SO2F2 mediated transformation of pyrazolones into pyrazolyl fluorosulfates

Article abstract of DOI:10.1039/c9ob00903e

The construction of a class of novel N-heterocyclic molecules containing both pyrazole and fluorosulfate functionalities was achieved through the reactions of pyrazolones with SO₂F₂ in good to excellent yields. The fluorosulfate moieties were utilized as versatile building blocks in the Suzuki coupling reaction and SuFEx click chemistry.

Full text of DOI:10.1039/c9ob00903e

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DOI: 10.1039/C9OB00903E
ARTICLE
SO F mediated transforming pyrozolones to pyrazolyl
2
2
fluorosulfates
Jing Leng and Hua-Li Qin *
Received 00th January 20xx,
Accepted 00th January 20xx
The construction of a class of novel N-heterocyclic molecules containing both pyrazole and fluorosulfate functionalities was
DOI: 10.1039/x0xx00000x
2 2
achieved through the reactions of pyrazolones with SO F in good to excellent yields. The fluorosulfate moieties were utilized
as versatile building blocks in Suzuki coupling reaction and SuFEx click chemistry.
8
Functionalized pyrazoles as core motifs are present in arylfluorosulfates in chemical synthesis and transformation,
9
medicinal chemistry and biological chemistry. Compared with
2
F), the lower intrinsic reactivity
of the fluorosulfate (R-OSO F) assured the reduced off-target
labeling in a cellular context and largely had no influence on
human proteome, what’s more, its higher chemical stability was
found to be valuable for the design of targeted covalent drugs
Figure 2). Therefore, the screening of libraries of chemically
diverse fluorosulfates play an extremely important role in drug
numerous biologically active molecules with wide applications
in pharmaceuticals, agrochemicals, and other functional
materials. Many pyrazole derivatives have been successfully
1
0
sulfonyl fluoride group (R-SO
1
2
developed as drugs or drug candidates for the treatment of a
2
variety of diseases (figure 1). Among various type of pyrazoles,
pyrazolones have been particularly recognized as an
outstanding scaffolds for the discovery and development of
(
new drugs since Knorr and Filehne developed phenazone, the
9h
modification and discovery. Based on the significance of both
3
very first antipyretic and analgesic in 1883. Because of the pyrazole and fluorosulfate, finding a portal to assembly of
great pharmaceutical importance of pyrazole moieties, molecules bearing both pyrazole and fluorosulfate moieties
development of efficient and reliable methods to synthesize would unquestionably increase the chance of identifying drug
1
1
candidates as well as lead compounds optimization.
pyrazole-containing scaffolds continues to be of great
significance, and therefore, extensive investigations have been
performed.4
Arylfluorosulfate Probe
O
O
O
O
O
O
N
Cl
N
NH
O
N
N
S
FO2SO
Bind selectively to intracellular lipid binding protein (iLBP) family
F3C
N
O
nPr
N
N
EtO
Sildenafil
Cl
N
Na
SO3
N
N
O
COOH
N
O
-
N
N
O
OSO2F
FO2SO
O
Cl
O
Cl
S
N
HN
N
O
Ph
NH2
Celecoxib
N
N
HO
Ph
N
Cl
Bind selectively to transthyretin (TTR)
New Drug Discovery
Rimonabant
Dipyrone
Phenazone
Bind selectively to Lys and Tyr side chains
Figure 1. Representative drugs containing pyrazole moieties
On the other hand, arylfluorosulfates as the phenolic
derivatives were reported in the early 1930s, however, studies
5
OH
O
C2F5
on this functionality (-OSO
decades, mainly due to the lack of applicable methods for their
preparation. Recently, the Sharpless group discovered a mild
and robust procedure of using phenols and SO
conditions to obtain a series of arylfluorosulfates compounds,
which further spurred comprehensive studies of
2
F) were very limited in the past
H
O
O
H
H
O
S
O
OSO2F
FO2SO
6
F
2 2
under base
Fluorosulfate derivative of Combretastatin A4
under clinical trials
Fluorosulfate derivative of Fulvenstrant
7
Figure 2. Application of arylfluorosulfate in fluorescent probe
and drug discovery
However, nowadays nearly all fluorosulfates are derived from
their phenolic compounds, which has unfortunately limited the
Chemistry, Chemical Engineering and Life Science, Wuhan University of diversifying and accessing to new fluorosulfates. Considering
Technology, 205 Luoshi Road, Wuhan, Hubei Province, 430070, P. R. China; that pyrazolones can be readily transformed into their enol
State Key Laboratory of Silicate Materials for Architectures; and School of
qinhuali@whut.edu.cn.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
forms under appropriate conditions, we envision that the
hydroxy group of the newly formed enols would have the
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
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ARTICLE
Journal Name
nucleophilic ability to react with SO
bases to provide a portal to a new class of fluorosulfates. Herein, fluorosulfate products (2f and 2l) in g
2
F
2
by the promotion of were also smoothly transformed to the coVirerweAsrpticolenOdnilninge
it iv
D
o
O
o
I
d
: 10
a
.1
n
0
d
39
q
/C
u
9
a
O
n
B
t
0
0
a
9
t
03E
e
we described the development of a new method for accessing yields, respectively. Heteroaryl substituted substrates on 2-
a library of pyrazole-containing fluorosulfates heterocycles position such as 1u and 1y produced their products 2u and 2y
though the reaction of pyrazolones with SO
2
F
2
under very mild in relatively lower yields (54% and 46% respectively) which
could probably be attributed to the strong electron-deficient
property of pyridine motif. Different substitutions on 5-position
condition (Scheme 1).
This work
R3
R3
of pyrazolones were also examined for their feasibility of
fluorosulfation. Phenyl, methyl, propyl, isopropyl, cyclopropyl
groups (1m, 1b, 1v, 1h, 1x) were also compatible to this reaction
to provide their corresponding products (2m, 2b, 2v, 2h, 2x)
smoothly with satisfactory yields. However, strong electron-
O
SO2F2
FO2SO
R2
Base condition
R2
N
N
R1
R1
N
N
Scheme 1. Base promoted fluorosulfation of pyrazolone.
We initially chose 5-methyl-2-phenyl-2,4-dihydro-3H- withdrawing group of CF3 substituted pyrazolone 1z
pyrazol-3-one 1a as model substrate to test feasibility of significantly affected the product yield, which could be
formation of fluorosulfate 2a (Table 1). After screening a large considered because of the weak stability and nucleophilicity of
variety of conditions, we were delighted to find that, a enol intermediates. Pyrazolones with an additional substitution
moderate yield of 46% was obtained when 3.0 equivalents of on 4-position (1aa and 1ab) were also smoothly transformed to
3
Et N was used as base in the solvent of DCM at room their corresponding fluorosulfates with excellent yields (2aa
temperature (entry 1). Organic bases were found to be more and 2ab). Non-protected pyrazolone 1ad was also tolerable to
efficient in this transformation than inorganic bases. The use of this condition providing a satisfactory 94% yield of product 2ad.
a
N, N-diisopropylethylamine (DIPEA) provided the desired Table 2. Substrate scope studies
3
R3
R
product 2a in 95% yield (entry 2) while most inorganic bases
O
SO2F2
FO2SO
1N
R2
DIPEA (1.5 equiv)
DCM, r.t.
R2
were found to be ineffective for promotion of this reaction
1N
R
N
R
N
(entry 3 and 4, more details see SI) which could be attributed to
1
2
their poor solubilities in organic solvents. A slight decreasing of
the yield (85%, entry 5) was detected when the loading of DIPEA
was reduced to 1.0 equivalent. The use of 1.5 equivalent of
DIPEA was found to be the best option (entry 6). The use of
FO2SO
FO2SO
FO2SO
N
FO2SO
FO2SO
N
N
N
N
N
N
N
N
N
Br
Cl
F
2a, 93 %
2b, 72 %
2c, 84 %
2d, 56 %
2e, 80 %
2
other solvents such as DMSO and H O (entry 7 and 8) were
FO2SO
found to be significant less effective than the use of DCM.
Control experiments indicated that no product was generated
without the assistance of base (entry 9).
FO2SO
FO2SO
FO2SO
FO2SO
N
i-Pr
N
N
N
i-Pr
N
i-Pr
Br
N
N
N
N
t-Bu
N
a
2f
2g, quant.
FO2SO
2h, 82 %
2i, 86 %
2j, 71 %
Table 1. Optimization of the reaction conditions.
, 76 %
O
2
FO SO
FO2SO
FO2SO
FO2SO
FO2SO
N
i-Pr
Ph
N
SO2F2
N
N
i-Pr
N
N
Ph
N
N
Ph
MeO
N
N
N
N
N
N
Base, solvent, r.t.
F
1
a
2a
2k, 83 %
2l, quant.
2m, 81 %
FO2SO
2n, 80 %
2o, 75 %
Entry
Base (X equiv.)
Et N (3.0)
DIPEA (3.0)
NaHCO
Cs CO
DIPEA (1.0)
DIPEA (1.5)
DIPEA (1.5)
DIPEA (1.5)
-
Solvent
Yield (%) b
FO2SO
FO2SO
FO2SO
FO2SO
N
Ph
1
2
3
4
5
6
7
8
9
3
DCM
DCM
DCM
DCM
DCM
DCM
DMSO
46
95
21
29
85
93
70
46
n.d.
Ph
Ph
Ph
N
N
N
Ph
N
N
N
N
N
Cy
t-Bu
N
Cl
F
3
(3.0)
(3.0)
2p, 66 %
2q, 73 %
FO2SO
2r, quant.
FO2SO
2s, quant.
FO2SO
2t, quant.
FO2SO
2
3
FO2SO
N
N
Ph
N
n-Pr
N
n-Pr
N
N
N
N
N
N
N
N
MeO
Cl
2u, 54 %
FO2SO
2v, 78 %
FO2SO
2w, 75 %
Bn
2x, quant.
FO2SO
2y, 46 %
2
H O
DCM
FO2SO
FO2SO
H
N
CF3
N
N
N
N
N
N
N
N
N
Ph
a
N
Reaction conditions: 1a (0.1 mmol), base (0.3 mmol, 3 equiv.)
MeO
and DCM (1.5 mL) were mixed in a tube with a SO
2
F
2
balloon
2z, 27 %
2aa, quant.
2ab, 97 %
2ac, 22 %
2ad, 94 %
and reacted at room temperature for 10 h. b The yield was
a
Reaction conditions: 1 (1.0 mmol), DIPEA (1.5 equiv., 194 mg)
determined by HPLC using pure 2a as the external standard. [t2a
and DCM (5 mL) were mixed in a tube with a SO
reacted at room temperature for 5-10h.
2 2
F balloon and
=
8.020 min, λmax = 241.7 nm, methanol / water = 70 : 30 (v / v)].
Under the optimal conditions (Table 1, entry 6), various
2
The fluorosulfate (-OSO F) unit was regarded as both a good
pyrazolones,
including
2,5-disubstituted
and
2,4,5-
leaving group and a robust connector in SuFEx chemistry. The
utilization of the new pyrazole-containing fluorosulfates for
further chemical transformations (Scheme 2) was also achieved.
In the presence of 10 mol % of 1,8-diazabicycloundec-7-ene
DBU), SuFEx reaction of 2a with the tert-butyldimethylsilyl (TBS)
ether of phenol in acetonitrile afforded the desired sulfonate 3
in 54% isolated yield. Similarly, sulfamide 4 was also generated
trisubstituted ones, were examined for the construction of the
corresponding fluorosulfates (Table 2). 2-Aryl or alkyl
substituted pyrazolones were all successfully transformed into
their corresponding fluorosulfates in nearly quantitative yields.
Both electron-donating and electron-withdrawing groups on 2-
position of phenyl rings were well compatible with this protocol
(
(
2i and 2k, 2o and 2q). Bis-substitutions on phenyl (1f and 1l)
2
| J. Name., 2012, 00, 1-3
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ARTICLE
in 76% yield when pyrrolidine was used as SuFEx coupling aromatic character of the products, the transformVaietwioAnrtioclef Onnolinne-
partner in THF. The fluorosulfate 2ad generated from the non- aromatic pyrazolone 1 to the fluorosu zo
D
l
O
faI:
t
1
e
0
d
.10
p
3
y
9
r
/C
a
9
O
n
B
e
009
2 is
03
E
protected pyrazolone was also smoothly transformed into the theoretically favoured.
O
S
corresponding sulfonate 5 after SuFEx click reaction with 3,4-
O
O
F
F
OSO2F
R3
dimethylphenol. Aryl fluorosulfates were reported to undergo
H
R1
Base
R1
R3
R2
O
R1
N
1
2
N
R3
N
+
F
Suzuki-Miyaura reaction with boronic acids, interestingly,
N
N
N
R2
R2
fluorosulfate-containing pyrazole 2a was applied to the Suzuki
1
I
2
2 3
reaction using the Pd (dba) catalysis to provide the desired
Scheme 4. Proposed mechanism.
product in 95% isolated yield. What’s more, the
6
tautomerization of pyridone 7 was also successfully converted
to the corresponding fluorosulfate 8 in 93% yield.
O
O
Conclusions
FO2SO
S
Ph
O
O
DBU (10 mol% )
CH3CN, r.t.
In conclusion, a method providing a portal to a class of novel
fluorosulfate-containing pyrazoles heterocycles was developed
through the reactions of corresponding pyrazolones with SO2F2
featuring a wide substrate scope and broad functional group
compatibility. The fluorosulfate moieties (-OSO F) served as
both SuFEx coupling partner and leaving group in SuFEx
chemistry and Suzuki reaction. This class of heterocycles have
great potential to be used as covalent probes and inhibitors for
the discovery of novel therapeutics. Further studies of these
scaffolds in chemical biology and drug discovery are ongoing in
our laboratory.
N
+
Ph
Ph
OTBS
(1)
N
N
N
2a
3
, 54%
O
N
FO2SO
S
2
O
H
THF, r.t.
O
N
N
+
(2)
N
Ph
N
N
MeO
2
o
MeO
4
, 76%
OH
FO2SO
H
K2CO3 (1.2 equiv)
O
S
+
O
(
3)
4)
N
Ph
3
CH CN, r.t.
N
O
O
Ph
N
H
N
2
ad
5
, 87%
Experimental section
General procedure for synthesis of pyrazolone derivatives 1
FO2SO
Pd2(dba)3 (5 mol% )
K2CO3 (3.0 equiv)
N
+
B(OH)2
OH
(
N
N
N
6
0 oC, toluene
1g, 1s, 1t, 1ab were prepared according to the literature,[13]
others were prepared according to the literature.[14]All
homemade starting materials are identical to those reported
2a
6
, 95%
O
OSO2F
SO2F2
(5)
DIPEA (1.5 equiv)
CH3CN, r.t.
Br
N
Br
N
Br
N
1
13
regarding the H and C NMR and melting points (if applicable).
7
7'
8, 93%
Scheme 2. SuFEx chemistry and Suzuki-Miyaura reaction of the
new fluorosulfates
General procedure for synthesis of compound 2
An oven-dried reaction tube (20 mL) was charged with
pyrazolone 1 (1 mmol), DIPEA (1.5 mmol), 5 mL DCM and a
SO F balloon. The mixture was stirred at room temperature for
2 2
To further demonstrate the practicality of this method, a
couple of 5.0 mmol scale reactions were carried out using
pyrazolones 1r and 1s. Notably, the efficiencies of the grams-
scale reactions were not decreased (Scheme 3) to obtain their 5-10 h with monitoring by TLC. After the reaction was
corresponding products 2r and 2s in 95% and 96% yields,
completed, the solution was concentrated to dryness and the
residue was purified through silica gel chromatography using a
mixture of ethyl acetate and PE to afford the desired products
respectively.
O
FO2SO
i-Pr
SO2F2
i-Pr
N
N
N
N
2
.
DIPEA (1.5 equiv)
DCM, r.t.
1
r
2r
1.468 g, 95%
General procedure for synthesis of compound 3
5
mmol, 1.15 g
An oven-dried reaction tube (20 mL) was charged with 3-
O
FO2SO
SO2F2
methyl-1-phenyl-1H-pyrazol-5-yl sulfurofluoridate (2a, 0.5
N
DIPEA (1.5 equiv)
DCM, r.t.
N
t-Bu
N
t-Bu
N
mmol,
128
mg),
([1,1'-biphenyl]-4-yloxy)(tert-
1
s
2s
5
mmol, 1.08 g
1.426 g, 96%
butyl)dimethylsilane (0.6 mmol, 171 mg), DBU (10 mol%, 7.6
Scheme 3. Gram-scale synthesis.
mg) and CH CN (3 mL), the mixture was reacted at room
3
temperature for 1 h with monitoring by TLC. After the reaction
A more detailed mechanism was proposed and illustrated in
Scheme 4. Initially, starting material pyrazolone 1 was
transformed into its enol form I under base condition (which
was completed, the solution was concentrated to dryness and
purified through silica gel chromatography using 5 % EtOAc / PE
to afford the desired products 3 in 54 % yield (110 mg).
2 2
was in equilibrium with its own ketone). Subsequently, SO F
was attacked by the enol oxygen to generate the product 2 with
the release of fluoride anion. Because of the aromaticity and
General procedure for synthesis of compound 4
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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Journal Name
An oven-dried reaction tube (20 mL) was charged with 1-(4-
methoxyphenyl)-3-phenyl-1H-pyrazol-5-yl sulfurofluoridate Colorless liquid, 194 mg, 72 %. H NMR (500 MHz, CDCl
2o, 0.5 mmol, 174 mg), pyrrolidine (0.6 mmol, 42.6 mg) and 7.34 (m, 2H), 7.30-7.29 (m, 1H), 7.22-7.20 (m, 1H), 6.20 (s, 1H),
3-Methyl-1-(m-tolyl)-1H-pyrazol-5-yl sulfurofluoridate (2b).
View Article Online
1
DOI: 10.1039/C9OB00903E
3
) δ 7.37-
(
1
3
THF (3 mL), the mixture was reacted at room temperature for 2.41 (s, 3H), 2.34 (s, 3H). C NMR (126 MHz, CDCl
3
) δ 149.2 (s),
overnight with monitoring by TLC. After the reaction was 141.2 (s), 139.8 (s), 136.7 (s), 129.28 (s), 129.27 (s), 124.2 (s),
1
9
3
completed, the solution was concentrated to dryness and 120.4 (s), 96.0 (s), 21.5 (s), 14.6 (s). F NMR (471 MHz, CDCl ) δ
purified through silica gel chromatography using 40 % DCM / PE 39.6 (s, 1F). ESI-MS HRMS calculated for C11
H12FN
O
2 3
S [M+H]+
to afford the desired products 4 in 76 % yield (153 mg).
271.0547, found 271.0543.
General procedure for synthesis of compound 5
1-(4-Bromophenyl)-3-methyl-1H-pyrazol-5-yl
sulfurofluoridate (2c). Colorless liquid, 281 mg, 84 %. H NMR
1
An oven-dried reaction tube (20 mL) was charged with 3-
phenyl-1H-pyrazol-5-yl sulfurofluoridate (2ad, 0.5 mmol, 121
mg), 3,4-dimethylphenol (0.6 mmol, 73.2 mg) and THF (3 mL),
the mixture was reacted at room temperature for overnight
with monitoring by TLC. After the reaction was completed, the
solution was concentrated to dryness and purified through silica
(
2
(
1
500 MHz, CDCl
H), 6.22 (s, 1H), 2.34 (s, 3H). C NMR (126 MHz, CDCl
s), 141.3 (s), 135.9 (s), 132.8 (s), 124.7 (s), 122.1 (s), 96.6 (s),
3
) δ 7.62 (d, J = 8.9 Hz, 2H), 7.42 (d, J = 8.9 Hz,
13
3
) δ 149.8
4.7 (s). 19F NMR (471 MHz, CDCl
3
) δ 39.7 (s, 1F). ESI-MS HRMS
[M+H]+ 334.9496, found
calculated for
34.9494.
10 9 2 3
C H BrFN O S
3
gel chromatography using a mixture of Et
1/20/100) to afford the desired products 5 in 87 % yield (150
mg).
3
N / EtOAc / PE
(
1-(4-Chlorophenyl)-3-methyl-1H-pyrazol-5-yl
sulfurofluoridate (2d). Yellow liquid, 162 mg, 56 %. H NMR
1
(
3
500 MHz, CDCl ) δ 7.49-7.45 (m, 4H), 6.22 (s, 1H), 2.33 (s, 3H).
General procedure for synthesis of compound 6
13C NMR (126 MHz, CDCl
3
) δ 149.7 (s), 141.3 (s), 135.3 (s), 134.2
(
s), 129.8 (s), 124.5 (s), 96.5 (s), 14.6 (s). 19F NMR (471 MHz,
An oven-dried reaction tube (20 mL) was charged with
CDCl
[
3
) δ 39.7 (s, 1F). ESI-MS HRMS calculated for C10
M+H] 291.0001, found 291.0001.
9
H ClFN
2 3
O S
2 3
phenylboronic acid (1.5 mmol, 183 mg), Pd (dba) (45 mg, 5
+
mol%), K CO (3 mmol, 414 mg) and 3-methyl-1-phenyl-1H-
2
3
pyrazol-5-yl sulfurofluoridate (2a, 1 mmol, 256 mg), the
reaction tube was then capped with a rubber septum and
placed under a nitrogen atmosphere (through a needle
attached to a vacuum manifold). 5 mL toluene was then added
1
-(4-Fluorophenyl)-3-methyl-1H-pyrazol-5-yl
sulfurofluoridate (2e). Yellow liquid, 219 mg, 80 %. H NMR (500
MHz, CDCl ) δ 7.51-7.48 (m, 2H), 7.20-7.16 (m, 2H), 6.21 (s, 1H),
1
3
13
2
1
1
.33 (s, 3H). C NMR (126 MHz, CDCl
49.5 (s), 141.3 (s), 132.9 (d, J = 3.1 Hz), 125.6 (d, J = 8.7 Hz),
16.6 (d, J = 23.1 Hz), 96.2 (s), 14.6 (s). F NMR (471 MHz, CDCl )
3
δ 39.5 (s, 1F), -112.38 – -112.43 (m, 1F). ESI-MS HRMS calculated
3
) δ 162.3 (d, J = 249.0 Hz),
o
using syringes. The resulting mixture was stirred at 60 C for
overnight with monitoring by TLC. After the reaction was
completed, the solution was concentrated to dryness and
purified through silica gel chromatography using 10 % EtOAc /
PE to afford the desired products 6 in 95 % yield (223 mg).
19
+
for C10
H F
9
2
N
2
O
3
S [M+H] 275.0296, found 275.0295.
1
-(3,4-Dimethylphenyl)-3-methyl-1H-pyrazol-5-yl
General procedure for synthesis of compound 8
1
sulfurofluoridate (2f). Yellow liquid, 217 mg, 76 %. H NMR (500
MHz, CDCl ) δ 7.30 (s, 1H), 7.21 (m, 2H), 6.18 (s, 1H), 2.34 (s,
H), 2.31 (s, 3H), 2.30 (s, 3H). C NMR (126 MHz, CDCl
s), 141.2 (s), 138.2 (s), 137.3 (s), 134.5 (s), 130.5 (s), 124.8 (s),
20.8 (s), 95.8 (s), 19.9 (s), 19.6 (s), 14.6 (s). F NMR (471 MHz,
CDCl
3
An oven-dried reaction tube (20 mL) was charged with 6-
bromopyridin-3-ol 7’ (1 mmol, 173 mg), DIPEA (1.5 mmol), 5 mL
DCM and a SO F balloon. The mixture was stirred at room
2 2
temperature for 3 h with monitoring by TLC. After the reaction
was completed, the solution was concentrated to dryness and
the residue was purified through silica gel chromatography
using 20 % EtOAc / PE to afford the desired products 8 in 93 %
yield (238 mg).
1
3
3
(
1
3
) δ 149.0
1
9
3
) δ 39.5 (s, 1F). ESI-MS HRMS calculated for C12
H14FN
2 3
O S
+
[
M+H] 285.0704, found 285.0704.
1
-(Tert-butyl)-3-methyl-1H-pyrazol-5-yl sulfurofluoridate
1
(
6
2g). Yellow liquid, 236 mg, quant. H NMR (500 MHz, CDCl ) δ
.00 (s, 1H), 2.22 (s, 3H), 1.60 (s, 9H). C NMR (126 MHz, CDCl )
3
δ 145.9 (s), 141.6 (s), 94.7 (s), 60.6 (s), 29.4 (s), 14.5 (s). F NMR
471 MHz, CDCl
3
1
3
3
-Methyl-1-phenyl-1H-pyrazol-5-yl sulfurofluoridate (2a).
1
9
1
Colorless liquid, 238 mg, 93 %. H NMR (500 MHz, CDCl
3
) δ 7.53-
(
C
3
) δ 39.3 (s, 1F). ESI-MS HRMS calculated for
S [M+H] 237.0704, found 237.0702.
1
3
7
.47 (m, 4H), 7.40 (t, J = 7.2 Hz, 1H), 6.22 (s, 1H), 2.35 (s, 3H). C
+
8
H
14FN
O
2 3
3
NMR (126 MHz, CDCl ) δ 149.4 (s), 141.3 (s), 136.8 (s), 129.6 (s),
1
28.5 (s), 123.5 (s), 96.2 (s), 14.7 (s). 19F NMR (471 MHz, CDCl
3
)
3
-Isopropyl-1-phenyl-1H-pyrazol-5-yl sulfurofluoridate (2h).
δ 39.6 (s, 1F). ESI-MS HRMS calculated for C10
H10FN
2
O
3
S [M+H]+
1
Yellow liquid, 233 mg, 82 %. H NMR (500 MHz, CDCl
J = 7.6 Hz, 2H), 7.49 (t, J = 7.9 Hz, 2H), 7.40 (t, J = 7.3 Hz, 1H),
3
) δ 7.55 (d,
2
57.0391, found 257.0390.
6
.24 (s, 1H), 3.02 (hept, J = 6.9 Hz, 1H), 1.32 (d, J = 7.0 Hz, 6H).
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 8
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
13C NMR (126 MHz, CDCl
ARTICLE
) δ 159.4 (s), 141.1 (s), 137.0 (s), 129.6 J = 7.4 Hz, 2H), 7.38 (t, J = 7.3 Hz, 1H), 7.33 (d, J =Vie8w.2ArtHiczle,O2nHlin)e,
3
s), 128.4 (s), 123.6 (s), 93.5 (s), 28.8 (s), 22.4 (s). F NMR (471 6.71 (s, 1H), 2.44 (s, 3H). 13C NMR (126 MHz, CDCl
) δ 151.1 (s),
1
9
DOI: 10.1039/C9OB00903E
(
3
MHz, CDCl
3
) δ 39.5 (s, 1F). ESI-MS HRMS calculated for 141.9 (s), 139.0 (s), 134.4 (s), 132.2 (s), 130.2 (s), 129.0 (s), 128.9
S [M+H] 285.0704, found 285.0701.
+
(s), 125.7 (s), 123.7 (s), 93.6 (s), 21.3 (s). 19F NMR (471 MHz,
12
C H14FN
O
2 3
3 2 3
CDCl ) δ 39.9 (s, 1F). ESI-MS HRMS calculated for C16H14FN O S
3
-Isopropyl-1-(p-tolyl)-1H-pyrazol-5-yl
sulfurofluoridate
) δ
+
[
M+H] 333.0704, found 333.0703.
1
(
2i). Yellow liquid, 257 mg, 86 %. H NMR (500 MHz, CDCl
3
7
(
.41 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 6.22 (s, 1H), 3.01
1-(4-Methoxyphenyl)-3-phenyl-1H-pyrazol-5-yl
hept, J = 7.0 Hz, 1H), 2.40 (s, 3H), 1.31 (d, J = 7.0 Hz, 6H). 13C sulfurofluoridate (2o). White solid, 260 mg, 75 %. Mp 79-80
o
1
NMR (126 MHz, CDCl
3
) δ 163.2 (s), 161.3 (s), 159.5 (s), 141.1 (s),
3
C. H NMR (500 MHz, CDCl ) δ 7.85 (d, J = 7.1 Hz, 2H), 7.52 (d, J
1
9
1
2
33.0 (d, J = 3.1 Hz), 125.6 (d, J = 8.7 Hz), 116.6 (d, J = 23.1 Hz), = 9.0 Hz, 2H), 7.44 (t, J = 7.4 Hz, 2H), 7.38 (t, J = 7.3 Hz, 1H), 7.03
1
9
13
3.5 (s), 28.8 (s), 22.3 (s). F NMR (471 MHz, CDCl
3
) δ 39.5 (s, (d, J = 9.0 Hz, 2H), 6.70 (s, 1H), 3.87 (s, 3H). C NMR (126 MHz,
S [M+H]+ CDCl
) δ 159.9 (s), 151.0 (s), 141.9 (s), 132.2 (s), 129.8 (s), 128.92
(s), 128.89 (s), 125.7 (s), 125.5 (s), 114.8 (s), 93.4 (s), 55.7 (s). F
NMR (471 MHz, CDCl ) δ 39.8 (s, 1F). ESI-MS HRMS calculated
S [M+H] 349.0653, found 349.0651.
F). ESI-MS HRMS calculated for C13
H16FN
2
O
3
3
1
9
99.0860, found 299.0860.
3
1
-(4-Bromophenyl)-3-isopropyl-1H-pyrazol-5-yl
+
2 4
for C16H14FN O
1
sulfurofluoridate (2j). Yellow liquid, 256 mg, 71 %. H NMR (500
MHz, CDCl ) δ 7.62 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.8 Hz, 2H),
.24 (s, 1H), 3.00 (hept, J = 7.1 Hz, 1H), 1.30 (d, J = 7.0 Hz, 6H). sulfurofluoridate (2p). Yellow liquid, 234 mg, 66 %. Mp 50-51
3
1-(4-Chlorophenyl)-3-phenyl-1H-pyrazol-5-yl
6
13C NMR (126 MHz, CDCl
o
1
3
) δ 159.8 (s), 141.1 (s), 136.0 (s), 132.8
3
C. H NMR (500 MHz, CDCl ) δ 7.84 (d, J = 8.3, 2H), 7.60 (d, J =
(
s), 124.8 (s), 122.0 (s), 94.0 (s), 28.9 (s), 22.3 (s). 19F NMR (471 8.6 Hz, 2H), 7.51 (d, J = 8.9 Hz, 2H), 7.45 (t, J = 7.98 Hz, 2H), 7.40
1
3
MHz, CDCl
C
3
) δ 39.7 (s, 1F). ESI-MS HRMS calculated for (t, J = 7.9 Hz, 1H), 6.73 (s, 1H). C NMR (126 MHz, CDCl
3
) δ 151.7
+
12
H
13BrFN
2
O
3
S [M+H] 362.9809, found 362.9807.
(s), 141.9 (s), 135.4 (s), 134.6 (s), 131.8 (s), 129.9 (s), 129.2 (s),
29.0 (s), 125.7 (s), 124.7 (s), 94.2 (s). F NMR (471 MHz, CDCl )
3
δ 40.1 (s, 1F). ESI-MS HRMS calculated for C15
M+H] 353.0157, found 353.0157.
1
9
1
1
-(4-Fluorophenyl)-3-isopropyl-1H-pyrazol-5-yl
H11ClFN
2 3
O S
1
sulfurofluoridate (2k). Green liquid, 252 mg, 83 %. H NMR (500
MHz, CDCl ) δ 7.53-7.50 (m, 2H), 7.20-7.16 (m, 2H), 6.23 (s, 1H),
.00 (hept, J = 6.9 Hz, 1H), 1.30 (d, J = 7.0 Hz, 6H). C NMR (126
MHz, CDCl
+
[
3
1
3
3
1-(4-Fluorophenyl)-3-phenyl-1H-pyrazol-5-yl
o
3
) δ 159.2 (s), 141.0 (s), 138.5 (s), 134.5 (s), 130.1 (s), sulfurofluoridate (2q). White solid, 246 mg, 73 %. Mp 59-61 C.
23.5 (s), 93.2 (s), 28.8 (s), 22.4 (s), 21.2 (s). F NMR (471 MHz, 1H NMR (500 MHz, CDCl
1
9
) δ 7.84 (d, J = 7.3 Hz, 2H), 7.62-7.59
3
) δ 39.5 (s, 1F), -112.57 - -112.62 (m, 1F). ESI-MS HRMS (m, 2H), 7.45 (t, J = 7.4 Hz, 2H), 7.39 (t, J = 7.3 Hz, 1H), 7.23 (t, J
1
CDCl
calculated for C12
3
+
13
H
13
F
2
N
2
O
3
S [M+H] 303.0609, found 303.0608. = 8.5 Hz, 2H), 6.72 (s, 1H). C NMR (126 MHz, CDCl
3
) δ 162.5 (d,
J = 249.4 Hz), 151.5 (s), 142.0 (s), 133.0 (d, J = 3.1 Hz), 131.9 (s),
1
-(3,4-Dimethylphenyl)-3-isopropyl-1H-pyrazol-5-yl
1
2
1
C
29.2 (s), 129.0 (s), 125.8 (d, J = 8.8 Hz), 125.7 (s), 116.7 (d, J =
3.2 Hz), 93.9 (s). 19F NMR (471 MHz, CDCl
) δ 39.9 (s, 1F), -
1
sulfurofluoridate (2l). Yellow liquid, 312 mg, quant. H NMR
3
(
(
500 MHz, CDCl
m, 1H), 2.31 (s, 3H), 2.30 (s, 3H), 1.31 (d, J = 6.7 Hz, 6H). 13
) δ 159.1 (s), 141.0 (s), 138.2 (s), 137.2 (s),
34.7 (s), 130.5 (s), 124.9 (s), 120.9 (s), 93.1 (s), 28.8 (s), 22.5 (s),
3
) δ 7.31 (s, 1H), 7.22 (s, 2H), 6.21 (s, 1H), 3.01
11.86 – -111.92 (m, 1F). ESI-MS HRMS calculated for
C
+
15
H
11
F
2
N
2
O
3
S [M+H] 337.0453, found 337.0452.
NMR (126 MHz, CDCl
3
1
2
1-(3,4-Dimethylphenyl)-3-phenyl-1H-pyrazol-5-yl
3
) δ 39.5 (s, 1F). ESI- sulfurofluoridate (2r). Yellow solid, 346 mg, quant. Mp 58-59
1
9
0.0 (s), 19.6 (s). F NMR (471 MHz, CDCl
S [M+H] 313.1017, found
+
o
1
MS HRMS calculated for C14
H18FN
O
2 3
C. H NMR (500 MHz, CDCl
3
) δ 7.85 (d, J = 8.5 Hz, 2H), 7.44 (t, J
3
13.1017.
= 7.4 Hz, 2H), 7.40-7.36 (m, 2H), 7.32-7.30 (m, 1H), 7.27 (d, J =
1
3
7
.2 Hz, 1H), 6.70 (s, 1H), 2.35 (s, 3H) 2.33 (s, 3H). C NMR (126
MHz, CDCl ) δ 151.0 (s), 141.9 (s), 138.3 (s), 137.7 (s), 134.5 (s),
32.2 (s), 130.6 (s), 128.93 (s), 128.90 (s) ,125.7 (s), 125.0 (s),
1
,3-Diphenyl-1H-pyrazol-5-yl sulfurofluoridate (2m). White
3
o
1
solid, 259 mg, 81 %. Mp 56-57 C. H NMR (500 MHz, CDCl
3
) δ
.86 (d, J = 7.1 Hz, 2H), 7.64 (d, J = 7.5 Hz, 2H), 7.54 (t, J = 7.8 Hz,
H), 7.45 (t, J = 7.4 Hz, 3H), 7.39 (t, J = 7.3 Hz, 1H), 6.73 (s, 1H).
) δ 151.4 (s), 142.0 (s), 136.9 (s), 132.1
s), 129.7 (s), 129.1 (s), 128.9 (s), 128.8 (s), 125.7 (s), 123.7 (s),
1
1
3
3
7
2
19
3
21.1 (s), 93.5 (s), 20.0 (s), 19.7 (s). F NMR (471 MHz, CDCl ) δ
S [M+H]+
9.9 (s, 1F). ESI-MS HRMS calculated for C17
47.0860, found 347.0859.
H16FN O
2 3
13C NMR (126 MHz, CDCl
3
(
1
9
9
3.9 (s). F NMR (471 MHz, CDCl
3
) δ 39.9 (s, 1F). ESI-MS HRMS
+
1-(Tert-butyl)-3-phenyl-1H-pyrazol-5-yl
S [M+H] 319.0547, found 319.0545. (2s). Yellow liquid, 298 mg, quant. H NMR (500 MHz, CDCl
sulfurofluoridate
) δ
1
calculated for C15
H12FN
2
O
3
3
7
1
.78 (d, J = 7.6 Hz, 2H), 7.40 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.3 Hz,
H), 6.53 (s, 1H), 1.70 (s, 9H). C NMR (126 MHz, CDCl ) δ 148.0
3
3
-Phenyl-1-(p-tolyl)-1H-pyrazol-5-yl sulfurofluoridate (2n).
13
o
1
White solid, 264 mg, 80 %. Mp 84-85 C. H NMR (500 MHz,
CDCl ) δ 7.85 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.44 (t,
(s), 142.3 (s), 132.8 (s), 128.7 (s), 128.3 (s), 125.3 (s), 92.4 (s),
3
6
19
3
1.4 (s), 29.4 (s). F NMR (471 MHz, CDCl ) δ 39.7 (s, 1F). ESI-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 6 of 8
ARTICLE
Journal Name
S [M+H] 299.0860, found Hz, 1H), 1.02-0.98 (m, 2H), 0.86-0.83 (m, 2H). 13C NMR (126
+
MS HRMS calculated for C13H16FN O
2 3
View Article Online
2
99.0860.
MHz, CDCl
1
3
) δ 155.9 (s), 151.1 (s), 148.2 (
D
s
O
),I:
1
1
4
0
1
.1
.
0
9
39(s/C),
9
1
O
3
B
8
0
.
0
7
90(s
),
3
E
1
9
22.2 (s), 115.1 (s), 95.9 (s), 10.0 (s), 8.3 (s). F NMR (471 MHz,
CDCl ) δ 42.0 (s, 1F). ESI-MS HRMS calculated for C11H11FN O S
3 3 3
1
-Cyclohexyl-3-phenyl-1H-pyrazol-5-yl
sulfurofluoridate
) δ
1
(2t). Yellow liquid, 324 mg, quant. H NMR (500 MHz, CDCl
3
+
[
M+H] 284.0500, found 284.0499.
7
1
2
.81 (d, J = 7.5 Hz, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.3 Hz,
H), 6.51 (s, 1H), 4.17 (m, 1H), 2.08-2.02 (m, 4H), 1.98-1.95 (m,
H), 1.78-1.76 (m, 1H), 1.51-1.42 (m, 2H), 1.38-1.32 (m, 1H). C sulfurofluoridate (2z). Yellow liquid, 92 mg, 27 %. H NMR (500
1-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl
1
3
1
NMR (126 MHz, CDCl
28.4 (s), 125.4 (s), 91.5 (s), 57.9 (s), 32.5 (s), 25.5 (s), 25.1 (s). 6.67 (s, 1H), 3.88 (s, 3H). C NMR (126 MHz, CDCl
19F NMR (471 MHz, CDCl
) δ 37.8 (s, 1F). ESI-MS HRMS 142.2 (q, J = 40.0 Hz), 141.6 (s), 128.7 (s), 125.9 (s), 120.3 (q, J =
calculated for C15 S [M+H] 325.1017, found 325.1014. 269.4 Hz), 115.0 (s), 94.9 (s), 55.8 (s). F NMR (471 MHz, CDCl
δ 40.7 (s, 1F), -63.3 (s, 1F). ESI-MS HRMS calculated for
3 3
) δ 149.8 (s), 141.1 (s), 132.9 (s), 128.7 (s), MHz, CDCl ) δ 7.45 (d, J = 9.0 Hz, 2H), 7.03 (d, J = 9.0 Hz, 2H),
1
3
1
3
) δ 160.7 (s),
3
+
19
H18FN
O
2 3
3
)
3
-Phenyl-1-(pyridin-2-yl)-1H-pyrazol-5-yl sulfurofluoridate
+
11 9 4 2 4
C H F N O S [M+H] 341.0214, found 341.0213.
o
1
(
2u). White solid, 172 mg, 54 %. Mp 80-81 C. H NMR (500 MHz,
CDCl ) δ 8.53 (d, J = 4.6 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.90-
3
3,4-Dimethyl-1-phenyl-1H-pyrazol-5-yl
sulfurofluoridate
1
7
.87 (m, 3H), 7.46 (t, J = 7.4 Hz, 2H), 7.41 (t, J = 7.3 Hz, 1H), 7.30 (2aa). Colorless liquid, 270 mg, quant. H NMR (500 MHz, CDCl
3
)
1
3
(t, J = 6.1 Hz, 1H), 6.74 (s, 1H). C NMR (126 MHz, CDCl
3
) δ 151.4 δ 7.52-7.46 (m, 4H), 7.37 (t, J = 7.2 Hz, 1H), 2.28 (s, 3H), 2.07 (s,
1
3
(
1
s), 151.3 (s), 148.3 (s), 142.7 (s), 138.9 (s), 131.8 (s), 129.3 (s), 3H). C NMR (126 MHz, CDCl
3
) δ 148.9 (s), 138.7 (s), 137.3 (s),
29.0 (s), 125.9 (s), 122.6 (s), 115.4 (s), 96.4 (s). 19F NMR (471 129.6 (s), 128.1 (s), 123.2 (s), 105.7 (s), 12.9 (s), 7.0 (d, J = 1.6
MHz, CDCl
C
3
) δ 42.3 (s, 1F). ESI-MS HRMS calculated for Hz). 19F NMR (471 MHz, CDCl
S [M+H] 320.0500, found 320.0457.
3
) δ 42.0 (s, 1F). ESI-MS HRMS
S [M+H] 271.0547, found 271.0546.
+
+
14
H11FN
3
O
3
calculated for C11H12FN
O
2 3
1
-(4-Methoxyphenyl)-3-propyl-1H-pyrazol-5-yl
4-Benzyl-3-methyl-1-phenyl-1H-pyrazol-5-yl
sulfurofluoridate (2v). Yellow liquid, 241 mg, 78 %. H NMR (500 sulfurofluoridate (2ab). Yellow liquid, 336 mg, 97 %. H NMR
MHz, CDCl ) δ 7.41 (d, J = 9.0 Hz, 2H), 6.98 (d, J = 9.0 Hz, 2H), (500 MHz, CDCl ) δ 7.57 (d, J = 9.4 Hz, 2H), 7.50 (t, J = 7.9 Hz,
.18 (s, 1H), 3.84 (s, 3H), 2.63 (t, J = 7.8 Hz, 2H), 1.71 (m, 2H), 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.5 Hz, 2H), 7.27-7.22 (m,
1
1
3
3
6
0
1
1
3
13
.99 (t, J = 7.4 Hz, 3H). C NMR (126 MHz, CDCl
53.5 (s), 141.1 (s), 129.8 (s), 125.4 (s), 114.7 (s), 94.7 (s), 55.7 (s), 139.0 (s), 138.1 (s), 137.1 (s), 129.6 (s), 128.8 (s), 128.30 (s),
s), 31.2 (s), 22.5 (s), 13.9 (s). F NMR (471 MHz, CDCl
s, 1F). ESI-MS HRMS calculated for C13
S [M+H]+ NMR (471 MHz, CDCl
15.0809, found 315.0807. S [M+H] 347.0860, found 347.0860.
3 3
) δ 159.6 (s), 3H), 3.90 (s, 2H), 2.17 (s, 3H). C NMR (126 MHz, CDCl ) δ 149.1
1
9
) δ 39.4 128.27 (s), 126.7 (s), 123.3 (s), 108.9 (s), 28.2 (s), 13.3 (s). 19
) δ 42.6 (s, 1F). ESI-MS HRMS calculated
(
(
3
F
H16FN
O
2 4
3
+
3
2 3
for C17H16FN O
1
-(4-Chlorophenyl)-3-propyl-1H-pyrazol-5-yl
3,4-Dimethyl-1-(pyridin-2-yl)-1H-pyrazol-5-yl
1
1
sulfurofluoridate (2w). Yellow liquid, 238 mg, 75 %. H NMR sulfurofluoridate (2ac). Yellow liquid, 60 mg, 22 %. H NMR (500
(
7
500 MHz, CDCl
3
) δ 7.50-7.45 (m, 4H), 6.23 (s, 1H), 2.63 (t, J = MHz, CDCl
3
) δ 8.45 (d, J = 4.6 Hz, 1H), 7.81-7.77 (m, 2H), 7.20-
1
3
13
.5 Hz, 2H), 1.71 (m, 2H), 1.00 (t, J = 7.4 Hz, 3H). C NMR (126 7.18 (m, 1H), 2.27 (s, 3H), 2.06 (s, 3H). C NMR (126 MHz, CDCl
3
)
3
MHz, CDCl ) δ 154.2 (s), 141.2 (s), 135.4 (s), 134.2 (s), 129.8 (s), δ 151.4 (s), 149.5 (s), 148.0 (s), 139.5 (s), 138.7 (s), 121.8 (s),
1
9
19
1
CDCl
24.5 (s), 95.6 (s), 31.2 (s), 22.4 (s), 13.9 (s). F NMR (471 MHz, 114.3 (s), 107.6 (s), 13.0 (s), 6.7 (s). F NMR (471 MHz, CDCl
3
) δ
) δ 39.7 (s, 1F). ESI-MS HRMS calculated for C12
H13ClFN
2 3
O S
46.1 (s, 1F). ESI-MS HRMS calculated for C10
272.0500, found 272.0500.
H11FN O
3 3
S [M+H]+
3
+
[
M+H] 319.0314, found 319.0313.
3
-Cyclopropyl-1-phenyl-1H-pyrazol-5-yl sulfurofluoridate
3-Phenyl-1H-pyrazol-5-yl sulfurofluoridate (2ad). white
1
o
1
(
2x). Yellow liquid, 282 mg, quant. H NMR (500 MHz, CDCl
3
) δ solid, 227 mg, 94 %. Mp 129-120 C. H NMR (500 MHz, CDCl
3
)
7
1
.53-7.47 (m, 4H), 7.39 (t, J = 7.2 Hz, 1H), 6.09 (s, 1H), 1.97 (m, δ 11.33 (s, 1H), 7.58 (d, J = 7.1 Hz, 2H), 7.50-7.45 (m, 3H), 6.45
H), 1.00-0.98 (m, 2H), 0.84-0.83 (m, 2H). 13C NMR (126 MHz, (s, 1H). 13C NMR (126 MHz, CDCl
) δ 154.2 (s), 145.9 (s), 130.1
3
1
9
3
CDCl ) δ 155.6 (s), 141.1 (s), 136.9 (s), 129.6 (s), 128.4 (s), 123.5 (s), 129.5 (s), 127.9 (s), 125.7 (s), 92.8 (s). F NMR (471 MHz,
1
9
(s), 93.4 (s), 10.0 (s), 8.2 (s). F NMR (471 MHz, CDCl
3
) δ 39.6 (s, CDCl
3
) δ 39.2 (s, 1F). ESI-MS HRMS calculated for C
9 8
H FN
2 3
O S
S [M+H]+ [M+H] 243.0234, found 243.0234.
+
1
2
F). ESI-MS HRMS calculated for C12
H12FN
2
O
3
83.0547, found 283.0546.
[
1,1'-Biphenyl]-4-yl
sulfate (3). White solid, 110 mg, 54 %. Mp 101-103 C. H NMR
sulfurofluoridate (2y). White solid, 130 mg, 46 %. Mp 44-45 C. (500 MHz, CDCl ) δ 7.52 (t, J = 8.8 Hz, 6H), 7.47 (t, J = 7.5 Hz, 2H),
1H NMR (500 MHz, CDCl
) δ 8.47 (d, J = 4.7 Hz, 1H), 7.83-7.78 7.41-7.37 (m, 3H), 7.31 (t, J = 7.4 Hz, 1H), 7.23 (d, J = 8.8 Hz, 2H),
(3-methyl-1-phenyl-1H-pyrazol-5-yl)
o
1
3
-Cyclopropyl-1-(pyridin-2-yl)-1H-pyrazol-5-yl
o
3
3
1
3
3
(m, 2H), 7.23 (t, J = 5.8 Hz, 1H), 6.10 (s, 1H), 1.97 (hept, J = 4.8 6.27 (s, 1H), 2.36 (s, 3H). C NMR (126 MHz, CDCl ) δ 149.5 (s),
6
| J. Name., 2012, 00, 1-3
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
ARTICLE
1
49.2 (s), 142.6 (s), 141.4 (s), 139.5 (s), 137.3 (s), 129.3 (s), 129.1
Ramsden, E. F. V. Scriven and R. J. K. Taylor, ElseVivewieArr,tiOclexOfonrlinde,
008, pp. 1–141.
2
(s), 128.8 (s), 128.1 (s), 127.8 (s), 127.2 (s), 123.4 (s), 121.2 (s),
DOI: 10.1039/C9OB00903E
2
(a) A. Ansari, A. Ali and M. Asif, New J. Chem., 2017, 41, 16. (b)
J. Elguero, A. R. Katritzky and C. W. Rees, Eds. In
Comprehensive Heterocyclic Chemistry, Pergamon Press:
Oxford, U.K., 1984, 5, 167. (c) J. Elguero, In Comprehensive
Heterocyclic Chemistry II, A. R. Katritzky , C. W. Rees and E. F.
V. Scriven, Eds. Pergamon Press: Oxford, U.K., 1996, 3, 1. (d)
B. Stanovnik and J. Svete, Pyrazoles In Science of Synthesis:
Houben-Weyl Methods of Organic Transformations, Georg
Thieme: Stuttgart, Germany, 2002, 12, 15. (e) A. R. Katritzky,
C. A. Ramsden, E. F. V. Scriven and R. J. K. Taylor, Eds.
Comprehensive Heterocyclic Chemistry III, Elsevier: Oxford,
U.K., 2008, 4, 1. (f) N. Uramaru, H. Shigematsu, A. Toda, R.
Eyanagi, S.Kitamura and S. Ohta, J. Med. Chem., 2010, 53,
8727.
9
5.6 (s), 14.6 (s). ESI-MS HRMS calculated for C22
19 2 4
H N O S
+
[
M+H] 407.1060, found 407.1060.
1
-(4-Methoxyphenyl)-3-phenyl-1H-pyrazol-5-yl pyrrolidine-
1
1
-sulfonate (4). Yellow liquid, 153 mg, 76 %. H NMR (500 MHz,
CDCl
J = 7.5 Hz, 2H), 7.34 (t, J = 7.3 Hz, 1H), 7.00 (d, J = 8.9 Hz, 2H),
.64 (s, 1H), 3.86 (s, 3H), 3.23 (t, J = 6.7 Hz, 4H), 1.77 (t, J = 6.7
3
) δ 7.85 (d, J = 7.3 Hz, 2H), 7.60 (d, J = 8.9 Hz, 2H), 7.41 (t,
6
1
3
Hz, 4H). C NMR (126 MHz, CDCl
3
) δ 159.2 (s), 150.8 (s), 144.5
(s), 133.0 (s), 131.0 (s), 128.8 (s), 128.4 (s), 125.6 (s), 125.2 (s),
1
14.4 (s), 93.6 (s), 55.7 (s), 49.5 (s), 25.7 (s). ESI-MS HRMS
+
3
4
(a) L. Knorr, Einwirk von acetessigester auf phenylhydrazin.
Ber. Dtsch. Chem. Ges. 1883, 16, 2597. (b) G. Mariappan, B. P.
Saha, L. Sutharson, G. Ankit, L. Pandey and D. Kumar, J. Pharm.
Res., 2010, 3, 2856. (c) K. Lalit, T. Chandresh and S. Vivek, Int.
J. Res. Pharm. Sci., 2012, 2, 13. (c) W. S. Hamama, H. G. El-
Gohary, N. Kuhnert and H. H. Zoorob, Curr. Org. Chem., 2012,
18 3 3
calculated for C14H N O S [M+H] 308.1063, found 308.1062.
3
,4-Dimethylphenyl (3-phenyl-1H-pyrazol-5-yl) sulfate (5).
o
1
White solid, 150 mg, 87 %, Mp 91-93 C. H NMR (500 MHz,
CDCl ) δ 11.25 (s, 1H), 7.55 (d, J = 7.2 Hz, 2H), 7.44-7.38 (m, 3H),
.17-7.13 (m, 2H), 7.09 (d, J = 8.3 Hz, 1H), 6.49 (s, 1H), 2.21 (s,
H), 2.21 (s, 3H). 13C NMR (126 MHz, CDCl
) δ 155.3 (s), 148.6
3
1
6, 373.
7
3
(a) S. Fustero, M. Sánchez-Roselló, P. Barrio and A. Simón-
Fuentes, Chem. Rev., 2011, 111, 6984. (b) V. Kumar, K. Kaur,
G. K. Gupta and A. K. Sharma, Eur. J. Med. Chem., 2013, 69,
735. (c) H. Kumar, D. Saini, S. Jain and N. Jain, Eur. J. Med.
Chem., 2013, 70, 248. (d) X. Bao, B. Wang, L. Cui, G. Zhu, Y. He,
J. Qu and Y. Song, Org. Lett., 2015, 17, 5168. (e) M. F. Khan,
M. M. Alam, G. Verma, W. Akhtar, M. Akhter and M.
Shaquiquzzaman, Eur. J. Med. Chem., 2016, 120, 170. (f) X.
Chen, G.-F. Zha, G. A. L. Bare, J. Leng, S.-M. Wang and H.-L.
Qin. Adv. Synth. Catal., 2017, 359, 3254. (g) Z. Xu, C. Gao, Q.-
C. Ren, X.-F. Song, L.-S. Feng and Z.-S. Lv, Eur. J. Med. Chem.,
3
(s), 145.3 (s), 138.9 (s), 136.6 (s), 130.9 (s), 129.6 (s), 129.4 (s),
1
28.3 (s), 125.6 (s), 122.2 (s), 118.5 (s), 93.2 (s), 20.0 (s), 19.3 (s).
+
ESI-MS HRMS calculated for C17
found 345.0904.
H
17
N
2
O
4
S [M+H] 345.0904,
[
15]
3
-Methyl-1,5-diphenyl-1H-pyrazole (6). Yellow liquid, 223
1
mg, 95 %. H NMR (500 MHz, CDCl
3
) δ 7.32-7.22 (m, 10H), 6.32
(s, 1H), 2.40 (s, 3H).
2
017, 139, 429.
W. Lange and E. Mgller, Ber. Dtsch. Chem. Ges., 1930, 63,
653.
Sulfuryl fluoride (SO F ) has been produced annually at more
5
6
6
-Bromopyridin-3-yl sulfurofluoridate (8).[12b] Colorless
2
1
liquid, 238 mg, 93 %. H NMR (500 MHz, CDCl
Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.43 (dd, J = 8.1, 4.7 Hz, 1H). F
NMR (471 MHz, CDCl ) δ 42.6 (s).
3
) δ 8.46 (d, J = 3.6
2
2
1
9
than 3 million kilograms per year since 2000, with a price as
low as $1/kg. see: (a) M. P. Sulbaek Andersen, D. R. Blake, F.
S. Rowland, M. D. Hurley and T. J. Wallington, Environ. Sci.
3
Technol., 2009, 43, 1067. (b) For small scale usage, SO
2 2
F was
reported to be accessible from the reaction of SO Cl with KF,
2
2
Conflicts of interest
There are no conflicts to declare.
see: C. Veryser, J. Demaerel, V. Bieliūnas, P. Gilles and W. M.
De Borggraeve, Org. Lett., 2017, 19, 5244.
J. Dong, L. Krasnova, M. G. Finn and K. B. Sharpless, Angew.
Chem., Int. Ed., 2014, 53, 9430.
(a) P. S. Hanley, M. S. Ober, A. L. Krasovskiy, G. T. Whiteker
and W. J. Kruper, ACS Catal., 2015, 5, 5041. (b) Q. Liang, P.
Xing, Z. Huang, J. Dong, K. B. Sharpless, X. Li and B. Jiang, Org.
Lett., 2015, 17, 1942. (c) E. Zhang, J. Tang, S. Li, P. Wu, J. E.
Moses and K. B. Sharpless, Chem. Eur. J., 2016, 22, 5692. (d)
B. Gao, L. Zhang, Q. Zheng, F. Zhou, L. M. Klivansky, J. Lu, Y Liu,
J. Dong, P. Wu and K. B. Sharpless, Nat. Chem., 2017, 9, 1083.
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8
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (Grant No. 21772150), the Wuhan applied fundamental
research plan of Wuhan Science and Technology Bureau (Grant
NO. 2017060201010216), the 111 Project (Grant No. B18038)
and Wuhan University of Technology for the financial support.
(
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