A one-step synthesis of 4,4′-(methylenedi-4,1-phenylene)bis-[5-(2- thienylmethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one]

Full text of DOI:10.1007/s10593-011-0770-8

Chemistry of Heterocyclic Compounds, Vol. 47, No. 3, May, 2011 (Russian Original Vol. 47, No. 3, March, 2011)
A ONE-STEP SYNTHESIS OF 4,4'-(METHYLENEDI-
4,1-PHENYLENE)BIS-[5-(2-THIENYLMETHYL)-
2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONE]
M. Pitucha1*
Keywords: 2,4-dihydro-3H-1,2,4-triazol-3-one, 4,4'-diphenylmethane diisocyanate, hydrazide.
Heterocyclic rings have played an important role in medicinal chemistry, serving as the key templates
central to the development of numerous important therapeutic agents. Among the numerous five-membered
heterocycles studied, 1,2,4-triazoles have been identified as active core structures in antimicrobial [1], antitumor
[2], anticonvulsant, and antiviral agents [3, 4]. One of the methods for the synthesis of these derivatives is the
cyclization reaction of acetylsemicarbazides in alkaline medium [57].
Here I report a simple, one-step procedure for the synthesis of 4,4'-(methylenedi-4,1-phenylene)bis-
[5-(2-thienylmethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one] (3) in good yield.
O
S
H
N
N
H
N
NH
O
O
S
N
NCO
NH
S

+
H
N
O
NH2
O
N
NCO
NH
1
2
S
O
NH
H
N
N
N
H
S
O
3
_______
* To whom correspondence should be addressed, e-mail: monika.pitucha@umlub.pl.
1 Department of Organic Chemistry, Medical University, 6 Staszica, Lublin 20-081, Poland.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 463-465, February, 2011. Original
article received October 27, 2010, in revised form January 27, 2011.
384
0009-3122/11/4703-0384©2011 Springer Science+Business Media, Inc.

The title compound 3 was obtained by heating a mixture of the 2-thienylacetic acid hydrazide (1) with
4,4'-diphenylmethane diisocyanate (2). The process was carried out by heating the substrates in an oil bath at
100°C. The reaction is complete within 10 h. The results of elemental analysis and the spectral data indicate that
the reaction leads to the formation of a cyclic five-membered ring system. The course of this reaction probably
includes the formation of an intermediate semicarbazide derivative that spontaneously undergoes a cyclization
reaction to the 1,2,4-triazole ring. The reaction mechanism will be the subject of further research. The method
presented is more simple (two reagents), faster (one stage), and cheaper (less reagents) than the traditional
cyclization method of semicarbazide derivatives.
Hydrazide 1 was prepared in our laboratory by a method described earlier [8]. IR spectra were recorded
1
in KBr using a Specord IR-75 spectrophotometer. The H and 13C NMR spectra were recorded on a Bruker
Avance 300 spectrometer (300 MHz) in DMSO-d6 with TMS as internal standard. Purity was checked on
Aluminum oxide 60 F254 TLC plates in CHCl3–EtOH, 10:1, solvent system with UV visualization.
4,4'-(Methylenedi-4,1-phenylene)bis[5-(2-thienylmethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one] (3). A
mixture of the hydrazide 1 (1.4 g, 20 mmol) and diisocyanate 2 (2.5 g, 10 mmol) was heated at 100–110ºC for
15 h. The product was washed with ether to remove the unreacted isocyanate, dried, and crystallized from
ethanol. Yield 4.43 g (85%); mp 220ºC. IR spectrum, ν, cm–1: 3185 (NH); 3069 (CH Ar); 2927, 1715 (C=O);
1448 (CH). 1H NMR spectrum, δ, ppm (J, Hz): 4.03 (6H, s, 3CH2); 6.56 (2H, d, J = 3.4, H thiophene); 6.79 (2H,
13
dd, J = 5.1, J = 3.5, H thiophene); 7.12–7.36 (10H, m, H Ar); 11.76 (2H, s, 2NH). C NMR spectrum, δ, ppm:
33.01 (CH2); 38.36 (CH2); 117.36, 123.64, 125.05, 125.29, 127.47 (CH Ar); 133.84, 135.29, 136.02, 153.96
(C Ar); 167.81 (C=O). Found, %: C 61.81; H 4.41; N 15.79. C27H22N6O2S2. Calculated, %: C 61.58; H 4.21;
N 15.96.
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