Heterocyclization of thiocarbonohydrazides: Facile synthesis of 5-unsubstituted-1,3,4-thiadiazoles

Article abstract of DOI:10.1016/j.cclet.2015.05.034

2-(Hydrazinecarbothioyl)-N-substituted hydrazinecarbothioamides react with 2,3,5,6-tetrachloro-1,4-benzoquinone in high yields in a novel fast and facile method to give 5-unsubstituted-1,3,4-thiadiazole-2-amine derivatives. The synthesized compounds were characterized by spectroscopic methods and confirmed by using X-ray crystallography. A rationale for the formation of the products is presented.

Full text of DOI:10.1016/j.cclet.2015.05.034

G Model
CCLET 3338 1–4
Chinese Chemical Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
1
2
Original article
3
4
Heterocyclization of thiocarbonohydrazides: Facile synthesis
of 5-unsubstituted-1,3,4-thiadiazoles
a
b
a
Q1 Alaa A. Hassan a, , Fathy F. Abdel-Latif , Mohamed Abdel Aziz , Sara M. Mostafa ,
*
5
6
Stefan Bra¨se c, Martin Nieger d
7
8
9
10
a Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt
b Department of Medicinal Chemistry, Faculty of Pharmacy, El-Minia University, 61519 El-Minia, Egypt
c Institute of Organic Chemistry, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
d Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, 00014 Helsinki, Finland
A R T I C L E I N F O
A B S T R A C T
Article history:
2-(Hydrazinecarbothioyl)-N-substituted hydrazinecarbothioamides react with 2,3,5,6-tetra-chloro-1,4-
benzoquinone in high yields in a novel fast and facile method to give 5-unsubstituted-1,3,4-thiadiazole-
2-amine derivatives. The synthesized compounds were characterized by spectroscopic methods and
confirmed by using X-ray crystallography. A rationale for the formation of the products is presented.
ß 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Received 4 February 2015
Received in revised form 13 April 2015
Accepted 22 April 2015
Available online xxx
Keywords:
Thiocarbonohydrazides
5-Unsubstituted 1,3,4-thiadiazol-2-amines
Tetrachloro-1,4-benzoquinone
X-ray crystallography
11
12
1. Introduction
DMF was proposed as a cyclizing agent for the synthesis of 5- 32
unsubstituted 1,3,4-thiadiazoles [16]. The latter were formed in 33
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
Thiadiazole is
a
prevalent and important five-membered
moderate yields by cyclization of thiohydrazides. 5-Unsubstituted 34
1,3,4-thiadiazoles are of interest as biologically active compounds 35
[17,18]. Further, they are used in the synthesis of various 36
heterocyclic system. There are several isomers of thiadiazole. A
glance at standard reference works shows that 1,3,4-thiadiazole
has been investigated more than other isomers [1].
heterocyclic compounds [19,20].
37
The most familiar thiadiazole containing compound could be
acetazolamide, the famous carbonic anhydrase inhibitor currently
used in treatment of glaucoma [2], high-altitude illness [3], cancer
[4,5], HIV [4], seizures [6], diabetes [7], and hypertension [8].
Synthesis of 1,3,4-thiadiazoles usually involves multi-step proce-
dures such as cyclization of thiosemicarbazide with di-(2-
pyridyl)thionocarbonate (DPT), dicyclohexylcarbodimide (DCC)
[9]. Oxidative cyclization of thiosemicarbazides with FeCl3 [10]
or reaction of thiosemicarbazides and CS2 under reflux [11] have
been reported. Treatment of isothiocyanates with pure lithiated
(trimethylsilyl)diazomethane (Me3SiCN2Li) in Et2O afforded
2-amino substituted-1,3,4-thiadiazoles [12,13].
2. Experimental
38
39
2.1. General experimental procedure
Melting points were determined using open glass capillaries on 40
a Gallenkamp melting point apparatus and are uncorrected. The IR 41
spectra (KBr discs) were recorded on a Bruker FT-IR and Shimadzu 42
408 instruments. 1H NMR and 13C NMR spectra were obtained 43
using a Bruker AM 400 spectrometer (400 MHz for 1H NMR and 44
100 MHz for 13C NMR) with tetramethylsilane as the internal 45
Although, there are many reports for the synthesis of 1,3,4-
thiadiazoles [14,15], few reports are available for the synthesis of
5-unsubstituted 1,3,4-thiadiazoles. Diethyl chlorophosphate in
standard; the chemical shifts are expressed in d and coupling 46
constants in Hz. The 13C NMR assignments (q = quaternary carbon 47
atoms) were made with the aid of DEPT 135/90 spectra. Mass 48
spectra (70 eV, electron impact mode) were recorded on a Finnigan 49
MAT 312 instrument. Elemental analyses were carried out at the 50
Microanalytical Center, Cairo University, Egypt. Preparative layer 51
chromatography (plc) used air-dried 1.0 mm thick layer of slurry 52
*
Corresponding author..
Q2
E-mail address: alaahassan2001@yahoo.com (A.A. Hassan).
http://dx.doi.org/10.1016/j.cclet.2015.05.034
1001-8417/ß 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: A.A. Hassan, et al., Heterocyclization of thiocarbonohydrazides: Facile synthesis of 5-unsubstituted-
1,3,4-thiadiazoles, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.05.034

G Model
CCLET 3338 1–4
2
A.A. Hassan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
˚
˚
˚
b
53
54
applied silica gel (Merck Pf254) on 48 cm wide and 20 cm high glass
plates using the solvent listed.
(no. 14), a = 11.3811(5) A, b = 5.3161(2) A, c = 14.3650(6) A,
=
113
114
115
116
117
118
119
120
121
122
123
124
125
112.249(5) A, V = 798.82(6) A , Z = 4, Dcalcd = 1.474 mg mꢀ3
F(000) = 368,
= 0.344 mmꢀ1, T = 173 K, 3093 measured reflection
(2
restraint, R1 [for 1604 I > 2
,
3
˚
˚
m
55
2.2. Starting materials
umax = 58.88), 1978 independent [Rint = 0.015], 112 parameters, 1
s
(1)] = 0.043, wR2 (for all data)ꢀ=30.097,
ꢀ3
˚
˚
56
57
58
59
60
2,3,5,6-Tetrachloro-1,4-benzoquinone (CHL-p, 2) was pur-
chased from Fluka. 2-(Hydrazinecarbonothioyl)-N-aryl/alkyl
hydrazinecarbo-thioamides 1a–d were prepared according to
published procedures for preparation compounds 1a [21] and
1b–d [22].
S = 1.07, largest diff. peak and hole = 0.232 eA /ꢀ0.218 eA
.
Crystallographic data (excluding structure factors) for the
structure reported in this work has been deposited with Cam-
bridge crystallographic Data Center on supplementary publica-
tion no. CCDC-1046364. Copies of the data can be obtained free
of charge on application to the director, CCDC, 12 Union Road,
Cambridge CB2 IEZ, UK (Fax: +44 1223 3360333; e-mail: deposit@
ccdc.cam.ac.uk).
61
2.3. Reaction of 1a–d with 2,3,5,6-tetrachloro-1,4-benzoquinone (2)
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
2-(Hydrazinecarbonothioyl)-N-substituted
hydrazinecar-
bothioamides 1a–d (1 mmol) in 20 mL dry ethyl acetate was
added to 246 mg (1 mmol) (CHL-p, 2) in 20 mL dry ethyl acetate at
room temperature. The reaction mixture was stirred for 3 h. After
standing for 24 h, the precipitate was filtered, washed with cold
ethyl acetate and identified as 2,3,5,6-tetrachloro-p-benzohydro-
quinone 4 [23]. The filtrate was pre-concentrated, then applied to
3. Results and discussion
126
For the synthesis of 5-unsubstituted 1,3,4-thiadiazoles as will
be outlined in detail below, we report the heterocyclization of
thiocarbonohydrazides 1a–d using 2,3,5,6-tetrachloro-1,4-benzo-
quinones (CHL-p, 2) as a reaction mediator.
After adding ethyl acetate solutions of 1a–d to an equimolar
quantity of 2,3,5,6-tetrachloro-1,4-bezoquinone (CHL-p, 2), in
ethyl acetate and letting it stand for 24 h at room temperature, the
initial green colored turned to violet, which gradually changed to
reddish brown. The isolated compounds 3a–d (Scheme 1) were
characterized by their IR, 1H NMR, 13C NMR, mass spectral data and
single X-ray crystallography.
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
3 plc plates and developed using toluene/ethyl acetate (
fr = 10:2
for 1a, 1b, and r = 10:4 for 1c, 1d) to give N-substituted-1,3,4-
f
thiadiazol-2-amines 3a–d, extracted by acetone and recrystallized
from listed solvents.
N-Phenyl-1,3,4-thiadiazol-2-amine (3a): red crystals (acetoni-
trile), yield 87% (0.154 g), mp: 173 8C (Iit. 171–172 8C) [16,20].
N-Benzyl-1,3,4-thiazol-2-amine (3b): red crystals (acetoni-
trile), yield 89% (0.170 g), mp: 109–110 8C (lit. 108 8C) [19]. IR
The IR spectrum of 3c as an example was characterized by the
presence of broad NH at 3426–3384, the band at 1600 was
assigned to C55N stretching. The bands attributed to C55S stretching
vibrations were not observed in the IR spectra of 3a–d.
(KBr, cmꢀ1):
(400 MHz, DMSO-d6):
CH55N), 7.36–7.31 (m, 3H, Ar–H), 7.29–7.28 (m, 2H, Ar–H), 4.51
(s, 2H, CH2). 13C NMR (100 MHz, DMSO-d6):
168.5 (C55N), 142.3
y
3421–3380 (NH str.), 1611 (C55N str.). 1H NMR
d
8.35 (br, 1H, NH–CH2Ph), 8.20 (s, 1H,
d
(CH55N), 138.7 (Ar–C), 128.3, 127.5, 127.0 (Ar–CH), 48.3 (CH2–Ph).
MS m/z (%) 191 (M+, 70), 163 (11), 86 (100), 91 (13), 76 (10).
N-Allyl-1,3,4-thiazol-2-amine (3c): red crystals (acetonitrile),
yield 85% (0.112 g), mp: 74–75 8C (lit. 73 8C) [19]. IR (KBr, cmꢀ1):
y
3426–3384 (NH str.), 1600 (C55N str.). 1H NMR (400 MHz,
DMSO-d6)
(m, 1H, allyl-CH55), 5.15–5.11 (m, 2H, allyl-CH255), 3.92–3.90 (m,
2H, allyl-CH2N). 13C NMR (100 MHz, DMSO-d6):
167.6 (C55N),
d 8.10 (br, 1H, NH-allyl), 7.90 (s, 1H, CH55N), 5.90–5.89
d
142.4 (CH55N), 135.00 (allyl-CH), 115.45 (allyl-CH255), 46.05
(allyl-CH2N). MS m/z (%) 141 (M+, 30), 113(28), 86 (100), 55 (40),
41 (75).
Scheme 1. Reaction of 1a–d with CHL-p (2).
N-Ethyl-1,3,4-thiazol-2-amine (3d): red crystals (acetonitrile),
yield 84% (0.108 g), mp: 71–72 8C (lit. 70 8C) [24]. IR (KBr, cmꢀ1):
y
3424–3372 (NH str.), 1601 (C55N str.). 1H NMR (400 MHz, DMSO-
d6): 8.20 (br, 1H, NH–C2H5), 7.96 (s, 1H, CH55N), 3.49 (q, 2H, CH2,
J = 7.50 Hz), 1.19 (t, 3H, J = 7.50 Hz). 13C NMR (100 MHz, DMSO-
d6): 166.8 (C55N), 143.1 (CH55N), 40.1 (CH2), 14.3 (CH3). MS m/z
d
d
(%) 129 (M+, 55), 101 (40), 86 (100), 43 (50), 29 (80).
2,3,5,6-Tetrachlorobenzene-1,4-diol (4) [23]: mp: 230–232 8C
(lit. 232 8C).
Fig. 1. Molecular structure of 3a in the crystal (one crystallographic independent
101
2.4. Single crystal X-ray structure determination of 3a
molecule is shown; displacement parameters are drawn at 50% probability level).
102
103
104
105
106
107
108
109
110
111
112
Single crystals were obtained by recrystallization from aceto-
nitrile. The single crystal X-ray diffraction study was carried out on
an Agilent SuperNova diffractometer with EOS detector at 173 K
˚
a radiation (l = 0.71073 A). Direct methods (SHELXS-
using Mo k
98) [25] were used for structure solution and refinement was
carried out using SHELXL-2013 [25] (full-matrix least-squares on
F2). Hydrogen atoms were localized by different Fourier synthesis
map and refined using a riding model [H(N) free]. A semi-empirical
absorption correction was applied.
3a:
C8H7N3S,
M = 177.23 g molꢀ1
,
red
crystal,
size
Fig. 2. Asymmetric unit of 3a with intermolecular hydrogen bonds shown as dotted
0.40 mm ꢁ 0.06 mm ꢁ 0.06 mm, monoclinic space group P21/n
lines.
Please cite this article in press as: A.A. Hassan, et al., Heterocyclization of thiocarbonohydrazides: Facile synthesis of 5-unsubstituted-
1,3,4-thiadiazoles, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.05.034

G Model
CCLET 3338 1–4
A.A. Hassan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
3
Scheme 2. The mechanism of formation 5-unsubstituted-1,3,4-thiadiazoles.
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
The chemical shifts obtained from 1H NMR spectrum of 3c
supported the proposed structure. Resonance assigned to allyl
group was detected at 3.92–3.90 (allyl-CH2N), 5.15–5.11(allyl-
CH255) and 5.90–5.89 (allyl-CH55). The 1H NMR clearly showed
singlet signal at 7.90 due to CH55N, whereas a broad band with D2O
exchangeable observed at 8.10 for NH-allyl.
13C NMR data of representative compounds 3a–d which were
obtained using DEPT technique at 100 MHz, also support the
carbon framework by discrimination of CH2, CH and quaternary
carbons. The 13C NMR of 3c showed downfield signals at 167.60,
142.40, 135.00 and 115.45 attributed to C55N, CH55N, allyl-CH55
and allyl-CH255 respectively. The upfield signal resonated at 46.05
due to (allyl-CH2N).
Appendix A. Supplementary data
188
Supplementary data associated with this article can be found, in 189
the online version, at http://dx.doi.org/10.1016/j.cclet.2015.05.034.
190
191
References
[1] Y. Hu, C.Y. Li, X.M. Wang, Y.H. Yang, H.L. Zhu, 1,3,4-Thiadiazole: synthesis, 192
reactions, and applications in medicinal, agricultural, and materials chemistry, 193
Chem. Rev. 114 (2014) 5572–5610.
[2] I.P. Kuar, R. Smitha, D. Aggarwal, M. Kapil, Acetazolamide: future perspective in 195
topical glaucoma therapeutics, Int. J. Pharm. 248 (2002) 1–14.
[3] A.M. Luks, S.E. McIntosh, C.K. Grissom, et al., Wilderness Medical Society practice 197
guidelines for the prevention and treatment of acute altitude illness: 2014 update, 198
Wilderness Environ. Med. 25 (2014) S4.
[4] D.E. Abdel Rahman, K.O. Mohamed, Synthesis of novel 1,3,4-thiadiazole analogues 200
with expected anticancer activity, Der Pharma Chem. 6 (2014) 323–335.
194
196
199
N-Phenyl-1,3,4-thiadiazol-2-amine (3a) was confirmed unam-
biguously by single crystal X-ray structure analysis (Fig. 1 and
Tables S1–S7 in Supporting information) (note that the crystallo-
graphic numbering does not correspond to systematic IUPAC
numbering rules).
201
[5] D. Kumar, G. Patel, A.K. Chavers, K.H. Chang, K. Shah, Synthesis of novel 1,2,4- 202
oxadiazoles and analogues as potential anticancer agents, Eur. J. Med. 46 (2011) 203
3085–3092.
204
[6] H.N. Hafez, M.I. Hegad, I.S. Ahmed-Farag, A.B.A. El-Gazzar, A facile regioselective 205
synthesis of novel spiro-thioxanthene and spiro-xanthene-90,2-[1,3,4]thiadiazole 206
derivatives as potential analgesic and anti-inflammatory agents, Bioorg. Med. 207
Chem. Lett. 18 (2008) 4538–4543.
[7] P.A. Datar, T.A. Deokule, Design and synthesis of thiadiazole derivatives as 209
antidiabetic agents, Med. Chem. 4 (2014) 390–399.
˚
The S(1)–C(5) bond length of 1.726(2) A and S(1)–C(2)
1.7323(19) has single bond character, whereas bond lengths
208
˚
˚
C(2)–N(3) 1.318(2) A, C(5)–N(4) 1.285(3) A suggest that these
bonds have double bond character, as they comparable to C55N
bond. The 2-phenyl amino-1,3,4-thiadiazole molecule (3a) is
planar (mean deviation from the L.S. plane through all non
210
[8] M. Yusuf, R.A. Khan, B. Ahmed, Syntheses and anti-depressant activity of 5-amino- 211
1,3,4-thiadiazole-2-thiol imines and thiobenzyl derivatives, Bioorg. Med. Chem. 212
16 (2008) 8029–8034.
213
˚
hydrogen atoms 0.042 A, angle between the L.S: planes of the 1,3,4-
[9] P. Puthiyapurayil, B. Poojary, C. Chikkanna, S.K. Buridipad, Design, synthesis and 214
biological evaluation of a novel series of 1,3,4-oxadiazole bearing N-methyl-4- 215
(trifluoromethyl)phenyl pyrazole moiety as cytotoxic agents, Eur. J. Med. Chem. 216
thiadiazole ring and the phenyl ring 3.08). Intermolecular hydrogen
bonding between N6A, N3A from one molecule to N3 and N6 of
another forms a dimer with Ci-symmetry (Fig. 2).
53 (2012) 203–210.
217
[10] X.M. Zhang, M. Qui, J. Sun, et al., Synthesis, biological evaluation, and molecular 218
docking studies of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan moi- 219
Since the aforementioned reactions do not take place when no 2
is added to the solution of 1a–d in ethyl acetate, the presence of
(CHL-p, 2), is definitely required for the transformation observed.
Charge-transfer complexes may (but not necessarily have to) play
an intermediate role. Since the cyclization involves intramolecular
attacks on the thiocarbonyl group, it is conceivable that (CHL-p, 2)
accelerates the process as a proton or a Lewis acid, possibly
through intermediate 5 (Scheme 2), activating the respective C55S
bond toward nucleophilic addition. This behavior may well be
supported by the polar nature of the solvent stabilizing Zwitter-
ionic adducts.
ety as potential anticancer agents, Bioorg. Med. Chem. 19 (2011) 6518–6524.
220
[11] H. Rajak, R. Deshmukh, R. Veerasamy, et al., Novel semicarbazones based 2,5- 221
disubstituted-1,3,4-oxadiazoles: one more step towards establishing four bind- 222
ing site pharmacophoric model hypothesis for anticonvulsant activity, Bioorg. 223
Med. Chem. Lett. 20 (2010) 4168–4172.
224
[12] T. Aoyama, M. Kabeya, A. Fukushima, T. Shioiri, New method and reagents in 225
organic synthesis. 53. Lithium trimethylsilyldiazomethane: a new synthon for the 226
preparation of 2-amino-1,3,4-thiadiazoles from isothiocyanates, Heterocycles 23 227
(1985) 2367–2369.
228
[13] D.R. Armstrong, R.P. Davies, R. Haigh, et al., A solid-state, solution, and theoretical 229
structural study of kinetic and thermodynamic lithiated derivatives of a simple 230
diazomethane and their reactivities towards aryl isothiocyanates, Eur. J. Inorg. 231
Chem. 2003 (2003) 3363–3375.
232
[14] C.Z. Zhao, J.L. Yu, X.L. Gu, H. Liu, Simultaneous determination of dihydroxybenzene 233
isomers utilizing a thiadiazole film electrode, Chin. Chem. Lett. 25 (2014) 370–374. 234
[15] L.H. Shen, H.Y. Li, H.X. Shang, et al., Synthesis and cytotoxic evaluation of new 235
colchicine derivatives bearing 1,3,4-thiadiazole moieties, Chin. Chem. Lett. 24 236
181
4. Conclusion
(2013) 299–302.
[16] V.N. Yarovenko, A.V. Shirokov, I.V. Zavarzin, et al., New cyclizing reagent for the 238
synthesis of 1,3,4-thiadiazoles, Synthesis (2004) 17–19.
[17] Y. Takatori, T. Yamaguchi, M. Nagakura, 2-b-Thenoylamido-1,3,4-thiadiazole, Jpn 240
KoKai Tohkyo Koko 8028,946 (1980), Chem. Abstr. 93 (1980) 114536e.
237
239
241
182
183
184
185
186
187
An efficient and fast reaction between thiocarbonohydrazides
1a–d and CHL-p, 2 was observed to give 1,3,4-thiadiazoles. These
oxidative cyclization reactions of 1a–d using CHL-p, which react as
a mediator, provide the products in higher yields with lower costs.
This environmentally benign procedure will be explored for other
substrates.
[18] R.C. Gadwood, M.R. Barbachyn, D.S. Toops, H.W. Smith, V.A. Vaillancourt, Prepa- 242
ration of azolylpiperaziylphenyloxazolidinones as antimicrobials, US pat. 243
5,736,545 (1998), Chem. Abstr. 128 (1998) 270612y.
244
Please cite this article in press as: A.A. Hassan, et al., Heterocyclization of thiocarbonohydrazides: Facile synthesis of 5-unsubstituted-
1,3,4-thiadiazoles, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.05.034

G Model
CCLET 3338 1–4
4
A.A. Hassan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
245
246
247
248
249
250
251
252
253
254
[19] D.H. Reid, F. Kurzer, Thiadiazoles and selenadiazoles, in: D.H. Reid (Ed.),
Organic Compound of Sulphur, Selenium and Tellurium, Specialist
[22] A.A. Hassan, F.F. Abdel-Latif, M. Abdel-Aziz, et al., Efficient and facile synthesis of
substituted aminothiadiazolylhydr-azonoindolin-2-ones, J. Heterocycl. Chem.
(2015) (in press).
[23] R. Pummerer, G. Schmidutz, H. Seifert, Institute of energy problems of chemical
physics, RAS, Chem. Ber. 85 (1952) 535–555.
[24] R.A. Coburn, B. Bhooshan, R.A. Glennon, The preparation of 2-alkylamino-1,3,4-
thiadiazoles, J. Org. Chem. 38 (1973) 3947–3949.
[25] (a) G.M. Sheldrick, A story history of Shelx, Acta Cryst. A 64 (2008) 112–122;
(b) G.M. Sheldrick, Crystal structure refinement with Shelx, Acta Cryst. C 71
(2015) 3–8.
255
256
Periodical Reports, vol. 3,
670–707.
The Chemical Society, London, 1975, pp.
Q3 257
258
[20] C.W. Bird, G.W.H. Cheeseman, P.A. Lowe, Condensation, in: C.W. Bird, G.W.H.
Cheeseman (Eds.), Aromatic and Heteroaromatic, Specialist Periodical Reports,
vol. 2, The Chemical Society, London, 1974, pp. 106–134.
[21] M.K. Burghata, S.V. Gandhe, M.G. Ajmire, B.N. Berad, Synthesis of 20-(sub-
stituted)benzylidene hydrazine-5-arylamino-1,3,4-thiadiazoles and their an-
timicrobial activity, J. Indian Chem. Soc. 84 (2007) 103–108.
259
260
261
262
263
264
Please cite this article in press as: A.A. Hassan, et al., Heterocyclization of thiocarbonohydrazides: Facile synthesis of 5-unsubstituted-
1,3,4-thiadiazoles, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.05.034