Three-component and one-pot synthesis of 1,2,4-triazole-3-thione derivatives under solvent-free conditions

Article abstract of DOI:10.3184/174751913X13735644147854

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

Full text of DOI:10.3184/174751913X13735644147854

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 511
AUGUST, 511–512
Three-component and one-pot synthesis of 1,2,4-triazole-3-thione
derivatives under solvent-free conditions
Alireza Hassanabadi*
Department of Chemistry, Zahedan Branch, Islamic Azad University, PO Box 98135-978, Zahedan, Iran
A novel method for 1,2,4-triazole-3-thiones formation is established using the reaction of ammonium thiocyanate
and aroyl chlorides with acylhydrazides under solvent-free conditions to afford triazole-3-thiones in good yields.
Keywords: acylhydrazides, aroyl chlorides, ammonium thiocyanate, triazole-3-thiones, solvent-free conditions
Multi-component reactions (MCRs) have been frequently used
by synthetic chemists as a facile means to generate molecular
diversity from bifunctional substrates that react sequentially in
an intramolecular fashion.1–4 1,2,4-Triazoles are of biological
interest5 and, as a consequence, a number of synthetic methods
have been developed to construct this ring system.6–9 To the
best of our knowledge, there has been no viable one-pot con-
vergent synthesis reported previously. 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 which illustrate the
utility of the last approach.10–12 As part of our current studies
on the development of new routes in organic synthesis,13–15 we
now report an efficient one-pot synthesis of functionalised
1,2,4-triazole-3-thiones, employing readily available starting
materials.
Structures of compounds 4a–f were confirmed by IR,
1H NMR, 13C NMR, and mass spectral data. A tentative
mechanism for this transformation is proposed in Scheme 2.
It is conceivable that the reaction starts with formation of
aroyl thiocyanate 5 followed by addition of acylhydrazides 1
to generate 6. Subsequent cyclisation of Intermediate 6 gener-
ates 7, which is converted into 4 by elimination of water.
In conclusion, the reaction of ammonium thiocyanate and
aroyl chlorides with acylhydrazides under solvent-free condi-
tions led to 1,2,4-triazole-3-thiones in good 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.
Experimental
Melting points were determined with an Electrothermal 9100 appara-
tus and are uncorrected. Elemental analyses were performed using a
Heraeus CHN-O-Rapid analyser. Mass spectra were recorded on a
FINNIGAN-MAT 8430 mass spectrometer operating at an ionisation
potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470
spectrometer.1H and 13C NMR spectra were recorded on a Bruker
DRX-500 Avance spectrometer in solution in CDCl3 using TMS as
internal standard. The chemicals used in this work were purchased
Results and discussion
Reaction of acylhydrazides 1 and aroyl chlorides 2 with
ammonium thiocyanate 3 under solvent-free conditions gives
1,2,4-triazole-3-thiones 4 in good yields (Scheme 1).
Scheme 1 Three-component reaction between ammonium thiocyanate and aroyl chlorides with acylhydrazides under
solvent-free conditions.
* Correspondent. E-mail: ar_hasanabadi@yahoo.com

512 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 2 Suggested mechanism for formation of compound 4.
from Fluka (Buchs, Switzerland) and were used without further
purification.
for C14H9ClN4OS: C, 53.08; H, 2.86; N, 17.69. Found: C, 53.15; H,
2.73; N, 17.60%. MS (m/z, %): 316 (10). 1H NMR (500 MHz,
d6-DMSO): δ 7.82 (2H, d, 3JHH = 5.2 Hz, 2CH pyridine), 8.95 (2H, d,
3JHH = 5.2 Hz, 2CH pyridine),7.67 (2H, d, 3JHH = 8 Hz, 2CH of C6H4Cl),
General procedure:
A mixture of ammonium thiocyanate (2 mmol) and an aroyl chloride
(2 mmol) was warmed at about 50 °C for 10 min. Then, acylhydrazide
(2 mmol) was added slowly. The resulting mixture was stirred for
6h at room temperature, and then poured into water (15 mL). The
resulting precipitate was collected by filtration on a Buchner funnel
and washed with cold diethyl ether (10 mL) to afford the pure title
compounds.
[5-Phenyl-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]furan-2-yl-methan-
one (4a): White powder, m.p. 226–228 °C, IR (KBr) (νmax cm−1): 3214,
1607, 1561, 1483, 1452, 1263. Anal. Calcd for C13H9N3O2S: C, 57.55;
H, 3.34; N, 15.49. Found: C, 57.60; H, 3.30; N, 15.41%. MS (m/z, %):
271 (10). 1H NMR (500 MHz, d6-DMSO): δ 6.42 (1H, m, CH furan),
7.55 (1H, s, CH furan), 7.68 (1H, d, 3JHH = 2 Hz, CH furan), 7.11–7.63
(5H, m, 5CH aromatic), 10.52 (1H, s, NH). ppm. 13C NMR
(125.8 MHz, d6-DMSO): δ 111.42, 121.06, 143.27 and 145.61 (4C
furan), 127.65, 128.80, 130.14 and 134.56 (4C aromatic), 165.38
(C=N), 166.22 (C=O), 166.81 (C=S) ppm.
7.94 (2H, d, 3JHH 8 Hz, 2CH of C6H4Cl), 10.50 (1H, s, NH).ppm. 13
C
NMR (125.8 MHz, d6-DMSO): δ 122.55, 141.54, and 151.89 (3C
pyridine), 128.46, 129.30, 132.82 and 135.94 (4C aromatic), 165.81
(C=N), 166.80 (C=O), 167.05 (C=S) ppm.
[5-(4-Nitrophenyl)-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]pyridin-
4-yl-methanone (4f): White powder, m.p. 246–249 °C, IR (KBr)
(νmax cm−1): 3200, 1617, 1575, 1526, 1455, 1359, 1250. Anal. Calcd
for C14H9N5O3S: C, 51.37; H, 2.77; N, 21.40. Found: C, 51.33;
1
H, 2.84; N, 21.48%. MS (m/z, %): 327 (5). H NMR (500 MHz,
d6-DMSO): δ 7.85 (2H, d, 3JHH = 5.2 Hz, 2CH pyridine), 8.97 (2H, d,
3
3JHH = 5.2 Hz, 2CH pyridine), 8.17 (2H, d, JHH = 8 Hz, 2CH of
C6H4NO2), 8.38 (2H, d, 3JHH = 8 Hz, 2CH of C6H4NO2), 10.71 (1H, s,
NH).ppm. 13C NMR (125.8 MHz, d6-DMSO): δ 122.73, 141.81,
and 151.94 (3C pyridine), 124.40, 128.73, 147.67 and 149.93 (4C
aromatic), 164.95 (C=N), 166.37 (C=O), 166. 92 (C=S) ppm.
[5-(4-Chlorophenyl)-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]furan-
2-yl-methanone (4b): White powder, m.p. 213–215 °C, IR (KBr)
(νmax cm−1): 3198, 1611, 1572, 1495, 1453, 1251. Anal. Calcd for
C13H8ClN3O2S: C, 51.07; H, 2.64; N, 13.74. Found: C, 51.15; H, 2.72;
We gratefully acknowledge financial support from the Research
Council of Islamic Azad University of Zahedan of Iran.
1
N, 13.65%. MS (m/z, %): 305 (6). H NMR (500 MHz, d6-DMSO):
Received 14 May 2013; accepted 4 June 2013
Paper 1301950 doi: 10.3184/174751913X13735644147854
Published online: 9 August 2013
δ 6.53 (1H, m, CH furan), 7.50 (1H, s, CH furan), 7.60 (1H, d, 3JHH
=
2 Hz, CH furan), 7.67 (2H, d, 3JHH = 8 Hz, 2CH of C6H4Cl), 7.94 (2H,
3
d, JHH = 8 Hz, 2CH of C6H4Cl), 10.53 (1H, s, NH).ppm. 13C NMR
(125.8 MHz, d6-DMSO): δ 112.05, 120.75, 139.82 and 142.94 (4C
furan), 128.88, 129.27, 133.14 and 135.90 (4C aromatic), 165.48
(C=N), 166.34 (C=O), 166.93 (C=S) ppm.
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(1H, d, JHH = 2 Hz, CH furan), 8.14 (2H, d, JHH = 8 Hz, 2CH of
C6H4NO2), 8.42 (2H, d, 3JHH = 8 HZ, 2CH of C6H4NO2), 10.75 (1H, s,
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[5-Phenyl-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]pyridin-4-yl-
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3184, 1609, 1577, 1498, 1468, 1252. Anal. Calcd for C14H10N4OS:
C, 59.56; H, 3.57; N, 19.84. Found: C, 59.61; H, 3.64; N, 19.73%.
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1
MS (m/z, %): 282 (8). H NMR (500 MHz, d6-DMSO): δ 7.76 (2H,
3
3
d, JHH = 5.2 Hz, 2CH pyridine), 8.93 (2H, d, JHH = 5.2 Hz, 2CH
pyridine), 7.23–7.60 (5H, m, 5CH aromatic), 10.32 (1H, s, NH). ppm.
13C NMR (125.8 MHz, d6-DMSO): δ 122.43, 141.50, and 151.84 (3C
pyridine), 127.70, 128.64, 130.11 and 134.45 (4C aromatic), 165.20
(C=N), 166.35 (C=O), 167.13 (C=S) ppm.
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[5-(4-Chlorophenyl)-3-thioxo-2,3-dihydro[1,2,4]triazol-1-yl]-
pyridin-4-yl-methanone (4e): White powder, m.p. 210–212 °C, IR
(KBr) (νmax cm−1): 3218, 1613, 1550, 1488, 1447, 1251. Anal. Calcd