Three-component reaction between benzohydrazide acid, ammonium thiocyanate and acid chlorides under solvent-free conditions

Article abstract of DOI:10.1080/17415993.2011.593636

A novel method for 1,2,4-triazole-3-thiones formation is established using the reaction of ammonium thiocyanate and acid chlorides with benzohydrazide acid under solvent-free conditions to afford triazole-3-thiones in good yields.

Full text of DOI:10.1080/17415993.2011.593636

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Three-component reaction between
benzohydrazide acid, ammonium
thiocyanate and acid chlorides under
solvent-free conditions
Alireza Hassanabadi a , Mohammad H. Mosslemin b , Mohammad
Anary-Abbasinejad b , Mohammad R. Hosseini-Tabatabaei a
Habibeh Mahmoudian b & Seyd Ehsan Tadayonfar b
,
a Department of Chemistry , Islamic Azad University , Zahedan
Branch, PO Box 98135-978, Zahedan, Iran
b Department of Chemistry , Islamic Azad University , Yazd
Branch, PO Box 89195-155, Yazd, Iran
Published online: 22 Jun 2011.
To cite this article: Alireza Hassanabadi , Mohammad H. Mosslemin , Mohammad Anary-
Abbasinejad , Mohammad R. Hosseini-Tabatabaei , Habibeh Mahmoudian & Seyd Ehsan Tadayonfar
(2011) Three-component reaction between benzohydrazide acid, ammonium thiocyanate and
acid chlorides under solvent-free conditions, Journal of Sulfur Chemistry, 32:4, 355-359, DOI:
10.1080/17415993.2011.593636
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Journal of Sulfur Chemistry
Vol. 32, No. 4, August 2011, 355–359
Three-component reaction between benzohydrazide acid,
ammonium thiocyanate and acid chlorides under
solvent-free conditions
Alireza Hassanabadia*, Mohammad H. Mossleminb, Mohammad Anary-Abbasinejadb,
Mohammad R. Hosseini-Tabatabaeia, Habibeh Mahmoudianb and Seyd Ehsan Tadayonfarb
aDepartment of Chemistry, Islamic Azad University, Zahedan Branch, PO Box 98135-978, Zahedan, Iran;
bDepartment of Chemistry, Islamic Azad University, Yazd Branch, PO Box 89195-155, Yazd, Iran
(Received 5 May 2011; final version received 31 May 2011)
A novel method for 1,2,4-triazole-3-thiones formation is established using the reaction of ammonium
thiocyanate and acid chlorides with benzohydrazide acid under solvent-free conditions to afford triazole-
3-thiones in good yields.
S
N
O
NH
Ar
NH2
O
Solvent free
r. t.
N
4
N
+
NH4 SCN
3
+
H
Ar
Cl
O
2
1
Keywords: benzohydrazide acid; acid chlorides; ammonium thiocyanate; triazole-3-thiones; solvent-free
1. Introduction
Multi-component reactions have been frequently used by synthetic chemists as a facile means to
generate molecular diversity from bifunctional substrates that react sequentially in an intramolec-
ular fashion (1–4). 1,2,4-Triazoles are of biological interest (5) and, as a consequence, a number
of synthetic methods have been developed to construct this ring system (6–9). To date, to the
best of our knowledge, there has been no viable one-pot convergent synthesis reported. However,
annulation reactions of suitably substituted acyclic precursors represent an attractive alternative
methodology, which may allow direct regioselective preparation of the target molecule. Recently,
several new methods have been developed that illustrate the utility of the last approach (10–30).
As part of our current studies on the development of new routes in organic synthesis (31, 32), we
report an efficient one-pot synthesis of functionalized 1,2,4-triazole-3-thiones, employing readily
available starting materials.
*Corresponding author. Email: ar_hasanabadi@yahoo.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2011.593636
http://www.informaworld.com

356 A. Hassanabadi et al.
2. Results and discussion
Reaction of benzohydrazide acid 1 and acid chlorides 2 with ammonium thiocyanate 3 under
solvent-free conditions affords 1,2,4-triazole-3-thiones 4 in excellent yields (Scheme 1).
S
N
O
NH
Ar
NH2
O
N
4
Solvent free
r. t.
N
H
NH4SCN
3
+
+
Ar
Cl
O
2
1
% Yield*
89
4
a
Ar
C6H5
b
c
4-ClC6H4
4-BrC6H4
3-NO2C6H4
91
92
89
d
e
4-NO2C6H4
4-CH3C6H4
90
91
f
*Isolated yield
Scheme 1. Three-component reaction between benzohydrazide acid, ammonium thiocyanate
and acid chlorides under solvent-free conditions.
Structures of compounds 4a–f were confirmed by IR, 1H- and 13C-NMR and mass spectral data.
1
For example, the H-NMR spectrum of 4a exhibited characteristic multiplets for the aromatic
protons together with a singlet at δ = 10.63 ppm for the NH group, in agreement with the proposed
structure. The 13C-NMR spectrum of 4a showed the thiocarbonyl resonance at δ = 166.7 ppm.
The mass spectrum of 4a displayed the molecular ion peak at m/z = 281.
A tentative mechanism for this transformation is proposed in Scheme 2.
O
S
O
H
N
1
2
3
+
Ar
N
C
S
Ar
N
H
N
H
O
5
6
_
S
H
N
Ar
HO
NH
-H2O
N
4
O
7
Scheme 2. Suggested mechanism for the formation of compound 4.
It is conceivable that the reaction starts with the formation of aroyl thiocyanate 5 followed by
the addition of benzohydrazide acid 1 to generate 6. Subsequent cyclization of intermediate 6
generates 7 which is converted to 4 by the elimination of water.

Journal of Sulfur Chemistry 357
In conclusion, the reaction of ammonium thiocyanate and acid chlorides with benzohydrazide
acid under solvent-free conditions led to 1,2,4-triazole-3-thiones in excellent yields. The present
procedure has the advantage that the reaction is performed under neutral conditions and the starting
material can be used without any activation or modification.
3. Experimental
Melting points were determined with an Electrothermal 9100 apparatus. Elemental analyses were
performed using a Costech ECS 4010 CHNS-O analyzer at analytical laboratory of Islamic Azad
UniversityYazd branch. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrom-
eter operating at an ionization potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470
spectrometer.1H- and 13C-NMR spectra were recorded on Bruker DRX-500 Avance spectrometer
at solution in DMSO-d6 using TMS as the internal standard. The chemicals used in this work
were purchased from Fluka (Buchs, Switzerland) and were used without further purification.
3.1. General procedure
A mixture of ammonium thiocyanate (0.15 g, 2 mmol) and an acid chloride (2 mmol) was warmed
at about 50◦C for 10 min. Then, benzohydrazide acid (2 mmol) was added slowly. The resulting
mixture was stirred for 4 h at room temperature, and then poured into 15 ml of water. The resulting
precipitate was collected by filtration on a Buchner funnel and washed with 10 ml of cold diethyl
ether to afford the pure title compounds.
3.1.1. Phenyl(5-phenyl-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl)methanone (4a)
White powder, m.p. 235–237◦C, IR (KBr) (νmax cm−1): 3192 (m), 1600 (s), 1564 (s), 1493 (s),
1456 (m), 1265 (m). Analyses: Calcd. for C15H11N3OS: C, 64.04; H, 3.94; N, 14.94%. Found: C,
64.18; H, 3.79; N, 14.80. MS (m/z, %): 281 (8).
1H-NMR (500 MHz, DMSO-d6): δ 7.16–7.59 (10 H, m, 10 CH aromatic), 10.43 (1 H, s,
NH) ppm. 13C-NMR (125.8 MHz, DMSO-d6): δ 128.30, 129.41, 129.56, 130.80, 132.07, 132.56,
=
=
=
133.38 and 135.24 (aromatic), 165.44 (C N), 166.28 (C O), 166.85 (C S) ppm.
3.1.2. Phenyl[5-(4-chlorophenyl)-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]methanone (4b)
White powder, m.p. 226–228◦C, IR (KBr) (νmax cm−1): 3195 (m), 1602 (s), 1564 (s), 1497 (s),
1457 (m), 1266 (m). Analyses: Calcd. for C15H10ClN3OS: C, 57.05; H, 3.19; N, 13.31%. Found:
C, 57.13; H, 3.35; N, 13.19. MS (m/z, %): 315 (10).
1H-NMR (500 MHz, DMSO-d6): δ 7.52–7.96 (5 H, m, 5 CH aromatic), 7.62 (2 H, d, 3JHH
=
8 Hz, 2 CH of C6H4Cl), 7.97 (2 H, d, 3JHH = 8 Hz, 2 CH of C6H4Cl), 10.56 (1 H, s, NH) ppm.
13C-NMR (125.8 MHz, DMSO-d6): δ 128.33, 129.39, 129.54, 130.26, 132.18, 132.76, 133.38
=
=
=
and 137.62 (aromatic), 165.74 (C N), 166.71 (C O), 166.92 (C S) ppm.
3.1.3. Phenyl[5-(4-bromophenyl)-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]methanone (4c)
White powder, m.p. 211–213◦C, IR (KBr) (νmax cm−1): 3185 (m), 1608 (s), 1577 (s), 1496 (s),
1458 (m), 1263 (m). Analyses: Calcd. for C15H10BrN3OS: C, 50.01; H, 2.80; N, 11.66%. Found:
C, 49.90; H, 2.68; N, 11.75. MS (m/z, %): 359 (5).

358 A. Hassanabadi et al.
1H-NMR (500 MHz, DMSO-d6): δ 7.50–7.94 (5 H, m, 5 CH aromatic), 7.74 (2 H, d, 3JHH
=
8 Hz, 2 CH of C6H4Br), 7.88 (2 H, d, 3JHH = 8 Hz, 2 CH of C6H4Br), 10.55 (1 H, s, NH) ppm.
13C-NMR (125.8 MHz, DMSO-d6): δ 128.15, 129.21, 130.03, 130.97, 132.01, 132.38, 132.93
=
=
=
and 133.28 (aromatic), 165.44 (C N), 166.27 (C O), 166.94 (C S) ppm.
3.1.4. Phenyl[5-(3-nitrophenyl)-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]methanone (4d)
White powder, m.p. 221–223◦C, IR (KBr) (νmax cm−1): 3226 (m), 1641 (s), 1616 (s), 1530 (s),
1487 (s), 1445 (m), 1348 (s), 1271 (m). Analyses: Calcd. for C15H10N4O3S: C, 55.21; H, 3.09;
N, 17.17%. Found: C, 55.35; H, 3.16; N, 16.95. MS (m/z, %): 326 (8).
1H-NMR (500 MHz, DMSO-d6): δ 7.52–8.76 (5 H, m, 9 CH aromatic), 10.67 (1 H, s, NH) ppm.
13C-NMR (125.8 MHz, DMSO-d6): δ 122.68, 127.04, 127.95, 129.04, 130.96, 132.47, 132.80,
=
=
=
134.27, 134.33 and 148.34 (aromatic), 164.34 (C N), 166.25 (C O), 166.98 (C S) ppm.
3.1.5. Phenyl[5-(4-nitrophenyl)-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]methanone (4e)
White powder, m.p. 242–244◦C, IR (KBr) (νmax cm−1): 3205 (m), 1611 (s), 1573 (s), 1518 (s),
1458 (m), 1345 (s), 1266 (m). Analyses: Calcd. for C15H10N4O3S: C, 55.21; H, 3.09; N, 17.17%.
Found: C, 55.35; H, 3.16; N, 16.95. MS (m/z, %): 326 (6).1H-NMR (500 MHz, DMSO-d6):
δ 7.49–7.88 (5 H, m, 5 CH aromatic), 8.07 (2 H, d, 3JHH = 8 Hz, 2 CH of C6H4NO2), 8.33 (2 H,
d, 3JHH = 8 Hz, 2 CH of C6H4NO2), 10.66 (1 H, s, NH) ppm. 13C-NMR (125.8 MHz, DMSO-d6):
=
δ 124.28, 127.94, 129.04, 129.47, 132.47, 132.79, 138.61 and 149.90 (aromatic), 164.81 (C N),
=
=
166.23 (C O), 166. 87 (C S) ppm.
3.1.6. Phenyl(3-thioxo-5-p-tolyl-2,3-dihydro[1,2,4]triazol-1-yl)methanone (4f)
White powder, m.p. 218–220◦C, IR (KBr) (νmax cm−1): 3172 (m), 1607 (s), 1560 (s), 1489 (s),
1443 (m), 1267 (m). Analyses: Calcd. for C16H13N3OS: C, 65.06; H, 4.44; N, 14.23%. Found: C,
64.87; H, 4.60; N, 14.39. MS (m/z, %): 295 (3).
1H-NMR (500 MHz, DMSO-d6): δ 2.31 (3 H, s, CH3), 7.49–7.83 (5 H, m, 5 CH aromatic), 7.45
(2 H, d, 3JHH = 8 Hz, 2 CH of C6H4Cl), 7.79 (2 H, d, 3JHH = 8 Hz, 2 CH of C6H4Cl), 10.48 (1
H, s, NH) ppm. 13C-NMR (125.8 MHz, DMSO-d6): δ 21.9 (CH3), 126.4, 128.05, 129.39, 129.54,
=
=
=
130.02, 132.18, 133.38 and 144.31 (aromatic), 164.53 (C N), 166.21 (C O), 166.79 (C S) ppm.
Acknowledgements
We gratefully acknowledge the financial support from the Research Council of Islamic Azad University of Zahedan and
The Islamic Azad University of Yazd of Iran.
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