Microwave assisted one-pot tandem three-component synthesis of 2,4,5-triary1-2-4-dihydro-3H-1,2,4-triazol-3-one derivatives

Article abstract of DOI:10.1016/j.cclet.2013.12.018

This work described a one-pot tandem three-component synthesis of 2,4,5-triaryl-2,4-dihydro-3H-1,2,4-triazol-3-ones using a simple reaction between phenylhydrazines, benzaldehydes and phenyl isocyanates under microwave irradiation and solvent-free conditi

Full text of DOI:10.1016/j.cclet.2013.12.018

Chinese Chemical Letters 25 (2014) 553–556
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Microwave assisted one-pot tandem three-component synthesis of
2,4,5-triary1-2-4-dihydro-3H-1,2,4-triazol-3-one derivatives
b
Bagher Mohammadi a, , Mehdi Adib
*
a Department of Chemistry, Payame Noor University, Tehran 19395-3697, Iran
b School of Chemistry, University College of Science, University of Tehran, Tehran 14155-6455, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
This work described a one-pot tandem three-component synthesis of 2,4,5-triaryl-2,4-dihydro-3H-
1,2,4-triazol-3-ones using a simple reaction between phenylhydrazines, benzaldehydes and phenyl
isocyanates under microwave irradiation and solvent-free conditions in good to excellent yields.
ß 2013 Bagher Mohammadi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Received 29 September 2013
Received in revised form 27 November 2013
Accepted 9 December 2013
Available online 25 December 2013
Keywords:
Tandem multicomponent reactions
Solvent free
Heterocycle
Microwave
Triazole
1. Introduction
involve a cyclization-dehydration sequence of acyl semicarba-
zides in alkaline solutions [22], reaction between 1,2,4-triazolium
Multicomponent reaction (MCR) is a chemical reaction where
three or more compounds react to form a single product. By
definition, MCRs are those reactions whereby more than two
reactants combine in a sequential manner to give highly selective
products that retain the majority of the atoms of the starting
material. In the past decade, multicomponent reactions involving
the condensation of three or more reactants either in tandem or in
single step havebecome an integral part of drugdiscovery [1–9]. The
1,2,4-triazol-3-one (1,2,4-triazolone) ring structure is found in a
number of biologically active compounds. Some 1,2,4-triazolones
havebeenshowntobeangiotensinIIantagonists[10], antimicrobial,
antitumor agents [11–13] and anticonvulsants [14]. Several drugs
possessing triazole nucleus have been approved for marketing, such
as alprazolam (anxiolytic agent, tranquilizer), vorozole (antineo-
plastics, nonsteroidal competitive aromatase inhibitors), etoper-
idone (antidepressant), TAK-187 and Syn-2869 (antifungal agents)
[15], nefazodone (antidepressant, 5-HT2 A-antagonist), rizatriptan
(antimigraine agent), trapidil (hypotensive), trazodone (antidepres-
sant, anxiolytic, selectively inhibits central serotonin uptake) and
triazolam (sedative and hypnotic) (Fig. 1) [16].
salts with aqueous potassium carbonate [23], the condensation of
mono Boc-protected hydrazines with acyl isocyanates and the
subsequent deprotection and then an intramolecular cyclization
of the intermediate [24],
a reaction of amidrazones and
isocyanate esters and the cyclization of the imidoylsemicarbazide
of ethyl chloroformate and N-1-tosylamidrazones [25], the
cyclization of 1-aryl-1 nitroso-3-(2-pyridylmethyl) ureas [26]
and a reaction between thiocarbohydrazide and substituted
benzoyl hydrazine [27].
High-speed synthesis promoted by microwaves irradiation has
attracted a considerable amount of attention in recent years. Using
a
microwave oven in microwave-assisted organic synthesis
(MAOS), not only reduces chemical reaction time from hours to
minutes, but also reduces side reactions, increases the yields, and
improves reproducibility. Therefore, many academic and industrial
research groups are already using MAOS as a forefront technology
for rapid optimization of reactions, for the efficient synthesis of
new chemical entities, and for discovering and probing new
chemical reactivity [28,29].
As a part of our efforts on the development of simple methods to
prepare biologically active organic compounds [30], I used one
such simple method for the synthesis of the scaffold (1,2,4-
triazole-3-ones). I wish to report the synthesis of a trisubstituted
1,2,4-triazole-3-one derivatives 4 by a tandem three-component
condensation of phenylhydrazines 1, benzaldehydes 2 and phenyl
isocyanates 3 (Scheme 1).
There are many methods reported for the synthesis of the 1,2,4-
triazolone ring [17–21]. The most common synthetic methods
*
Corresponding author.
E-mail address: Bagher.mohammadi@yahoo.com (B. Mohammadi).
1001-8417/$ – see front matter ß 2013 Bagher Mohammadi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.12.018

554
B. Mohammadi, M. Adib / Chinese Chemical Letters 25 (2014) 553–556
CH3
was purified by column chromatography using petroleum ether–
O
CF3
ethyl acetate (4:1) as the eluent. The solvent was removed, and the
product was obtained as colorless crystals. The characterizationdata
of the compounds are given below.
O
R
N
R
N
N
H3CO
O
H3CO
O
N
N
4-(3-Chloro-4-methylphenyl)-5(3-methylphenyl)-2-phenyl-
2,4-dihydro-3H-1,2,-triazol-3-one (4a): Colorless crystals, the
yield was 330 mg (88%), Rf = 0.46 (petroleum ether:ethyl acetate,
a
N
N
c
CH3
CH3
O
CH3
4:1), mp 168–169 8C, 1H NMR (300 MHz, CDCl3):
d 2.34 and 2.41
O
F3C
OH
O
N
N
(2s, 6H), 7.04 (dd, 1H, J = 2.1 and 8.1 Hz), 7.06 (d, 1H, J = 7.5 Hz),
7.19 (t, 1H, J = 7.6 Hz), 7.24 (d, 1H, J = 7.9 Hz), 7.25 (t, 1H, J = 7.4 Hz),
7.28 (d, 1H, J = 7.8 Hz), 7.37 (d, 1H, J = 2.1 Hz), 7.40 (s, 1H), 7.46 (dd,
2H, J = 8.4 and 7.4 Hz), 8.10 (d, 2H, J = 7.7 Hz); 13C NMR
N
N
N
NH
N
OCH2CF2H
O
S
N
N
O
N
b
d
(75.47 MHz, CDCl3):
d 19.88 and 21.35 (2C), 118.90, 125.09,
125.52 and 125.59 (4C), 125.94 (1C), 127.76, 128.43, 12,861,
128.99, 131.28 and 131.44 (6C), 132.06, 134.97, 137.09, 137.71 and
Fig. 1. Examples of biologically active 1,2,4-triazolones: (a and c) agricultural
fungicides, (b) TAK-187 (antifungal), and (d) AT1-receptor antagonist.
138.67 (5C), 145.17 (1C), 151.64 (1C), IR (KBr, cmꢀ1):
y 1709
(C55O), 1637, 1608, 1595, 1556, 1499, 1458, 1418, 1371, 1325,
1184, 1055, 800, 758, MS (m/z): 375 (M+), 327 (11), 208 (20), 149
(8), 91 (100), 69 (23), anal. calcd. for C22H18ClN3O (375.5): C, 70.30;
H, 4.83; N, 11.18. Found: C, 70.15; H, 4.93; N, 11.04.
5-(4-Chlorophenyl)-2,4-diphenyl-2H-1,2,4-triazol-3(4H)-one
(4b): Colorless crystals, the yield was 319 mg (92%), Rf = 0.65
(petroleum ether:ethyl acetate, 4:1), mp 176–177 8C, 1H NMR
2. Experimental
All starting materials and solvents were obtained from Merck
(Germany) or Fluka (Switzerland) and were used without further
purification. The methods used to monitor the reactions were TLC
and NMR. Melting points were measured on an Electrothermal
9100 apparatus and were uncorrected. IR spectra were measured
on a Jasco 6300 FTIR spectrometer. 1H NMR and 13C NMR spectra
(CDCl3) were recorded on a BRUKER DRX-300 AVANCE spectrom-
eter at 300 MHz and 75.5 MHz, respectively. Elemental analyses
were performed using a Heraeus CHN-O-Rapid analyzer. Mass
spectra were recorded on a FINNIGAN-MATT 8430 mass spec-
trometer operating at an ionization potential of 70 eV. Preparative
layer chromatography (PLC) plates were prepared from Merck
silica gel (F254) powder.
(300 MHz, CDCl3):
(d, 2H, J = 8.8 Hz), 7.44–7.52 (m, 5H), 8.10 (d, 2H, J = 7.6), 13C NMR
(75.47 MHz, CDCl3): 118.86 (1C),124.80 (1C), 125.66,
127.32,128.93, 129.03, 129.08, 129.22 and 129.70 (7C), 133.25,
136.53 and 137.70 (3C), 144.18 (1C), 151.71 (1C), IR (KBr, cmꢀ1):
d 7.26–7.31 (m, 3H), 7.31 (d, 2H, J = 8.8 Hz), 7.36
d
y
1715 (C55O), 1639, 1619, 1599, 1497, 1427, 1369, 1321, 1150, 1095,
831, 760, MS (m/z): 347 (M+), 228 (13), 91 (100), 277 (22), anal.
calcd. for C20H14ClN3O (347.5): C, 69.07; H, 4.06; N, 12.08. Found:
C, 68.91; H, 4.12; N, 12.03.
General procedure for the preparation of 4a–k: This reaction was
carried out using two protocols, namely microwave and conven-
tional heating methods. Both methods were carried out by first
mixing the arylhydrazine 1 and the arylaldehyde 2 at room
temperature. After a few minutes and nearly a complete conversion
to the corresponding arylhydrazone 5 was achieved, as indicated by
TLC monitoring, the isocyanate 3 was added to the reaction mixture
andinthefirstmethod, themixturewasirradiatedundermicrowave
irradiation and in the second method the reaction mixture was
heatedand stirredonamagneticstirrer. The workupprocessofthese
methods is the same. 1H NMR analysis of the reaction mixtures
clearly indicated the formation of 1,2,4-triazol-3-ones 4. The
structures of the isolated products were assigned on the basis of
IR, 1H NMR and 13C NMR spectroscopy, mass spectrometry and
elemental analysis. The mass spectrum of 4a displayed the
molecular ion (M+) peak at m/z 375, which was consistent with a
1:1:1 adduct of phenylhydrazine, 3-methyl benzaldeyde and 3-
chloro-4-methylpenyl isocyanate, losing two hydrogen atoms.
A mixture of phenylhydrazine (0.216 g, 2 mmol) and 3-methyl-
benzaldehyde (0.240 g, 2 mmol) was stirred at 25 8C for 10 min.
Then 3-chloro-4-methylphenylisocyanate (0.335 g, 2 mmol) was
added to the reaction mixture and in the first method, the reaction
mixture was irradiated (ETHOS 1600 Milestone) in a sealed 5 mL
vial at 600 W for 15 min and in the second method, the reaction
mixture was heated at 250 8C for 1 h. In both methods, the residue
4-(3-Chloro-4-methylphenyl)-2,5-di(4-methylphenyl)-2H-
1,2,4-triazol-3(4H)-one (4c): Colorless crystals, the yield was
342 mg (88%), Rf = 0.54 (petroleum ether:ethyl acetate, 4:1), mp
175–177 8C, 1H NMR (300 MHz, CDCl3):
d 2.36, 2.38 and 2.42 (3s,
3H), 7.05 (dd, 1H, J = 2.1 and 8.1 Hz), 7.15 (d, 2H, J = 8.1 Hz), 7.25 (d,
2H, J = 7.5 Hz), 7.28 (d, 1H, J = 8.3 Hz), 7.31 (d, 2H, J = 8.3 Hz), 7.37
(d, 1H, J = 2.1 Hz), 7.96 (d, 2H, J = 8.5 Hz), 13C NMR (75.47 MHz,
CDCl3):
d 19.88, 20.97 and 21.41 (3C), 118.88 (1C), 123.28 (1C),
125.58, 127.84, 127.85, 129.36, 129.50 and 131.45 (6C), 132.21,
134.98, 135.22, 135.34, 137.03 and 140.67 (6C), 144.86 (1C),
151.61 (1C), IR (KBr, cmꢀ1):
y 1708 and 1695 (C55O), 1637, 1616,
1512, 1427, 1371, 1326, 1151, 1053, 818, 735, MS (m/z): 389 (M+),
105 (89), 78 (13), anal. calcd. for C23H20ClN3O (389.5): C, 70.86; H,
5.17; N, 10.78. Found: C, 70.83; H, 5.24; N, 10.73.
4-(3-Chloro-4-methylphenyl)-5-(4-methoxyphenyl)-2-phe-
nyl-2H-1,2,4-triazol-3(4H)-one (4d): Colorless crystals, the yield
was 320 mg (82%), Rf = 0.50 (petroleum ether/ethyl acetate,
4:1), mp: 174–175 8C, 1H NMR (300 MHz, CDCl3):
d 2.42 (s, 3H),
3.02 (s, 3H), 6.85 (d, 2H, J = 8.9 Hz), 7.05 (dd, 1H, J = 2.1 and 8.1 Hz),
7.24 (t, 1H, J = 7.4 Hz), 7.29 (d, 1H, J = 8.1 Hz), 7.36 (d, 2H,
J = 8.8 Hz), 7.37 (d, 1H, J = 2.1 Hz), 7.45 (dd, 2H, J = 8.2 and 7.8 Hz),
8.09 (d, 2H, J = 8.3 Hz), 13C NMR (75.47 MHz, CDCl3):
d 19.90 (1C),
55.33 (1C), 114.14 (1C), 118.33 (1C), 118.79, 125.46, 125.64,
127.89, 128.97, 129.51 and 131.52 (7C), 132.18, 135.02, 137.13,
137.78 and 144.88 (5C), 151.65 (1C), 161.19 (1C), IR (KBr, cmꢀ1):
y
1711 (C55O), 1637, 1610, 1595, 1512, 1500, 1458, 1429, 1373, 1327,
1256, 1179, 1150, 1026, 835, 754, MS (m/z): 391 (M+), 327 (31), 209
(11), 91 (100), 69 (38), anal. calcd. for C22H18ClN3O2 (391.5): C,
67.43; H, 4.63; N, 10.72. Found: C, 67.34; H, 4.72; N, 10.70.
4-(3-Chloro-4-methylphenyl)-2-phenyl-5-(4-methyl phenyl)-
2H-1,2,4-triazol-3(4H)-one (4e): Colorless crystals, the yield was
319 mg (85%), Rf = 0.52 (petroleum ether: ethyl acetate, 4:1), mp
Ar''
Ar'
N
solvent-free
'
''
ArNHNH + ArCHO + ArNCO
O
2
N
MW, 600 W, 15 min
N
4
1
3
2
Ar
175–177 8C, 1H NMR (300 MHz, CDCl3):
7.05 (dd, CH, J = 2.1 and 8.1 Hz), 7.16 (d, 2H, J = 8.1 Hz), 7.25 (t, 1H,
d 2.37 and 2.42 (2s, 2CH3),
Scheme 1. One pot synthesis of 2,4,5-triary1-2-4-dihydro -3H-1,2,4-triazol-3-ones.

B. Mohammadi, M. Adib / Chinese Chemical Letters 25 (2014) 553–556
555
Table 1
J = 7.4 Hz), 7.27 (d, 1H, J = 8.2 Hz), 7.33 (d, 2H, J = 8.2 Hz), 7.38 (d,
1H, J = 2.1 Hz), 7.47 (dd, 2H, J = 8.5 and 7.5 Hz), 8.11 (d, 2H,
Synthesis of 3H-1,2,4-triazol-3-ones 4a–k using microwave irradiation and
conventional heating methods.
J = 7.6 Hz), 13C NMR (75.47 MHz, CDCl3):
d 19.90 and 21.43 (2C),
Product Ar
Ar0
Ar00
Yield (%)
118.86 (1C), 123.20 (1C), 125.53, 125.60, 127.85, 127.88, 128.98,
129.40 and 131.49 (7C), 132.14, 135.02, 137.12, 137.76 and 140.79
Microwavea Conventionalb
(5C), 145.09 (1C), 151.67 (1C), IR (KBr, cmꢀ1):
y 1711 (C55O), 1639,
4a
4b
4c
4d
4e
4f
Ph
2-MePh
4-ClPh
3-Cl-4-MePh 88
Ph 92
3-Cl-4-MePh 88
–
8
–
–
–
–
–
5
7
2
–
1616, 1599, 1497, 1427, 1373, 1321, 1150, 1051, 824, 750, MS (m/
z): 375 (M+), 327 (17), 149 (32), 91 (71), 81 (46), 69 (100), 57 (55),
anal. calcd. for C22H18ClN3O (375.5): C, 70.30; H, 4.83; N, 11.18.
Found: C, 70.33; H, 4.82; N, 11.12.
5-(4-Chlorophenyl)-4-phenyl-2-(4-methylphenyl)-2H-1,2,4-
triazol-3(4H)-one (4f): Colorless crystals, the yield was 317 mg
(88%), Rf = 0.62 (petroleum ether: ethyl acetate, 4:1), mp 193–
Ph
4-Meph
ph
4-MePh
4-MeOPh 3-Cl-4-MePh 82
ph
4-MePh
4-ClPh
3-Cl-4-MePh 85
4-MePh
4-MePh
Ph
Ph
Ph
Ph
Ph
88
4g
4h
4i
4-MePh
2-MePh
4-MePh
90
82
Ph
91
87
195 8C, 1H NMR (300 MHz, CDCl3):
d
2.39 (s, 3H), 7.26 (d, 2H,
J = 7.9 Hz), 7.28–7.33 (m, 4H), 7.36 (d, 2H, J = 8.7 Hz), 7.42–7.49 (m,
3H), 7.97 (d, 2H, J = 8.5 Hz), 13C NMR (75.47 MHz, CDCl3):
= 20.98
4j
Ph
4-MeOPh Ph
4k
4-Me Ph 4-ClPh
3-Cl-4-MePh 83
a
Yields of microwave irradiation’s method.
Yields of conventional heating’s method.
d
b
(1C), 118.90 (1C), 124.89 (1C), 127.32, 128.90, 129.01, 129.20,
129.55 and 129.66 (6C), 133.32, 135.29, 135.39 and 136.43 (4C),
143.94 (1C), 151.65 (1C), IR (KBr, cmꢀ1):
y 1709 and 1690 (C55O),
1639, 1610, 1515, 1427, 1377, 1153, 1100, 841, 820, MS (m/z): 361
(M+), 327 (8), 105 (36), 91 (12), 84 (100), anal. calcd. for
2H, J = 8.7 Hz), 7.39–7.46 (m, 5H), 8.10 (d, 2H, J = 8.3 Hz), 13C NMR
(125.8 MHz, CDCl3): 55.28 (1C), 114.01 (1C), 118.66 (1C), 118.79,
d
C
21H16ClN3O (361.5): C, 69.71; H, 4.46; N, 11.61. Found: C,
125.34, 127.43, 128.77, 128.93, 129.49 and 129.53 (7C), 133.64 and
137.92 (2C), 145.10 (1C), 151.83 (1C), 161.08 (C–O), IR (KBr, cmꢀ1):
69.50; H, 4.43; N, 11.55.
4-Phenyl-2,5-di(4-methylphenyl)-2H-1,2,4-triazol-3(4H)-one
(4g): Colorless crystals, the yield was 306 mg (90%), Rf = 0.60
(petroleum ether:ethyl acetate, 4:1), mp 192–194 8C, 1H NMR
y 1707 (C55O), 1639, 1614, 1512, 1375, 1258, 1177, 1028, 966, 837,
760, MS (m/z): 343 (M+), 224 (10), 209 (12), 149 (26), 91 (69), 81
(50), 69 (100), 57 (69), anal. calcd. for C21H17N3O2 (343): C, 73.45;
H, 4.99; N, 12.24. Found: C, 73.51; H, 4.82; N, 12.28.
(300 MHz, CDCl3):
7.25–7.33 (m, 6H), 7.41–7.48 (m, 3H), 8.00 (d, 2H, J = 8.5 Hz), 13C
NMR (75.47 MHz, CDCl3): 20.99 and 21.41 (2C), 118.88 (1C),
d 2.35 and 2.39 (2s, 6H), 7.13 (d, 2H, J = 8.0 Hz),
4-(3-Chloro-4-methylphenyl)-5-(4-chlorophenyl)-2-(4-
d
methylphenyl)-2H-1,2,4-triazol-3(4H)-one (4k): Colorless crys-
tals, the yield was 339 mg (83%), Rf = 0.56 (petroleum ether: ethyl
123.56 (1C), 127.38, 127.91, 128.72, 129.26, 129.47 and 129.50
(6C), 133.66, 135.11, 135.50 and 140.50 (4C), 145.10 (1C), 151.79
acetate, 4:1), mp 194–195 8C, 1H NMR (300 MHz, CDCl3):
d 2.39
(1C), IR (KBr, cmꢀ1):
y
1707 and 1695 (C55O), 1637, 1615, 1512,
and 2.43 (2s, 6H), 7.04 (dd, 1H, J = 2.0 and 8.1 Hz), 7.27 (d, 2H,
J = 8.5 Hz), 7.28 (t, 1H, J = 7.2 Hz), 7.32–7.40 (m, 5H), 7.94 (d, 2H,
1427, 1375, 1313, 1151, 966, 816, 733, MS (m/z): 341 (M+), 105
(10), 84 (100), anal. calcd. for C22H19N3O (341): C, 77.04; H, 5.23; N,
12.84. Found: C, 76.74; H, 5.41; N, 12.66.
2,4-Diphenyl-5-(2-methylphenyl)-2H-1,2,4-triazol-3(4H)-one
(4h): Colorless crystals, the yield was 267 mg (82%), Rf = 0.66
(petroleum ether:ethyl acetate, 4:1), mp: 177–179 8C, 1H NMR
J = 8.5 Hz), 13C NMR (75.5 MHz, CDCl3):
d 19.91 and 20.99 (2C),
118.90 (1C), 124.63 (1C), 125.50, 127.79, 129.03, 129.15, 129.56
and 131.64 (6C), 131.87, 135.17, 135.21, 135.50, 136.61 and 137.42
(6C), 143.71 (1C), 151.47 (1C), IR (KBr, cmꢀ1):
y 1697 (C55O), 1636,
1605, 1504, 1427, 1377, 1151, 918, 825, 727, MS (m/z): 409 (M+),
327 (13), 208 (3), 105 (23), 84 (100), anal. calcd. for C22H17Cl2N3O
(409): C, 64.40; H, 4.18; N, 10.24. Found: C, 64.32; H, 4.27; N, 10.18.
(300 MHz, CDCl3): d 2.32 (s, 3H), 7.11 (d, 1H, J = 7.3 Hz), 7.18 (t, 1H,
J = 7.5 Hz), 7.22 (d, 1H, J = 8.0 Hz), 7.28 (d, 1H, J = 7.3 Hz), 7.30 (dd,
1H, J = 7.9 and 1.7 Hz), 7.37 (s, 1H), 7.44 (m, 4H), 7.48 (dd, 2H,
J = 7.6 and 8.3 Hz), 8.16 (d, J = 8.8 Hz, 2H), 13C NMR (75.47 MHz,
3. Results and discussion
CDCl3):
d 21.34 (1C), 118.89, 125.17 and 125.50 (3C), 126.24 (1C),
127.36, 128.36, 128.68, 128.80, 129.01, 129.48 and 131.11 (7C),
133.54, 137.89 and 138.50 (3C), 145.39 (1C), 151.83 (1C), IR (KBr,
Arylhydeazines, benzaldehydes and arylisocyanates undergo a
simple reaction under microwave irradiation and solvent-free
conditions producing 2,4,5-triary1-2-4-dihydro-3H-1,2,4-triazol-
3-ones 4a–k in 82%–92% yields. This reaction proceeded better
under microwave irradiation (the first method), compared to the
conventional heating (the second method) in 250 8C for 1 h whose
yields are less than 10% and the main product in this method was
(E)-1,2,4-triarylesemicarbazides 6 (Table 1), (Scheme 2).
cmꢀ1):
y 1705 (C55O), 1593, 1555, 1495, 1456, 1416, 1373, 1319,
1148, 806, 756, 690, MS (m/z): 327 (M+), 208 (23), 91 (98), 77 (18),
anal. calcd. for C21H17N3O (327): C, 77.04; H, 5.23; N, 12.84. Found:
C, 76.74; H, 5.41; N, 12.66.
2,4-Diphenyl-5-(4-methylphenyl)-2H-1,2,4-triazol-3(4H)-one
(4i): Colorless crystals, the yield was 297 mg (91%), Rf = 0.68
(petroleum ether:ethyl acetate, 4:1), mp 165–166 8C, 1H NMR
(500 MHz, CDCl3):
J = 7.4 Hz), 7.27–7.30 (m, 4H), 7.40–7.47 (m, 5H), 8.12 (d, 2H,
J = 8.1 Hz), 13C NMR (125.8 MHz, CDCl3):
21.38 (1C), 118.84 (1C),
d 2.33 (s, 3H), 7.11 (d, 2H, J = 8.0 Hz), 7.23 (t, 1H,
1) Ar''NCO (3)
d
r. t.
'
'
ArNHN=CHAr
ArNHNH
+
ArCHO
2
123.49 (1C), 125.41, 127.38, 127.91, 128.76, 128.95, 129.26 and
129.47 (7C), 133.60, 137.91 and 140.57 (3C), 145.31 (1C), 151.85
2) MW, 600 W, 15 min
5
1
2
(1C), IR (KBr, cmꢀ1):
y 1718 (C55O), 1637, 1613, 1597, 1499, 1425,
1373, 1320, 1148, 966, 824, 755, MS (m/z): 327 (M+), 312 (19), 211
(29), 119 (79), 105 (31), 91 (91), 77 (16), anal. calcd. for C21H17N3O
(327): C, 77.04; H, 5.23; N, 12.84. Found: C, 77.05; H, 5.21; N, 12.76.
5-(4-Methoxyphenyl)-4-phenyl-2-(4-methylphenyl)-2H-1,2,4-
triazol-3(4H)-one (4j): Colorless crystals, the yield was 298 mg
(87%), Rf = 0.48 (petroleum ether:ethyl acetate, 4:1), m.p. 173–
'
'
'
Ar''
A
r''
A
r
Ar''
Ar
Ar
N
N
HN
-
2H
N
N
HN
N
O
N
O
N
O
Ar
Ar
Ar
7
4
6
174 8C, 1H NMR (500 MHz, CDCl3):
J = 8.7 Hz), 7.22 (t, 1H, J = 7.4 Hz), 7.29 (d, 2H, J = 7.1 Hz), 7.33 (d,
d 3.78 (s, 3H), 6.81 (d, 2H,
Scheme 2. A possible mechanism for the formation of products 4.

556
B. Mohammadi, M. Adib / Chinese Chemical Letters 25 (2014) 553–556
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Mechanistically, it is reasonable to assume that the first step
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may involve the condensation of arylhydrazine 1 and arylaldehyde
2 to form hydrazone 5 in situ and then the addition of one molecule
of isocyanate 3 leads to the formation of semicarbazone 6, which is
cyclized to produce 1,2,4-triazolan-3-one 7. Intermediate 7 was
finally oxidized under the reaction conditions to produce 2,4-
dihydro-3H-1,2,4-triazol-3-ones 4 (Scheme 2).
4. Conclusion
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The method reported here offers a simple tandem three-
component reaction under microwave irradiation and solvent-free
conditions for the preparation of 1,2,4-triazol-3-ones of synthetic
and pharmacological interest. The use of commercial starting
materials, good yields of the products and fairly short reaction
times are the main advantages of this method.
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Acknowledgments
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I
gratefully acknowledge the financial support from the
Research Council of Payame Noor University (PNU), abhar-Iran,
and also I wish to thank Mr. Alireza Halvaei.
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