13 × 0.10 mm
0.15 × 0.12 × 0.10 mm
θ range for data
collection
0.89 to 25.05◦
1.80 to 25.05◦
Limiting indices
−9 ≤ h ≤ 9, −6 ≤ k ≤
10, −24 ≤ l ≤ 27
7675/6059 [R(int) =
0.0217]
−13 ≤ h ≤ 8, −9 ≤ k ≤ 9,
−19 ≤ l ≤ 19
Reflections
7610/4854 [R(int) = 0.016]
collected/unique
Completeness to θ =
25.05◦
99.4%
99.7%
Absorption correction
Max. and min.
transmission
Multiscan
0.9814 and 0.9705
Multiscan
0.9901 and 0.9851
Refinement method
Full-matrix
Full-matrix least-squares
on F2
4854/1/371
least-squares on F2
Data/restraints/parameters 6059/3/722
Goodness-of-fit on F2
1.051
1.14
Final R indices [I > 2σ(I)]
R1 = 0.0462, wR2 =
R1 = 0.0368, wR2 =
0.1122
0.0860
R indices (all data)
R1 = 0.0673, wR2 =
0.1341
R1 = 0.0508, wR2 =
0.0946
Largest diff. peak and
hole extinction
parameter
0.23 and −0.25 e. Å−3
0.21 and −0.10 e. Å−3
0.018 (2)
0.0083 (15)
and 3g are compiled in Table 1, whereas important bond lengths and angles
are depicted in Tables 2 and 3.
In the crystal asymmetric unit of 3d there are two independent molecules
(A and B, Fig. 2), whereas in 3g there is one molecule (Fig. 3). The most distinct
structural differences between both molecules of 3d are found in the angles
between the planes of the phenyl and the pyrazole ring. The p-chlorophenyl
[C(29)–C(34)] and pyrazole ring [N(3), N(4), C(35)–C(37)] are almost coplanar
in B with a dihedral angle of 1.5(4)◦, while the dihedral angles are 19.5(4)◦ for

S. Lian et al.
6
Table 2: Selected bond lengths [Å] and angles [◦] for 3d
Cl(1)-C(1)
Cl(2)-C(29)
O(1)-C(17)
O(2)-C(17)
O(2)-C(18)
O(3)-C(18)
O(3)-C(22)
O(10)-C(45)
O(11)-C(45)
O(11)-C(46)
O(12)-C(46)
O(12)-C(50)
N(1)-C(7)
1.737(6)
1.729(6)
1.183(6)
1.344(6)
1.430(5)
1.406(6)
1.435(5)
1.194(5)
1.352(5)
1.419(5)
1.405(5)
1.426(5)
1.341(6)
1.345(5)
1.347(6)
1.469(6)
1.341(6)
1.342(5)
1.431(5)
N(4)-C(37)
N(4)-C(38)
1.377(6)
1.453(5)
1.473(6)
1.390(6)
1.378(6)
1.464(6)
1.475(7)
1.383(7)
1.372(6)
1.454(6)
117.5(4)
106.2(3)
109.4(3
106.8(4)
108.8(4)
104.6(3)
107.1(3)
108.0(4)
110.7(3)
C(4)-C(7)
C(7)-C(8)
C(8)-C(9)
C(9)-C(17)
C(32)-C(35)
C(35)-C(36)
C(36)-C(37)
C(37)-C(45)
C(17)-O(2)-C(18)
O(3)-C(18)-O(2)
C(18)-O(3)-C(22)
O(4)-C(19)-C(18)
O(6)-C(20)-C(21)
O(8)-C(21)-C(20)
O(12)-C(46)-O(11)
O(11)-C(45)-C(37)
C(46)-O(12)-C(50)
N(1)-N(2)
N(2)-C(9)
N(2)-C(10)
N(3)-C(35)
N(3)-N(4)
O(4)-C(19)
the p-chlorophenyl [C(1)–C(6)] and pyrazole ring [N(1), N(2), C(7)–C(9)] in A
and 13.8(2)◦ for the p-methoxyphenyl [C(2)–C(7)] and pyrazole ring [N(1), N(2),
C(8)–C(10)] in 3g. The bond lengths between the phenyl and pyrazole ring are
˚
˚
˚
1.473(6) A [C(4)–C(7)], 1.475(7) A [C(32)–C(35)], and 1.464(3) A [C(5)–C(8)] for
A, B, and 3g, respectively.
It is interesting to find that the pyranose moiety of A and B adopts normal
◦
4C1 conformation,[30] with puckering parameters Q = 0.569(5) A, θ = 10.4(5) ,
˚
Table 3: Selected bond lengths [Å] and angles [◦] for 3g
O(1)-C(1)
O(1)-C(2)
O(2)-C(18)
O(3)-C(18)
O(3)-C(19)
O(4)-C(19)
O(4)-C(23)
O(5)-C(22)
O(5)-C(28)
O(6)-C(28)
O(7)-C(21)
O(7)-C(26)
O(8)-C(26)
O(9)-C(20)
O(9)-C(24)
O(10)-C(24)
N(1)-C(8)
1.145(3)
1.377(3)
1.200(3)
1.347(2)
1.445(2)
1.378(3)
1.430(3)
1.445(3)
1.348(3)
1.195(3)
1.436(3)
1.342(3)
1.188(3)
1.435(3)
1.329(3)
1.201(3)
1.335(3)
1.341(2)
N(2)-C(10)
N(2)-C(11)
C(5)-C(8)
1.359(3)
1.471(3)
1.464(3)
1.388(3)
1.360(3)
1.454(3)
1.495(4)
C(8)-C(9)
C(9)-C(10)
C(10)-C(18)
C(11)-C(12)
C(2)-O(1)-C(1)
C(18)-O(3)-C(19)
C(19)-O(4)-C(23)
C(22)-O(5)-C(28)
C(21)-O(7)-C(26)
C(20)-O(9)-C(24)
C(8)-N(1)-N(2)
N(1)-N(2)-C(10)
N(1)-N(2)-C(11)
C(10)-N(2)-C(11)
117.66(19)
117.37(16)
114.18(17)
116.35(17)
117.45(18)
117.93(18)
105.70(16)
111.77(15)
118.40(16)
129.23(17)
N(1)-N(2)

Novel 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate Derivatives
7
◦
◦
◦
˚
and φ = 341(3) for A and Q = 0.566(5) A, θ = 11.6(5) , and φ = 330(3) for
B, in which all substituents are equatorial. By contrast, that of 3g adop◦ts 1C4
˚
conformation with puckering parameters Q = 0.484(2) A, θ = 172.9(2) , and
φ = 147(2)◦ and axial disposition for all substituents.[31,32]
Based on data of the crystalline state, it is easily observed that the
compounds 3d and 3g are β-anomers, which is consistent with the mecha-
nism of SN2 reaction of 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide and nu-
cleophilic reagents.
In the unit cell of 3d, two symmetry-independent molecules A and B are
held together by one weak hydrogen b◦ond between H(54C) and O(9) [C(54)-
˚
˚
H(54C)—O(9), 2.41 A, 3.118(14) A, 131 ]. Ladder-like one-dimensional aggre-
gates result from an intermolecular C-Cl—π of the pyrazole ring and Cl(2)
◦
˚
[Cl—Cg1: 3.914(4) A, 109.9(3) , symmetry code: −1 + x, y, −1 + z; Cg1 is
the centroid of the N(1)/N(2)/C(7)/C(8)/C(9) ring] and π-π interactions between
the four p-chlorophenyl rings of the neighboring units [Cg3—Cg7: 3.900(5) A,
˚
◦
◦
˚
β = 14.10 , symmetry code: 1 + x, y, 1 + z; Cg(7)—Cg(3): 3.900(5) A, β = 13.73 ,
symmetry code, −1 + x, y, −1 + z; Cg3 is the centroid of the C(1)–C(6) ring and
Cg7 is the centroid of the C(29)–C(34) ring] (Fig. 4). These ladders are further
assembled into a two-dimensional layer via weak hydrogen bonding of C(26)-
H(26C)—O(18). The adjacent layers are further interconnected though weak
hydrogen bonds of C(10)-H(10B)—O(5) and C(44)-H(44)—O(14) (Table 4).
There are two types of super-molecular interactions in the crystal of 3g,
namely, C-H—O hydrogen bonding and C-H—π interactions (Fig. 5, Table 4).
Figure 4: Crystal packing of 3d. C-Cl—π interaction, π–π stacking interaction, C-H—O
hydrogen bonding (color figure available online).

S. Lian et al.
8
Table 4: Intermolecular “weak” hydrogen bond data for compounds 3d and 3g
D–H H—A
(Å) (Å)
D—A
(Å)
∠DHA
Symmetry
codes
Compound
D-H—A
(◦)
3d
C(10)-H(10B)—O(5)
0.97 2.56 3.502(7)
165 −1 + x, 1 + y, z
C(26)-H(26C)—O(18) 0.96 2.51 3.265(10) 136 2 + x, y, z
C(44)-H(44)—O(14)
C(54)-H(54C)—O(9) 0.96 2.41 3.118(14) 131
C(15)-H(15)—O(8)
C(22)-H(22)—O(10)
C(23)-H(23B)—O(1)
C(25)-H(25)—O(2)
C(25)-H(25)—O(4)
0.93 2.51 3.366(8)
153 x, −1 + y, z
3g
0.93 2.59 3.497(4)
0.98 2.49 3.193(3)
0.97 2.59 3.241(3)
0.96 2.53 3.168(3)
0.96 2.59 3.465(3)
166 −1 + x, 1 + y, z
129 x, 1 + y, z
125 −x, 1/2 + y, -z
124 −x, −1/2 + y, 1-z
152 −x, −1/2 + y, 1-z
The molecules of 3g form a one-dimensional columnar structure via the C-
H—O hydrogen bond of C(23)-H(23B)—O(1) and C(22)-H(22)—O(10) along the
b-axis. In the one-dimensional columnar structure, the molecules of 3g are
antiparallel each other. These one-dimensional columnar structures are con-
˚
nected via C(27)-H(27A)—π interaction [H(27A)—Cg4 = 2.84 A, C(27)—Cg4 =
◦
˚
3.697(4) A, ∠C(27)H(27A) Cg4 = 149 , Cg4 is the centroid of the C(11)–C(16)
ring] and C-H—O hydrogen bonding [C(15)-H(15)—O(8)] cross-links to form
a two-dimensional layer. The two-dimensional layer is extended into a three-
dimensional structure by C(25)-H(25B)—O(2) and C(25)-H(25B)—O(4) weak
hydrogen bond.
Figure 5: Crystal packing of 3g. C-H—π interaction, C-H—O hydrogen bonding (color figure
available online).

Novel 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate Derivatives
9
CONCLUSION
A series of novel (2S,3R,4S,5R)-3,4,5-triacetoxy-tetrahydro-2H-pyran-2-yl 1-
benzyl-3-phenyl-1H-pyrazole-5-carboxylate derivatives (3) were synthesized
by the reaction of 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide (2) and
1-benzyl-3-phenyl-1H-pyrazole-5-carboxylic acid (1) in the presence of sodium
bicarbonate and tetrabutylammonium bromide in dichloromethane at reflux
temperature. The structures of new compounds were determined by IR and 1H
NMR spectroscopy and HR mass spectrometry (HRMS). Representatively, the
spatial structures of compounds 3d and 3g were determined by using X-ray
diffraction analysis. Currently, investigations are under way to elucidate the
bioactivity of these pyrazole derivatives with xylose moiety, and the results
will be reported in due course.
EXPERIMENTAL
Reagents and Apparatus
All solvents were predried and distilled prior to use. All reactions were
carried out under nitrogen and monitored by TLC on silica gel 60 F254 plates
(Merck KGaA). 1H NMR spectra were recorded on a Bruker Avance 400
(400 MHz) spectrometer, using CDCl3 as solvents and tetramethylsilane (TMS)
as internal standard. Melting points were determined on an XD-4 digital mi-
cro melting point apparatus. IR spectra were recorded with an IR spectropho-
tometer Avtar 370 FT-IR (Termo Nicolet). HRMS spectra were recorded on an
LTQ Orbitrap Hybrid mass spectrograph. Crystals of 3d and 3g mounted on
glass fiber were studied with a Bruker SMART CCD Detector single-crystal
X-ray diffractometer with a graphite-monochromated Mo Kα radiation (λ =
◦
˚
0.71073 A) source at 0 C. All structures were solved by the direct method using
the SHELXS program of the SHELXTL package and refined by the full-matrix
least-squares methods with SHELXL.[33] The nonhydrogen atoms were located
in successive difference Fourier syntheses and refined with anisotropic ther-
mal parameters on F2. The organic hydrogen atoms were generated geomet-
˚
rically (C-H 0.93–0.98 A). The absolute configuration for both 3d and 3g was
established by the structure determination of a compound containing a chiral
moiety of known absolute configuration. Friedel opposites for 3g were merged,
but for 3d (containing Cl atoms), the absolute configuration was confirmed by
anomalous dispersion effects in diffraction measurements on the crystal with
a Flack parameter of 0.09(10).[34] A summary of crystallographic data collec-
tion parameters and refinement parameters for 3d and 3g are compiled in
Table 1.

S. Lian et al.
10
General Procedure for the Synthesis of Compound 3
To a flask compound 1a–i (1 mmol) and saturated aqueous NaHCO3 (5 mL)
were added. Then 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide 2 (1 mmol),
TBAB (1 mmol), and CH2Cl2 (5 mL) were added and the mixture was stirred
at reflux for 2 to 4 h. The progress of the reaction was monitored by TLC.
The aqueous layer was separated and extracted with CH2Cl2 (10 mL × 3).
The combined organic layer was dried over anhydrous MgSO4 and evaporated
under reduced pressure. The crude product was further purified by column
chromatography (petroleum ether/ethyl acetate = 2:1) on silica gel to afford
compound 3a–i.
(2S,3R,4S,5R)-2-((1-benzyl-3-phenyl-1H-pyrazole-5-carbonyl)oxy)tetrahydro-2H
-pyran-3,4,5-triyl triacetate (3a)
Yield: 60.9%, white solid, mp: 155–158◦C; IR (KBr) ν: 1745 (C O) cm−1; 1H
NMR (400M Hz, CDCl3) δ: 1.88 (s, 3H, CH3), 2.09 (s, 6H, 2 × CH3), 3.60 (dd,
1H, J1 = 12.1 Hz, J2 = 7.9 Hz, C5a-H), 4.19 (dd, 1H, J1 = 12.1 Hz, J2 = 4.7 Hz,
C5b-H), 4.98–5.02 (m, 1H, C4-H), 5.15 (t, 1H, J = 7.2 Hz, C2-H), 5.25 (t, 1H,
J = 7.9 Hz, C3-H), 5.76 (d, 1H, J = 16.5 Hz, NCH2Ar), 5.81 (d, 1H, J = 16.5 Hz,
NCH2Ar), 5.89 (d, 1H, J = 6.4 Hz, C1-H), 7.18 (s, 1H, 4-H), 7.26–7.31 (m, 6H,
ArH), 7.35 (d, 1H, J = 7.3 Hz, ArH), 7.43 (t, 2H, J = 7.3 Hz, ArH), 7.83 (d, 2H,
J = 7.2 Hz, ArH); HRMS m/z calcd for [M+H]+ C28H29N2O9: 537.1873; Found:
537.1876.
(2S,3R,4S,5R)-2-((1-(4-(tert-butyl)benzyl)-3-phenyl-1H-pyrazole-5-carbonyl)oxy)
tetrahydro-2H-pyran-3,4,5-triyl triacetate (3b)
Yield: 45.4%, white solid, mp: 172–173◦C; IR (KBr) ν: 1757, 1737 (C O)
1
cm−1; H NMR (400 MHz, CDCl3) δ: 1.28 (s, 9H, C(CH3)3), 1.87 (s, 3H, CH3),
2.09 (s, 6H, 2 × CH3), 3.61 (dd, 1H, J1 = 12.2 Hz, J2 = 7.8 Hz, C5a-H), 4.20 (dd,
1H, J1 = 12.1 Hz, J2 = 4.7 Hz, C5b-H), 4.98–5.03 (m, 1H, C4-H), 5.16 (t, 1H, J =
7.2 Hz, C2-H), 5.26 (t, 1H, J = 7.8 Hz, C3-H), 5.72 (d, 1H, J = 14.6 Hz, NCH2Ar),
5.79 (d, 1H, J = 14.6 Hz, NCH2Ar), 5.91 (d, 1H, J = 6.4 Hz, C1-H), 7.17 (s,
1H, 4-H), 7.27 (d, 2H, J = 7.4 Hz, p-tertbutylbenzyl), 7.34 (t, 3H, J = 7.3 Hz,
p-tertbutylbenzyl ArH + ArH), 7.42 (t, 2H, J = 7.5 Hz, ArH), 7.82 (d, 2H,
J = 7.8 Hz, ArH); HRMS m/z calcd for [M+H]+ C32H37N2O9: 593.2499; Found:
593.2490.
(2S,3R,4S,5R)-2-((1-((6-chloropyridin-3-yl)methyl)-3-phenyl-1H-pyrazole-5-
carbonyl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (3c)
1
Yield: 66.5%, white solid, mp: 75–80◦C; IR (KBr) ν: 1741 (C O) cm−1; H
NMR (400 MHz, CDCl3) δ: 2.03 (s, 3H, CH3), 2.09 (s, 3H, CH3), 2.10 (s, 3H,
CH3), 3.62 (dd, 1H, J1 = 12.2 Hz, J2 = 7.8 Hz, C5a-H), 4.22 (dd, 1H, J1
=
12.2 Hz, J2 = 4.8 Hz, C5b-H), 4.99–5.04 (m, 1H, C4-H), 5.16 (t, 1H, J =

Novel 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate Derivatives
11
7.2 Hz, C2-H), 5.27 (t, 1H, J = 7.9 Hz, C3-H), 5.76 (s, 2H, NCH2Ar), 5.89 (d, 1H,
J = 6.4 Hz, C1-H), 7.17 (s, 1H, 4-H), 7.27 (d, 1H, J = 9.2 Hz, PyH), 7.36 (t, 1H,
J = 7.1 Hz, ArH), 7.43 (t, 2H, J = 7.4 Hz, ArH), 7.66 (dd, 1H, J1 = 8.3 Hz, J2 =
2.4 Hz, PyH), 7.80 (d, 2H, J = 7.2 Hz, ArH), 8.46 (d, 1H, J = 2.2 Hz, PyH);
HRMS m/z calcd for [M+H]+ C27H27ClN3O9: 572.1436; Found: 572.1423.
(2S,3R,4S,5R)-2-((1-benzyl-3-(4-chlorophenyl)-1H-pyrazole-5-carbonyl)oxy)
tetrahydro-2H-pyran-3,4,5-triyl triacetate (3d)
Yield: 50.3%, white solid, mp: 160–163◦C; IR (KBr) ν: 1746 (C O) cm−1; 1H
NMR (400M Hz, CDCl3) δ: 1.99 (s, 3H, CH3), 2.08 (s, 6H, 2 × CH3), 3.59 (dd,
1H, J1 = 12.1 Hz, J2 = 8.0 Hz, C5a-H), 4.18 (dd, 1H, J1 = 12.1 Hz, J2 = 4.8 Hz,
C5b-H), 4.98–5.03 (m, 1H, C4-H), 5.16 (t, 1H, J = 7.4 Hz, C2-H), 5.29 (q, 1H,
J = 8.0 Hz, C3-H), 5.74 (d, 1H, J = 14.7 Hz, NCH2Ar), 5.80 (d, 1H, J = 14.7 Hz,
NCH2Ar), 5.88 (d, 1H, J = 6.6 Hz, C1-H), 7.15 (s, 1H, 4-H), 7.26–7.31 (m, 5H,
ArH), 7.39 (d, 2H, J = 8.5 Hz, p-chlorophenyl ArH), 7.76 (d, 2H, J = 8.5 Hz,
p-chlorophenyl ArH); HRMS m/z calcd for [M+H]+ C28H28ClN2O9: 571.1483;
Found: 571.1470.
(2S,3R,4S,5R)-2-((1-(4-(tert-butyl)benzyl)-3-(4-chlorophenyl)-1H-pyrazole-5-
carbonyl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (3e)
Yield: 57.8%, white solid, mp: 179–182◦C; IR (KBr) ν: 1756 (C O) cm−1; 1H
NMR (400M Hz, CDCl3) δ: 1.28 (s, 9H, C(CH3)3), 1.98 (s, 3H, CH3), 2.08 (s, 6H,
2 × CH3), 3.60 (dd, 1H, J1 = 12.1 Hz, J2 = 8.0 Hz, C5a-H), 4.19 (dd, 1H, J1 =
12.1 Hz, J2 = 4.8 Hz, C5b-H), 4.99–5.04 (m, 1H, C4-H), 5.16 (t, 1H, J = 7.4 Hz,
C2-H), 5.26 (t, 1H, J = 8.0 Hz, C3-H), 5.71 (d, 1H, J = 14.6 Hz, NCH2Ar), 5.78
(d, 1H, J = 14.6 Hz, NCH2Ar), 5.90 (d, 1H, J = 6.2 Hz, C1-H), 7.14 (s, 1H, 4-H),
7.27 (d, 2H, J = 7.2 Hz, ArH), 7.33 (d, 2H, J = 8.4 Hz, p-tertbutylbenzyl ArH),
7.38 (d, 2H, J = 8.5 Hz, p-tertbutylbenzyl ArH), 7.75 (d, 2H, J = 8.5 Hz, ArH);
HRMS m/z calcd for [M+H]+ C32H36ClN2O9: 627.2109; Found: 627.2166.
(2S,3R,4S,5R)-2-((3-(4-chlorophenyl)-1-((6-chloropyridin-3-yl)methyl)-1H-
pyrazole-5-carbonyl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
(3f)
1
Yield: 46.5%, white solid, mp: 76–80◦C; IR (KBr) ν: 1756 (C O) cm−1; H
NMR (400M Hz, CDCl3) δ: 2.03 (s, 3H, CH3), 2.09 (s, 6H, 2 × CH3), 3.61 (dd,
1H, J1 = 11.7 Hz, J2 = 8.0 Hz, C5a-H), 4.21 (dd, 1H, J1 = 11.9 Hz, J2 = 4.5 Hz,
C5b-H), 4.97–5.07 (m, 1H, C4-H), 5.16 (t, 1H, J = 7.3 Hz, C2-H), 5.27 (t, 1H, J =
8.0 Hz, C3-H), 5.75 (s, 2H, NCH2Ar), 5.88 (d, 1H, J = 6.4 Hz, C1-H), 7.14 (s, 1H,
4-H), 7.28 (d, 1H, J = 10.3 Hz, PyH), 7.40 (d, 2H, J = 8.2 Hz, ArH), 7.66 (d,
1H, J = 8.1 Hz, PyH), 7.73 (d, 2H, J = 8.3 Hz, ArH), 8.46 (s, 1H, PyH); HRMS
m/z calcd for [M+H]+ C27H26Cl2N3O9: 606.1046; Found: 606.1037.

S. Lian et al.
12
(2S,3R,4S,5R)-2-((1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbonyl)oxy)
tetrahydro-2H-pyran-3,4,5-triyl triacetate (3g)
Yield: 64.2%, white solid, mp: 145–146◦C; IR (KBr) ν: 1757, 1732 (C O)
1
cm−1; H NMR (400M Hz, CDCl3) δ: 1.99 (s, 3H, CH3), 2.08 (s, 6H, 2 × CH3),
3.59 (dd, J1 = 12.2 Hz, J2 = 7.9 Hz, C5a-H), 3.85 (s, 3H, CH), 4.18 (dd, 1H, J1 =
12.1 Hz, J2 = 4.7 Hz, C5b-H), 4398–5.03 (m, 1H, C4-H), 5.15 (t, 1H, J = 7.3 Hz,
C2-H), 5.25 (t, 1H, J = 7.9 Hz, C3-H), 5.74 (d, 1H, J = 14.8 Hz, NCH2Ar), 5.80
(d, 1H, J = 14.8 Hz, NCH2Ar), 5.88 (d, 1H, J = 6.4 Hz, C1-H), 6.95 (d, 2H, J =
8.7 Hz, p-methoxyphenyl ArH), 7.10 (s, 1H, 4-H, ArH), 7.26–7.31 (m, 5H, ArH),
7.75 (d, 2H, J = 8.7 Hz, p-methoxyphenyl ArH); HRMS m/z calcd for [M+H]+
C29H31N2O10: 567.1979; Found: 567.1967.
(2S,3R,4S,5R)-2-((1-(4-(tert-butyl)benzyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-
carbonyl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (3h)
1
Yield: 52.3%, white solid, mp: 83–87◦C; IR (KBr) ν: 1756 (C O) cm−1; H
NMR (400M Hz, CDCl3) δ: 1.28 (s, 9H, C(CH3)3), 1.99 (s, 3H, CH3), 2.08 (s, 6H,
2 × CH3), 3.66 (dd, 1H, J1 = 12.1 Hz, J2 = 7.9 Hz, C5a-H), 4.19 (dd, 1H, J1 =
12.2 Hz, J2 = 4.8 Hz, C5b-H), 4.98–5.03 (m, 1H, C4-H), 5.15 (t, 1H, J = 7.3 Hz,
C2-H), 5.25 (t, 1H, J = 7.9 Hz, C3-H), 5.70 (d, 1H, J = 14.7 Hz, NCH2Ar), 5.77 (d,
1H, J = 14.7 Hz, NCH2Ar), 5.90 (d, 1H, J = 6.4 Hz, C1-H), 6.95 (d, 2H, J = 8.8
Hz, ArH), 7.09 (s, 1H, 4-H), 7.26 (d, 2H, J = 8.3 Hz, p-tertbutylbenzyl ArH),
7.32 (d, 2H, J = 8.4 Hz, p-tertbutylbenzyl ArH), 7.75 (d, 2H, J = 8.7 Hz, ArH);
HRMS m/z calcd for [M+H]+ C33H39ClN2O10: 623.2605; Found: 623.2602.
(2S,3R,4S,5R)-2-((1-((6-chloropyridin-3-yl)methyl)-3-(4-methoxyphenyl)-1H-
pyrazole-5-carbonyl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (3i)
Yield: 60.3%, white solid, mp: 119–121◦C; IR (KBr) ν: 1745 (C O) cm−1
;
1H NMR (400M Hz, CDCl3) δ: 2.03 (s, 3H, CH3), 2.07 (s, 3H, CH3), 2.09 (s, 3H,
CH3), 3.62 (dd, 1H, J1 = 12.0 Hz, J2 = 7.9 Hz, C5a-H), 3.85 (s, 3H, CH), 4.22
(dd, 1H, J1 = 12.1 Hz, J2 = 4.6 Hz, C5b-H), 5.02 (dd, 1H, J1 = 12.4 Hz, J2 = 7.5
Hz, C4-H), 5.16 (t, 1H, J = 7.2 Hz, C2-H), 5.27 (t, 1H, J = 7.8 Hz, C3-H), 5.74 (s,
2H, NCH2Ar), 5.88 (d, 1H, J = 6.4 Hz, C1-H), 6.96 (d, 2H, J = 8.4 Hz, ArH),
7.01 (s, 1H, 4-H), 7.27 (d, 1H, J = 6.8 Hz, PyH), 7.65 (d, 1H, J = 7.4 Hz, PyH),
7.72 (d, 2H, J = 8.4 Hz, ArH), 8.45 (s, 1H, PyH); HRMS m/z calcd for [M+H]+
C28H29ClN3O10: 602.1541; Found: 602.1536.
SUPPLEMENTARY MATERIALS
CCDC 773566 and 773567 contain the supplementary crystallographic data
for this paper. This data can be obtained free of charge via www.ccdc.cam.ac.

Novel 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate Derivatives
13
uk/data request/cif, by e-mailing data request@ccdc.cam.ac.uk, or by contact-
ing the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB21EZ, UK; fax: +44 1223 336033.
ACKNOWLEDGMENTS
This study was supported by the Science and Technology Developmen-
tal Project of Shandong Province (2008GG10002034) and 973 Program
(2009CB526507).
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