Synthesis and x-ray structure of (1 Z,2 Z)-1,2-Bis(2-(phenylsulfonyl)-1-(4-tolyl)ethylidene)hydrazine

Article abstract of DOI:10.1155/2014/929401

The title compound (1Z,2Z)-1,2-bis(2-(phenylsulfonyl)-1-(4-tolyl)ethylidene)hydrazine (5) was prepared, in 78% yield, by the reaction of 2-(phenylsulfonyl)-1-(4-tolyl)ethan-1-one (3) with hydrazine hydrate in acetic acid at 90°C under microwave irradiatio

Full text of DOI:10.1155/2014/929401

Hindawi Publishing Corporation
Journal of Chemistry
Volume 2014, Article ID 929401, 5 pages
http://dx.doi.org/10.1155/2014/929401
Research Article
Synthesis and X-Ray Structure of (1Z,2Z)-1,2-Bis(2-
(phenylsulfonyl)-1-(4-tolyl)ethylidene)hydrazine
Hatem A. Abdel-Aziz,1,2 Hazem A. Ghabbour,1
Khalid A. Al-Rashood,1 and Hoong-Kun Fun1,3
1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
2Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt
3X-Ray Crystallography Unit, School of Physics, Universiti Sains Malaysia (USM), 11800 Penang, Malaysia
Correspondence should be addressed to Hatem A. Abdel-Aziz; hatem 741@yahoo.com
Received 7 September 2014; Accepted 26 October 2014; Published 22 December 2014
Academic Editor: Hakan Arslan
Copyright © 2014 Hatem A. Abdel-Aziz et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
e title compound (1Z,2Z)-1,2-bis(2-(phenylsulfonyl)-1-(4-tolyl)ethylidene)hydrazine (5) was prepared, in 78% yield, by the
reaction of 2-(phenylsulfonyl)-1-(4-tolyl)ethan-1-one (3) with hydrazine hydrate in acetic acid at 90∘C under microwave irradiation
in a closed vessel with power 100 W for 3 min. e structure of the newly synthesized compound was established under the basis of its
1
˚
IR, mass, H NMR, and X-ray single crystal analysis. e crystal of 5 belongs to monoclinic space group, P2 /c, with a = 5.2944 (3) A,
1
3
b = 17.5748 (9) A, c = 15.4701 (8) A, ꢀ = 105.767 (4) , Z = 2, V = 1385.30 (13) A , Dc = 1.306 Mg m−3, ꢁ = 2.05 mm−1, F(000) = 572, R =
0.075, and wR = 0.224 for 1419 observed reflections with I > 2ꢂ(I). e asymmetric unit of compound 5 contains one molecule with
Z configuration about the C7=N1 and C7A=N1A double bond. is Z configuration of 5 is stabilized by intramolecular hydrogen
bonds C1–H1A⋅ ⋅ ⋅ N1 and C1A–H1AA⋅ ⋅ ⋅ N1A. e molecular packing in the crystal structure of 5 is stabilized by intermolecular
interactions forming a three-dimensional network.
∘
˚
˚
˚
1. Introduction
chromene-based hydrazones showed cytotoxicity against
K562, MDA-MB-468, and HT-29 cell lines [8]. Furthermore,
aroylhydrazone derivatives have been reported as inhibitors
of carbonic anhydrases from the extremophilic bacteria
SspCA and SazCA [9].
Hydrazones are a very important class of compounds with
effective biological activities. ey are found to possess anti-
HIV [1], anticonvulsant [2], and antitubercular [3] activi-
ties. Furthermore, hydrazones have been reported as active
antimicrobial agents where hydrazone function is the main
scaffold in several marketed antimicrobial drugs such as the
potent intestinal antiseptic drug nifuroxazide [4]. In addition,
(Z)-Nꢀ-(2-oxoindolin-3-ylidene)formohydrazide exhibited a
good activity against S. aureus microbe which is almost
similar to that of ciprofloxacin [5]. Moreover, hydrazone
derivatives have been reported as potent anticancer agents;
for example, the modulation of activity of the well-known
anticancer drug doxorubicin occurred through a conjuga-
tion with fatty acyl and terphenyl hydrazones [6]. In addi-
tion, isatin-based hydrazones have been reported as active
agents against multidrug-resistant cancer cells [7] whereas
On the other hand, sulfones received a special interest due
to their significant biological activity; for example, sulfone
function is essential in the antimicrobial drug dapsone [10].
ꢀ-Keto sulfones have been reported as key intermediates in
the synthesis of several biologically active compounds [11]; for
example, novel celecoxib analogs were synthesized as potent
anti-inflammatory agents starting from some ꢀ-keto sulfone
derivatives [12].
In the light of previous research publications and in con-
tinuation of our interests in the synthesis of biologically
active compounds containing hydrazone function and/or
sulfone moiety [5, 7–9, 12], we have reported in this study
the microwave-assisted synthesis and X-ray single crystal

2
Journal of Chemistry
O
O
O O
S
analysis of the title compound which is a sulfone-based
hydrazone derivative.
O
O
S
Br
R = Me
Na
+
Me
R
1
2
3
2. Experimental
NH2 NH2
(i)
2.1. Chemistry
Me
2.1.1. General. Melting point was determined on a Gal-
lenkamp melting point apparatus and it is uncorrected.
Infrared (IR) spectrum was recorded as KBr disks using the
Perkin Elmer FT-IR Spectrum BX apparatus. NMR spectrum
was scanned in DMSO-ꢀ6 on a Bruker NMR spectrometer
operating at 500 MHz for 1H and 125 MHz for 13C. Chemical
shifs are expressed in ꢁ-values (ppm) relative to TMS as an
internal standard. Coupling constants (ꢂ) are expressed in
Hz. e mass spectrum was measured on an Agilent Triple
Quadrupole 6410 QQQ LC/MS equipped with an ESI (elec-
trospray ionization) source. e microwave irradiations were
carried out in an Explorer-48 microwave reactor from CEM,
USA.
NH2
S
O
(Z)
N
O O
O
N
3
S
N
O
O
(Z)
S
Me
5
4
Me
Scheme 1: Synthetic pathway of compound 5. Reagents and condi-
tions: (i) NH –NH (99%)/AcOH, MWI, 100 W, 90∘C, 3 min, 78%
2
2
yield.
selected for X-ray diffraction analysis. Data were collected
on a Bruker APEX-II CCD diffractometer equipped with
graphite monochromatic CuK\ꢅ radiation (ꢆ = 1.54178) at
293 (2) K. Cell refinement and data reduction were done
by Bruker SAINT; program used to solve structure and
refine structure is SHELXS-97 [14]. e final refinement
was performed by full-matrix least-squares techniques with
2.1.2. Synthesis of 2-(Phenylsulfonyl)-1-(4-tolyl)ethan-1-one
(3). To a solution of 2-bromo-1-(4-tolyl)ethan-1-one (1)
(2.13 g, 10 mmol) in absolute ethanol (50 mL), sodium ben-
zenesulfinate (2) (13 mmol) was added. e mixture was
refluxed for 2 h and then lef to cool. e reaction mixture
was poured into cold water and the solid product was filtered
off, washed with water, dried, and finally recrystallized from
EtOH to afford compound 3 [13].
2
anisotropic thermal data for nonhydrogen atoms on ꢇ . All
the hydrogen atoms were placed in calculated positions and
constrained to ride on their parent atoms. Multiscan absorp-
tion correction was applied by the use of SADABS sofware.
2.1.3. Synthesis of (1Z,2Z)-1,2-Bis(2-(phenylsulfonyl)-1-
(4-tol-yl)ethylidene)hydrazine (5)
2.2.2. Crystal Data of 5. Molecular formula: C H N O S ,
30 28
2
4
2
˚
MWI Synthesis. A mixture of 2-(phenylsulfonyl)-1-(4-tol-
yl)ethan-1-one (3) (0.55 g, 2 mmol) and hydrazine hydrate
(99%, 1.1 mmol) in glacial acetic acid (5 mL) was added to
a closed vessel in a microwave reactor. e closed vessel
was irradiated with microwaves at 100 W and 90∘C and with
200 psi maximum pressure for 3 min (holding time). e
vessel was cooled and the solid that formed was collected by
filtration and washed with ethanol, dried, and finally recrys-
tallized from AcOH to afford compound 5 in 78% yield.
formula weight: 544.66, monoclinic, ꢈꢉ1ꢄꢊ, ꢋ = 5.ꢉ944∘(3) A,
˚
˚
ꢌ = 17.5748 (9) A, ꢊ = 15.4701 (8) A, ꢍ = 105.767 (4) , ꢎ =
3
1385.30 (13) A , and ꢏ = 1.306 Mg m−3. A total of 5664
˚
calc
reflections were measured, of which 2120 were independent.
ꢐ
= 0.037, dataset (ℎ; ꢑ; ꢒ) = −6, 4; −20, 18; −14, 17. Refine-
int
2
2
2
ment of ꢇ , against all reflections, led to ꢐꢓꢇ > ꢉꢔ(ꢇ )] =
2
0.075, ꢕꢐ(ꢇ ) = 0.224, ꢖ = 1.04. e labeled displacement
ellipsoid plot of this molecule showing the three intramolec-
ular interactions is shown in Figure 2.
Conventional Synthesis. A mixture of 2-(phenylsulfonyl)-1-(4-
tolyl)ethan-1-one (3) (0.55 g, 2 mmol) and hydrazine hydrate
(1.1 mmol) in glacial acetic acid (30 mL) was refluxed for 10 h
and then lef to cool. e precipitated product was filtered
off, washed with ethanol, and dried. Recrystallization from
AcOH afforded the corresponding compound 5 in 42% yield;
m.p. 140–142∘C; IR ] 1612 (C=N) cm−1; 1H NMR (DSMO-ꢀ6,
500 MHz) ꢁ 2.26 (s, 6H, 2CH ), 4.80 (s, 4H, 2CH ), 7.05-7.06
3. Results and Discussion
3.1. Chemistry. Hydrazones can be synthesized by reacting
hydrazines with carbonyl compounds in various organic
solvents such as MeOH, EtOH, BuOH, THF, AcOH, or
AcOH/EtOH. Also hydrazones can be synthesized by the
coupling of aryldiazonium salts with active methylene
compounds [15]. In this study, 2-(phenylsulfonyl)-1-(4-
tolyl)ethan-1-one (3) [13] was synthesized by the reaction of
2-bromo-1-(4-tolyl)ethan-1-one (1) with sodium benzenesul-
finate (2) (Scheme 1). e reaction of 2-(phenylsulfonyl)-1-
(4-tolyl)ethan-1-one (3) with hydrazine hydrate in acetic acid
at 90∘C under microwave irradiation in a closed vessel with
power 100 W for 3 min (holding time) resulted in the forma-
tion of the title compound 5, as final isolable product, in 78%
yield (Scheme 1). e conventional synthesis of 5 at reflux-
ing temperature for 10 h afforded 42% yield. However, the
3
2
(m, 4H, ArHs), 7.47 (d, ꢂ = 8.0 Hz, 4H, ArHs), 7.58–7.61 (m,
4H, ArHs), 7.69–7.72 (m, 2H, ArHs), 7.92 (d, ꢂ = 8.0 Hz, 4H,
ArHs); 13C NMR (DSMO-ꢀ6, 125 MHz) ꢁ 20.62, 51.58, 125.11,
127.89, 128.43, 129.16, 132.14, 133.95, 135.22, 136.35, 139.50; MS
(ESI) ꢃꢄ/ 544.4 [M]+.
2.2. X-Ray Crystallography
2.2.1. General. Single crystals were obtained by slow evapora-
tion from acetic acid. A good crystal with a suitable size was

Journal of Chemistry
3
O
O O
S
+H2O
H
+H2O
H
N
Me
Me
∙∙
HO
−O
+N
3
Me
S
H3O+
−H2O
S
O
H3O+/H2O
O
O
H
H
∙∙
H
N
O O
S
O
∙∙
NH2
H2O
N
O
O
S
N
O
O
S
Me
4
6
7
Me
Me
Me
Me
Me
H2O+
N
S
O
O
S
S
O
+
O
∙∙
O
+N H
H
O O
S
N
O
−
H3O
H2O
N
N
O
O
S
N
O
O
S
5
9
8
Me
Me
Me
Figure 1: Mechanistic pathway of the reaction of intermediate 4 with compound 3.
C3A
C15A
C2A
C1A
C4A
C5A
C8A
S1A
C13A
02A
C14A
C9A
C12A
C6A
N1A
C7A
C10
01
S1
C11A
C11
C10A
01A
N1
C1
C12
C13
C9
C7
C6 C8
C5
C14
02
C2
C3
C15
C4
Figure 2: ORTEP diagram of compound 5 40% probability ellipsoid, showing intramolecular hydrogen bonds.
reaction of compound 3 with hydrazine hydrate in MeOH,
EtOH, BuOH, THF, or AcOH/EtOH, under the previous
conditions, gave a poor yield of compound 5 whereas using
of AcOH gave the highest yield of 5 (78%). Recently, we
have reported the reaction of sulfone 3 (R=Cl) with hydrazine
hydrate in ethanol, in the presence of catalytic amount of
acetic acid, at 90∘C/100 W/30 sec to give hydrazone 4 (R=Cl),
in 86% yield, as final isolable product [16].
deposit@ccdc.cam.ac.uk; http://www.ccdc.cam.ac.uk/].). e
1HNMR (DSMO-ꢀ6, 500 MHz) of 5 revealed the singlet
signal of methylene protons at ꢁ 4.80 in addition to the singlet
signal of methyl protons which appeared at ꢁ 2.26. 13C NMR
(DSMO-ꢀ6, 125 MHz) of compound 5 exhibited the signal of
two methyl carbons at ꢁ 20.62 while the signal of methylene
carbons appeared at ꢁ 51.58. e MS (ESI) of compound 5
revealed a pek at ꢂꢃ/ 544.4 equal to [M]+.
e structure of compound 5 was confirmed using
spectral data and X-ray single crystal analysis (crystallo-
graphic data for the structure 5 has been deposited with
the Cambridge Crystallographic Data Center (CCDC) under
the numbers CCDC 943715-16. Copies of the data can be
obtained, free of charge, on application to CCDC 12 Union
Road, Cambridge CB2 1EZ,UK [Fax:+44-1223-336033; e-mail:
e condensation reaction of intermediate 4 with com-
pound 3 through loss of water can be described as an
addition-elimination reaction. In the presence of acidic
medium, nucleophilic addition of the –NH group of 4 to the
2
C=O function of sulfone 3 was followed by the elimination of
a H O molecule (Figure 1).
2

4
Journal of Chemistry
∘
∘
˚
Table 1: Selected bond distances (A), bond angles ( ), and torsion angles ( ) of compound 5.
Bond distances
S1–O1
S1–O2
S1–C8
1.419 (5)
1.424 (4)
1.792 (5)
S1–C9
N1–C7
N1–N1A
1.766 (5)
1.290 (7)
1.419 (5)
Bond angles
O1–S1–O2
O1–S1–C8
O1–S1–C9
O2–S1–C8
O2–S1–C9
C8–S1–C9
Torsion angles
O1–S1–C8–C7
O2–S1–C8–C7
118.6 (3)
108.8 (2)
109.0 (3)
108.8 (2)
108.4 (2)
101.9 (2)
N1i–N1–C7
N1–C7–C6
N1–C7–C8
S1–C8–C7
S1–C9–C10
S1–C9–C14
113.8 (4)
116.8 (4)
122.8 (4)
112.3 (4)
119.6 (5)
119.2 (4)
−43.1 (4)
C5–C6–C7–C8
C10–C9–C14–C13
S1–C9–C10–C11
C5–C6–C7–N1
3.8 (8)
0.2 (11)
87.4 (4)
C9–S1–C8–C7
C14–C9–S1–C8
S1–C8–C7–N1
−158.2 (4)
−97.4 (5)
91.7 (5)
−177.3 (7)
−179.3 (6)
Symmetry code: (i) −ꢀ − 2, −ꢁ − 1, −ꢂ−.
∘
˚
Table 2: Hydrogen-bond geometry (A, ) of compound 5.
D–H⋅ ⋅ ⋅ ꢀ
D–H
0.9300
0.9700
0.9700
0.9300
H⋅ ⋅ ⋅ ꢀ
D⋅ ⋅ ⋅ ꢀ
D–H⋅ ⋅ ⋅ ꢀ
C1–H1A⋅ ⋅ ⋅ N1
2.4200
2.3300
2.5600
2.5300
2.744 (9)
2.683 (7)
3.444 (7)
2.905 (8)
101.00
C8–H8A⋅ ⋅ ⋅ N1i
100.00
C8–H8B⋅ ⋅ ⋅ O1ii
151.00
105.00
C14–H14A⋅ ⋅ ⋅ O2
Symmetry codes: (i) −ꢀ − 2, −ꢁ − 1, −ꢂ − 2; (ii) ꢀ ꢃ 1, ꢁ, ꢂ.
3.2. X-Ray Crystallography. e asymmetric unit of the
titled compound 5, C H N O S , contains one-half of a
30 28
2
4
2
molecule. e other half of the molecule is generated by a
21 screw axis with symmetry operator (−ꢁꢂ ꢃ + 1/2ꢂ −ꢄ). e
full molecule has a ꢅ configuration about the C7=N1 and
C7A=N1A double bond (Figure 2).
b
c
0
is ꢅ configuration of compound 5 is stabilized
by intramolecular hydrogen bonds C1–H1A⋅ ⋅ ⋅ N1, C1A–
H1AA⋅ ⋅ ⋅ N1A, and C14–H14A⋅ ⋅ ⋅ O2.
a
e single bond N1–N1A is clearly characterized by the
˚
distance of 1.419 (5) A. e double bond of C7=N1 is char-
˚
acterized by the distance of 1.290 (7) A. e dihedral angle
between the two benzene (C1–C6) and (C9–C14) rings is 16.89
(5)∘. e hydrazine group is twisted slightly, with a C6–C7–
N1–N1A torsion angle of −177.79 (2)∘. e molecules packing
in the crystal structure of 5 is stabilized by intermolecular
interactions forming a three-dimensional network (Figure 3).
∘
˚
Selected bond distances (A), bond angles ( ), and torsion
angles (∘) of compound 5 are illustrated in Table 1. Hydrogen
bonds geometry of the crystal 5 is showed in Table 2.
Figure 3: Crystal packing of 5 showing intermolecular hydrogen
bonds as dashed lines.
4. Conclusion
In conclusion, the title compound 5 was prepared efficiently
by the reaction of sulfone 3 with hydrazine hydrate in acetic
acid at 90∘C/MWI/100 W/3 min. e 3D structure of the
newly synthesized compound 5 determined by X-ray single
crystal analysis.

Journal of Chemistry
5
Conflict of Interests
bearing arylsulfonyl moiety: novel celecoxib analogs as potent
anti-inflammatory agents,” European Journal of Medicinal
Chemistry, vol. 80, pp. 416–422, 2014.
e authors declare that there is no conflict of interests
regarding the publication of this paper.
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Acknowledgment
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