Isolation, characterization and X-ray structure determination of 2,5-bis(4-methylbenzylthio)-1,3,4-thiadiazole

Article abstract of DOI:10.1007/s10870-013-0474-2

The reaction of hydrazine hydrate with carbon disulfide and 4-methylbenzyl chloride in basic solution yielded 2,5-bis(4-methylbenzylthio)-1,3,4-thiadiazole (C₁₈H₁₈N₂S₃, compound 1) in addition to the expected S-4-methylbenzyldithiocarbazate. The molecule has approximate twofold symmetry with the C=S bond lying on the pseudo axis. The five membered ring is planar with the three S atoms mutually syn, and with pendent 4-methylbenzylthio substituents; the dihedral angle between the terminal rings is 52.21(7). The compound 1 crystallizes in the triclinic space group P 1 with a = 6.0139(3) A, b = 11.8694(7) A, c = 12.6330(7) A, α = 72.583(5), β = 82.827(4), γ = 89.882(4) and Z = 2. Graphical Abstract: In situ cyclization of an authenticated dithiocarbazate gave rise to a supramolecular layerered assembly of new molecules containing a 1,3,4-thiadiazole ring system having a strictly planar central core with mutually syn sulfur atoms and terminal aryl groups twisted out of this plane.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-013-0474-2

J Chem Crystallogr (2014) 44:1–5
DOI 10.1007/s10870-013-0474-2
ORIGINAL PAPER
Isolation, Characterization and X-ray Structure Determination
of 2,5-Bis(4-methylbenzylthio)-1,3,4-thiadiazole
•
Shahedeh Tayamon Edward R. T. Tiekink
•
•
Farzad Nikpour Thahira Begum S. A. Ravoof
•
•
Mohamad Ibrahim Mohamed Tahir Karen A. Crouse
Received: 30 May 2013 / Accepted: 19 September 2013 / Published online: 25 October 2013
Ó Springer Science+Business Media New York 2013
Abstract The reaction of hydrazine hydrate with carbon
disulfide and 4-methylbenzyl chloride in basic solution yielded
2,5-bis(4-methylbenzylthio)-1,3,4-thiadiazole (C18H18N2S3,
compound 1) in addition to the expected S-4-methylbenzyl-
dithiocarbazate. The molecule has approximate twofold sym-
metry with the C=S bond lying on the pseudo axis. The five
membered ring is planar with the three S atoms mutually syn,
and with pendent 4-methylbenzylthio substituents; the dihedral
angle between the terminal rings is 52.21(7)°. The compound 1
structures [1, 2] and their biological activity towards fungi,
bacteria and cancer cells [3–5]. In the presence of acid or
base, 3-acyldithiocarbazic acid esters, N-aroyldithiocar-
bazates and their salts can convert to 1,3,4-oxadiazole/
thiadiazole-2-thiones [6, 7]. Common synthetic methods
such as cyclization of thiosemicarbazides, thiocarbazides,
dithiocarbazates, thioacylhydrazines, acylhydrazines, bit-
hioureas have been used to synthesize thiadiazoles [7–9].
In general, to prepare 1,3,4-thiadiazole derivatives, appro-
priate rearrangements accompanied by ring closure and
substitution are required [10]. 1,3,4-Thiadiazole ring sys-
tems are also of interest in medicine and agriculture as they
have found application as dyes, in determination of trace
elements and in the preparation of optically active liquid
crystals and photographic materials [11, 12]. Many deriv-
atives have been reported to be herbicides, insecticides,
fungicides, bactericides, anthelmintics [13], antihyperten-
sives, and anticonvulsives [14–16]. 1,3,4-Thiadiazole ring
systems having different substituents at positions 2 and 5,
have been isolated as by-products during crystallization of
dithiocarbazate derivatives in our laboratory [17–19]. In
continuation of these studies, herein we report the crystal
structure and spectroscopic characterization of a new
symmetric 2,5-disubstituted thiadiazole ring system,
namely 2,5-bis(4-methylbenzylthio)-1,3,4-thiadiazole (1).
ꢀ
crystallizes in the triclinic space group P1 with a =
˚
˚
˚
6.0139(3) A, b = 11.8694(7) A, c = 12.6330(7) A, a =
72.583(5)°, b = 82.827(4)°, c = 89.882(4)° and Z = 2.
Keywords Dithiocarbazate ꢀ 1,3,4-Thiadiazole ꢀ
Supramolecular structure ꢀ Crystal structure
Introduction
During the past few decades, reports on substituted deriv-
atives of the dithiocarbazate anion, NH2NHC(SR)S-, and
their metal complexes have focused on differences in their
S. Tayamon ꢀ T. B. S. A. Ravoof ꢀ M. I. M. Tahir ꢀ
K. A. Crouse (&)
Department of Chemistry, Faculty of Science, Universiti Putra
Malaysia, 43400 Serdang, Selangor, Malaysia
e-mail: kacrouse@gmail.com; karen@upm.edu.my
Experimental
Materials and Physical Measurements
E. R. T. Tiekink
Department of Chemistry, University of Malaya,
50603 Kuala Lumpur, Malaysia
All chemicals and solvents were of analytical grade and were
used as received. The melting point was determined using an
Electrothermal IA9100 digital melting point apparatus.
Microanalyses for carbon, hydrogen, and nitrogen were
F. Nikpour
Department of Chemistry, University of Kurdistan, Sanandaj,
Iran
123

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J Chem Crystallogr (2014) 44:1–5
carried out using a LECO TruSpec CHN/CHNS instrument.
The IR spectra were recorded using a Perkin-Elmer FT IR
1750X spectrophotometer (4,000–400 cm-1). NMR spectra
were acquired on a JOEL JNM-ECX500 MHz spectrometer
in deuterated chloroform with TMS as the internal standard.
All chemical shift values were recorded in ppm (d). The mass
spectrum was determined using a DIMS QP5050A Shima-
dzu Gas Chromatograph–Mass Spectrometer.
Table 1 Crystal data and refinement details for (1)
Formula
C18H18N2S3
358.52
Formula weight
Crystal habit, color
Crystal system
Space group
Prism, colorless
Triclinic
ꢀ
P1
˚
a (A)
6.0139 (3)
˚
b (A)
11.8694 (7)
˚
c (A)
12.6330 (7)
Isolation of 2,5-Bis(4-methylbenzylthio)-1,3,
4-thiadiazole
a (°)
b (°)
c (°)
72.583 (5)
82.827 (4)
89.882 (4)
Crystals of the title compound suitable for X-ray analysis
were isolated as a by-product from the preparation of S-4-
methylbenzyldithiocarbazate (S-4MBDTC). The procedure
was adapted from Ravoof et al. [20]. Potassium hydroxide
(11.4 g, 0.2 mol) was dissolved in absolute ethanol
(70 mL) to which hydrazine hydrate (10 g, 0.2 mol) was
added followed by cooling in an ice salt bath to 0 °C.
Carbon disulphide (15.2 g, 0.2 mol) was added drop wise
with constant stirring over a period of 1 h. The two layers
that subsequently formed were separated. The lower light
brown layer was taken up in 40 % ethanol (60 mL) below
5 °C. The mixture was kept in an ice-bath and 4-methyl-
benzyl chloride (26.5 mL, 0.2 mol) was added drop wise
with vigorous stirring. The major product (sticky, white
S-4MBDTC) was filtered and left overnight to dry over
anhydrous silica gel in a desiccator. S-4MBDTC, was fil-
tered immediately after recrystallization from ethanol. The
title compound, 2,5-bis(4-methylbenzylthio)-1,3,4-thiadia-
zole (1), precipitated from the filtrate after a period of days.
Yield: 32 %, m.p. 132.2 °C. C18H18N2S3 calc. (found): C
60.30 (60.76), H 5.06 (5.13), N 7.81 (8.05). 1H NMR
[500 MHz, CDCl3, d (ppm)]: 7.26 (d, 4H, J = 8 Hz, CH–
C–CH3), 7.11 (d, 4H, J = 8 Hz, CH–C–CH2), 4.44 (s, 4H,
CH2), 2.31 (s, 6H, CH3). 13C NMR [500 MHz, CDCl3, d
(ppm)]: 164.79 (2C, thiadiazole-C), 137.72 (C–CH3 in
benzene rings), 132.58 (C–CH2), 129.40, 129.05 (C of
benzene rings), 38.20 (CH2S), 21.13 (CH3–Bz).
3
˚
Volume (A )
853.09 (8)
Z
2
Density (calculated, g cm-3
Absorption coefficient (mm-1
)
1.396
)
3.959
F(000)
376
Crystal size (mm)
0.18 9 0.21 9 0.36
h range for data collection (°)
Reflections collected
Independent reflections
Rint
3.7–71.4
11,074
3,266
0.023
Reflections with I C 2r(I)
Number of parameters
Goodness-of-fit on F2
Final R indices [I C 2r(I)]
R indices [all data]
3,086
210
0.99
R1 = 0.033, wR2 = 0.112
R1 = 0.035, wR2 = 0.114
0.36, -0.33
-3
)
˚
Largest difference peak and hole (A
CCDC deposition no.
926,368
their calculated positions and a weighting scheme of the
form w = 1/[r2(F2o) ? 0.1P2] where P = (Fo2 ? 2F2c)/3.
Crystal data and refinement details are given in Table 1.
Figure 2, showing the atom labeling scheme, was drawn
with 50 % displacement ellipsoids using ORTEP-3 for
Windows [24] and the remaining figures were drawn with
DIAMOND [25] but with arbitrary spheres. Additional data
manipulation and interpretation were accomplished using
WinGX [24] and PLATON [26].
X-ray Crystallography
A single crystal of 1 was selected and mounted in a loop
using perfluoropolyether oil and cooled rapidly to 100 K in
the cold stream of an Oxford Cryosystems open-flow
nitrogen cryostat [21] with a nominal stability of 0.1 K.
Diffraction data were measured using an Agilent Gemini
diffractometer (graphite monochromated CuKa radiation,
Results and Discussion
Dithiocarbazate salts are generally produced on treatment
of substituted hydrazines with carbon disulfide at low
temperature in the presence of base. Acidification of dith-
iocarbazate solutions can afford free dithiocarbazic acids
(NH2–NH2–CS2H) that precipitate, for example, when the
potassium salt is treated with dilute HCl at 0 °C. It is also
known that the so called dithiocarbazate route is one of the
synthetic pathways to 1,3,4-thiadiazole derivatives [10].
˚
k = 1.54180 A) so that 2hmax was 142.7° [22]. The
structure was solved by direct methods with SHELXS-97
[23] and refined by a full-matrix least-squares procedure on
F2 using SHELXL-97 [23] with anisotropic displacement
parameters for non-hydrogen atoms, hydrogen atoms in
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J Chem Crystallogr (2014) 44:1–5
3
Cyclized thiadiazole compounds have also been isolated as
co-products during synthesis of dithiocarbazate derivatives
[17] and have been produced during recrystallization of
S-substituted dithiocarbazates in our laboratory [18, 19].
The title compound, 1, was formed during the preparation
of (S-4MBDTC) where the cyclization reaction appears to
apparent at m/z 358. The methylbenzyl fragment (m/z 105)
appeared as the base peak. Another prominent peak was at
m/z 162 and is ascribed to the disulfurthiadiazole ion,
[C2N2S3]?.. The structure was unambiguously confirmed
by X-ray crystal structure determination.
The molecular structure of 1 is shown in Fig. 2 and
selected geometric parameters are collected in Table 2.
The central 1,3,4-thiadiazole ring is strictly planar with the
have occurred during the addition of carbon disulphide. It
?
is almost impossible to obtain pure zwitterionic NH3
–
-
˚
r.m.s deviation of the fitted atoms being 0.002 A. Within
NH2–CS2 as it evolves hydrogen sulfide to give 1,3,4-
thiazolidine-2,5-dithione [27]. Since hydrazine possesses
two primary amino groups, reaction with carbon disulfide
could take place at both sites. The general proposed
mechanism for the formation of the cyclized product is
given in Fig. 1.
˚
Table 2 Selected geometric parameters (A, °) for (1)
Atoms
Parameter
Atoms
Parameter
S1–C1
1.7461(15)
1.7395(15)
1.7440(15)
1.3913(17)
1.296(2)
S1–C3
S2–C2
S3–C11
N1–C1
1.8302(15)
1.7438(14)
1.8260(15)
1.298(2)
Spectral evidence and elemental analyses confirmed the
presence of a thiadiazole-like product as, for example,
m(C=O), m(C=S), and m(N–H) bands were not observed in
the spectrum of 1. The appearance of weak bands at 1611,
2920, and 3029 cm-l indicate the presence of C=N, ali-
phatic CH and aromatic CH, respectively. In the NMR
spectra, the chemical shifts (1H and 13C), multiplicity and
integration (1H) observed in CDCl3 solution is in line with
the solid state structure (see below). In particular, there is
S2–C1
S3–C2
N1–N2
N2–C2
C1–S1–C3
C2–S3–C11
C2–N2–N1
S2–C2–S3
S2–C2–N2
S3–C11–C12
99.79(7)
C1–S2–C2
C1–N1–N2
S1–C1–S2
S1–C1–N1
S1–C3–C4
86.10(7)
112.25(12)
120.06(9)
114.69(11)
108.04(10)
100.64(7)
112.46(12)
120.37(9)
114.50(11)
106.61(10)
1
no evidence in the H NMR spectrum for the presence of
N–H or S–H type protons. The molecular ion peak is
Fig. 1 Proposed reaction
mechanism for the formation of
cyclized thiadiazole derivatives
from dithiocarbazates
Fig. 2 Molecular structure of
the (1) showing atom labeling
scheme. Displacement
ellipsoids are drawn at the 70 %
probability level (color figure
online)
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J Chem Crystallogr (2014) 44:1–5
Symmetry operation
˚
Table 3 Intermolecular interactions (A–HꢀꢀꢀB; A, °) operating in the crystal structure of (1)
A
H
B
HꢀꢀꢀB
A–HꢀꢀꢀB
AꢀꢀꢀB
C3
H3A
H9
Cg(C4–C9)
2.71
2.94
2.94
2.80
132
163
167
160
3.4507(16)
3.8557(17)
3.8985(18)
3.7063(17)
2-x, 2-y, -z
1 ? x, y, z
C9
Cg(S2,N1,N2,C1,C2)
Cg(C12–C17)
C10
C17
H10B
H17
2 ? x, 1 ? y, z
-1 ? x, y, z
Cg(S2,N1,N2,C1,C2)
and the molecule has approximate twofold symmetry with
the S2 atom lying on the axis. In terms of global confor-
mation, the three sulfur atoms in 1 are mutually syn, lying
to the same side of the molecule.
In the crystal packing, molecules of 1 assemble into
supramolecular layers parallel to (012) via edge-to-face C–
Hꢀꢀꢀp interactions (Table 3). Each of the aromatic rings
function as acceptor with the 1,3,4-thiadiazole ring forming
two such interactions, and the donors are either phenyl-,
methylene- or methyl-H, Table 3. Connections between the
layers are of the type SꢀꢀꢀS with the S3ꢀꢀꢀS3i separation of
˚
3.4587(5) A being less than the sum of the van der Waals
˚
radii, i.e., 3.60 A [28]; symmetry operation i: -x, 1-y,
1-z, Fig. 3.
While not numerous there are precedents for the structure
of 1 in the crystallographic literature [29], notably 2,5-
bis(benzylthio)-1-thia-3,4-diazacyclopenta-2,4-diene
[30]
and 4,40-[(1,3,4-thiadiazole-2,5-diyl)bis(thiomethylene)]dib-
enzonitrile [31]. In the same way, the coordination chemistry
ofsuchmoleculesisstillinitsinfancy.Theobservationofboth
monodentate N- and bidentate N,N-bridging modes have been
observed in some rhenium complexes [32].
Conclusion
Fig. 3 View in projection down the a-axis of the unit cell contents of
(1). The C–Hꢀꢀꢀp and SꢀꢀꢀS contacts are shown as purple and orange
dashed lines, respectively (color figure online)
A new molecule containing a 1,3,4-thiadiazole ring system,
arising from the in situ cyclization of its authenticated
dithiocarbazate precursor, has been fully characterized. In
the molecular structure the central core is strictly planar but
the terminal aryl groups are twisted out of this plane. The
sulfur atoms are mutually syn.
the ring the N–N and C=N bond lengths are consistent with
the cyclic product shown in Fig. 1, and the sequence of
intra-ring angles is C–S–C\S–N–N\C–C–N, Table 2, with
the difference between the latter two angles subtended at
nitrogen and carbon being about 2° only. The C–S bond
lengths involving the ring carbons are significantly shorter
than the exocycliuc S–C bond lengths, Table 2. Two pen-
dent S-bound 4-methylbenzylthio residues are connected to
the ring at the C1 and C3 atoms. The phenyl groups in
these are inclined differently with respect to the five
membered ring forming dihedral angles of 70.28(7) and
64.87(7)°, respectively; the dihedral angle between the
phenyl rings is 52.21(7)°. Overall, differences in chemi-
cally equivalent geometric parameters are not significant
Supplementary Material
CCDC-926368 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre (CCDC), 12 Union
Road, Cambridge CB2 1EZ, UK; fax ?44(0)1223-336033;
email: deposit@ccdc.ccam.ac.uk].
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J Chem Crystallogr (2014) 44:1–5
5
Acknowledgments The authors gratefully acknowledge University
Putra Malaysia (UPM) for supporting this project under their
Research University Grant Scheme (RUGS No. 05–01–11–1243RU)
and the Malaysian Fundamental Research Grant Scheme (FRGS No.
01–13–11– 986FR). ST also thanks Siti Khadijah Densabali for col-
lecting the X-ray data. Support from the Ministry of Higher Educa-
tion, Malaysia, High-Impact Research scheme (UM.C/HIR-MOHE/
SC/03) is also gratefully acknowledged.
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