A Novel Synthesis of Arylsulfonyl Hydrazine Derivatives Via the Reaction of Arylsulfonyl Hydrazone Salts and Hydrazonoyl Chlorides

Article abstract of DOI:10.1080/10426507.2013.865122

An efficient method for the synthesis of arylsulfonyl hydrazines and diazo compounds via arylsulfonyl hydrazone salts is described. The reaction was performed in DMF using hydrazonoyl chlorides and sodium arylsulfonyl hydrazones, which were easily prepare

Full text of DOI:10.1080/10426507.2013.865122

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Phosphorus, Sulfur, and Silicon and the Related
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A novel synthesis of arylsulfonyl hydrazine derivatives
via the reaction of arylsulfonyl hydrazone salts and
hydrazonoyl chlorides
a
Gholamhossein Khalili
a
Chemistry Department, Bushehr Branch, Islamic Azad University, PO Box 7519619555,
Bushehr, Iran
Accepted author version posted online: 30 Jul 2014.
To cite this article: Gholamhossein Khalili (2014): A novel synthesis of arylsulfonyl hydrazine derivatives via the reaction
of arylsulfonyl hydrazone salts and hydrazonoyl chlorides, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2013.865122
To link to this article: http://dx.doi.org/10.1080/10426507.2013.865122
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ACCEPTED MANUSCRIPT
A novel synthesis of arylsulfonyl hydrazine derivatives via the reaction of arylsulfonyl
hydrazone salts and hydrazonoyl chlorides
Gholamhossein Khalili*
Chemistry Department, Bushehr Branch, Islamic Azad University, PO Box 7519619555,
Bushehr, Iran
Email: khalili_gh1352@yahoo.com
Abstract: An efficient method for the synthesis of arylsulfonyl hydrazines and diazo
compounds via arylsulfonyl hydrazone salts is described. The reaction was performed in DMF
using hydrazonoyl chlorides and sodium arylsulfonyl hydrazones, which were easily prepared
from carbonyl compounds.
O
O
O
O
Ar''
N
Ph
Ar
Ar
N
S
DMF
Ph
N
S
N
Ar'
N
Ar'
+
N2
+
N
H
100 °C , 2 h
H
R
Cl
R
Ar''
Na
Key words: arylsulfonyl hydrazone salt; sulfone; diazo; arylsulfonyl hydrazine; hydrazonoyl
chloride
1
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INTRODUCTION
The sulfone functional group is frequently present in synthetic targets in medicinal chemistry
research. For example, sulfone derivatives were found to be potent inhibitors for several
1
-3
enzymes such as cyclooxygenase-2, HIV-1 reverse transcriptase, and matrix metalloproteinase.
On the other hand, sulfones exhibit interesting chemical properties and are useful intermediates
4
in organic synthesis. Therefore, among the various sulfur-containing organic compounds
5
,6
sulfones occupy an important position. The most common methods for sulfone preparation
7
-9
10-13
include the oxidation of sulfides and the alkylation of sulfinate salts
. Though these
methods are attractive for their simplicity, they are incompatible with numerous functional
groups, including amines, olefins, and some nitrogen heterocycles.
Diazo compounds can be generated from their corresponding sulfonyl hydrazone salts, by
1
4
15
16-20
photolysis, vacuum pyrolysis, thermolysis of a suspension in a suitable solvent ,
or
21
thermolysis in a biphasic medium in the presence of a phase transfer catalyst (PTC). We
observed the formation of corresponding sulfonyl hydrazines and diazo compounds in good
yields when hydrazone salts were heated in the presence of hydrazonoyl chlorides in DMF.
RESULTS AND DISCUSSION
Our studies commenced by thermal decomposition of sulfonyl hydrazine salts in the presence of
hydrazonoyl chloride compounds in DMF. A facile reaction occurred affording two products of
diazo 3 and arylsulfonyl hydrazine 4. (Scheme 1)
2
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Table 1 contains the results of our study. The structures of compounds 3a-3f are well known in
2
2
the literature. The products of 4a-4f were deduced from their elemental analyses and their IR,
1
13
1
H NMR and C NMR spectra. For example, In the H NMR spectrum of 4a, the methyl protons
resonated at δ = 2.38 ppm as singlet and NH group was discernible at δ = 7.70 ppm. The
1
13
aromatic protons signals were visible between δ = 6.85 and δ = 7.69 ppm. The H and C NMR
spectra of 4b-4f were similar to those for 4a except for the alkyl/aryl regions. Partial assignment
of these resonances is given in the experimental.
A mechanistic rationalization for the reaction is given in Scheme 2. The initial event is the
2
3
formation of the sodium arylsulfinate 5 and diazo 3 by thermolysis of hydrazone salt 1 in DMF.
The arylsulfinate ion can add to hydrazonoyl chloride 2 resulting in the formation of arylsulfonyl
hydrazine derivatives 4.
In summary, we have found a simple and efficient method for sulfonylation of hydrazonoyl
chlorids by in situ generation of the diazo and sodium sulfinate compounds. Furthermore, we
have designed the simplest route to access diazo compounds by thermolysis of hydrazone salts in
DMF without any activation or modification. We hope that this method may successfully employ
as the key step in the synthesis of products with unique properties for medicinal chemistry
programs.
3
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EXPERIMENTAL
Compounds arylsulfonyl hydrazone salt 1 and hydrazonoyl chloride 2 were prepared according
2
4,25
to the literature
. M.p.: Electrothermal-9100 apparatus. IR Spectra: Shimadzu-IR-460
−
1
1
13

spectrometer;
00.1 and 100.6 MHz, resp.; δ in ppm, J in Hz. MS: Finnigan-MAT-8430EI-MS mass
spectrometer; at 70 eV; in m/z (rel. %). Elemental analyses: Vario EL III CHNOS elemental
in cm . H- and C-NMR spectra: Bruker DRX-400 Avance instrument at
4
1
13
analyzer. Sample H and C NMR spectra for 4a and 4b are presented in the Supplemental
Materials (Figures S 1 – S 4)
General procedure for the synthesis of 3 and 4: A solution of sodium arylsulfonyl hydrazone
1
(2 mmol) and hydrazonoyl chloride 2 (2.2 mmol) in DMF (7 mL) was heated at 100 °C for 2 h.
The mixture was poured onto H O (10 ml), extracted with AcOEt (15 ml), dried (MgSO ), and
the solvent was removed under reduced pressure. The residue was purified by silica gel column
chromatography using hexan/AcOEt (8:1) as eluent to give products 3 (R = 0.69) and 4 (R
.24).
-Phenyl-2-((4-chlorophenyl)(p-tosyl)methylene)hydrazine (4a)
2
4
f
f
=
0
1
−
1
Pale yellow powder, yield: 0.29 g (76%), m.p. 137-140 °C. IR (KBr) (νmax/cm ): 3270 (NH),
1
2
925, 2346, 1585, 1507, 1283 (SO
2
), 1140 (SO
2
), 1082, 992, 591. H NMR (400.1 MHz,
3
CDCl
3
): δ = 2.38 (3 H, s, Me), 6.85-6.87 (3 H, m, 3 CH), 7.17 (2 H, d, J = 8.4 Hz, 2 CH),
3
3
3
7
.21 (2 H, d, J = 8.4 Hz, 2 CH), 7.25 (2 H, d, J = 8.4 Hz, 2 CH), 7.43 (2 H, d, J = 8.4 Hz, 2
13
CH), 7.68-7.69 (2 H, m, 2 CH), 7.70 (1 H, b, NH). C NMR (100.6 MHz, CDCl
3
): δ = 21.7
(
(
Me), 113.9 (2 CH), 122.6 (CH), 124.5 (C), 128.9 (2 CH), 129.3 (2 CH), 129.6 (2 CH), 130.2
2 CH), 131.3 (2 CH), 135.3 (C), 137.3 (C), 141.5 (C), 142.1 (C), 144.5 (C). EI-MS: 384
4
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+
(
M , 10), 141 (35), 91 (100), 77 (76). Anal. Calcd for C20
H17ClN
2
2
O S (385.85): C 62.41, H
4
.45, N 7.27, S 8.31%. Found: C 62.13, H 4.29, N 7.38, S 8.12 %.
-Phenyl-2-(( 4-chlorophenyl)(phenylsulfonyl)methylene)hydrazine (4b)
1
−
1
Pale yellow powder, yield: 0.28 g (78%), m.p. 128-130 °C. IR (KBr) (νmax/cm ): 3273
1
(
NH), 2926, 2348 , 1585, 1504, 1283 (SO
2
), 1141 (SO
2
), 1082, 995, 689. H NMR (400.1
3
3
MHz, CDCl
3
): δ = 6.47 (2 H, d, J = 7.6 Hz, 2 CH), 6.88 (1 H, t, J = 7.2 Hz, CH), 7.13-7.16
1
3
(
3 H, m, 3 CH), 7.19-7.22 (4 H, m, 4 CH), 7.64-7.67 (4 H, m, 4 CH), 7.73 (1 H, b, NH). C
NMR (100.6 MHz, CDCl ): δ = 112.6 (2 CH), 122.4 (CH), 124.0 (C), 128.7 (2 CH), 129.0 (2
3
CH), 129.2 (2 CH), 130.0 (2 CH), 130.3 (2 CH), 134.3 (CH), 136.7 (C), 139.5 (C), 141.8 (C),
+
1
44.9 (C). EI-MS: 370 (M , 10), 141 (40), 77 (100). Anal. Calcd for C19
H15ClN
2
2
O S
(
370.83): C 61.53, H 4.07, N 7.55, S 8.64%. Found: C 61.34, H 4.12, N 7.45, S 8.75 %.
-Phenyl-2-(( p-tosyl)(p-tolyl)methylene)hydrazine (4c)
1
−
1
Pale yellow powder, yield: 0.29 g (80%), m.p. 118-121 °C. IR (KBr) (νmax/cm ): 3274 (NH),
1
2
928, 2313, 1585, 1506, 1286 (SO
2
), 1145 (SO
2
), 1076, 982, 595. H NMR (400.1 MHz,
3
CDCl
3
): δ = 2.34 (3 H, s, Me), 2.36 (3 H, s, Me), 6.86 (4 H, d, J = 7.2 Hz, 4 CH), 7.11-7.15
3
(
3 H, m, 3 CH), 7.20-7.24 (4 H, m, 4 CH), 7.68 (2 H, d, J = 8.0 Hz, 2 CH), 7.86 (1 H, b,
13
NH). C NMR (100.6 MHz, CDCl
3
): δ = 21.5 (Me), 21.6 (Me), 113.8 (2 CH), 122.2 (CH),
1
1
23.1 (C), 126.4 (C), 128.9 (2 CH), 129.2 (2 CH), 129.5 (2 CH), 129.7 (2 CH), 130.4 (2 CH),
+
36.2 (C), 141.2 (C), 142.4 (C), 144.2 (C). EI-MS: 364 (M , 8), 155 (63), 91 (100), 77 (65).
Anal. Calcd for C21
H
20
N
2
O
2
S (364.44): C 69.20, H 5.53, N 7.68, S 8.79%. Found: C 69.45, H
5
.44, N 7.58, S 8.69 %.
5
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1
-Phenyl-2-((phenylsulfonyl)(p-tolyl)methylene)hydrazine (4d)
−
1
Pale yellow powder, yield: 0.27 g (78%), m.p. 120-123 °C. IR (KBr) (νmax/cm ): 3272 (NH),
1
2
918, 2328 , 1567, 1521, 1287 (SO
2
), 1136 (SO
2
), 1080, 987, 593. H NMR (400.1 MHz,
3
CDCl
3
): δ = 2.43 (3 H, s, Me), 6.88-7.25 (7 H, m, 7 CH), 7.30 (2 H, d, J = 7.9 Hz, 2 CH),
3
3
7
.53 (2 H, d, J = 7.7 Hz, 2 CH), 7.68 (1 H, t, J = 7.2 Hz, CH), 7.80 (1 H, b, NH), 7.92 (2 H,
3
13
d, J = 7.9 Hz, 2 CH). C NMR (100.6 MHz, CDCl
3
): δ = 21.4 (Me), 113.7 (2 CH), 122.2
(
CH), 129.9 (C), 128.5 (2 CH), 128.9 (2 CH), 129.2 (2 CH), 129.6 (2 CH), 130.4 (2 CH),
+
1
33.2 (CH), 139.2 (C), 141.4 (C), 142.3 (C), 142.9 (C). EI-MS: 350 (M , 12), 209 (80), 141
(
15), 91 (100), 77 (75). Anal. Calcd for C20
H
18
N O
2 2
S (350.43): C 68.55, H 5.18, N 7.99, S
9
1
.14%. Found: C 68.08, H 5.22, N 7.78, S 9.23 %.
-Phenyl-2-(phenyl(tosyl)methylene)hydrazine (4e)
−
1
Pale yellow powder, yield: 0.28 g (80%), m.p. 115-117 °C. IR (KBr) (νmax/cm ): 3276 (NH),
1
2
921, 2310, 1585, 1506, 1285 (SO
2
), 1139 (SO
2
), 1015, 982, 565. H NMR (400.1 MHz,
CDCl
3
): δ = 2.45 (3 H, s, Me), 6.92-6.95 (4 H, m, 4 CH), 7.15-7.19 (3 H, m, 3 CH), 7.50-
3
13
7
.56 (5 H, m, 5 CH), 7.76 (2 H, d, J = 8.2 Hz, 2 CH), 7.85 (1 H, b, NH). C NMR (100.6
MHz, CDCl ): δ = 21.6 (Me), 113.9 (2 CH), 122.3 (CH), 126.2 (C), 128.8 (2 CH), 129.2 (2
3
CH), 129.5 (2 CH), 129.7 (2 CH), 129.8 (2 CH), 130.8 (CH), 136.2 (C), 142.3 (C), 142.8 (C),
+
1
44.3 (C). EI-MS: 350 (M , 15), 155 (100), 141 (71), 91 (82), 77 (65). Anal. Calcd for
C
20
H
18
N
2
2
O S (350.43): C 68.55, H 5.18, N 7.99, S 9.14%. Found: C 68.29, H 5.27, N 7.68, S
9
.28 %.
6
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1
-Phenyl-2-(phenyl(phenylsulfonyl)methylene)hydrazine (4f)
−
1
Pale yellow powder, yield: 0.25 g (75%), m.p. 110-114 °C. IR (KBr) (νmax/cm ): 3268 (NH),
1
2
917, 2321, 1575, 1532, 1284 (SO
2
), 1128 (SO
2
), 1061, 928, 578. H NMR (400.1 MHz,
CDCl
3
): δ = 6.86-6.90 (5 H, m, 5 CH), 7.75-7.80 (4 H, m, 4 CH), 7.86-7.97 (6 H, m, 6 CH),
1
3
7
1
.85 (1 H, b, NH). C NMR (100.6 MHz, CDCl ): δ = 113.8 (2 CH), 122.4 (CH), 126.0 (C),
3
28.8 (2 CH), 128.9 (2 CH), 129.2 (2 CH), 129.7 (2 CH), 129.8 (2 CH), 130.9 (CH), 133.5
+
(
(
CH), 149.1 (C), 142.2 (C), 142.6 (C). EI-MS: 336 (M , 7), 195 (63), 141 (25), 105 (83), 91
100), 77 (85). Anal. Calcd for C19
H
16
N
2
O S (336.40): C 67.84, H 4.49, N 8.33, S 9.53%.
2
Found: C 67.70, H 4.58, N 8.16, S 9.37 %.
7
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[
[
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O
O
O
O
Ar''
N
Ph
Ar
Ar
N
S
DMF
Ph
N
S
Ar'
Ar'
N
N
+
N2
+
N
H
100 °C , 2 h
H
Ar''
R
Cl
R
3
4
Na
2
1
Scheme 1
O O
S
Ar''
N
Ph
Ar
Ar
N
DMF
00 °C
'
N
Ar'
2
N2
+
ArSO Na
N
+
1
H
R
R
Cl
5
1
Na
3
2
O O
S
-NaCl
Ph
N
N
Ar'
H
Ar''
4
Scheme 2
1
0
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Table 1. Yields of diazo and arylsulfonyl hydrazine compounds from sodium arylsulfonyl
hydrazones
Ar'
Ar''
Entry
Diazo Arylsulfonyl hydrazine Yield (3, 4)%
R
Ar
7
0, 76
0, 78
75, 80
3, 78
1
2
3
Me 4-NO C H
4-MeC H4
4-ClC H4
3a
4a
4b
2
6
4
6
6
8
Et
Ph
4-ClC H4
3b
3c
Ph
6
Me
4-MeC H
4-MeC H
4-MeC H4
6
4
6
4
6
4c
7
4
5
Me
Me
Ph
Ph
4-MeC H4
4d
4e
4f
6
3d
4-ClC H
3e
3f
72, 80
68, 75
6
4
4-MeC H
Ph
Ph
6
4
6
Ph
Ph
Ph
1
1
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