ISSN 1070-4280, Russian Journal of Organic Chemistry, 2023, Vol. 59, No. 4, pp. 652–655. © Pleiades Publishing, Ltd.

, 2023.
Russian Text © The Author(s), 2023, published in Zhurnal Organicheskoi Khimii, 2023, Vol. 59, No. 4, pp. 541–546.

Synthesis of 2-(Benzenesulfonyl)-1,1,1-tribenzylhydrazin-1-ium
Chloride and Its Heterocyclization
with Various Dipolarophiles
A. A. Makhmudovaa,*
a Azerbaijan State Pedagogical University, Baku, 1000 Azerbaijan

*e-mail: iradam@rambler.ru

Received July 12, 2022; revised July 23, 2022; accepted July 26, 2022

Abstract—2-(Benzenesulfonyl)-1,1,1-tribenzylhydrazin-1-ium chloride has been synthesized by the reaction of

tribenzylamine with N-chlorobenzenesulfonamide (chloramine B). A new method has been developed for the
synthesis of polyfunctionalized pyrazoles via 1,3-dipolar cycloaddition of 2-(benzenesulfonyl)-1,1,1-tribenzyl-
hydrazin-1-ium chloride and dipolarophiles. It has been found that activation of the methylene groups of
tribenzylamine by the electron-withdrawing sulfonamide group and aromatic ring accelerates the cyclization.

Keywords: pyrazole, pyridazine, sulfonamide, tribenzylamine, 2-(benzenesulfonyl)-1,1,1-tribenzylhydrazin-1-

ium chloride, dipolarophile, chloramine B

DOI: 10.1134/S1070428023040139

INTRODUCTION sulfonamides containing various heterocycles and

Sulfonamides containing a pyrazole ring exhibit
various biological activities. For example, benzo-
[3.2.1] bicyclic sulfonamide-pyrazoles were reported
as potent selective γ-secretase inhibitors [1]. Other
functionally substituted pyrazoles exhibited analgesic
activity and can be used in inflammations [2]. Sulfon-
amides containing an urea fragment and pyrazole ring
showed high antidiabetic activity [3].
RESULTS AND DISCUSSION
Pyrazoles are generally synthesized by hetero-
cyclization of functionally substituted hydrazines with
1,3-dipolarophiles [4, 5]. Diazolesulfonamide deriva-
tives were obtained by three-component reaction of
acylhydrazines, isocyanates, and sulfonyl chlorides
in the presence of phosphazine [6]. Heterocyclization
of tolyl isocyanate with 2-(4-R-benzoylmethyl)-
3-(furan-2-yl)prop-2-enehydrazide gave pyrazole
derivatives [7].
2-Aminophenyl-1H-pyrazole was utilized as a re-
movable bidentate directing group for copper-mediated
aerobic oxidative amidation and sulfonamidation of
Csp2–H bond [8]. However, the synthesis of hetarene-
polyheterocyclic fragments via reaction of quaternary
ammonium salts with dipolarophiles have been poorly
studied. Syntheses of pyridine N-imines from pyridine
and hydrazinesulfonate [9] or aminosulfonic acids [10]
were described. A new method for the synthesis of
N-imines was reported in [11]. Pyridine N-imines were
also obtained by the reaction of pyridine with N-mono-
chloroamines [12]. Heterocyclizations of pyridine
N-imine with alkenes and alkynes were studied
[13, 14]. Pyridine N-imines readily cyclized even with
dipolarophiles to give pyrazolopyridines [15–18].
No data were found in the literature for the synthesis
of N-imines from other tertiary amines and their
behavior in dipolar addition reactions.
Herein, the addition of tribenzylamine to chlor-
amine B was studied (Scheme 1) [19]. The presence of
an electron-withdrawing benzenesulfonamide fragment
activates benzylic methylene protons in quaternary
salt 1, so that it readily undergoes heterocyclization
with dipolarophiles in a protic solvent in the presence
of alkali. Depenting on the dipolarophile structure,
pyrazole or pyridazine derivatives were formed. The
reactions of 1 with chlorine-containing dipolarophiles
such as N-(2,3-dichloropropyl)benzenesulfonamide,

652
 SYNTHESIS OF 2-(BENZENESULFONYL)-1,1,1-TRIBENZYLHYDRAZIN-1-IUM CHLORIDE 653
Scheme 1.
Ph Ph
Ph
N Ph + PhSO2NCl Na+ N Cl–
–NaCl
HN SO2Ph
Ph Ph
1

2-bromopropionic acid, 3-chloropropane-1,2-diol, and anion by the action of alkali. Elimination of water with
chloroacetonitrile afforded pyrazole derivatives 2–6 participation of the sulfonamide NH group generated
(Scheme 2). Presumably, these reactions begin with unsaturated ketone, and the subsequent cyclization via
substitution of halogen by the sulfonamido group, addition to the benzylic methylene group afforded the
followed by cyclization involving the benzylic methy- final product. Unlike acetylacetone, 4-hydroxy-4-
lene group. The 1H NMR spectrum of 1-benzenesul- methylpentan-2-one reacted with 1 to produce pyrida-
fonyl-2-benzyl-4-hydroxy-5-methyl-3-phenyl-2,3-di- zine derivative 7 (Scheme 3). Heterocyclization of 1
hydro-1H-pyrazole (3) in DMSO-d6 showed a signal at with epichlorohydrin and 1-benzenesulfonyl-2-(chloro-
δ 2.00 ppm due to methyl group, a signal at δ 3.90 ppm methyl)aziridine led to the formation of tetrahydro-
due to benzylic protons, and aromatic proton signals pyridazines 8 and 9, respectively (Scheme 4).
in the region δ 7.20–7.39 ppm with appropriate
intensities. Scheme 4.
Ph
Scheme 2.
Ph 1 + Cl Ph N
Y X
Ph N
X N PhSO2 XH
1 + R2 R1
N 8, 9
R1 PhSO2
R2 8, X = O; 9, X = NSO2Ph.
2–6
In the 1H NMR spectrum of N-(1-benzyl-6-phenyl-
2, R1 = CH2NHSO2Ph, R2 = H; 3, R1 = OH, R2 = Me; 4, R1 =
CH2OH, R2 = Me; 5, R1 = COMe, R2 = Me; 6, R1 = NH2, R2 = H. hexahydropyridazin-4-yl)benzenesulfonamide (9),
protons of the two CH2 and two CH groups resonated
The 1H NMR spectrum of N-[(1-benzenesulfonyl- in the region δ 3.06–3.80 ppm which was obscured
2-benzyl-3-phenyl-2,3-dihydro-1H-pyrazol-4-yl)- by the solvent signal. The NH proton resonated as
methyl]benzenesulfonamide (2) showed a singlet at a doublet at δ 5.46 ppm. Aromatic protons gave rise to
δ 1.50 ppm due to methylene protons, two doublets in an unresolved multiplet in the region δ 7.02–7.56 ppm.
the region of 2.95 due to CH protons in the pyrazole The reaction of 1 with dimedone afforded indazole
ring, a signal at δ 3.60 ppm due to CH2N protons, and 10 (Scheme 5).
a doublet at δ 5.20 ppm due to NH proton. Aro-
matic proton signals were located in the region Scheme 5.
δ 7.20–7.70 ppm. O O Ph
Acetylacetone reacted with ammonium salt 1 to Ph
give pyrazole derivative 3. Presumably, the reaction 1 + N
involved initial formation of the corresponding carb- Me Me
N
O
Me Me
Scheme 3. SO2Ph
10
Ph
Me
HO Me Base Ph N EXPERIMENTAL
1 +
Me Me N
O PhSO2 The IR spectra were recorded on a Nicolet iS-10
Me
Me FTIR spectrometer (USA). The 1H NMR spectra were
7 recorded on a Tesla-BS 567 spectrometer at 90 MHz.

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 59 No. 4 2023

654 MAKHMUDOVA
2-Benzenesulfonyl-1,1,1-tribenzylhydrazin-1-
ium chloride (1). A mixture of 28.7 g (0.1 mol) of
tribenzylamine and 100 mL of ethanol was acidified
with aqueous HCl to pH 5.0 and heated to 65–70°C,
29.4 g (0.11 mol) of chloramine B and 20 mL of water
were added, and the mixture was refluxed for 1–2 h.
The solvent was distilled off to a half of the initial
volume, the mixture was cooled to 0°C, and the crys-
talline solid was filtered off and recrystallized from
ethanol. Yield 38.7 g (80.9%), mp 85–87°C. Found, %:
N 5.28. C27H27ClN2O2S. Calculated, %: N 5.85.
N-[(1-Benzenesulfonyl-2-benzyl-3-phenyl-2,3-
dihydro-1H-pyrazol-4-yl)methyl]benzenesulfon-
amide (2). N-(2,3-dichloropropyl)benzenesulfonamide
(2.3 g, 1 mmol), and alkali (0.4 g) were added to
a solution of 1 (4.8 g, 1 mmol) in anhydrous ethanol
(10–15 mL). The mixture was refluxed for 3–4 h and
filtered while hot, the filtrate was cooled, and the
crystalline solid was filtered off and recrystallized
from 85% ethanol. Yield 70.8%, mp 115–117°C. IR
spec trum, ν, cm –1 : 1450 (SO 2 N), 1160. Found, %:
N 7.27; S 11.37. C29H29N3O4S2. Calculated, %: N 7.68;
S 11.70.
2-Benzenesulfonyl-1-benzyl-3-methyl-5-phenyl-
pyrazolidin-4-one (3) was synthesized as described
above for compound 2 using 1.5 g of 2-bromopropionic
acid. Yield 74.2%, mp 102–104°C. IR spectrum, ν,
cm–1: 1695 (C=O), 1451 (SO 2N), 1150. Found, %:
N 6.79; S 7.12. C25H23N2O3S. Calculated, %: N 7.68;
S 11.70.
(1-Benzenesulfonyl-2-benzyl-5-methyl-3-phenyl-
2,3-dihydro-1H-pyrazol-4-yl)methanol (4) was syn-
thesized as described above for compound 2 using
1.1 g of 3-chloropropane-2,3-diol and 0.6 g of alkali.
The product was recrystallized from isopropyl alcohol.
Yield 69.4%, mp 106–108°C. IR spectrum, ν, cm–1:
3381 (O–H), 1454 (SO2N), 1120. Found, %: N 7.02;
S 7.68. C23H24N3O4S. Calculated, %: N 6.86; S 7.84.
1-(1-Benzenesulfonyl-2-benzyl-5-methyl-3-
phenyl-2,3-dihydro-1H-pyrazol-4-yl)ethanone (5)
was synthesized as described above for compound 2
using 1 g of acetylacetone and 0.1 mmol of alkali.
Yield 71.2%, mp 163–165°C. IR spectrum, ν, cm–1:
1659 (C=O), 1453 (SO2N), 1119. Found, %: N 7.23;
S 7.56. C23H22N2O3S. Calculated, %: N 6.90; S 7.88.
1-Benzenesulfonyl-2-benzyl-3-phenyl-2,3-dihy-
dro-1H-pyrazol-4-amine (6) was synthesized as de-
scribed above for compound 2 using 1.02 g of chloro-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 59 No. 4 2023
acetonitrile and 0.4 g of alkali. Yield 73.9%, mp 82–
84°C. Found, %: N 10.57; S 7.92. C22H21N3O2S. Cal-
culated, %: N 10.74; S 8.18.
2-Benzenesulfonyl-1-benzyl-3,3,5-trimethyl-6-
phenylhexahydropyridazine (7) was synthesized as
described above for compound 2 from 4-hydroxy-
4-methylpentan-2-one using 0.44 g (1.1 mmol) of
sodium hydroxide. Yield 59.8%, mp 185–187°C.
Found, %: N 6.69; S 7.87. C 26H 28N 2O 2S. Calculat-
ed, %: N 6.48; S 7.41.
2-Benzenesulfonyl-1-benzyl-6-phenylhexahydro-
pyridazin-4-ol (8) was synthesized as described above
for compound 2 from epichlorohydrin using 0.44 g
(1.1 mmol) of sodium hydroxide. Yield 67.9%,
mp 113–115°C. IR spectrum, ν, cm–1: 3392 (O–H),
1461 (SO 2 N), 1156. Found, %: N 7.29; S 11.46.
C23H23N2O3S. Calculated, %: N 7.68; S 11.70.
N-(2-Benzenesulfonyl-1-benzyl-6-phenylhexahy-
dro pyridazin-4-yl)benzenesulfonamide (9) was
synthesized as described above for compound 2 from
1-benzenesulfonyl-2-(chloromethyl)aziridine. Yield
69.8%, mp 112–114°C. IR spectrum, ν, cm–1: 3348
(N–H), 1450 (SO2N), 1150. Found, %: N 7.79; S 5.92.
C29H29N3O4S2. Calculated, %: N 8.16; S 6.21.
1-Benzenesulfonyl-2-benzyl-6,6-dimethyl-3-
phenyl-1,2,3,5,6,7-hexahydro-4H-indazol-4-one (10)
was synthesized as described above for compound 2
from 5,5-dimethylcyclohexane-1,3-dione. Yield 68.3%,
mp 183–185°C. IR spectrum, ν, cm–1: 1709.5 (C=O),
1454 (SO 2 N), 1175. Found, %: N 5.63; S 6.59.
C27H28N2O3S. Calculated, %: N 5.98; S 6.84.
CONCLUSIONS
A new method has been developed for the synthesis
of polyfunctionalized pyrazoles via 1,3-dipolar cyclo-
addition of 2-(benzenesulfonyl)-1,1,1-tribenzylhydra-
zin-1-ium chloride and dipolarophiles. Activation of
the benzylic methylene groups by the electron-with-
drawing sulfonamide group and aromatic ring increases
the cyclization rate. The use of active dipolarophiles
containing a sulfonamide group makes it possible to
easily synthesize five- and six-membered nitrogen
heterocycles by [3+2]- or [4+2]-cycloaddition.
AUTHOR INFORMATION
A.A. Makhmudova, ORCID: https://orcid.org/0000-
0003-2326-1994
 SYNTHESIS OF 2-(BENZENESULFONYL)-1,1,1-TRIBENZYLHYDRAZIN-1-IUM CHLORIDE
CONFLICT OF INTEREST
The author declares the absence of conflict of interest.
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