Synthesis, crystal structures, and fungicidal activity of novel 1,5-diaryl-3-(glucopyranosyloxy)-1H-pyrazoles

Article abstract of DOI:10.1002/hlca.201100509

Five novel pyrazole-coupled glucosides, 1,5-diaryl-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosides 5a-5e, were synthesized by the phase-transfer catalytic reaction of 1,5-diaryl-1H-pyrazol-3-ols 4a-4e with acetobromo-α-D-glucose in H₂O/CHCl₃ under alkaline conditions, using Bu₄N⁺Br^- as catalyst. Then, glucosides 5a-5c were deacetylated in a solution of Na₂CO ₃/MeOH to yield the 1,5-diaryl-3-(β-D-glucopyranosyloxy)-1H- pyrazoles 6a-6c. Their structures were characterized by ¹H, ¹H-COSY, ¹H-, ¹³C-, and ¹⁹F-NMR spectroscopy, as well as elemental analysis. The structures of 5d and 6c were also determined by single-crystal X-ray diffraction analysis. A preliminary in vitro bioassay indicated that compounds 4e and 5d exhibited excellent-to-medium fungicidal activity against Sclerotinia sclerotiorum at the dosage of 10μg/ml.

Full text of DOI:10.1002/hlca.201100509

Helvetica Chimica Acta – Vol. 95 (2012)
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Synthesis, Crystal Structures, and Fungicidal Activity of Novel 1,5-Diaryl-3-
(glucopyranosyloxy)-1H-pyrazoles
by Yuan-Yuan Liu, Hong Shi, Guang-Ke He, Guang-Liang Song, and Hong-Jun Zhu*
Department of Applied Chemistry, College of Science, Nanjing University of Technology, Jiangsu Key
Laboratory of Industrial Water-Conservation & Emission Reduction, Nanjing 210009, P. R. China
(phone/fax: þ 86-25-83172358; e-mail: zhuhjnjut@hotmail.com)
Five novel pyrazole-coupled glucosides, 1,5-diaryl-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-b-d-gluco-
pyranosides 5a – 5e, were synthesized by the phase-transfer catalytic reaction of 1,5-diaryl-1H-pyrazol-3-
ols 4a – 4e with acetobromo-a-d-glucose in H2O/CHCl3 under alkaline conditions, using Bu4NþBrꢀ as
catalyst. Then, glucosides 5a – 5c were deacetylated in a solution of Na2CO3/MeOH to yield the 1,5-
diaryl-3-(b-d-glucopyranosyloxy)-1H-pyrazoles 6a – 6c. Their structures were characterized by 1H,1H-
COSY, 1H-, 13C-, and 19F-NMR spectroscopy, as well as elemental analysis. The structures of 5d and 6c
were also determined by single-crystal X-ray diffraction analysis. A preliminary in vitro bioassay
indicated that compounds 4e and 5d exhibited excellent-to-medium fungicidal activity against Sclerotinia
sclerotiorum at the dosage of 10 mg/ml.
Introduction. – Modern crop production cannot be developed without chemical
means for pathogens control, which are referred to as fungicides or pesticides [1 – 3].
However, as a result of the application of the same fungicide or fungicides with the
same mode of action over many years, plant pathogens become resistant to these
chemicals. Therefore, the design and synthesis of novel fungicides with unique
structures and mechanisms of action, low mammalian toxicity, and a broad spectrum of
bioactivities, are an increasingly active area of current pesticide research [4][5].
In recent years, the ever-increasing importance of glycobiology and the chemistry of
glycoconjugates have gained enormous attention due to the understanding of the role
played by these carbohydrates in biological events [6 – 9], such as inflammation,
immune responses, cell growth, and adhesion [10]. Among these compounds, glyco-
sides of heterocycles are essential and reliable platforms for the development of many
anticancer and antitumor drugs [11][12], and have been regarded as good glycosyl
donors, in addition to their biological activities such as the inhibition of enzyme activity
[13 – 16]. For example, 5-fluorouracil (1; Scheme 1), an excellent representative of anti-
metabolic anticancer drugs in curing gastrointestinal [17] and breast cancer [18], was
transferred to galactosides by the phase-transfer catalysis [19] or the KoenigsꢀKnorr
reaction [20] to form O- or N-galactopyranosides of 5-fluorouracil (2 and 3, resp.;
Scheme 1), which could then slowly release 5-fluorouracil in vivo, reduce its toxicity
toward mammalian cells, and improve its inhibitory effects on tumor cells [21].
Therefore, the efficient synthesis of heterocycle-coupled glycosides is of great value,
and represents a continuing challenge that is at the forefront of organic chemistry.
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 1. 5-Fluorouracil (1) and its Transformation to its O- or N-Galactopyranosides
Since the discovery of the strobilurin fungicide pyraclostrobin (¼ methyl {2-[1-(4-
chlorophenyl)-1H-pyrazol-3-yloxymethyl]phenyl}methoxycarbamate) by BASF scien-
tists in the year 2000 (Scheme 2) [22 – 24], 1H-pyrazol-3-oxy derivatives have attracted
considerable attention in pesticide research because of their low mammalian toxicity
and diverse bioactivities such as fungicidal [25 – 27], insecticidal [28], herbicidal [29],
Scheme 2. Design Strategy of the Target Pyrazole-Coupled Saccharides

Helvetica Chimica Acta – Vol. 95 (2012)
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and plant-growth-regulatory activities [30]. 1,5-Diaryl-1H-pyrazol-3-oxy derivatives
represent one of the most active classes of these compounds and can be used not only as
precursors to a variety of N-containing heterocycles with fungicidal activity [31][32],
but also as analgesic [33], anti-inflammatory [34], and enzyme inhibitory agents [35]
with wide medicinal applications. Motivated by these findings, we conceived that
transforming the 1,5-diaryl-1H-pyrazol-3-oxy structure 4 to glucosides might result in
new pyrazole-coupled saccharide molecules [36] with good bioactivities (Scheme 2).
In this study, the synthesis of a series of novel 1,5-diaryl-3-(glucopyranosyloxy)-1H-
pyrazole derivatives containing a per-O-acetylated glucopyranosyl (5a – 5e) or a
glucopyranosyl (6a – 6c) moiety, and the crystal structures of 5d and 6c are reported.
Meanwhile, the fungicidal activity of 4a – 4e, 5a – 5e, and 6c has been investigated with
the aim of understanding the structureꢀactivity relationships (SAR) and developing
novel fungicides. A preliminary in vitro bioassay indicated that some compounds
displayed good fungicidal activity at the dosage of 10 mg/ml.
Results and Discussion. – Synthesis and Characterization. 1,5-Diaryl-1H-pyrazol-3-
ols 4a – 4e (Scheme 3) were prepared from methyl 3-arylacrylates via two steps
including addition-cyclization and oxidation [31]. ꢂAcetobromo-a-d-glucoseꢃ, a sig-
nificant glucosyl donor for the synthesis of heterocycle-coupled glucosides, was
obtained from glucose by acylation and treatment of the pentaacetyl-b-d-glucopyr-
anose with HBr in AcOH [37].
Scheme 3. Synthesis of 1,5-Diaryl-3-(glucopyranosyloxy)-1H-pyrazole Derivatives 5a – 5e and 6a – 6c

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Helvetica Chimica Acta – Vol. 95 (2012)
Several methods are known for the formation of glycosidic bonds [19][38 – 40],
among which the phase-transfer catalysis and the KoenigsꢀKnorr method are preferred
due to the experimental simplicity and readily accessible materials. In contrast to the
phase-transfer catalysis, the catalysts for the KoenigsꢀKnorr method are expensive
silver salts (Ag2CO3 or Ag2O) [38][41]. Therefore, in our procedure, the five novel
pyrazole-glucosides, 1,5-diaryl-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-b-d-glucopyra-
nosides 5a – 5e, were prepared by the phase-transfer catalytic reaction of ꢂacetobro-
mo-a-d-glucoseꢃ with 4a – 4e in an alkaline H2O/CHCl3 system, using tetrabutyl-
ammonium bromide (Bu4NþBrꢀ) as catalyst (Scheme 3). The crude products were
recrystallized from EtOH, and no other glucoside type products were detected.
Taking some special properties of glucosides such as hygroscopicity into full
consideration, the deacetylation of the glucosides 5a – 5c was carried out in dry MeOH
in the presence of dry Na2CO3. Good yields of 1,5-diaryl-3-(b-d-glucopyranosyloxy)-
1H-pyrazoles 6a – 6c were obtained after recrystallization from dry MeOH (Scheme 3).
The 1H,1H-COSY spectrum of product 5a enables us to assign the chemical shifts of
the anomeric H-atom from the saccharide ring (Fig. 1). As a result of the deshielding
Fig. 1. 1H,1H-COSY Correlations of compound 5a

Helvetica Chimica Acta – Vol. 95 (2012)
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effect of C¼O, the anomeric HꢀC(1’) appeared at low field (5.67 ppm) as a doublet with
a coupling constant of 7.6 Hz. The coupling constant confirmed the b-anomeric form.
The H-atoms HꢀC(2’), HꢀC(3’), HꢀC(4’), HꢀC(5’), and CH2(6’) formed a coupling
system. A multiplet appearing at 5.32 – 5.28 ppm was attributed to HꢀC(2’) and
HꢀC(3’), whereas a triplet at 5.20 ppm (J ¼ 9.5) was assigned to HꢀC(4’). Due to the
different chemical environment, the CH2 H-atoms HaꢀC(6’) and HbꢀC(6’) gave rise to
two dds at 4.19 ppm (J ¼ 2.3, 12.3) and 4.28 ppm (J ¼ 4.9, 12.3), respectively. A
multiplet locating at high field (3.92 – 3.90 ppm) was attributed to HꢀC(5’). Further-
more, the 13C-NMR spectra of 5a – 5e and 6a – 6c confirmed the presence of the
glycoconjugated products, as the anomeric C-atom was identified at 102.7 – 97.6 ppm.
The AcO groups present in the saccharide moiety of 5a – 5e were well resolved in both
1H- and 13C-NMR spectra. The AcO H-atoms of 5a – 5e resonated in the region of
1
2.06 – 2.00 ppm in H-NMR spectra, and the 13C-NMR signals were observed around
20.7 – 20.6 ppm. As expected, such signals were absent in the spectra of 6a – 6c. Because
of the different shielding effect in O-acetylated glucopyranosyl (5a – 5e) and
glucopyranosyl groups (6a – 6c), the chemical shift of the CH of the pyrazole ring
displayed at 6.10 – 5.97 and 6.23 – 6.18 ppm, respectively. The 1H-NMR spectra of these
glucosides exhibited a multiplet of aromatic H-atoms in the range of 7.55 – 6.81 ppm.
Structural Discussion. To further validate the structures and understand the effect of
structural factors on their interactions, the crystal structures of 5-(4-fluorophenyl)-1-
phenyl-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-b-d-glucopyranoside (5d) and 5-(4-fluo-
rophenyl)-1-[4-(propan-2-yl)phenyl]-1H-pyrazol-3-yl b-d-glucopyranoside (6c) were
investigated.
Compound 5d crystallizes in an orthorhombic space group P212121. The detailed
crystal and structure refinement data for 5d are collected in Table 1. An ORTEP view
of the molecule 5d (Fig. 2) reveals that the saccharide moiety in 5d is a glucopyranose.
The glucopyranose ring is in the usual 4C1 conformation, and the anomeric center of the
saccharide has the b-configuration, which is also confirmed from the torsion angles
O(1)ꢀC(20)ꢀO(2)ꢀC(16) ꢀ 174.548 and O(2)ꢀC(20)ꢀC(19)ꢀO(6) ꢀ 168.068. The
torsion angle C(17)ꢀC(16)ꢀC(21)ꢀO(3) is 56.68, pointing out that the AcO group
attached to the primary OH group is in the gt position, which is known to be the favored
orientation for a glucopyranose. The pyrazole ring is nearly coplanar with the anomeric
C-atom C(20) by making a torsion angle of C(20)ꢀO(1)ꢀC(15)ꢀC(14) 19.58, and this
orientation facilitates delocalization of electrons from the lone-pair orbitals of O(1)
with the p orbitals of the pyrazole ring. The intramolecular H-bond (CꢀH ··· O) results
in the formation of one planar five-membered pseudo-ring A (O(9)/C(26)/O(5)/C(18)/
H(18)). The N-linked benzene ring B (C(1) to C(6)) and C-linked benzene ring C (C(7)
to C(12)) are twisted 43.158 and 45.568, respectively, from the plane of the pyrazole ring
(N(1), N(2), C(13) to C(15)). Rings B and C are planar and the dihedral angle between
them is 58.98.
Compound 6c crystallizes in a monoclinic space group P21. The detailed crystal and
structure refinement data for 6c are also listed in Table 1. An ORTEP view of the
molecule 6c is shown in Fig. 3. The saccharide adopts the 4C1 conformation along with
its b-anomeric form, which is further confirmed by the torsion angles
O(1)ꢀC(19)ꢀO(2)ꢀC(20) ꢀ 179.08 and O(2)ꢀC(19)ꢀC(23)ꢀO(6) ꢀ 180.08. The H2O
molecule in the crystal is linked to HꢀC(11) of the N-linked benzene ring by an

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 1. Crystallographic Data for Compounds 5d and 6c
Compound
5d
6c
Empirical formula
CCDC No.
C29H29FN2O10
823219
C24H29FN2O7
697145
Formula weight
Temp. [K]
584.54
180(2)
476.49
291(2)
Wavelength [ꢄ]
Crystal system
Space group
0.71073 ꢄ
Orthorhombic
P212121
0.71073 ꢄ
Monoclinic
P21
Z
4
2
Crystal dimensions [mm]
q Range for cell determination [8]
0.26 ꢁ 0.29 ꢁ 0.35
1.66 – 31.18
8.222(2)
0.24 ꢁ 0.26 ꢁ 0.30
2.49 – 27.99
8.216(2)
Unit cell parameters
a [ꢄ]
b [ꢄ]
c [ꢄ]
b [8]
14.205(5)
24.558(7)
90.00
2868.2(15)
0.107
9.149(2)
15.529(4)
94.766(3)
1163.3(5)
0.105
1.360
504
Volume [ꢄ3]
m [mmꢀ1
]
Dx [g cmꢀ3
F(000)
]
1.354
1224
Index ranges
ꢀ 11 ꢂ h ꢂ 11
ꢀ 20 ꢂ k ꢂ 20
ꢀ 35 ꢂ l ꢂ 34
60086
ꢀ 10 ꢂ h ꢂ 8
ꢀ 11 ꢂ k ꢂ 8
ꢀ 20 ꢂ l ꢂ 20
7263
Reflections collected
Independent reflections (Rint
Refinement method on F2
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
)
8743 (Rint ¼ 0.0377)
Full-matrix least-squares
0.9727/0.9635
8743/0/383
1.251
2930 (Rint ¼ 0.0556)
Full-matrix least-squares
0.98/0.97
2930/1/309
1.016
Final R indices [I > 2s(I)]; R1, wR2
R1, wR2 (all data)
0.0694, 0.1833
0.0753, 0.1888
0.280; ꢀ 0.243
0.0658, 0.1244
0.0852, 0.1292
0.394; ꢀ 0.314
Largest diff. peak and hole [eꢄꢀ3
]
intermolecular H-bond C(11)ꢀH(11) ··· O(7). An intramolecular OꢀH ··· O H-bond
results in the formation of a non-planar pseudo-ring D (O(2), C(20), C(24), O(3),
H(3A)). The N-linked benzene ring E (C(10) to C(15)) and C-linked benzene ring F
(C(4) to C(9)) are twisted 53.668 and 39.418, respectively, from the plane of the
pyrazole ring (N(1), N(2), C(1) to C(3)). Rings E and F are planar and the dihedral
angle between them is 54.928.
Fungicidal Activity Studies. The compounds 4a – 4e, 5a – 5e, and 6c were screened
for bioactivity against three fungi, namely Sclerotinia sclerotiorum, Gibberella zeae, and
Rhizoctonia cerealis, at a concentration of 10 mg/ml each. As can be seen in Table 2,
most compounds have weak fungicidal activity, except 4e (X ¼ CF3, Y¼ H, OH group
at C(3) of the pyrazole ring) and 5d (X ¼ F, Y ¼ H, O-acetylated glucopyranosyl group
at C(3) of the pyrazole ring), which exhibited excellent-to-medium inhibitory activity
against Sclerotinia sclerotiorum. This might imply that the introduction of the electron-
withdrawing group or O-acetylated glucopyranosyl group by taking the electronic
effect into full consideration was important for improving its fungicidal activity. In

Helvetica Chimica Acta – Vol. 95 (2012)
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Fig. 2. ORTEP Plot of the molecular structure of 5d showing atom-numbering scheme; 50% probability
thermal ellipsoids
Fig. 3. ORTEP Plot of the molecular structure of 6c showing atom-numbering scheme; 50% probability
thermal ellipsoids
terms of X, compounds with electron-withdrawing groups on the 5-phenyl ring
displayed higher fungicidal activity than that with electron-donating groups, as seen in
the comparison of compounds 4d (X ¼ F) and 4e (X ¼ CF3) vs. 4a (X ¼ MeO) and 4b
(X ¼ Me), 5c and 5d (X ¼ F) vs. 5a (X ¼ MeO) and 5b (X ¼ Me). However,
compounds 4c and 6c (X ¼ F), and 5e (X ¼ CF3) are three exceptions: 4c and 6c
showed no fungicidal activity against Sclerotinia sclerotiorum and Rhizoctonia cerealis,
and 5e only weak activity, which indicated switching the substituents Y from H to iPr, or

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 2. Antifungal Activity of Tested Compounds (% inhibition)
Compounds
X
Y
Effect of test compound (10 mg/ml)a)
S. sclerotiorum
G. zeae
R. cerealis
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
6c
MeO
Me
F
H
H
Me2CH
H
H
H
H
Me2CH
H
0
18
0
39
100
0
10
29
53
0
1
13
4
30
23
1
5
11
8
5
8
0
17
9
0
0
19
2
6
0
F
CF3
MeO
Me
F
F
CF3
F
H
Me2CH
1
6
0
a) 0 ¼ no activity and 100 ¼ total kill.
O-acetylated glucopyranosyl to glucopyranosyl had no effective impact on the
inhibition rates. The present work indicated that 4e and 5d could be used as potential
lead compounds for further studies of novel fungicides.
Conclusions. – In summary, a series of novel 1,5-diaryl-3-(glucopyranosyloxy)-1H-
pyrazole derivatives containing per-O-acetylated glucopyranosyl (5a – 5e) or glucopyr-
anosyl (6a – 6c) moieties were synthesized by the phase-transfer catalytic reaction of
1,5-diaryl-1H-pyrazol-3-ols 4a – 4e with acetobromo-a-d-glucose, followed by deace-
tylation with Na2CO3/MeOH. The fungicidal activities of 4a – 4e, 5a – 5e, and 6c were
tested in vitro against Sclerotinia sclerotiorum, Gibberella zeae, and Rhizoctonia
cerealis. Only 4e and 5d exhibited excellent-to-medium inhibitory activity against
Sclerotinia sclerotiorum. This implies that the introduction of the electron-withdrawing
group or the O-acetylated glucopyranosyl residue is important for improving their
fungicidal activity. The most promising compounds in this study, 4e and 5d, can be used
as potential lead compounds for further studies of novel fungicides.
This work was jointly supported by the National High Technology Research and Development
Program (ꢂ863ꢃ Program) of China (Grant No. 2009AA032901) and the Postgraduate Innovation Fund of
Jiangsu Province (No. CXZZ11_0365).
Experimental Part
General. All starting materials were used in analytical grades, and solvents were dried by standard
methods and distilled before use. Compounds 4a [42], 4b – 4d [34], and 4e [43] were prepared according
to the published procedures. TLC: precoated silica-gel plates (Merck silica gel 60 F254); detection by UV
light. M.p.: X-4 microscope electrothermal apparatus; uncorrected. 1H-, 13C-, and 19F-NMR spectra:
Bruker spectrometer at 300 or 500 MHz; in CDCl3 or (D6)DMSO; chemical shifts d in ppm rel. to Me4Si
as internal standard, and coupling constants J in Hz. Elemental analyses: Vario EL III elemental
analyzer.
Fungicidal Assays. The fungicidal activity of compounds 4a – 4e, 5a – 5e, and 6c against fungi
Sclerotinia sclerotiorum, Gibberella zeae, and Rhizoctonia cerealis was investigated. The fungi were

Helvetica Chimica Acta – Vol. 95 (2012)
1653
obtained from Jiangsu Pesticide Research Institute Co., Ltd., P. R. China. The tested compounds were
dissolved in acetone and added to a sterile agarized Czapek-Dox medium at 458. In preliminary
screenings, the compounds were used in a concentration of 10 mg/ml. The control sample contained only
one equivalent of acetone. The media were poured onto 8-cm Petri dishes (10 ml for each dish) and after
2 d inoculated with 5-mm PDA discs of overgrown mycelium. In the case of Sclerotinia sclerotiorum, the
medium was inoculated by a prick of laboratory needle containing fungus spores. The Petri dishes were
incubated at r.t. in the dark. After 4 d, the diameters of the inoculation of the cultures were measured.
The percentage inhibition of fungal growth was determined by comparison between the development of
fungi colonies on media containing compounds and on the control. Three replicates of each test were
carried out.
Suitable crystals of 5d and 6c were obtained by slow evaporation of EtOH soln. at r.t. Further details
about the data collection are listed in Table 1. Crystal data1) were collected on a Nonius CAD-4
diffractometer by using MoKa (0.71073 ꢄ) irradiation. The data of 5d were collected at 180 K and those
of 6c at 291 K. The structures were solved by direct method using SHELXS-97 [44] and refined by full-
matrix least-squares on F2 for all data using SHELXL-97 [44]. The H-atoms of the H2O molecules in 6c
were located in the difference Fourier map. Their thermal displacement parameters were fixed to 1.5
times the equivalent one of the parent O-atom. All other H-atoms were added at calculated positions and
refined using a riding model. Their isotropic temp. factors were fixed to 1.2 times (1.5 times for Me
groups) the equivalent isotropic displacement parameters of the C-atom the H-atom is attached to.
Anisotropic thermal displacement parameters were used for all non-H-atoms.
General Procedure for the Synthesis of 1,5-Diaryl-1H-pyrazol-3-yl 2,3,4,6-Tetra-O-acetyl-b-d-
glucopyranosides 5a – 5e. A mixture of CHCl3 (20 ml), Bu4NþBrꢀ (2.3 g, 7.1 mmol), and H2O (15 ml)
was heated to 558, and then a soln. of 1,5-diaryl-1H-pyrazol-3-ol (4a – 4e; 10.5 mmol) in CHCl3 (15 ml)
and 5% aq. NaOH (15 ml) were added dropwise. The pH value was adjusted to 8 – 10, and acetobromo-a-
d-glucose (5.4 g, 13.0 mmol) was added under vigorous stirring. The mixture was stirred at 558 for
another 4 h, and then left to cool to r.t. The org. layer was separated, washed with 5% aq. NaOH, and
dried (MgSO4). Then, the solvent was removed in vacuo. The pure product 5a – 5e was obtained by
recrystallization from dry EtOH.
5-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-3-yl 2,3,4,6-Tetra-O-acetyl-b-d-glucopyranoside (5a).
1
Yield: 3.70 g (59%). Colorless crystals. M.p. 181 – 1828. H-NMR (CDCl3, 500 MHz): 7.30 – 7.23 (m, 5
arom. H); 7.12 (d, J ¼ 8.8, 2 arom. H); 6.81 (d, J ¼ 8.8, 2 arom. H); 5.97 (s, HꢀC(4)); 5.67 (d, J ¼ 7.6,
HꢀC(1’)); 5.32 – 5.28 (m, HꢀC(2’), HꢀC(3’)); 5.20 (t, J ¼ 9.5, HꢀC(4’)); 4.28 (dd, J ¼ 4.9, 12.3, HbꢀC(6’));
4.19 (dd, J ¼ 2.3, 12.3, HaꢀC(6’)); 3.92 – 3.90 (m, HꢀC(5’)); 3.79 (s, MeO); 2.05, 2.04, 2.03, 2.01 (4s, 4
MeCO). 13C-NMR (CDCl3, 75 MHz): 170.6; 170.2; 169.4; 169.3; 164.8; 161.0; 142.7; 139.5; 133.8; 129.1;
128.9; 127.6; 125.5; 125.2; 97.7; 95.6; 73.0; 72.3; 71.1; 68.3; 61.9; 55.8; 20.7; 20.6. Anal. calc. for C30H32N2O11
(596.58): C 60.40, H 5.41, N 4.70; found: C 60.25, H 5.39, N 4.72.
5-(4-Methylphenyl)-1-phenyl-1H-pyrazol-3-yl 2,3,4,6-Tetra-O-acetyl-b-d-glucopyranoside (5b).
1
Yield: 2.93 g (48%). Colorless crystals. M.p. 147 – 1488. H-NMR (CDCl3, 500 MHz): 7.34 – 7.09 (m, 9
arom. H); 6.00 (s, HꢀC(4)); 5.66 (d, J ¼ 7.7, HꢀC(1’)); 5.33 – 5.26 (m, HꢀC(2’), HꢀC(3’)); 5.20 (t, J ¼ 9.5,
HꢀC(4’)); 4.28 (dd, J ¼ 4.9, 12.4, HbꢀC(6’)); 4.18 (dd, J ¼ 2.4, 12.4, HaꢀC(6’)); 3.92 – 3.89 (m, HꢀC(5’));
2.34 (s, Me); 2.06, 2.04, 2.03, 2.01 (4s, 4 MeCO). 13C-NMR (CDCl3, 75 MHz): 170.6; 170.2; 169.4; 169.3;
162.7; 138.6; 132.3; 129.7; 129.2; 129.0; 128.6; 127.1; 125.2; 125.1; 97.7; 94.7; 77.4; 77.2; 77.0; 76.6; 61.9; 21.2;
20.7; 20.6. Anal. calc. for C30H32N2O10 (580.58): C 62.06, H 5.56, N 4.83; found: C 61.88, H 5.58, N 4.85.
5-(4-Fluorophenyl)-1-[4-(propan-2-yl)phenyl]-1H-pyrazol-3-yl 2,3,4,6-Tetra-O-acetyl-b-d-glucopyr-
anoside (5c). Yield: 3.03 g (46%). Colorless crystals. M.p. 151 – 1528. 1H-NMR (CDCl3, 500 MHz): 7.26 –
6.97 (m, 8 arom. H); 5.99 (s, HꢀC(4)); 5.67 (d, J ¼ 7.7, HꢀC(1’)); 5.32 – 5.26 (m, HꢀC(2’), HꢀC(3’)); 5.19
(t, J ¼ 9.5, HꢀC(4’)); 4.28 (dd, J ¼ 4.7, 12.4, HbꢀC(6’)); 4.18 (dd, J ¼ 2.4, 12.4, HaꢀC(6’)); 3.91 – 3.88 (m,
HꢀC(5’)); 2.93 – 2.87 (m, Me2CH); 2.05, 2.04, 2.03, 2.01 (4s, 4 MeCO); 1.23 (d, J ¼ 6.9, Me2CH).
13C-NMR (CDCl3, 75 MHz): 170.6; 170.2; 169.4; 164.4; 161.1; 160.8 (J(C,F) ¼ 36.8); 148.2; 143.2; 137.4;
130.5 (J(C,F) ¼ 8.3); 126.9 (J(C,F) ¼ 5.2); 126.5; 125.0; 115.6 (J(C,F) ¼ 21.0); 97.6; 94.6; 77.4; 77.2; 76.6;
1
)
CCDC-823219 (5d) and 697145 (6c) contain the supplementary crystallographic data for this artilce.
These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif.

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Helvetica Chimica Acta – Vol. 95 (2012)
76.0; 61.9; 33.7; 23.9; 20.7; 20.6. 19F-NMR (CDCl3, 282 MHz): ꢀ 111.3. Anal. calc. for C32H35FN2O10
(626.63): C 61.34, H 5.63, N 4.47; found: C 61.52, H 5.61, N 4.45.
5-(4-Fluorophenyl)-1-phenyl-1H-pyrazol-3-yl 2,3,4,6-Tetra-O-acetyl-b-d-glucopyranoside (5d).
1
Yield: 2.58 g (42%). Colorless crystals. M.p. 116 – 1178. H-NMR (CDCl3, 500 MHz): 7.31 – 7.16 (m, 7
arom. H); 7.00 – 6.98 (m, 2 arom. H); 6.01 (s, HꢀC(4)); 5.67 (d, J ¼ 7.6, HꢀC(1’)); 5.32 – 5.28 (m, HꢀC(2’),
HꢀC(3’)); 5.19 (t, J ¼ 9.5, HꢀC(4’)); 4.27 (dd, J ¼ 4.8, 12.4, HbꢀC(6’)); 4.18 (dd, J ¼ 2.4, 12.3, HaꢀC(6’));
3.91 – 3.90 (m, HꢀC(5’)); 2.05, 2.04, 2.03, 2.00 (4s, 4 MeCO). 13C-NMR (CDCl3, 75 MHz): 170.6; 170.2;
169.4; 169.3; 164.5; 160.3 (J(C,F) ¼ 84.8); 144.2; 139.9; 130.5 (J(C,F) ¼ 8.3); 130.0; 128.8 (J(C,F) ¼ 5.3);
127.0; 125.0; 115.6 (J(C,F) ¼ 21.8); 97.6; 94.4; 76.6; 73.0; 72.2; 68.3; 61.9; 20.7; 20.6. 19F-NMR (CDCl3,
282 MHz): ꢀ 111.0. Anal. calc. for C29H29FN2O10 (584.55): C 59.59, H 5.00, N 4.79; found: C 59.72, H
4.98, N 4.77.
1-Phenyl-5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-3-yl 2,3,4,6-Tetra-O-acetyl-b-d-glucopyranoside
1
(5e). Yield: 3.40 g (51%). Colorless crystals. M.p. 158 – 1598. H-NMR (CDCl3, 500 MHz): 7.55 (d, J ¼
8.2, 2 arom. H); 7.35 – 7.22 (m, 7 arom. H); 6.10 (s, HꢀC(4)); 5.69 (d, J ¼ 7.5, HꢀC(1’)); 5.32 – 5.29 (m,
HꢀC(2’), HꢀC(3’)); 5.20 (t, J ¼ 9.4, HꢀC(4’)); 4.28 (dd, J ¼ 4.8, 12.4, HbꢀC(6’)); 4.19 (dd, J ¼ 2.0, 12.3,
HaꢀC(6’)); 3.93 – 3.90 (m, HꢀC(5’)); 2.06, 2.05, 2.04, 2.01 (4s, 4 MeCO). 13C-NMR (CDCl3, 75 MHz):
170.6; 170.2; 169.4; 169.3; 161.0; 142.7; 139.5; 133.7; 130.8; 129.1; 128.9; 127.6; 125.6; 125.5; 125.4 – 125.2
(m); 97.7; 95.6; 77.4; 77.2; 77.0; 76.6; 61.9; 20.7; 20.6. 19F-NMR ((D6)DMSO, 282 MHz): ꢀ 60.2. Anal.
calc. for C30H29F3N2O10 (634.55): C 56.78, H 4.61, N 4.41; found: C 56.64, H 4.63, N 4.39.
General Procedure for the Synthesis of 1,5-Diaryl-1H-pyrazol-3-yl b-d-Glucopyranosides (6a – 6c).
To a soln. of 5a – 5c (1.0 mmol) in dry MeOH (10 ml) was added dry Na2CO3 (0.16 g, 1.5 mmol). The
mixture was then stirred at r.t. until the starting material had been completely consumed as judged by
TLC analysis. The solvent was then evaporated in vacuo, and the residue was recrystallized from dry
MeOH to give the pure products 6a – 6c.
5-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-3-yl b-d-Glucopyranoside (6a). Yield: 0.27 g (63%).
1
Colorless crystals. M.p. 119 – 1208. H-NMR (CD3OD, 500 MHz): 7.37 – 7.32 (m, 3 arom. H); 7.24 – 7.22
(m, 2 arom. H); 7.14 (d, J ¼ 8.9, 2 arom. H); 6.85 (d, J ¼ 8.8, 2 arom. H); 6.18 (s, HꢀC(4)); 5.14 (d, J ¼ 7.7,
HꢀC(1’)); 3.88 (dd, J ¼ 2.3, 12.0, HꢀC(2’)); 3.78 (s, MeO); 3.70 (dd, J ¼ 5.8, 12.0, HꢀC(3’)); 3.49 – 3.45 (m,
HꢀC(4’), CH2(6’)); 3.41 – 3.39 (m, HꢀC(5’)). 13C-NMR (CD3OD, 75 MHz): 163.8; 161.6; 146.2; 141.2;
130.1; 129.5; 128.7; 126.8; 126.5; 126.2; 102.7; 94.8; 78.5; 78.0; 74.9; 71.4; 62.7; 55.7. Anal. calc. for
C22H24N2O7 (428.44): C 61.67, H 5.65, N 6.54; found: C 61.82, H 5.63, N 6.52.
5-(4-Methylphenyl)-1-phenyl-1H-pyrazol-3-yl b-d-Glucopyranoside (6b). Yield: 0.24 g (59%).
Colorless crystals. M.p. 127 – 1288. 1H-NMR (CD3OD, 300 MHz): 7.39 – 7.06 (m, 9 arom. H); 6.21 (s,
HꢀC(4)); 5.15 (d, J ¼ 7.5, HꢀC(1’)); 3.89 (dd, J ¼ 2.2, 12.0, HꢀC(2’)); 3.69 (dd, J ¼ 5.4, 12.1, HꢀC(3’));
3.49 – 3.44 (m, HꢀC(4’), CH2(6’)); 3.41 – 3.38 (m, HꢀC(5’)); 2.32 (s, Me). 13C-NMR (CD3OD, 75 MHz):
163.8; 146.3; 141.2; 130.2; 129.8; 129.5; 128.6; 126.8; 126.5; 126.2; 102.7; 95.0; 78.5; 78.0; 74.9; 71.4; 62.7;
21.2. Anal. calc. for C22H24N2O6 (412.44): C 64.07, H 5.87, N 6.79; found: C 64.18, H 5.89, N 6.76.
5-(4-Fluorophenyl)-1-[4-(propan-2-yl)phenyl]-1H-pyrazol-3-yl b-d-Glucopyranoside (6c). Yield:
1
0.27 g (58%). Colorless crystals. M.p. 104 – 1058. H-NMR (CD3OD, 500 MHz): 7.28 – 7.24 (m, 4 arom.
H); 7.15 (d, J ¼ 8.5, 2 arom. H); 7.06 (d, J ¼ 8.8, 2 arom. H); 6.23 (s, HꢀC(4)); 5.13 (d, J ¼ 7.6, HꢀC(1’));
3.90 (dd, J ¼ 2.2, 12.0, HꢀC(2’)); 3.70 (dd, J ¼ 5.7, 12.1, HꢀC(3’)); 3.48 – 3.45 (m, HꢀC(4’), CH2(6’));
3.40 – 3.36 (m, HꢀC(5’)); 2.94 – 2.91 (m, Me2CH); 1.25 (d, J ¼ 6.9, Me2CH). 13C-NMR (CDCl3, 75 MHz):
165.9; 163.1 (J(C,F) ¼ 76.9); 150.2; 145.0; 138.7; 132.0 (J(C,F) ¼ 8.2); 128.1; 127.9 (J(C,F) ¼ 3.8); 126.8;
116.5 (J(C,F) ¼ 22.0); 102.7; 95.1; 78.5; 77.9; 74.8; 71.4; 62.6; 35.0; 24.2. 19F-NMR (CDCl3, 282 MHz):
ꢀ 110.9. Anal. calc. for C24H27FN2O6 (458.48): C 62.87, H 5.94, N 6.11; found: C 62.72, H 5.96, N 6.13.
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