Trichloroisocyanuric acid as a novel oxidizing agent for the oxidation of 1,3,5-trisubstituted pyrazolines under both heterogeneous and solvent free conditions

Article abstract of DOI:10.1016/j.tetlet.2004.01.038

Trichloroisocyanuric acid is used as an effective oxidizing agent for the oxidation of 1,3,5-trisubstituted pyrazolines to their corresponding pyrazoles under both heterogeneous and also solvent free conditions with good yields at room temperature.

Full text of DOI:10.1016/j.tetlet.2004.01.038

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2181–2183
Trichloroisocyanuric acid as a novel oxidizing agent for the
oxidation of 1,3,5-trisubstituted pyrazolines under both
heterogeneous and solvent free conditions
*
Mohammad Ali Zolfigol, Davood Azarifar and Behrooz Maleki
Chemistry Department, College of Science, Bu-Ali Sina University, PO Box 4135, Hamadan 65174, Iran
Received 17 November 2003; revised 22 December 2003; accepted 9 January 2004
Abstract—Trichloroisocyanuric acid is used as an effective oxidizing agent for the oxidation of 1,3,5-trisubstituted pyrazolines to
their corresponding pyrazoles under both heterogeneous and also solvent free conditions with good yields at room temperature.
Ó 2004 Published by Elsevier Ltd.
7
;8
9
11
Some of five-membered heterocyclic compounds are
used commercially as pharmaceuticals, pesticides, and
dyestuffs. These compounds are also important constit-
uents in many biologically active natural products and
VII), Ag(I), Zr(IV) within the molecular structure
of the reagents); (b) to devise a solvent free synthesis
especially, useful for industry, with many advantages:
reduced pollution, low costs, and simplicity in process-
12–14
1;2
synthetic compounds of medicinal interest. The con-
version of 1,3,5-trisubstituted pyrazolines with sensitive
functional groups to their corresponding pyrazole
derivatives are a tricky step. A variety of reagents such
ing and handling;
(c) to develop a high-yielding
synthesis of pyrazoles by using a commercially available
reagent. Therefore, we were interested to find a hetero-
geneous system for pyrazoline oxidation. In continua-
3
4
15–18
as Pd/C/acetic acid, cobalt soap of fatty acids, lead
5
tion of our studies in this regard,
we have found that
6
tetraacetate, mercury or lead oxide, manganese diox-
8
ide, potassium permanganate, silver nitrate, iodo-
trichloroisocyanuric acid, a cheap commercially avail-
able reagent used primarily as a disinfectant and
deodorant, has found little application in organic
7
9
1
0
11
benzene diacetate, and zirconium nitrate are all
capable of effecting the pyrazoline oxidation. However,
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, or are difficult to remove from the sensitive
1
8–21
chemistry.
Therefore, we wish to report a simple,
cheap, and convenient method for the effective conver-
sion of 1,3,5-trisubstituted pyrazolines 1 to their corre-
sponding pyrazoles 2 using trichloroisocyanuric acid
both under heterogeneous and also solvent free condi-
tions (Table 1).
4
pyrazoles. Another major drawback to the older pro-
cedures is their use of reagents, which are either highly
toxic, or produce serious disposal problems (or both).
A good range of 1,3,5-trisubstituted pyrazolines were
subjected to oxidation in the presence of trichloroiso-
4
cyanuric acid in CCl or solvent free conditions (Table
Our goals, in undertaking this work, were (a) to over-
come the limitations and drawbacks of the reported
1). The oxidation reactions were performed under mild
conditions at room temperature with good yields. The
1,3,5-trisubstituted pyrazoles 2 were obtained by simple
filtration and evaporation of the solvent. The results and
3
methods such as tedious work-up, acidic media, and
safety problems (presence of toxic transition metal
4
5
6
22–24
cations such as Co(II), Pb(IV), Hg(II), Mn(IV and
reaction conditions are given in Table 2.
In conclusion, a practical and efficient oxidation of
1,3,5-trisubstituted pyrazolines has been achieved by the
new methodology described. This reagent could be used
for the oxidation of a wide variety of pyrazoline deriv-
atives under safe conditions.
Keywords: Trichloroisocyanuric; 1,3,5-Trisubstituted pyrazolines; Pyr-
azoles; Solvent free conditions.
*
Corresponding author. Tel.: +98-811-8271075; fax: +98-811-827-
404; e-mail: zolfi@basu.ac.ir
2
0
040-4039/$ - see front matter Ó 2004 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2004.01.038

2182
M. A. Zolfigol et al. / Tetrahedron Letters 45 (2004) 2181–2183
Table 1
References and notes
O
N
Cl
Cl
O
N
N
1. Azarifar, D.; Shaebanzadeh, M. Molecules 2002, 7, 885–
895.
R2
R2
N
R1
O
N
R1
N
Cl
N
2. (a) Gilchrist, T. L. Heterocyclic Chemistry. 2nd ed. John
Willey: 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
R3
CCl
or
solid phase, rt
4
, rt
R3
1
2
1
2
3
Substrate Product
R
R
R
2
000, 2049–2053; (d) Froggett, J. A.; Hockley, M. H.;
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
a
b
c
d
e
f
2a
2b
2c
2d
2e
2f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2-Naphthyl
2-Naphthyl
Ph
2-CH
Ph
3
C
C
6
6
H
H
4
4
Titman, R. B. J. Chem. Res. 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.; Pallich, S.; McCarthy, T. D. J. Chem.
Soc., Perkin Trans. 1 2001, 1817–2822; (h) Elgemeie, G.
H.; Matwally, N. H. J. Chem. Res. 1999, 384–385; (i)
Chang, K. T.; Choi, Y. H.; Kim, S. H.; Yoon, Y. J.; Lee,
W. S. J. Chem. Soc., Perkin Trans. 1 2002, 207–210.
. Nakamichi, N.; Kawashita, Y.; Hayashi, M. Org. Lett.
Ph
4-CH
3-CH
4-CH
4-CH
4-CH
4-CH
3-CH
3
3
3
3
3
3
3
C
C
6
6
H
H
4
3-CH
3
4
6 4
2-ClC H
OC
OC
OC
OC
6
6
6
6
H
H
H
H
4
4
4
4
3-CH
2-CH
Ph
3
C
6
6
H
H
4
4
g
h
i
2g
2h
2i
3
C
4-ClC
4-ClC
6
H
H
4
j
2j
C
6
H
4
6
4
k
l
2k
2l
2-Naphthyl
2-Naphthyl
2-Naphthyl
3-CH
4-ClC
2-ClC
3
C
6
H
4
3
4
5
6
6
H
H
4
4
2
002, 4, 3955–3957.
. Shah, J. N.; Shah, C. K. J. Org. Chem. 1978, 43, 1266–
267.
m
n
o
p
2m
2n
2o
2p
3-CH
2-CH
4-CH
3
3
3
C
C
6
6
H
H
4
4-(CH
4-(CH
3
)
)
2
NC
NC
4
6
H
H
4
1
4
3
2
6
4
. Goldstone, W. A. F.; Norman, R. O. C. J. Chem. Soc.,
Chem. Commun. 1966, 1536–1540.
OC
6
H
4
6
4-ClC H
6
7
. Auwers, K.; Heimke, P. Liebigs Ann. 1927, 458, 186–220.
. Bhatnagar, I.; George, M. V. Tetrahedron 1968, 24, 1293–
1
298.
. Smith, L. I.; Howard, K. L. J. Am. Chem. Soc. 1943, 65,
59–164.
. Dodwadmath, R. P.; Wheeler, T. S. Proc. Ind. Acad. Sci.
935, 2A, 438–451.
8
9
Table 2. Oxidation of 1,3,5-trisubstituted pyrazolines 1 to their cor-
1
4
responding pyrazoles 2 with trichloroisocyanuric acid both in CCl (I)
and solvent free conditions (II) at room temperature
1
a
c
Substrate Product
Reagent/
substrate
Time
(h)
Yield
(%)
10. Singh, S. P.; Kumar, D.; Prakash, O.; Kapoor, R. P.
Synth. Commun. 1997, 27, 2683–2689.
b
1
1. Sabitha, G.; Kumar Reddy, G. S. K.; Reddy, Ch. S.;
Fatima, N.; Yadav, J. S. Synthesis 2003, 1267–1271.
2. Varma, R. S. Green Chem. 1999, 1, 43–55.
3. Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025–1074.
4. Krchnak, V.; Holladay, M. W. Chem. Rev. 2002, 102, 61–
I
II
I (II)
I (II)
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
a
b
c
d
e
f
2a
2b
2c
2d
2e
2f
1.25
1.25
1.25
2.25
2.5
3.5
0.8 (1.3) 90 (80)
0.75 (1.5) 92 (80)
0.75 (1.3) 85 (80)
0.8 (1.75) 85 (75)
0.8 (1.3) 74 (70)
1
1
1
3.25
3.25
4.25
4.25
4.25
4.75
3.75
4
9
5. Zolfigol, M. A.; Ghorbani-Choghamarani, A.; Hazark-
1.
1
1
1
1
1
2
2.75
3.25
2
0.5 (1)
92 (80)
hani, H. Synlett 2002, 1002–1004.
g
h
i
2g
2h
2i
0.5 (1.3) 90 (78)
0.6 (1.5) 92 (70)
0.6 (1.75) 70 (70)
0.9 (1.5) 85 (72)
0.9 (1.3) 85 (80)
0.8 (1.5) 82 (75)
0.8 (1.5) 78 (65)
0.5 (1.2) 82 (70)
0.5 (1.5) 85 (68)
6. Zolfigol, M. A.; Mallakpour, S. E.; Madrakian, E.;
Ghaemi, E. Synlett 2002, 1633–1636.
7. Zolfigol, M. A.; Ghaemi, E.; Madrakian, E. Synlett 2003,
91–194.
8. Zolfigol, M. A.; Madrakian, E.; Ghaemi, E. Synlett 2003,
222–2224.
9. Firouzabadi, H.; Iranpoor, N.; Hazarkhani, H. Synlett
001, 1641–1643.
0. Xiog, Z. X.; Huang, N. P.; Zhong, P. Synth. Commun.
001, 31, 245–248.
2.25
3.25
2.25
3.5
j
2j
4.75
4.75
5.25
5.25
4.75
5.25
4
1
k
l
2k
2l
2
m
n
o
p
2m
2n
2o
2p
3.25
2.5
2
2.5
2.5
0.5 (1)
90 (75)
2
a
b
c
21. Mendonßca, G. F.; Sanseverino, A. M.; Mattos, M. C. S.
All of the isolated products are known compounds and their spectra
and physical data have been reported in the literature.
2–11
D. Synthesis 2003, 45–48.
22. Chemicals were purchased from Fluka, Merck, Riedel-
dehaen AG, and Aldrich chemical companies. Yields refer
to isolated pure products. The oxidation products were
Molar ratio of trichloroisocyanuric acid in CCl
solvent free conditions (II) mmol.
Isolated yields.
4
(I) mmol and under
1
characterized by comparison of their spectral (IR, and H
NMR) and physical data with authentic samples. All
1,3,5-trisubstituted pyrazolines were synthesized according
1
to our previously reported procedure.
2
3. General procedure for oxidation of pyrazoline: A suspen-
sion of trichloroisocyanuric acid (the molar ratios of
trichloroisocyanuric acid to the substrate 1 are given in
Acknowledgements
Financial support for this work by the Research Council
of Bu-Ali Sina University, Hamadan, Iran, is gratefully
acknowledged.
4
Table 2), pyrazoline 1 (2 mmol) and CCl (10 mL) were
stirred vigorously at room temperature. The progress of
the reaction was followed by TLC. Reactions were

M. A. Zolfigol et al. / Tetrahedron Letters 45 (2004) 2181–2183
2183
completed after 0.5–1.75 h (Table 2). After the reaction
was completed, dry silica gel (1 g) was added to the
reaction mixture, the solid materials were removed by
filtration and washing with dichloromethane (10 mL). The
solvent was evaporated and the pyrazoles 2 were obtained
acid (the molar ratio of trichloroisocyanuric acid to the
substrate 1 are given in Table 2), pyrazoline 1 (2 mmol)
was shaken at rt for 1–1.75 h (the progress of the reaction
was monitored by TLC), followed by CH
addition and filtration of the resulting mixture. Dichlo-
2 2
Cl (20 mL)
1
8
(
Table 2). If further purification is needed, flash chroma-
romethane was finally removed by heating (35–40 °C)
tography on silica gel (eluent: acetone/petroleum ether 1:5)
was used to give highly pure 2.
simple distillation, and the pyrazoles 2 were obtained
(Table 2). If further purification is needed, flash chroma-
tography on silica gel (eluent: acetone/petroleum ether 1:5)
was used to give highly pure 2.
2
4. General procedure for oxidation of pyrazoline under
solvent free conditions: A mixture of trichloroisocyanuric