4-(p-Chloro)phenyl-1,2,4-triazole-3,5-dione as a novel and reusable reagent for the oxidation of 1,3,5-trisubstituted pyrazolines under mild conditions

Article abstract of DOI:10.1016/j.tetlet.2005.11.088

4-(p-Chloro)phenyl-1,3,4-triazole-3,5-dione is used as an effective oxidizing agent for the oxidation of 1,3,5-trisubstituted pyrazolines to their corresponding pyrazoles under mild conditions with moderate to good yields at room temperature.

Full text of DOI:10.1016/j.tetlet.2005.11.088

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 833–836
4-(p-Chloro)phenyl-1,2,4-triazole-3,5-dione as a novel and
reusable reagent for the oxidation of 1,3,5-trisubstituted
pyrazolines under mild conditions
Mohammad Ali Zolfigol,a,* Davood Azarifar,a Shadpour Mallakpour,b,
Iraj Mohammadpoor-Baltork,c Ali Forghaniha,a Behrooz Malekia and
Mohammad Abdollahi-Alibeikc
aChemistry Department, College of Science, Bu-Ali Sina University, Hamadan 65174, Iran
bOrganic Polymer Chemistry Research Laboratory, College of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
cChemistry Department, College of Science, Isfahan University, Isfahan, Iran
Received 11 February 2005; revised 31 October 2005; accepted 11 November 2005
Available online 2 December 2005
Abstract—4-(p-Chloro)phenyl-1,3,4-triazole-3,5-dione is used as an effective oxidizing agent for the oxidation of 1,3,5-trisubstituted
pyrazolines to their corresponding pyrazoles under mild conditions with moderate to good yields at room temperature.
Ó 2005 Elsevier Ltd. All rights reserved.
Five-membered heterocycles such as pyrazole moieties
are important constituents in many biologically active
natural products and synthetic compounds of medicinal
interest.1,2 The conversion of 1,3,5-trisubstituted pyrazo-
lines containing sensitive functional groups to their
corresponding pyrazole derivatives is a difficult step to
accomplish. Although a variety of reagents such as
Pd/C/acetic acid,3 cobalt soap of fatty acids,4 lead tetra-
acetate,5 mercury or lead oxide,6 manganese dioxide,7
potassium permanganate,8 silver nitrate,9 iodobenzene
diacetate,10 and zirconium nitrate11 are all capable of
effecting pyrazoline oxidation, this transformation
remains capricious because these compounds are very
sensitive to oxidizing agents and the reaction conditions.
Moreover, most of the reported reagents produce some
by-products, which either destroy the sensitive pyra-
zoles, or are difficult to remove.4 Another major draw-
back to these procedures is the use of reagents, which
are either highly toxic or produce serious disposal prob-
lems (or both).
Our goals in undertaking this work were: (a) to overcome
the limitations and drawbacks of the reported methods
such as tedious work-up, acidic media,3 and safety prob-
lems [the presence of toxic transition metal cations, e.g.,
Co(II),4 Pb(IV),5 Hg(II),6 Mn(IV and VII),7,8 Ag(I),9
Zr(IV)11]; (b) to devise a heterogeneous system, espe-
cially useful for industry, with many advantages such
as reduced pollution, lower costs and simplicity in pro-
cessing and handling;12–14 (c) to develop a high-yielding
synthesis of pyrazoles using a recyclable reagent.
On the other hand, among five-membered hetero-
cyclic compounds, 4-substituted-1,2,4-triazole-3,5-diones
1 (TADs) are notable for their ability to participate in a
wide range of reaction types, for example, [4+2] and
[2+2] cycloadditions, ene reactions, electrophilic aro-
matic substitution, oxidation of alcohols to the corre-
sponding carbonyl compounds, and aromatization of
1,4-dihydropyridines.15,16 Therefore, we were interested
to find a ÔgreenÕ system for the oxidation of pyrazolines17
and 2-imidazolines.18 In continuation of our studies in
this regard,16 we found that 4-(p-chloro)phenyl-1,3,4-tri-
azole-3,5-dione 1e was a suitable reagent for this
purpose (Fig. 1). Herein, we wish to report a simple
and convenient method for the effective conversion of
Keywords: 4-(p-Chloro)phenyl-1,3,4-triazole-3,5-dione; Aromatization;
Oxidation; 1,3,5-Trisubstituted pyrazolines; Pyrazoles; Urazoles; 4-
Substituted-1,3,4-triazole-3,5-dione; Triazolinediones; 2-Imidazolines;
Imidazoles.
*
Corresponding author. Tel.: +98 8118 271075; fax: +98 8118
272404; e-mail: Zolfi@basu.ac.ir
Previous name: Shadpour E. Mallakpour.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.088

834
M. A. Zolfigol et al. / Tetrahedron Letters 47 (2006) 833–836
N
N
N
N
N
X
O
O
N
Y
O
O
O
N
O
N
N
1g-h
1a-f
Y =n-propyl (1a), n-butyl (1b), cyclohexyl (1c), Ph (1d), 4-Cl-C6H4- (1e), 3,4-(Cl)2-C6H3- (1f)
1g: X =-(CH2)6-,
1h: X =-C6H4-CH2-C6H4-
Figure 1.
1,3,5-trisubstituted pyrazolines 2 to their corresponding
pyrazoles 3 using 4-(p-chloro)phenyl-1,3,4-triazole-3,5-
dione 1e under mild conditions (Scheme 1 and Table 1).
simple as 4-(p-chloro)phenyl-1,3,4-triazole-3,5-dione 1e
has a deep red color and is soluble in CH2Cl2 and is con-
verted to 4-(p-chloro)phenyl urazole 4, which is white in
color and is insoluble in CH2Cl2. This also simplifies the
work-up as 4-(p-chloro)phenyl urazole 4 was isolated by
simple filtration. The results and reaction conditions are
given in Table 1. 4-(p-Chloro)phenyl urazole 4 can be
readily converted to 4-(p-chloro)phenyl-1,3,4-triazole-
3,5-dione21 1e and reused (Scheme 2).
A good range of 1,3,5-trisubstituted pyrazolines were
subjected to aromatization in the presence of 4-(p-chlo-
ro)phenyl-1,3,4-triazole-3,5-dione 1e in CH2Cl2 (Scheme
1).19,20 The oxidation reactions were performed under
mild conditions at room temperature with moderate to
good yields. The crude 1,3,5-trisubstituted pyrazoles 3
were obtained by simple filtration and evaporation of
the solvent. Highly pure pyrazoles 3 could be obtained
simply by column chromatography (eluent EtOAc–n-
hexane, 2:8). The results and reaction conditions are
given in Table 1. Monitoring of the reaction is very
In continuation of our studies on the oxidation of 2-imi-
dazolines18 we were also interested in using 4-substi-
tuted-1,3,4-triazole-3,5-diones 1 for the oxidation of
different kinds of imidazoline derivatives 5 but the reac-
tions were sluggish and not practical. Several efforts for
optimizing the reaction conditions failed and the yields
of the desired products (i.e., imidazoles 6) were very
low and some unidentified by-products were also pro-
duced (Scheme 3).
R1
N
1
R
N
N
Ph
R2
1e
N
Ph
R2
In conclusion, a practical and efficient oxidation of
1,3,5-trisubstituted pyrazolines has been achieved by
the methodology described. The reagent can be used
for the aromatization of a wide variety of pyrazolines
derivatives under safe conditions.
CH2Cl2, rt
2
3
Scheme 1.
Table 1. Oxidation of 1,3,5-trisubstituted pyrazolines 2a–n to their corresponding pyrazoles 3a–n with 4-(p-chloro)phenyl-1,3,4-triazole-3,5-dione 1e
in CH2Cl2 at room temperature
Substrate
Producta
R1
R2
Reag./Subst.b
Time (min)
Yield (%)c
Melting point (°C)
Found
Literature
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
2-Naphthyl
Ph
o-CH3C6H4
Ph
m-CH3C6H4
o-CH3C6H4
m-CH3C6H4
Ph
p-ClC6H4
m-CH3C6H4
p-ClC6H4
2-Furyl
o-ClC6H4
p-NO2C6H4
p-CH3OC6H4
mClC6H4
1.25
1.00
1.50
1.25
1.25
1.50
1.50
1.50
1.25
1.50
1.50
1.50
1.50
1.50
25
15
30
30
35
25
35
35
45
35
30
35
30
35
70
70
65
60
68
76
62
65
60
63
70
66
65
73
148–150
133–134
94–96
70–71
80–82
74–76
98–100
90–91
129–130
96–98
66–68
151–15217c
138–13910
95–9817c
70–7217c
84–8617c
75–7717c
101–10317c
75–7817c
130–13317c
93–9510
p-CH3C6H4
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
2-Naphthyl
2-Naphthyl
p-CH3C6H4
p-CH3OC6H4
Ph
2g
2h
2i
3g
3h
3i
2j
3j
2k
2l
3k
3l
63–6517c
142–14311
77–7810
144–146
79–80
112–114
2m
2n
3m
3n
Ph
Ph
114–11511
a All of the isolated products were known compounds and their spectra and physical data have been reported in the literature.17
b Molar ratio of 1e.
c Isolated pure yields after column chromatography (eluent EtOAc–n-hexane, 2:8).

M. A. Zolfigol et al. / Tetrahedron Letters 47 (2006) 833–836
835
H
H
O
N
N
N
N
O
N
O
N
O
+2H
[O]
Cl
Cl
4
1e
Soluble in CH2Cl2
Insoluble in CH2Cl2
Cl
N
2
O
O
N
N
H
H
1
R2
R
N
N
Ph
R1
N
N
Ph
R2
3
Scheme 2.
2. (a) Gilchrist, T. L. Heterocyclic Chemistry, 2nd ed.; John
Wiley & Sons: New York, 1992; p 294; (b) Gao, X. C.;
Cao, H.; Zhang, L. Q.; Zhang, B. W.; Cao, Y.; Huang, C.
H. J. Mater. Chem. 1999, 9, 1077–1080; (c) Claramunt, R.
M.; Lopez, C.; Garcia, M. D. L. A.; Pierrot, M.; Giorgi,
M.; Elguero, J. J. Chem. Soc., Perkin Trans. 2 2000, 2049–
2053; (d) Froggett, J. A.; Hockley, M. H.; Titman, R. B. J.
Chem. Res. (S) 1997, 30–31; (e) Baldwin, J. E.; Pritchard,
G. J.; Rathmell, R. E. J. Chem. Soc., Perkin Trans. 1 2001,
2906–2908; (f) Voznesenskii, S. A.; BelenÕkii, L. I.;
Dudinov, A. A.; Struchkova, M. I.; Krayushkin, M. M.
Mendeleev Commun. 1998, 1–42; (g) Donohue, A. C.;
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1 2001, 1817–2822; (h) Elgemeie, G. H.; Matwally, N. H.
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N
N
N
1
R
Unidentified products
R
+
N
CH2Cl2 , rt
H
H
6
5
R = alkyl, cycloalkyl, aryl, pyridyl,
Very low yields
Scheme 3.
Acknowledgement
Financial support for this work by the Research Council
of Bu-Ali Sina University, Hamadan, Iran, is gratefully
acknowledged.
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chloro)phenyl-1,3,4-triazole-3,5-dione 1e (0.209 g, 1 mmol)
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