A convenient method for synthesis of bis-2,2′-(1,3,4-thiadiazole) and bis-3,3′-(1,2,4-triazole) derivatives

Article abstract of DOI:10.1080/17415993.2011.586456

Reactions of the bis-hydrazonoyl chloride 1 with ketene N,S-acetal 2 and the active methine thioanilides 4 and 6 provide a new convenient site-selective synthetic strategy to functionalized bis-3,3′-(1,2,4-triazoles) 3 and bis-2,2′-(1,2,4-thiadiazoles) 5 and 7.

Full text of DOI:10.1080/17415993.2011.586456

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A convenient method for synthesis
of bis-2,2′-(1,3,4-thiadiazole) and
bis-3,3′-(1,2,4-triazole) derivatives
Ahmad S. Shawali a , Abdelwahed R. Sayed a & Mohie M. Zayed a
a Department of Chemistry, Faculty of Science , University of
Cairo , Giza, Egypt
Published online: 31 May 2011.
To cite this article: Ahmad S. Shawali , Abdelwahed R. Sayed & Mohie M. Zayed (2011) A
convenient method for synthesis of bis-2,2′-(1,3,4-thiadiazole) and bis-3,3′-(1,2,4-triazole)
derivatives, Journal of Sulfur Chemistry, 32:4, 311-314, DOI: 10.1080/17415993.2011.586456
To link to this article: http://dx.doi.org/10.1080/17415993.2011.586456
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Journal of Sulfur Chemistry
Vol. 32, No. 4, August 2011, 311–314
A convenient method for synthesis of bis-2,2ꢀ-(1,3,4-thiadiazole)
and bis-3,3ꢀ-(1,2,4-triazole) derivatives
Ahmad S. Shawali*, Abdelwahed R. Sayed and Mohie M. Zayed
Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
(Received 2 March 2011; final version received 4 May 2011)
Reactions of the bis-hydrazonoyl chloride 1 with ketene N,S-acetal 2 and the active methine thioanilides 4
and 6 provide a new convenient site-selective synthetic strategy to functionalized bis-3,3ꢀ-(1,2,4-triazoles)
3 and bis-2,2ꢀ-(1,2,4-thiadiazoles) 5 and 7.
R
Ph
Ph
N
(
N
N
)
Cl
2
(C=NNHPh)2
R
Ph
N
S
N
(
)
2
Keywords: ketene N,S-acetal; hydrazonoyl chlorides; thioanilides; heterocycles; dithiocarbamates
1. Introduction
In continuation of our research in the chemistry of nitrilimines and their precursors (1–5) and our
recent study of the reaction of hydrazonoyl halides with acyclic ketene aminals (6), it was thought
worthwhile to study the reactions of the bis-hydrazonoyl chloride 1 with ketene N, S-acetal 2 and
the active methine thioanilides 4 and 6 which have not been reported hitherto (Scheme 1) to shed
light on their site selectivity and to explore their utility in the synthesis of the title ring systems.
As outlined below, the studied reactions proved to be site-selective and appear to develop a new
convenient synthetic strategy to functionalized n, nꢀ-bis(azoles) namely 3,3ꢀ-bis(1,2,4-triazoles)
3 and 2,2ꢀ-bis(1,2,4-thiadiazoles) 5 and 7 (Schemes 1 and 2).
*Corresponding author. Email: as_shawali@mail.com; as_shawali@yahoo.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2011.586456
http://www.informaworld.com

312 A.S. Shawali et al.
Cl
NC
CN
NC
CN
Et3N
(C=NNHPh)2
1
-
K+
PhNH
S
PhNH
S-Me
-2 HCl
-2 KCl
NC
2
4
CN
S
NC
CN
Ph
Ph
N
H
N
(
SMe
)
(
2
NNH-Ph
)
Ph-NHN
2
- 2 MeSH
CN
NC
H
CN
S
NC
Ph
Ph
N
PhNH
Ph
N
(
N
-2 CH2(CN)2
N-Ph
N
)
2
N
(
)
2
3
Cl
PhNH-CS-SMe
KOH
Ph
N
S
(C=NNHPh)2
1
N
(
)
2
5
Scheme 1. Reaction of bis-hydrazonoyl chloride with N, S-acetals.
NC
R
Cl
NC
R
S
(C=NNHPh)2
- 2 KCl
1
Ar
(
2
N
H
S
-
K+
ArNH
)
6
2
Ph-NHN
H
NC
N
R
R
S
NC
ArNH
Ph
Ph
S
N
- 2 ArNH2
N
(
N
)
(
)
2
2
7
R / Ar : a, PhCO / Ph; b, EtOOC / Ph; c, 2-Thenoyl / Ph;
d, EtOOC / 4-ClC6H4
Scheme 2. Synthesis of bis-2,2ꢀ-(1,2,4-thiadiazoles).
2. Results and discussion
The required precursors namely the bis-hydrazonoyl chloride 1 (7) and 2-cyano-3-methylthio-3-
phenylaminoacrylonitrile 2 (8) were prepared in this work by literature methods. In our hands,
treatment of 1 with two mole equivalents of 2 in refluxing ethanol in the presence of triethylamine
proceeded smoothly to give a product that was identified as 3,3ꢀ-bis(1,2,4-triazole) derivative 3
(Scheme 1). The structure of the latter product was elucidated on the basis of its microanalysis and
spectra (see Section 3). On the other hand, treatment of 1 with two equivalents of the potassium salt
of dicyanothioacetanilide 4 in dimethylformamide (DMF) in the presence of potassium hydroxide
gave 2,2ꢀ-bis(1,3,4-thiadiazole) derivative 5 (Scheme 1). The IR spectrum of the latter product
−
showed the absence of absorption bands due to C ≡ N and NH groups. Its structure was further

Journal of Sulfur Chemistry 313
evidenced by its alternate synthesis. Thus, reaction of 1 with methyl N-phenyldithiocarbamate in
ethanol in the presence of triethylamine yielded 5 identical in all respects with that one obtained
above from 1 and 4 (Scheme 1).
Similar reactions of 1 with potassium salts of the other active methine thioanilides 6a–c were
found to give the respective bis(1,3,4-thiadiazole) derivatives 7a–c (Scheme 2). In these cases, it
seemsthattheinitiallyformedthiohydrazonateintermediatescyclizedwithconcurrentelimination
of aniline to give 7 as end products. This suggestion was evidenced by our finding that reaction of
1 with N-(p-chlorophenyl)-2-cyano-2-ethoxycarbonyl-thioacetanilide 6d in DMF in the presence
of potassium hydroxide yielded also 7b (Scheme 2).
3. Experimental
The melting points (mp’s) were measured on an electrothermal Gallenkamp mp apparatus and are
uncorrected. 1H and 13C NMR spectra were recorded in DMSO-d6 with tetramethylsilane as an
internal standard using 300 MHzVarian Gemini spectrometer. The IR spectra were measured on a
Fourier transform and Pye Unicam infrared spectrophotometers using potassium bromide wafer.
Mass spectra were recorded on a GCMS-QP 1000 EX spectrometer at an ionizing potential
of 70 eV. Elemental microanalyses were carried out at the microanalytical laboratory of Cairo
University, Giza, Egypt. The identification of compounds from different experiments was secured
by mixed mp’s and superimposable IR spectra. The bis-hydrazonoyl chloride 1 (7), 2-cyano-
3-methylthio-3-phenylaminoacrylonitrile 2 (8) and methyl N-phenyldithiocarbamate (9) were
prepared as previously described.
3.1. 3,3ꢀ-Bis(1,4-diphenyl)-5-dicyanomethylene-1,2,4-triazole) (3)
Toamixtureofthebis-hydrazonoylchloride 1(0.005 mol)andtheketene N,S-acetal 2 (0.010 mol)
in ethanol (40 ml) was added triethylamine (1.4 ml, 0.010 mol) and the mixture was refluxed till
methanethiol ceased to evolve (1–1.5 h). The precipitate that was formed was filtered off and
crystallized from DMF–ethanol (EtOH) mixture to give the 3,3ꢀ-bis(1,2,4-triazole) derivative 3 as
brown solid (1.14 g, 40%), mp > 300 ◦C. IR (KBr) ν 2197, 2189 cm−1; 1H NMR δ 7.38–8.52 (m);
MS m/z (%) 569 (M+ + 1, 11), 568 (M+, 25), 401 (12), 310 (11), 283 (7), 235 (4), 168 (18), 177
(5), 121 (8), 91 (67), 77 (93), 64 (100). Anal. Calcd. C34H20N10 (568.6): C, 71.82; H, 3.55; N,
24.63; Found: C, 71.50; H, 3.30; N, 24.41%.
3.2. Reactions of the bis-hydrazonoyl chloride with potassium salts of thioanilides 6a–c
General method: To a stirred suspension of potassium hydroxide (0.56 g, 0.01 mol) in DMF
(30 ml), malonitrile (0.01 mol) was added. To the resulting solution was added phenyl isothio-
cyanate (0.01 mol) and the reaction mixture was stirred at room temperature. After stirring for 3 h,
bis-hydrazonoyl chloride 1 (1.50 g, 0.005 mol) was added and the reaction mixture was refluxed
for 5 h, then cooled and poured onto ice-cold hydrochloric acid solution. The solid that precipitated
was filtered, washed with water, dried and finally crystallized from the proper solvent to give 5.
When the above procedure was repeated using benzoylacetonitrile, ethyl cyanoacetate and 2-
theonylacetonitrile each in place of malonitrile, the bis(1,3,4-thiadiazole) derivatives 7a–c were
produced, respectively.
Also, repetition of the above procedure using p-chlorophenyl isothiocyanate in place of phenyl
isothiocyanate in the reaction with ethyl cyanoacetate yielded 7b. The physical constants of the
products 5 and 7a–c are listed below.

314 A.S. Shawali et al.
3.2.1. 2,2ꢀ-Bis-(4-phenyl-5-phenylimino-1,3,4-thiadiazole) (5)
1
Yellow brown solid (1.26 g, 50%), mp 310 ◦C. IR (KBr) ν 1600, 1560 cm−1; H NMR δ 7.07–
7.79 (m); MS m/z (%) 505 (M+ + 1, 7), 504 (M+, 19), 252 (3), 135 (10), 91 (100), 77 (57). Anal.
Calcd. C28H20N6S2 (504.6): C, 66.64; H, 3.99; N, 16.65; found: C, 66.54; H, 3.84; N, 16.53%.
3.2.2. 2,2ꢀ-Bis-[4-phenyl-5-(cyanobenzoylmethylene)-1,3,4-thiadiazole] (7a)
Brown solid (1.22 g, 40%), mp. 170 ◦C (EtOH). IR (KBr) ν 2191, 1640 cm−1; 1H NMR δ 6.72–
7.65 (m); MS m/z (%) 609 (M+ + 1, 5), 608 (M+, 7), 278 (2), 143 (2), 105 (100), 77 (98). Anal.
Calcd. C34H20N6O2S2 (608.7): C, 67.09; H, 3.31; N, 13.81; found: C, 67.20; H, 3.41; N, 13.75%.
3.2.3. 2,2ꢀ-Bis-[4-phenyl-5-(ethoxycarbonylcyanomethylene)-1,3,4-thiadiazole] (7b)
Brown solid (1.36 g, 50%), mp. 195◦C (EtOH). IR (KBr) ν 2206, 1659 cm−1; 1H NMR δ 1.24 (t,
J = 7 Hz, 6H), 4.23 (q, J = 7 Hz, 4H), 7.03–7.97 (m, 10H); 13C NMR δ 14.9, 15.0, 62.1, 62.2,
113.6, 120.9, 123.6, 125.4, 128.1, 128.4, 128.5, 129.7, 129.9, 130.1, 130.6, 131.8, 132.0, 138.2,
139.0, 147.7, 167.3, 167.4; MS m/z (%) 545 (M+ + 1, 52), 544 (M+, 100), 271 (2), 246 (2), 155
(2), 91 (16, 77 (43). Anal. Calcd. C26H20N6O4S2 (544.6): C, 57.41; H, 3.82; N, 15.38; found: C,
57.34; H, 3.70; N, 15.43%.
3.2.4. 2,2ꢀ-Bis-[4-phenyl-5-(2-thenoylcyanomethylene)-1,3,4-thiadiazole] (7c)
Brown solid (1.39 g, 45%), mp. 215 ◦C (EtOH). IR (KBr) ν 2207, 1660 cm−1; 1H NMR δ 7.42–
8.99 (m); MS m/z (%) 621 (M+ + 1, 3), 620 (M+, 12), 310 (14), 284 (15), 207 (100), 110 (13).
Anal. Calcd. C30H16N6O2S4 (620.7): C, 57.05; H, 2.60; N, 13.54; found: C, 58.34; H, 2.41; N,
13.50%.
3.3. Alternate synthesis of (5)
To a stirred solution of methyl N-phenyldithiocarbamate (3.20 g, 0.02 mol) in ethanol (60 ml)
containing triethylamine (2.8 ml, 0.02 mol), the bis-hydrazonoyl chloride 1 (3.07 g, 0.01 mol)
was added and the mixture was stirred for 7 h at room temperature. The precipitated solid was
filtered off, washed with water, dried and finally crystallized from EtOH–DMF to give 5 (1.89 g,
75%) as yellow brown solid which proved identical in all respects with that one obtained above
from 1 and 2.
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