1
13
uncorrected. H NMR and C NMR were determined on Agilent DD2-400 OneNMR probe
Agilent Technologies, Santa Clara, CA, USA). NMR spectra were calibrated to the residual
(
1
13
solvent shifts for H and, C. Infrared (IR) spectroscopy was performed by FTIR spectrometer
iS5 (Thermo Fisher Scientific, Rockfort, USA) and the spectrum was recorded by ATR
(
(
attenuated total reflection). Mass spectra (MS) were measured by MS/MS Xevo TQ-S
Waters, USA) using electrospray ionization (ESI). Elemental analysis was performed for C, H,
N and S with the elemental analyzer EA3000 from EuroVector (Italy). 4-(3-(hydroxymethyl)-5-
(
p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide
(1):
The
synthesis
of
7
(pyrazolyl)benzenesulfonamide 1 was previously described and we followed the described
procedure. (1-(4-sulfamoylphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)methyl nitrate (2): To a ice
cooled mixture of 4-(3-(hydroxymethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide (1,
0.20 g, 0.58 mmol) in 8.1 mL acetonitrile were added under argon atmosphere silver nitrate
(0.27 g, 1.57 mmol), triphenylphosphine (0.21 g, 0.79 mmol) and N-bromosuccinimide (0.14
g, 0.79 mmol). The solution was stirred 1 h at 0°C followed by 22 h stirring at room
temperature. Ethyl acetate (20 mL) was added to the mixture, the solution was filtered and
washed two times with water (20 mL) followed by brine (15 mL). The aqueous solution was
extracted with ethyl acetate. The collected organic solution was dried and purified by column
chromatography (ethyl acetate-petroleum ether, 5:5 ꢀ 10:10, v/v). 2 was obtained as a
yellow solid (0.07 g, 32.6%). Moreover, starting material 1 could be re-isolated. mp 179-
1
1
82°C; R
DMSO-d
CH Ph), 7.21 (d, J = 8.4 Hz, 2H, CH
f
0.44 (ethyl acetate/petroleum ether; 5/5; v/v); purity: 97.2%; H NMR (400 MHz,
3
6
) δ (ppm) 2.31 (s, 3H, CH
3
), 5.67 (s, 2H, CH
Ph), 7.48 – 7.44 (m, 4H, H-3,5 NH
Ph); C NMR (151 MHz, DMSO-d ) δ (ppm) 20.78 (CH
2
), 6.78 (s, 1H, CH), 7.15 (d, J = 8.2 Hz, 2H,
3
3
3
3
2
SO
2
Ph, NH
2
), 7.83 (d, J =
), 68.56 (CH ),
1
3
8.6 Hz, 2H, H-2,6 NH
2
SO
2
6
3
2
1
08.79 (Cpyrazolyl), 125.29 (CHaromatic), 126.29, 126.68 (CHaromatic), 128.52 (CHaromatic), 129.39
S [Mmonoisotopic] requires 388.1,
(CHaromatic), 138.53, 141.63, 143.09, 144.31, 145.49; C17
H
16
N
4
O
5
-
-1
2 2
ESI-MS (ES-) m/z: 387.0 ([M-H] ); IR (ATR) ѵ = 1639, 1275 (s, O-NO ), 1163 (s, SO ) cm . 4-(4-
chloro-3-(chloromethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide (3): Synthesis of 3
was carried out under Schlenk-conditions (nitrogen atmosphere). A suspension of 1 (0.30 g,
0.87 mmol) and thionyl chloride (1.92 mL, 16.66 mmol) was heated for 1 h at 80°C. After
cooling, thionyl chloride was removed under vacuum. After purification by column
chromatography (ethyl acetate-petroleum ether, 4:6, v/v) an additional purification step was
carried out by semi-preparative HPLC (Varian ProStar; acetonitrile-water + 0.1% TFA; 5:5; v/v;
7
mL/min). Compound 3 was obtained as white solid (53.4%, 0.16 g). mp 246-249°C; R
f
0.43
ethyl acetate/petroleum ether; 5/5; v/v); purity: 99.6%; H NMR (400 MHz, DMSO-d ) δ
Ph), 7.28 (d, J = 8.3 Hz,
1
(
(
6
3
3
ppm) 2,34 (s, 3H, CH
H, CH Ph), 7.47 – 7.41 (m, 4H, H-3,5 NH
NH SO
3 2 3
), 4,86 (s, 2H, CH ), 7.21 (d, J = 8.2 Hz, 2H, CH
3
2
3
2
SO
2
Ph, NH
) δ (ppm) 20.92 (CH
2
), 7.81 (d, J = 8.6 Hz, 2H, H-2,6
), 36.39 (CH ), 66.76 (Cl-
1
3
2
2
Ph); C NMR (101 MHz, DMSO-d
6
3
2
Cpyrazolyl), 123.97, 125.09 (CHaromatic), 126.68 (CHaromatic), 129.55, 139.40 (2 x CHaromatic), 140.24,
1
41.24, 143.28, 146.36; C17
H
15Cl S [Mmonoisotopic] requires 395.0, MS (ES+) m/z: 395.9
2 3 2
N O
3
5
+
37
+
(
[M( Cl)+H] ), 397.9 ([M( Cl)+H] ); IR (ATR) ѵ = 1163 (s, SO
2
), 1093 (m, Cl-Aryl), 659 (m, Cl-
Alkyl) cm . 4-(3-(chloromethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide (4): 4-(3-
chloromethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide (4) could be isolated as
byproduct of the synthesis of 3 and was obtained as a white solid (3.0%, 0.01 g). mp 154-
-
1
(
1
158°C; R
f
0.42 (ethyl acetate/petroleum ether; 5/5; v/v); H NMR (400 MHz, DMSO-d
6
) δ
3
), 6.73 (s, 1H, CH), 7.15 (d, J = 8.0 Hz, 2H, CH
(
(
ppm) 2.31 (s, 3H, CH
3
), 4.80 (s, 2H, CH
Ph), 7.48 – 7.42 (m, 4H, H-3,5 NH
2
3
Ph), 7.21
), 7.82 (d, J = 8.5 Hz, 2H,
3
d, J = 7.9 Hz, 2H, CH
3
3
2
SO
2
Ph, NH
Ph); C NMR (101 MHz, DMSO-d ) δ (ppm) 20.77 (CH
2
1
3
H-2,6 NH
2
SO
2
6
3
), 31.13 (CH
2
), 108.15
(Cpyrazolyl), 125.12 (CHaromatic), 126.46, 126.63 (CHaromatic), 128.47 (CHaromatic), 129.37 (CHaromatic),
1
38.44, 141.71, 142.86, 149.71, 149.94; C17
H
16ClN S [Mmonoisotopic] requires 361.1, MS (ES+):
3 2
O
3
5
+
37
+
362,0 ([M( Cl)+H] ), 364.1 ([M( Cl)+H] ). (4-chloro-1-(4-sulfamolyphenyl)-5-(p-tolyl)-1H-
pyrazol-3-yl)methyl nitrate (5): A suspension of 3 (0.16 g, 0.40 mmol) and silver nitrate (0.21
g, 1.22 mmol) in acetonitrile (4.3 mL) was heated 24 h at 80°C. The silver salt was filtered off
and the clear solution was dried under vacuum conditions. After resuspension with ethyl