One-pot synthesis of sulfonylhydrazones from sulfonyl chloride, hydrazine hydrate and vinyl azide in water

Article abstract of DOI:10.1007/s13738-021-02226-8

A facile and eco-friendly protocol for the synthesis of sulfonylhydrazones from sulfonyl chlorides, hydrazine hydrate and vinyl azides was developed. The unique advantage of this approach is that desired products can be obtained efficiently in water, which meets the requirements of green chemistry and provides good perspectives for the sustainable production of new drug candidate. Also, this reaction proceeded in moderate to good yields with a wide tolerance of functional groups.

Full text of DOI:10.1007/s13738-021-02226-8

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-021-02226-8
ORIGINAL PAPER
One‑pot synthesis of sulfonylhydrazones from sulfonyl chloride,
hydrazine hydrate and vinyl azide in water
Mengqiang Luo1 · Hai Wang2 · Xiaorong Ren1 · Ruijuan Lu1 · Chenze Qi1 · Yaohong Zhang1 · Runpu Shen1
Received: 22 October 2020 / Accepted: 23 February 2021
© Iranian Chemical Society 2021
Abstract
A facile and eco-friendly protocol for the synthesis of sulfonylhydrazones from sulfonyl chlorides, hydrazine hydrate and
vinyl azides was developed. The unique advantage of this approach is that desired products can be obtained efciently in
water, which meets the requirements of green chemistry and provides good perspectives for the sustainable production of
new drug candidate. Also, this reaction proceeded in moderate to good yields with a wide tolerance of functional groups.
Keywords Sulfonylhydrazone · Vinyl azide · Sulfonyl chloride · Water · One pot
Introduction
reactions using environmentally benign catalysts or additives
have attracted signifcant attention and displays good poten-
tiality in organic synthesis because they are eco-friendly
and cost efective [7–11]. However, many in-water chemi-
cal procedures employing environmentally benign cata-
lysts or additives commonly sufer from low yields or high
temperature [12–14]. Therefore, it is still highly desired to
discover the reactions proceeding in water with environmen-
tally benign catalysts or additives.
As people increasingly focus on the living environment of
human beings, great eforts have been made by chemists on
developing the green and sustainable procedures to reduce
or eliminate the generation or use of harmful substances in
both the academy and industry in the past decades. Gener-
ally, the harmful substances in the chemical reactions are
mainly from the application of organic solvents and envi-
ronmentally harmful catalysts or additives. Therefore, the
development of environmentally benign catalysts or addi-
tives, in-water green chemical strategies in organic reac-
tions has been becoming one of the most fascinating felds
in chemical research. Water is usually considered to be a
green solvent in organic synthesis because water has the
advantages of being cheap, non-toxic, eco-friendly, fac-
ile, highly stable and non-fammable [1–6]. In addition,
Sulfonylhydrazones are considered as privileged scaf-
folds in new the drug development owing to their broad
spectrum of biological and pharmacological properties,
such as anti-cancer [15], anti-nociceptive [16], anti-diabetic
[17], anti-fungal [18], anti-depressant [19] and anti-tumor
[20] activities, and it can also act as ROCK [21] and CAII
enzyme inhibitors [22], as well as PPAR-gamma agonist
[23]. And also, sulfonylhydrazones exhibit chemical diver-
sity and serve as very important chemical intermediates in
multifarious organic transformations; for example, sulfo-
nylhydrazones are used as precursors in Bamford–Stevens
[24–28] reactions, Shapiro [29–31] reactions and various
coupling reactions [32–37]. Moreover, sulfonylhydrazones
are also useful synthons to construct N/O-bearing hetero-
cyclic compounds [38–46], ketones [47, 48], fuoroalkanes
[49], diazocompounds [50], alkynes [51], sulfones [52, 53],
alcohols [54], ethers or thioethers [55, 56], sulfonamides
[57], α-arylacrylic acids [58] and so on.
Mengqiang Luo and Hai Wang contributed equally to this work
* Yaohong Zhang
zhangyhsxu@126.com
* Runpu Shen
shenrfsxu@126.com
1
School of Chemistry and Chemical Engineering, Zhejiang
Key Laboratory of Alternative Technologies for Fine
Chemicals Process, Shaoxing University, Shaoxing 312000,
Zhejiang, People’s Republic of China
Many protocols for the preparation of sulfonylhydra-
zones have been presented. Sulfonylhydrazones were gen-
erally constructed via condensation of sulfonylhydrazides
2
School of Life Science, Shaoxing University,
Shaoxing 312000, Zhejiang, People’s Republic of China
Vol.:(0123456789)
1 3

Journal of the Iranian Chemical Society
Table 1 Optimization of reaction conditionsa
with aldehydes or ketones usually using various organic
solvents (such as methanol, dioxane tetrahydrofuran, PhMe
or CH2Cl2) with further addition of acid as catalyst (such as
HOAc, p-MePhSO3H or HCl) [59–65]. As a result, these
methods sufer from the use of corrosive acids and envi-
ronmentally harmful organic solvents. In addition, sulfonyl-
hydrazones were also prepared from carbonyl-compounds
and sulfonylhydrazides by microwave-assisted synthesis [66,
67] or by Grindstone chemistry [68]. Recently, the one-pot
reaction from sulfonyl chlorides, hydrazine hydrates and
aldehydes [69] and the hydrohydrazination of arylalkynes
catalyzed by N-heterocyclic carbene (er-NHC) gold com-
plex [70], and visible light-mediated oxidative cleavage of
C=C bonds of alkenes [71] to achieve sulfonylhydrazones
were reported. Even though these reported protocols have
proved to be efcient in synthesis of sulfonylhydrazones,
great eforts have still been made in our group with respect
to green and sustainability. Herein, we present a green and
efcient approach for the efcient one-pot synthesis of sul-
fonylhydrazones in water from the easily available starting
materials of sulfonyl chlorides, hydrazine hydrate and vinyl
azides.
Entry
Additive
Solvent
Temperature Yieldb (%)
(°C)
1
2
3
4
5
6
7
8
n-Bu4NF
n-Bu4NCl
n-Bu4NBr
n-Bu4NI
n-Bn4NBr
Me4NCl
_
_
_
_
_
Me4NCl
Me4NCl
Me4NCl
Me4NCl
Me4NCl
Me4NCl
Me4NCl
Me4NCl
THF
THF
THF
THF
THF
THF
THF
EtOH
i-PrOH
DMF
PEG-400
CH3CN
EtOAc
CHCl3
DMF
H2O
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
25
100
73
80
76
75
77
82
65
76
73
60
81
77
68
72
70
90
90
61
85
9
10
11
12
13
14
15
16
17
18
19
C2H5OH
H2O
H2O
aThe reaction conditions: hydrazine hydrate (conc. 80%, 1.2 mmol),
4-methylbenzene sulfonyl chloride (1.0 mmol), Et3N (1.2 mmol),
vinyl azide (1.0 mmol), additive (10% mmol), 10 mL of solvent, 4 h
only for the second step reaction.
Results and discussion
Initially, to establish the optimal reaction conditions,
the synthesis of 4-methylbenzenesulfonohydrazide
was explored from 4-methylbenzene sulfonyl chloride,
hydrazine hydrate (conc. 80%) and α-phenylvinyl azide
according to the reported procedures [72, 73], hydrazine
hydrate(1.2 equiv.) was added dropwise to a solution of
the sulfonyl chloride (1.0 equiv) in 10 mL water at 0 °C.
Then, Et3N (1.2 equiv.) was added dropwise to the reac-
tion system and the resulting solution was stirred at 0 °C
to room temperature. After the complete consumption of
sulfonyl chloride, additive (10 mol%) and α-phenylvinyl
azide (1.0 mmol) were added to the reaction system. A
range of additives were frstly screened in THF at 60 °C,
and the results showed that n-Bu4NF, n-Bu4NBr, n-Bu4NI
and n-Bn4NBr (Table 1, entries1, 3, 4 and 5) performed less
efciently than n-Bu4NCl and Me4NCl (Table 1, entries 2
and 6). Subsequently, the reactions were also carried out in
bIsolated yield; the most efcient entry is highlighted in bold.
c“_” means additive-free.
diferent solvents without additives (Table 1, entries 7–11).
The highest yield (81%) was obtained in PEG-400 (Table 1,
entry 11), which is slightly lower than that with additive of
Me4NCl in THF (Table 1, entry 6). The efect of diferent
solvents was then investigated using Me4NCl as the additive.
It was found that H2O and EtOH had the same efciency
in the reaction, and H2O and EtOH were superior solvents
compared to CH3CN, EtOAc, CHCl3 and DMF (Table 1,
entries 12–17). In consideration of saving money and eco-
friendliness, H2O was chosen as the solvent. Lastly, diferent
temperatures were tried and it was found that the yield of
3b decreased sharply with the lowering of the temperature
(Table 1, entry 18), while the yield of 3b decreased slightly
at 100 °C (Table 1, entry 19).
1 3

Journal of the Iranian Chemical Society
Table 2 Scope of the reaction of
vinyl azides, sulfonyl chlorides
and hydrazine hydrate under
optimal conditions
Entry
1
2
3
Yield(%)b
1
88
3a
2
3
4
5
6
7
8
90
87
90
91
85
79
81
3b
3c
3d
3e
3f
3g
3h
3i
9
85
83
10
3j
11
12
75
86
85
3k
3l
13
14
3m
86
88
3n
15
16
17
18
3o
90
87
94
3p
3q
3r
3s
3t
19
93
75
20
a. The reaction conditions: hydrazine hydrate (conc. 80%, 1.2 mmol), sulfonyl chloride (1.0 mmol),
Et3N (1.2 mmol), vinyl azide (1.0 mmol), Me4NCl (10%mmol), 10 mL of solvent, 4 h only for the
second step reaction.
b. Isolated yield.
1 3

Journal of the Iranian Chemical Society
Table 2 (continued)
aThe reaction conditions: hydrazine hydrate (conc. 80%, 1.2 mmol), 4-methylbenzene sulfonyl chloride
(1.0 mmol), Et3N (1.2 mmol), vinyl azide (1.0 mmol), additive (10% mmol), 10 mL of solvent, 4 h only for
the second step reaction.
bIsolated yield; The most efcient entry is highlighted in bold.
c“_” means additive-free.
In addition, diferent vinyl azides were also applied in the
reaction and the results indicated that the electronic charac-
ter of the vinyl azides had a little efect on arylsulfonylhy-
drazones formation (Table 2). Vinyl azides bearing electron-
withdrawing and electron-donating substituents were applied
in the reaction and provided the desired sulfonylhydrazones
in moderate to good isolated yields. Compared to electron-
Scheme 1 Control experiment
poor vinyl azides, the reactions of electron-rich vinyl azides
caused slightly lower yield (entries 13–16, Table 2). As a
result, electron-withdrawing groups (Cl- and Br-) of vinyl
azides and electron-donating group (CH3-) of sulfonylhy-
drazides both slightly increase the reactivity resulting in a
high conversion rate to the sulfonylhydrazones (entries 18
and 19, Table 2). Thus, reduced reactivity of the arylsulfo-
nylhydrazides associated with the electron-rich character of
the vinyl azides has probably established a synergic efect
that interfered on the product formation and consequently
reduced yields (entry 20, Table 2). In summary, the general
applicability of the developed methodology was established
by the investigations with a variety of substrates.
With the optimized reaction conditions in hand, the appli-
cability and versatility of this protocol were investigated.
The results showed that the reaction was suitable for the
formation of sulfonylhydrazones in good to excellent yields
(Table 2). Firstly, various arylsulfonylhydrazides were pre-
pared from the corresponding sulfonyl chlorides to react
with α-phenylvinyl azide, and the results demonstrated that
arylsulfonylhydrazides containing electron-withdrawing
groups aforded lower yield compared to those contain-
ing electron-donating substituents (entries 2–6 and 7–9,
Table 2), because of the low efciency in the formation of
arylsulfonylhydrazides containing electron-withdrawing
groups producing the arylsulfonic acids as by products; thus,
the yields of the desired products were diminished. 2-Naph-
thylsulfonylhydrazide and 2-thienylsulfonylhydrazide were
also formed to react with α-phenylvinyl azide and provided
the corresponding sulfonylhydrazones with the yield of 83%
and 86%, respectively (entries 10 and 12, Table 2). As for the
reaction of methylsulfonyl chloride, it gave the desired prod-
uct with lower yield (75%) due to the low efciency in the
formation of methylsulfonylhydrazide (entry 11, Table 2).
One control experiment in Scheme 1 was carried out for
the second step reaction to elucidate the generation of the
product 3. When the reaction of α-phenylvinyl azide was
performed in the presence of Me4NCl (10% mmol) at 60 °C
in water for 1 h and 3 h, 8.2% and 31.8% of acetophenone
were detected by GC-2010 Plus SHIMADZU, respectively.
Based on the presented experimental results and literature
reports, a plausible mechanism for the formation of product
Scheme 2 Proposed mechanism
1 3

Journal of the Iranian Chemical Society
3 was proposed in Scheme 2 In the pathway, starting mate-
rial of vinyl azides 2 might undergo thermal decomposi-
tion at 60 °C with the loss of one molecular of N2 to aford
vinylnitrene intermediate (A), which then reacted with water
to form the related oximes (B) [74]. The resultant interme-
diated (B) next converted to acetophenone derivatives (C)
after hydrolysis in the presence of ammonium salts [75].
Subsequently, intermediated (C) underwent condensation
with sulfonylhydrazides (D) that prepared from the nucleo-
General procedure for the synthesis
of sulfonylhydrazones
At 0 °C, hydrazine hydrate (Conc.80%, 1.2 mmol, 1.2 equiv)
was added dropwise to a solution of the sulfonyl chloride
(1.0 mmol) in 10 mL water. Then, Et3N (1.2 mmol, 1.2
equiv) was added dropwise to the reaction system and the
resulting solution was stirred at 0 °C to room temperature
until the completion of sulfonyl chloride. Subsequently,
Me4NCl (11 mg, 10 mol%) and vinyl azides (1.0 mmol,
1.0 equiv) were added to the reaction system. The reaction
mixture was heated and magnetically stirred at 60 °C for
4 h. Upon completion of the reaction, the resulting mix-
ture was diluted with saturated NaCl solution and extracted
with ethylacetate; the combined organic extracts were dried
over Na2SO4, concentrated and purifed by chromatography
(petroleum ether/ethylacetate) on silica gel to provide the
corresponding products 3a-3t.
.
philic substitution of NH2NH2 H2O with sulfonyl chloride
to furnish the desired product 3 with the elimination of one
molecular of H2O. The detection of acetophenone during the
reaction supports this proposed pathway.
Conclusions
In conclusion, a novel, convenient and eco-friendly one-pot
strategy to prepare functionalized sulfonylhydrazone deriva-
tives from sulfonyl chlorides, hydrazine hydrate and vinyl
azides has been developed. The unique advantages of this
strategy are environmentally benign because this reaction
proceeded smoothly and efciently in water with Me4NCl as
additive, which meets the requirements of green chemistry
and provides good perspectives for the sustainable produc-
tion of new drug candidate.
N’‑(1‑Phenylethylidene)benzenesulfonohydrazide (3a)
1
White solid, m.p: 84.5–85.5 °C. H NMR (400 MHz,
DMSO-d6) δ 10.51 (s, 1H), 7.94–7.93 (m, 1H), 7.93–7.92
(m, 1H), 7.68–7.63 (m, 2H), 7.62–7.60 (m, 3H), 7.37–7.36
(m, 3H), 2.18 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ153.50, 139.07, 137.36, 133.02, 129.46, 129.07, 128.40,
127.56, 125.99, 14.36. HRMS (ESI) M/Z calcd for
C14H15N2O2S. [M+H]+: 275.0854. Found: 275.0855.
Experimental section
4‑Methyl‑N’‑(1‑phenylethylidene)benzenesulfonohydrazide
(3b)
General
1
All solvents were purifed according to standard methods
prior to use. Purifcations of reaction products were carried
out by chromatography using silica gel (200–300 mesh).
The chemical shifts are reported in ppm and the data are
reported as follows: chemical shift, integration, multiplicity
(s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet)
and the coupling constants J are given in Hz. The 1H NMR
spectra were recorded at 400 MHz; DMSO (δ = 2.50) or
CDCl3 (δ=7.26) served as internal standard and 13 C NMR
spectra were recorded at 400 MHz, DMSO (δ= 39.50) or
CDCl3 (δ=77.2) was used as internal standard, and spectra
were obtained with complete proton decoupling. HRMS data
were obtained using Agilent Technologies 6224 TOF LC/
MS. Melting points were recorded on a BÜCHI B-540 melt-
ing point apparatus. The starting material vinyl azides were
prepared according to methods mentioned in the literature
[72, 73].
White solid, m.p: 320.5–321.5 °C. H NMR (400 MHz,
DMSO-d6) δ 10.52 (s, 1H), 7.82 (d, J = 8.2 Hz, 2H),
7.63–7.61 (m, 2H), 7.41 (d, J = 8.1 Hz, 2H), 7.37–7.36
(m, 3H), 2.36 (s, 3H), 2.18 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ 153.16, 143.37, 137.40, 136.21, 129.48,
129.39, 128.38, 127.59, 125.96, 21.02, 14.29. HRMS (ESI)
M/Z calcd for C15H17N2O2S. [M+H]+: 289.1011. Found:
289.1006.
N‑(4‑((2‑(1‑Phenylethylidene)hydrazinyl)sulfonyl)phenyl)
acetamide (3c)
1
White solid, m.p: 238.7–240.2 °C. H NMR (400 MHz,
DMSO-d6) δ 10.46 (s, 1H), 10.34 (s, 1H), 7.85 (d,
J=7.9 Hz, 2H), 7.77 (d, J=8.7 Hz, 2H), 7.63–7.61 (m, 2H),
7.38–7.36 (m, 3H), 2.17 (s, 3H), 2.07 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 169.05, 153.14, 143.26, 137.38,
132.55, 129.37, 128.79, 128.37, 125.96, 118.37, 24.14,
14.27. HRMS (ESI) M/Z calcd for C16H18N3O3S. [M+H]+:
332.1069. Found: 332.1074.
1 3

Journal of the Iranian Chemical Society
2,4,6‑Trimethyl‑N’‑(1‑phenylethylidene)
benzenesulfonohydrazide (3d)
2H), 7.36–7.32 (m, 3H), 2.27 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ 153.65, 138.15, 137.15, 134.31, 133.64,
132.07, 130.84, 129.82, 129.61, 128.40, 126.03, 14.54.
HRMS (ESI) M/Z calcd for C14H13Cl2N2O2S. [M + H]+:
343.0075. Found: 343.0084.
1
Brown solid, m.p: 234.1–235.5 °C. H NMR (400 MHz,
DMSO-d6) δ 10.65 (s, 1H), 7.57–7.55 (m, 2H), 7.34–7.33
(m, 3H), 7.03 (s, 2H), 2.66 (s, 6H), 2.22 (s, 3H), 2.19 (s, 3H);
13C NMR (100 MHz, DMSO-d6) δ 151.01, 142.22, 139.47,
137.65, 133.44, 131.54, 129.16, 128.35, 125.78, 22.82,
20.42, 14.15. HRMS (ESI) M/Z calcd for C17H21N2O2S.
[M+H]+: 317.1318. Found: 317.1323.
4‑Chloro‑N’‑(1‑phenylethylidene)benzenesulfonohydrazide
(3i)
Light yellow solid, m.p: 104.3–105.7 °C. 1H NMR
(400 MHz, CDCl3) δ 7.97(d, J = 8.4 Hz, 2H), 7.65–7.63
(m, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.37–7.36 (m, 3H),
2.17 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 154.10,
137.94, 137.82, 137.22, 129.53, 129.49, 129.24, 128.40,
126.02, 14.41. HRMS (ESI) M/Z calcd for C14H14ClN2O2S.
[M+H]+: 309.0465. Found: 309.0457.
4‑Methoxy‑N’‑(1‑phenylethylidene)
benzenesulfonohydrazide (3e)
1
White solid, m.p: 254.3–255.5 °C. H NMR (400 MHz,
DMSO-d6) δ 10.44 (s, 1H), 7.87–7.85 (m, 2H), 7.63–7.61
(m, 2H), 7.37 (t, J=3.2 Hz, 3H), 7.13 (d, J=8.9 Hz, 2H),
3.82 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ 162.58, 153.03, 137.44, 130.68, 129.74, 129.36, 128.37,
125.95, 114.20, 55.65, 14.27. HRMS (ESI) M/Z calcd for
C15H17N2O3S. [M+H]+: 305.0954. Found: 305.0960.
N’‑(1‑phenylethylidene)naphthalene‑2‑sulfonohydrazide
(3j)
1
Yellow solid, m.p: 116.5–117.4 °C. H NMR (400 MHz,
DMSO-d6) δ 10.68 (s, 1H), 8.60 (s, 1H), 8.22 (d, J=7.6 Hz,
1H), 8.14 (d, J=8.8 Hz, 1H), 8.03 (d, J=7.6 Hz, 1H), 7.95
(dd, J=8.4, 1.6 Hz, 1H), 7.72–7.67 (m, 2H), 7.72–7.60 (m,
2H), 7.35–7.33 (m, 3H), 2.19 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 155.41, 135.92, 135.78, 135.72, 134.56, 132.20,
130.86, 129.80, 129.74, 129.70, 129.49, 129.03, 128.20,
127.92, 123.14, 14.45. HRMS (ESI) M/Z calcd for
C18H17N2O2S. [M+H]+: 325.1005. Found: 325.1008.
N’‑(1‑phenylethylidene)‑[1,1′‑biphenyl]‑4‑sulfonohydraz
ide (3f)
1
Yellow solid, m.p: 150.1–151.4 °C. H NMR (400 MHz,
DMSO-d6) δ 10.66 (s, 1H), 8.01 (d, J=8.5 Hz, 2H), 7.91 (d,
J=8.5 Hz, 2H), 7.72 (d, J=7.2 Hz, 2H), 7.66–7.63 (m, 2H),
7.51–7.47 (m, 2H), 7.44–7.42 (m, 1H), 7.38–7.36 (m, 3H),
2.21 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 153.57,
144.46, 138.46, 137.84, 137.37, 129.46, 129.13, 128.57,
128.41, 128.24, 127.26, 127.14, 126.03, 14.39. HRMS (ESI)
M/Z calcd for C20H19N2O2S. [M+H]+: 351.1162. Found:
351.1165.
N’‑(1‑phenylethylidene)methanesulfonohydrazide (3 k)
1
Brown solid, m.p: 102.7–104.1 °C. H NMR (400 MHz,
CDCl3) δ 7.29–7.28 (m, 3H), 7.09 (d, J=8.4 Hz, 2H), 6.65
(s, 1H), 2.51 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ 153.03, 130.68, 129.74, 129.36, 128.37, 55.65,
14.27. HRMS (ESI) M/Z calcd for C9H13N2O2S. [M+H]+:
213.0692 Found: 213.0698.
4‑Nitro‑N’‑(1‑phenylethylidene)benzenesulfonohydrazide
(3 g)
1
Brown solid, m.p: 255.9–256.7 °C. H NMR (400 MHz,
DMSO-d6) δ 10.93 (s, 1H), 8.45 (d, J= 9.0 Hz, 2H), 8.18
(d, J=9.0 Hz, 2H), 7.65–7.62 (m, 2H), 7.39–7.38 (m, 2H),
7.37–7.36 (m, 1H), 2.21 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ 154.88, 149.96, 144.31, 137.07, 129.66,
129.19, 128.43, 126.11, 124.43, 14.53. HRMS (ESI) M/Z
calcd for C14H14N3O4S. [M + H]+: 320.0700. Found:
320.0708.
N’‑(1‑Phenylethylidene)thiophene‑2‑sulfonohydrazide (3 l)
1
Yellow solid, m.p: 108.2–109.5 °C. H NMR (400 MHz,
DMSO-d6) δ 10.72 (s, 1H), 8.00 (d, J=4.4 Hz, 1H), 7.71 (d,
J=2.4 Hz, 3H), 7.42–7.39 (m, 3H), 7.21 (t, J=4.4 Hz, 1H),
2.20 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 154.14,
138.98, 137.24, 133.91, 132.76, 129.56, 128.40, 127.40,
126.08, 14.42. HRMS (ESI) M/Z calcd for C12H13N2O2S2.
[M+H]+: 281.0418. Found: 281.0425.
2,5‑Dichloro‑N’‑(1‑phenylethylidene)
benzenesulfonohydrazide (3 h)
N’‑(1‑(p‑Tolyl)ethylidene)benzenesulfonohydrazide (3 m)
1
Brown solid, m.p: 148.0–149.8 °C. H NMR (400 MHz,
1
DMSO-d6) δ 11.22 (s, 1H), 8.01(d, J=2.8 Hz, 2H), 7.76 (dd,
J=8.4, 2.8 Hz, 1H), 7.70 (d, J=8.4 Hz, 1H), 7.55–7.53 (m,
White solid, m.p: 135.0–140.6 °C. H NMR (400 MHz,
DMSO-d6) δ10.52 (s, 1H), 7.93 (dd, J = 8.4, 1.6 Hz,
1 3

Journal of the Iranian Chemical Society
2H), 7.66–7.59 (m, 3H), 7.51 (d, J = 8.0 Hz, 2H), 7.17
(d, J = 8.0 Hz, 2H), 2.29 (s, 3H), 2.15 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 153.54, 139.08, 134.79, 134.61,
132.95, 129.02, 128.95, 127.55, 125.92, 20.79, 14.26.
HRMS (ESI) M/Z calcd for C15H17N2O2S. [M + H]+:
289.1011 Found: 289.1003.
N’‑(1‑(4‑Chlorophenyl)
ethylidene)‑4‑methylbenzenesulfonohydrazide (3r)
Light brown solid, m.p: 149.7–153.0 °C. 1H NMR
(400 MHz, DMSO-d6) δ 10.61 (s, 1H), 7.81 (d, J=8.4 Hz,
2H), 7.63 (d, J = 8.4 Hz, 2H), 7.44–7.38 (m, 4H),2.35
(s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ
151.92, 143.43, 136.21, 136.16, 134.12, 129.52, 128.42,
127.72, 127.57, 21.02, 14.18. HRMS (ESI) M/Z calcd for
C15H16ClN2O2S. [M+H]+: 323.0621. Found: 323.0625.
N’‑(1‑(4‑Bromophenyl)ethylidene)
benzenesulfonohydrazide (3n)
Light brown solid, m.p: 139.5–141.7 °C. 1H NMR
(400 MHz, DMSO-d6) δ 10.70 (s, 1H), 7.94–7.91 (m, 2H),
7.66–7.64 (m, 1H), 7.63–7.59 (m, 2H), 7.57–7.55(m, 4H),
2.17 (s, 3H). 13C NMR(100 MHz, DMSO-d6) δ 152.30,
139.00, 136.53, 133.06, 131.36, 129.11, 128.01, 127.51,
122.95, 14.19. HRMS(ESI) M/Z calcd for C14H14BrN2O2S.
[M+H]+: 352.9959. Found: 352.9965.
N’‑(1‑(4‑Bromophenyl)
ethylidene)‑4‑methylbenzenesulfonohydrazide (3 s)
1
White solid, m.p: 169.5–171.0 °C. H NMR (400 MHz,
DMSO-d6) δ 10.61 (s, 1H), 7.80 (d, J = 8.0 Hz, 2H),
7.57–7.55 (m, 4H), 7.40 (d, J = 8.0 Hz, 2H), 2.36 (s,
3H), 2.15 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ
151.99, 143.44, 136.58, 136.14, 131.35, 129.53, 127.99,
127.56, 122.89, 21.03, 14.13. HRMS (ESI) M/Z calcd for
C15H16BrN2O2S. [M+H]+: 367.0116. Found: 367.0111.
N’‑(1‑(4‑Chlorophenyl)ethylidene)
benzenesulfonohydrazide (3o)
1
White solid, m.p: 149.3–151.1 °C. H NMR (400 MHz,
DMSO-d6) δ 10.70 (s, 1H), 7.94–7.93 (m, 1H), 7.92–7.91
(m, 1H), 7.66–7.59 (m, 5H), 7.43 (d, J = 8.8 Hz, 2H),
2.17 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 152.24,
139.00, 136.17, 134.17, 133.07, 129.12, 128.44, 127.75,
127.52, 14.24. HRMS (ESI) M/Z calcd for C14H14ClN2O2S.
[M+H]+: 309.0459. Found: 309.0465.
4‑Nitro‑N’‑(1‑(p‑tolyl)ethylidene)benzenesulfonohydrazide
(3t)
1
Brown solid, m.p: 181.8–183.5 °C. H NMR (400 MHz,
DMSO-d6) δ 10.84 (s, 1H), 8.44 (d, J=8.8 Hz, 2H), 8.17 (d,
J=9.2 Hz, 2H), 7.53 (d, J=8.4 Hz, 2H), 7.18 (d, J=8.0 Hz,
2H), 2.29 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ 154.96, 149.95, 144.37, 139.38, 134.34,
129.23, 129.02, 126.07, 124.40, 20.82, 14.45. HRMS (ESI)
M/Z calcd for C15H15N3O4S. [M+H]+: 333.0783. Found:
333.0779.
N’‑(1‑(4‑Fluorophenyl)ethylidene)
benzenesulfonohydrazide (3p)
1
White solid, m.p: 159.4–160.8 °C. H NMR (400 MHz,
DMSO-d6) δ 10.62 (s, 1H), 7.99 (q, J = 8.0, 5.2 Hz, 2H),
7.62–7.61 (m, 2H), 7.47 (t, J = 8.8 Hz, 2H), 7.40–7.35
(m, 3H), 2.19 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ 164.96 (d, JCF = 250.0 Hz),153.90, 137.27, 135.36,
130.62 (d, JCF = 10.0 Hz),129.49, 128.39, 126.00, 116.27
(d, JCF = 23.0 Hz),14.39. HRMS (ESI) M/Z calcd for
C14H14FN2O2S. [M+H]+: 293.0755. Found: 293.0757.
Acknowledgements We gratefully acknowledge the fnancial support
from Zhejiang Provincial Natural Science foundation of China (No.
LQ16H090004) and Research Project of Shaoxing University (No.
2017LG1003). We also thank Anna Kerkula for English language
editing.
Declaration
Conflict of interest There are no conficts to declare.
N’‑(1‑(4‑methoxyphenyl)ethylidene)
benzenesulfonohydrazide (3q)
References
1
White solid, m.p: 157.1–158.6 °C. H NMR (400 MHz,
DMSO-d6) δ 10.42 (s, 1H), 7.80 (d, J=8.2 Hz, 2H), 7.51 (d,
J=8.2 Hz, 2H), 7.40 (d, J=8.2 Hz, 2H), 7.17(d, J=8.2 Hz,
2H), 2.36 (s, 3H), 2.29 (s, 3H), 2.14 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 153.22, 143.30, 139.01, 136.24,
134.65, 129.42, 128.93, 127.59, 125.89, 21.00, 20.78,
14.20. HRMS (ESI) M/Z calcd for C16H19N2O2S. [M+H]+:
303.1162. Found: 303.1164.
1. M.B. Gawande, V.D. Bonifácio, R. Luque, P.S. Branco, R.S.
Varma, Benign by design: catalyst-free in-water, on-water green
chemical methodologies in organic synthesis. Chem. Soc. Rev.
42, 5522–5551 (2013). https://doi.org/10.1039/C3CS60025D
2. J.Á. Martín-Illán, D. Rodríguez-San-Miguel, C. Franco, I. Imaz,
D. Maspoch, J. Puigmartí-Luis, F. Zamora, Green synthesis of
imine-based covalent organic frameworks in water. Chem. Com-
mun. 56, 6704–6707 (2020). https://doi.org/10.1039/D0CC0
2033H
1 3

Journal of the Iranian Chemical Society
19. K.N. De Oliveira, P. Costa, J.R. Santin, L. Mazzambani, C.
Bürger, C. Mora, R.J. Nunes, M.M. De Souza, Synthesis and
antidepressant-like activity evaluation of sulphonamides and sul-
phonyl-hydrazones. Bioorg. Med. Chem. 19, 4295–4306 (2011).
https://doi.org/10.1016/j.bmc.2011.05.056
3. L.Y. LinY, Y. Zheng, R. Nie, L. Guo, Y. Wu, Green and ef-
cient synthesis of N-sulfenyl sulfoximines in water. ACS Sustain.
Chem. Eng. 6, 13644–13649 (2018). https://doi.org/10.1021/acssu
schemeng.8b03549
4. B. Wang, L. Tang, L. Liu, Y. Li, Y. Yang, Z. Wang, Base-mediated
tandem sulfonylation and oximation of alkenes in water. Green
Chem. 19, 5794–5799 (2017). https://doi.org/10.1039/C7GC0
3051G
20. A. Queen, P. Khan, D. Idrees, A. Azam, M.I. Hassan, Biological
evaluation of p-toluene sulphonylhydrazone as carbonic anhydrase
IX inhibitors: an approach to fght hypoxia-induced tumors. Int. J.
Biol. Macromol. 106, 840–850 (2018). https://doi.org/10.1016/j.
ijbiomac.2017.08.082
5. V.M. Muzalevskiy, K.V. Belyaeva, B.A. Trofmov, V.G. Nena-
jdenko, Diastereoselective synthesis of CF 3-oxazinoquinolines
in water. Green Chem. 21, 6353–6360 (2019). https://doi.org/10.
1039/C9GC03044A
21. R.G.D. Oliveira, F.S. Guerra, C.D.S. Mermelstein, P.D. Fer-
nandes, I.T.D.S. Bastos, F.N. Costa, R.C.R. Barroso, F.F. Fer-
reira, C.A.M. Fraga, Synthesis and pharmacological evaluation
of novel isoquinoline N-sulphonylhydrazones designed as ROCK
inhibitors. J. Enzym. Inhib. Med. Chem. 33, 1181–1193 (2018).
https://doi.org/10.1080/14756366.2018.1490732
6. R.N. Butler, A.G. Coyne, Water: nature’s reaction enforcercom-
parative efects for organic synthesis “In-Water” and “On-Water.”
Chem. Rev. 110, 6302–6337 (2010). https://doi.org/10.1021/cr100
162c
22. Ü.Ö. Özdemir, A. Altuntaş, A.B. Gündüzalp, F. Arslan, F.
Hamurcu, New aromatic/heteroaromatic propanesulfonylhydra-
zone compounds: Synthesis, physical properties and inhibition
studies against carbonic anhydrase II (CAII) enzyme. Spectro-
chim. Acta A 128, 452–460 (2014). https://doi.org/10.1016/j.saa.
2014.02.049
7. S.-T. Hou, N.-Q. Chen, P.-F. Zhang, S. Dai, Heterogeneous violo-
gen catalysts for metal-free and selective oxidations. Green Chem.
21, 1455–1460 (2019). https://doi.org/10.1039/c8gc03772h
8. P. Liu, G.-H. Zhang, P.-P. Sun, Transition metal-free decarboxyla-
tive alkylation reactions. Org. Biomol. Chem. 14, 10763–10777
(2016). https://doi.org/10.1039/c6ob02101h
23. G. Zapata-Sudo, L.M. Lima, S.L. Pereira, M.M. Trachez, F.P.
da Costa, B.J. Souza, C.E.S. Monteiro, N.C. Romeiro, E.D.
D’Andrea, R.T. Sudo, Docking, synthesis and anti-diabetic activ-
ity of novel sulfonylhydrazone derivatives designed as PPAR-
gamma agonists. Curr. Top Med. Chem. 12, 2037–2048 (2012).
https://doi.org/10.2174/156802612804910205
9. R.-K. Wang, L.-Q. Jiang, W.-B. Yi, Metal-free electrophilic
trifuoroethylthiolation with NaSO2CH2CF3. J. Org. Chem 83,
7789–7798 (2018). https://doi.org/10.1021/acs.joc.8b00676
10. A.T. Kelly, A.K. Franz, Metal-free synthesis of 1,3-disiloxanedi-
ols and aryl siloxanols. ACS Omega 4, 6295–6300 (2019). https://
doi.org/10.1021/acsomega.9b00121
24. J. Smith, H. Shechter, J. Bayless, L. Friedman, Intramolecular
processes in carbenic and cationic decomposition of cyclopro-
panecarboxaldehyde p-tosylhydrazone. J. Am. Chem. Soc. 87,
659–661 (1965). https://doi.org/10.1021/ja01081a052
11. D. Liu, M.-J. Jiao, X.-Z. Wang, P.-F. Xu, Metal-free visible-light-
induced construction of difuoro-dontaining dibenzazepines. Org.
Lett. 21, 4745–4749 (2019). https://doi.org/10.1021/acs.orglett.
9b01629
25. A.G. Stern, M.C. Ilao, A. Nickon, Hydrogen migrations in a con-
strained cyclohexylidene. Hax/Heq shift ratios in thermal and
photic Bamford-Stevens reactions. Tetrahedron 49, 8107–8118
(1993). https://doi.org/10.1016/S0040-4020(01)88030-3
26. V.V. Khripach, V.N. Zhabinskii, A.I. Kotyatkina, G.P.
Fando, A.S. Lyakhov, A.A. Govorova, J. van der Louw, M.B.
Groen, A. de Groot, An unusul Bamford-Stevens reaction of
17-toluenesulfonylhydrazono-3β-acetoxy-14α-hydroxyandrost-
5-ene. Mendeleev Commun. 11, 144–145 (2001). https://doi.org/
10.1070/MC2001v011n04ABEH001448
12. X. Liu, L.-M. Dai, Carbon-based metal-free catalysts. Nat. Rev.
Mater. 1, 1–12 (2016). https://doi.org/10.1038/natrevmats.2016.
64
13. W. Li, L. Gao, W. Zhuge, X. Sun, G. Zheng, Catalyst-free synthe-
sis of 3-sulfone nitrile from sulfonyl hydrazides and acrylonitrile
in water. Org. Biomol. Chem. 15, 7819–7823 (2017). https://doi.
org/10.1039/C7OB01558E
14. M.-Y. Han, J. Lin, W. Li, W.-Y. Luan, P.-L. Mai, Y. Zhang, Cat-
alyst-free nucleophilic addition reactions of silyl glyoxylates in
water. Green Chem. 20, 1228–1232 (2018). https://doi.org/10.
1039/C7GC03775A
27. F. Jin, Y. Xu, Y. Ma, Facile conversion of trifuoroacetyltriphenyl-
silane 2, 4, 6-triisepropylbenzenesulfonylhydrazone to 2, 2, 2-tri-
fuorodiazoethane. An unusual example of the bamford-stevens
reaction. Tetrahedron let. 33, 6161–6164 (1992). https://doi.org/
10.1002/chin.199310203
15. T.B. Fernandes, R.A. De Azevedo, R. Yang, S.F. Teixeira, G.H.
GoulartTrossini, J.A. MarzagaoBarbuto, A.K. Ferreira, R. Parise-
Filho, Arylsulfonylhydrazone induced apoptosis in MDA-MB-231
breast cancer cells. Lett. Drug Des. Discov. 15, 1288–1298 (2018).
https://doi.org/10.2174/1570180815666180321161513
16. K.N. Oliveira, M.M. Souza, P.C. Sathler, U.O. Magalhães, C.R.
Rodrigues, H.C. Castro, P.R. Palm, M. Sarda, P.E. Perotto, S.
Cezar, Sulphonamide and sulphonyl-hydrazone cyclic imide
derivatives: antinociceptive activity, molecular modeling and
in silico ADMET screening. Arch. Pharm. Res. 35, 1713–1722
(2012). https://doi.org/10.1007/s12272-012-1002-1
28. S. Jana, F. Li, C. Empel, D. Verspeek, P. Aseeva, R.M. Koenigs,
Stoichiometric photochemical carbenetransfer by Bamford-Ste-
vensreaction. Chem. Eur. J. 26, 2586–2591 (2020). https://doi.
org/10.1002/chem.201904994
29. J. Powell, M. Whiting, The decomposition of sulphonyl-hydrazone
salts-I: mechanism and stereochemistry. Tetrahedron 7, 305–310
(1959). https://doi.org/10.1016/S0040-4020(01)93200-4
30. W.J. Kerr, A.J. Morrison, M. Pazicky, T. Weber, Modifed Shapiro
reactions with bismesitylmagnesium as an efcient base reagent.
Org. lett. 14, 2250–2253 (2012). https://doi.org/10.1002/chin.
201234048
17. G. Zapata-Sudo, I.K. da Costa Nunes, J.S.C. Araujo, J.S. da Silva,
M.M. Trachez, T.F. da Silva, F.P. da Costa, R.T. Sudo, E.J. Bar-
reiro, L.M. Lima, Synthesis, solubility, plasma stability, and phar-
macological evaluation of novel sulfonylhydrazones designed as
anti-diabetic agents. Drug Des. Dev. Ther. 10, 2869–2879 (2016).
https://doi.org/10.2147/DDDT.S108327
31. M.-H. Yang, S.S. Matikonda, R.A. Altman, Preparation of fuoro-
alkenes via the shapiro reaction: direct access to fuorinated pep-
tidomimetics. Org. lett. 15, 3894–3897 (2013). https://doi.org/10.
1021/ol401637n
18. H. Wang, S.-X. Ren, Z.-Y. He, D.-L. Wang, X.-N. Yan, J.-T. Feng,
X. Zhang, Synthesis, antifungal activities and qualitative structure
activity relationship of carabronehydrazone derivatives as poten-
tial antifungal agents. Int. J. Mol. Sci. 15, 4257–4272 (2014).
https://doi.org/10.3390/ijms15034257
32. Q. Xiao, Y. Xia, H. Li, Y. Zhang, J. Wang, Coupling of N-tosylhy-
drazones with terminal alkynes catalyzed by copper (I): synthesis
of trisubstituted allenes. Angew. Chem. Int. Edit 50, 1114–1117
(2011). https://doi.org/10.1002/anie.201005741
1 3

Journal of the Iranian Chemical Society
33. H. Jiang, L. He, X. Li, H. Chen, W. Wu, W. Fu, Facile synthesis of
dibranched conjugated dienes via palladium-catalyzed oxidative
coupling of N-tosylhydrazones. Chem. Commun. 49, 9218–9220
(2013). https://doi.org/10.1021/ol401637n
48. D.-J. Chen, D.-P. Cheng, Z.-C. Chen, Hypervalent iodine in syn-
thesis. 61. Regeneration of carbonyl function from carbonyl deriv-
atives using polymer-supported phenyliodinebis (trifuoroacetate).
Synth. Commun. 31, 3847–3850 (2001). https://doi.org/10.1081/
SCC-100108235
34. H. Tan, I. Houpis, R. Liu, Y. Wang, Z. Chen, Olefn preparation
via palladium-catalyzed oxidative de-azotative and de-sulfta-
tiveinternal cross-coupling of sulfonylhydrazones. Org. let. 17,
3548–3551 (2015). https://doi.org/10.1002/chin.201542098
35. D.M. Allwood, D.C. Blakemore, A.D. Brown, S.V. Ley, Metal-
free coupling of saturated heterocyclic sulfonylhydrazones with
boronic acids. J. Org. Chem. 79, 328–338 (2014). https://doi.org/
10.1021/jo402526z
49. A.K. Yadav, V.P. Srivastava, L.D.S. Yadav, An easy access to
fuoroalkanes by deoxygenative hydrofuorination of carbonyl
compounds via their tosylhydrazones. Chem. Commun. 49,
2154–2156 (2013). https://doi.org/10.1039/C3CC00122A
50. Z. Liu, K.R. Babu, F. Wang, Y. Yang, X. Bi, Infuence of sulfonyl
substituents on the decomposition of N-sulfonylhydrazones at
room temperature. Org. Chem. Front. 6, 121–124 (2019). https://
doi.org/10.1039/C8QO00802G
36. Y. Liu, P. Liu, Y. Liu, Y. Wei, B. Dai, Metal-free reductive cou-
pling of biphenyl tosylhydrazones with phenols or benzyl alco-
hols. Lett. Org. Chem. 14, 748–757 (2017). https://doi.org/10.
2174/1570178614666170608084019
51. X. Li, X. Liu, H. Chen, W. Wu, C. Qi, H. Jiang, Copper-catalyzed
aerobic oxidative transformation of ketone-derived N-tosylhydra-
zones: an entry to alkynes. Angew. Chem. Int. Edn. 126, 14713–
14717 (2014). https://doi.org/10.1002/anie.201405058
52. Z. Luo, Y. Fang, Y. Zhao, X. Xu, C. Feng, Z. Li, X. Zhang, J.
He, PhI (OAc)2-mediated decomposition of N-arylsulfonylhy-
drazones: metal-free synthesis of (E)-vinyl sulfones. Tetrahedron
Lett. 57, 4105–4108 (2016). https://doi.org/10.1016/j.tetlet.2016.
07.099
37. S. Liu, M. Fang, D. Yin, Y. Wang, L. Liu, X. Li, G. Che, Synthe-
sis of 1-aryl-benzocycloalkane derivatives via one-pot two-step
reaction of benzocyclonone, tosylhydrazide, and arylboronic acid.
Synth. Commun. 49, 942–949 (2019). https://doi.org/10.1002/
chin.201542098
38. T. Naret, T. Bzeih, P. Retailleau, M. Alami, A. Hamze, One-pot
selective functionalization of nitrogen-containing heterocycles
with N-tosylhydrazones and amines. Adv. Synth. Catal. 360,
584–594 (2018). https://doi.org/10.1002/adsc.201701374
39. D.-F. Jiang, J.-Y. Hu, W.-J. Hao, S.-L. Wang, S.-J. Tu, B. Jiang,
Tunable Cu (I)-catalyzed site-selective dehydrogenative amination
of β, γ-unsaturated hydrazones for divergent synthesis of pyrazol-
4-ones and 1,6-dihydropyradazines. Org. Chem. Front. 5, 189–196
(2018). https://doi.org/10.1039/C7QO00743D
53. J.-L. Zhao, S.-H. Guo, J. Qiu, X.-F. Gou, C.-W. Hua, B. Chen, Iron
(III) phthalocyanine-chloride-catalyzed synthesis of sulfones from
sulfonylhydrazones. Tetrahedron Lett. 57, 2375–2378 (2016).
https://doi.org/10.1016/j.tetlet.2016.04.044
54. Á. García-Muñoz, A.I. Ortega-Arizmendi, M.A. García-Carrillo,
E. Diaz, N. Gonzalez-Rivas, E. Cuevas-Yañez, Direct, metal-free
synthesis of benzyl alcohols and deuterated benzyl alcohols from
p-toluenesulfonylhydrazones using water as solvent. Synthesis 44,
2237–2242 (2012). https://doi.org/10.1055/s-0031-1290372
55. Q. Ding, B. Cao, J. Yuan, X. Liu, Y. Peng, Synthesis of thioethers
via metal-free reductive coupling of tosylhydrazones with thiols.
Org. Biomol. Chem. 9, 748–751 (2011). https://doi.org/10.1039/
C0OB00639D
40. Y. Huang, P. Zhou, W. Wu, H. Jiang, Selective construction of
2-substituted benzothiazoles from o-iodoanilinederivatives S8 and
N-tosylhydrazones. J. Org. Chem. 83, 2460–2466 (2018). https://
doi.org/10.1021/acs.joc.7b03118
41. C. Wang, X. Geng, P. Zhao, Y. Zhou, Y.-D. Wu, Y.-F. Cui, A.-X.
Wu, I2/CuCl2-promoted one-pot three-component synthesis of ali-
phatic or aromatic substituted 1,2,3-thiadiazoles. Chem. Commun.
55, 8134–8137 (2019). https://doi.org/10.1039/C9CC04254G
42. S.-K. Mo, Q.-H. Teng, Y.-M. Pan, H.-T. Tang, Metal-and oxi-
dant-free electrosynthesis of 1, 2, 3-thiadiazoles from element
sulfur and N-tosylhydrazones. Adv. Synth. Catal. 361, 1756–1760
(2019). https://doi.org/10.1002/adsc.201801700
56. R. Grandi, A. Marchesini, U.M. Pagnoni, R. Trave, Conversion
of conjugated p-tosylhydrazones to the corresponding ethers by
sodium borohydride, sodium alkoxide or potassium carbonate in
alcohol solvents. J. Org. Chem. 41, 1755–1758 (1976). https://doi.
org/10.1021/jo00872a019
57. A.S. Tsai, J.M. Curto, B.N. Rocke, A.-M.R. Dechert-Schmitt,
G.K. Ingle, V. Mascitti, One-step synthesis of sulfonamides from
N-tosylhydrazones. Org. lett. 18, 508–511 (2016). https://doi.org/
10.1021/acs.orglett.5b03545
43. J. Chen, Y. Jiang, J.-T. Yu, J. Cheng, TBAI-catalyzed reaction
between N-tosylhydrazones and sulfur: a procedure toward
1,2,3-thiadiazole. J. Org. Chem. 81, 271–275 (2016). https://doi.
org/10.1021/acs.joc.5b02280
58. S. Sun, J.-T. Yu, Y. Jiang, J. Cheng, Cs2CO3-promoted car-
boxylation of N-tosylhydrazones with carbon dioxide toward
α-Arylacrylicacids. J. Org. Chem. 80, 2855–2860 (2015). https://
doi.org/10.1021/jo502908v
44. Z. Chen, Q. Yan, H. Yi, Z. Liu, A. Lei, Y. Zhang, Efcient syn-
thesis of 1, 2, 3-triazoles by copper-mediated C-N and N-N bond
formation starting from n-tosylhydrazones and amines. Chem.
Eur. J. 20, 13692–13694 (2014). https://doi.org/10.1002/chem.
201403515
59. S. Goyal, M. Budhiraja, D. Mandal, V. Tyagi, Experimental and
computational insights into the water-mediated decomposition of
N-sulfonylhydrazones: a catalyst-free synthesis of γ-keto/nitrile
sulfones. Asian J. Org. Chem. 9, 251–258 (2020). https://doi.org/
10.1002/ajoc.201900728
45. A. Ragupathi, A. Sagadevan, V.P. Charpe, C.-C. Lin, J.-R. Hwu,
K.C. Hwang, Visible-light-driven copper-catalyzed aerobic oxi-
dative cascade cyclization of N-tosylhydrazones and terminal
alkynes: regioselective synthesis of 3-arylcoumarins. Chem.
Commun. 55, 5151–5154 (2019). https://doi.org/10.1039/C9CC0
1801H
60. J. Gu, Z. Fang, Z. Yang, X. Li, N. Zhu, L. Wan, P. Wei, K. Guo,
A two-step continuous fow synthesis of 1, 4-disubstituted 1, 2,
3-triazoles under metal-and azide-free conditions. RSC Adv. 6,
89073–89079 (2016). https://doi.org/10.1039/C6RA19022G
61. S. Ito, A. Kakehi, T. Miwa, Reaction of α-bromoacetophenone
phenylsulfonylhydrazones. A new synthetic route to 2-arylimi-
dazoisoquinolines and-quinolines. Heterocycles 32, 2372–2380
(1991). https://doi.org/10.3987/COM-91-5851
46. Z.-G. Luo, P. Liu, Y.-Y. Fang, X.-M. Xu, C.-T. Feng, Z. Li, X.-M.
Zhang, J. He, Cs2CO3-mediated decomposition of N-tosylhy-
drazones for the synthesis of azines under mild conditions. Res.
Chem. Intermediat. 43, 1139–1148 (2017). https://doi.org/10.
1007/s11164-016-2688-3
62. A.K. Yadav, V.P. Srivastava, L.D.S. Yadav, An easy access to
fuoroalkanes by deoxygenative hydrofuorination of carbonyl
compounds via their tosylhydrazones. Chem. Commun. 49,
2154–2156 (2013). https://doi.org/10.1039/c3cc00122a
47. A. Kamal, M. Arifuddin, N. VenugopalRao, Facile transformation
of N, N-dimethylhydrazones and tosylhydrazones to ketones with
dimethyl sulfate and potassium carbonate. Synth. Commun. 28,
3927–3931 (1998). https://doi.org/10.1080/00397919808004950
1 3

Journal of the Iranian Chemical Society
63. V.P. Miller, D.-Y. Yang, T.M. Weigel, O. Han, H.-W. Liu, Studies
of the mechanistic diversity of sodium cyanoborohydride reduc-
tion of tosylhydrazones. J. Org. Chem. 54, 4175–4188 (1989).
https://doi.org/10.1021/jo00278a035
hydrazones via one-pot reaction. ACS Sustain. Chem. Eng. 4,
1899–1905 (2016). https://doi.org/10.1021/acssuschemeng.6b001
93
70. O.S. Morozov, P.S. Gribanov, A.F. Asachenko, P.V. Dorovatovskii,
V.N. Khrustalev, V.B. Rybakov, M.S. Nechaev, Hydrohydrazina-
tion of arylalkynescatalyzed by an expanded ring N-heterocyclic
carbene (er-NHC) gold complex under solvent-free conditions.
Adv. Synth. Catal. 358, 1463–1468 (2016). https://doi.org/10.
1002/chin.201637045
64. J. Wang, S. Zha, K. Chen, J. Zhu, Cp* Co (III)-catalyzed, N-N
bond-based redox-neutral synthesis of isoquinolines. Org. Chem.
Front. 3, 1281–1285 (2016). https://doi.org/10.1039/C6QO0
0367B
65. X.-W. Feng, J. Wang, J. Zhang, J. Yang, N. Wang, X.-Q. Yu, Cop-
per-catalyzed nitrogen loss of Sulfonylhydrazones: a reductive
strategy for the synthesis of sulfones from carbonyl compounds.
Org. Lett. 12, 4408–4411 (2010). https://doi.org/10.1021/ol101
955x
71. Y. Ding, H. Li, Y. Meng, T. Zhang, J. Li, Q.-Y. Chen, C. Zhu,
Directs ynthesis of hydrazones by visible light mediated aero-
bic oxidative cleavage of the C=C bond. Org. Chem. Front. 4,
1611–1614 (2017). https://doi.org/10.1039/C7QO00276A
72. X. Zhu, S. Chiba, Construction of 1-pyrroline skeletons by Lewis
acid-mediated conjugate addition of vinyl azides. Chem. Com-
mun. 52, 2473–2476 (2016). https://doi.org/10.1039/C5CC1
0299E
66. N. Karaman, E.E. Oruç-Emre, Y. Sıcak, B. Çatıkkaş, A.
Karaküçük-İyidoğan, M. Öztürk, Microwave-assisted synthe-
sis of new sulfonyl hydrazones, screening of biological activi-
ties and investigation of structure-activity relationship. Med.
Chem. Res. 25, 1590–1607 (2016). https://doi.org/10.1007/
s00044-016-1592-0
73. Y.F. Wang, M. Hu, H. Hayashi, B. Xing, S. Chiba, Linking of
alcohols with vinyl azides. Org. let. 18, 992–995 (2016). https://
doi.org/10.1021/acs.orglett.6b00116
67. P. Nun, C. Martin, J. Martinez, F. Lamaty, Solvent-free synthesis
of hydrazones and their subsequent N-alkylation in a Ball-mill.
Tetrahedron 67, 8187–8194 (2011). https://doi.org/10.1016/j.tet.
2011.07.056
74. A. Benjamin, J. Belinka, H. Alfred, Facile conversion of vinyl
azides to ketones or aldehydes. J. Org. Chem. 44(25), 4712–4713
(1979). https://doi.org/10.1021/jo00393a056
68. Q. Yang, W. Hao, Y. He, Q. Zhang, X. Yu, Y. Hua, A green syn-
thesis and antibacterial activity of N-arylsulfonylhydrazone com-
pounds. Heterocycl. Commun. 25, 152–156 (2019). https://doi.
org/10.1515/hc-2019-0023
75. X. Zhang, B. Lu, X. Wang, J. Zhao, Q. Cai, Deoximation reaction
in room temperature ionic liquids under mild conditions. Chin. J.
Chem. 29, 1846–1850 (2011). https://doi.org/10.1002/cjoc.20110
0041
69. M.R. Cunha, M.T. Tavares, C.F. Carvalho, N.A. Silva, A.D.
Souza, G.J. Pereira, F.B.F. Ferreira, R. Parise-Filho, Environmen-
tally safe condition for the synthesis of aryl and alkyl sulfonyl
1 3