Solvent-free condensation of aromatic aldehydes and 2,3-dimethyl-1-phenyl-3-pyrazolin-5-one by p-toluenesulfonic acid

Article abstract of DOI:10.1002/jhet.5570390538

Solvent-free condensation easily occurred by mixing aromatic aldehydes and 2,3-dimethyl-1-phenyl-3-pyrazoline-5-one (antipyrine) in the presence of p-toluenesulfonic acid as a solid acid catalyst at room temperature to give the corresponding disubstituted

Full text of DOI:10.1002/jhet.5570390538

Sep-Oct 2002
Solvent-Free Condensation of Aromatic Aldehydes and 2,3-Dimethyl-
1-phenyl-3-pyrazolin-5-one by p-Toluenesulfonic Acid
Hideko Koshima* and Mitsuo Hamada
1087
Department of Applied Chemistry, Faculty of Engineering, Ehime University,
Matsuyama 790-8577, Japan
Received February 25, 2002
Solvent-free condensation easily occurred by mixing aromatic aldehydes and 2,3-dimethyl-1-phenyl-3-
pyrazoline-5-one (antipyrine) in the presence of p-toluenesulfonic acid as a solid acid catalyst at room tem-
perature to give the corresponding disubstituted products as sole products in high yields.
J. Heterocyclic Chem., 39, 1087 (2002).
Introduction.
p-toluenesulfonic acid gave bis[1-(2,3-dimethyl-1-phenyl-
3-pyrazolin-5-one)]-2-nitrophenylmethane 3b as a sole
product in 40%, 74%, 96% and 96% yield, respectively.
Thereafter 5 molar equivalents p-toluenesulfonic acid was
used for the reaction.
Solvent-free reactions of substituted benzaldehydes 1a–f
and 2 in the presence of p-toluenesulfonic acid were
undertaken to give the corresponding bis[1-(2,3-dimethyl-
1-phenyl-3-pyrazolin-5-one)]arylmethane 3a–f in high
yields (Table 1). Most reactions were completed within 1
hour, except 24 hours for 3- and 4-nitrobenzaldehyde 1c,
1d, probably due to the deactivation of the carbonyl carbon
by the nitro moiety (entries 3 and 4). The products were
separated by extraction into chloroform because filtration
of the aqueous reaction mixture gave incomplete separa-
tion due to their high solubility in water. These reactions
proved to be more highly selective than the solid state
Organic reactions in the solid state and in the absence of
solvents are of increasing interest [1-3]. Most solid state
reactions occur more efficiently and with higher selectivity
than solution phase reactions, providing the synthetic util-
ity for various types of organic reactions. Further, such
solvent-free organic synthesis is valuable from the envi-
ronmental aspect and preservation of our earth [4]. Solid-
state photochemical reaction between 4-hydroxybenzalde-
hyde and 2,3-dimethyl-1-phenyl-3-pyrazoline-5-one
(antipyrine) in polycrystalline simple mixtures gives dis-
ubstituted product [5]. Solvent-free thermal reactions have
been reported between aromatic aldehydes and 3-methyl-
1-phenyl-2-pyrazolin-5-one [6]. Herein we report efficient
condensations of aromatic aldehydes with antipyrine by p-
toluenesulfonic acid as a solid acid catalyst in the absence
of solvent (Scheme 1).
Results and Discussion.
photoreaction. Because in the previous report [5], irradia-
tion of polycrystalline mixtures of 4-hydroxybenzaldehyde
1e and 2 for 24 hours gave 3e in only 11% yield and
4-hydroxybenzoic acid in 37% yield.
The solvent-free condensation of aldehyde 1 with
antipyrine 2 occurs by the activation of carbonyl carbon by
protonation because absence of p-toluenesulfonic acid
does not cause any reaction. Further study is necessary to
elucidate the reaction mechanism.
In the context of our work on the condensation of aro-
matic aldehydes 1 with 1-2,3-dimethyl-1-phenyl-3-pyra-
zolin-5-one 2 in the absence of solvent, we first examined
the extent that p-toluenesulfonic acid should be used as a
solid protic acid catalyst. For the reaction of 2-nitroben-
zaldehyde 1b and 2 in 1:2 molar ratio at room temperature
for 1 hour, the presence of 1, 3, 5 and 10-fold excess of

1088
H. Koshima and M. Hamada
Vol. 39
Bis[1-(2,3-dimethyl-1-phenyl-3-pyrazolin-5-one)]-3-nitro-
phenylmethane (3c).
This compound was obtained as yellow prisms; mp 175-176
-1
1
°C (from ethyl acetate); IR (KBr) 1632 (C=O) cm ; H nmr
(deuteriochloroform) δ 7.19-8.23 (m, 14H), 5.37 (s, 1H), 3.08 (s,
6H), 2.18 (s, 6H).
Anal. Calcd. for C H N O : C, 68.34; H, 5.34; N, 13.74.
29 27
5 4
Found: C, 68.35; H, 5.51; N, 13.72.
Bis[1-(2,3-dimethyl-1-phenyl-3-pyrazolin-5-one)]-4-nitro-
phenylmethane (3d).
This compound was obtained as yellow prisms; mp 238-240
-1
1
°C (from ethyl acetate); IR (KBr) 1660 (C=O) cm ; H nmr
(deuteriochloroform) δ 7.26-8.18 (m, 14H), 5.36 (s, 1H), 3.07 (s,
6H), 2.17 (s, 6H).
EXPERIMENTAL
Anal. Calcd. for C H N O : C, 68.34; H, 5.34; N, 13.74.
Found: C, 68.32; H, 5.45; N, 13.60.
29 27
5 4
1
H nmr spectra were measured on a JEOL JNM-GSX270 spec-
trometer with tetramethylsilane as an internal standard. IR spec-
tra were recorded on a Horiba FT-IR-210 spectrophotometer.
Melting points (mp) were not corrected. Elemental analysis was
carried out with a Yanaco CHN Corder MT-5. All the reagents
were commercially available.
Bis[1-(2,3-dimethyl-1-phenyl-3-pyrazolin-5-one)]-4-hydrox-
yphenylmethane (3e).
This compound was obtained as red prisms; mp 245-246 °C
-1 1
(from ethyl acetate) ; IR (KBr) 3226 (OH), 1672 (C=O) cm ; H
nmr (deuteriochloroform) δ 7.21-7.46 (m, 14H), 5.21 (s, 1H),
General Procedure for Solvent-free Reaction.
3.02 (s, 6H), 2.12 (s, 6H).
A mixture of aldehyde 1 (5 mmol) and antipyrine 2 (10 mmol)
was ground with p-toluenesulfonic acid monohydrate (p-
Anal. Calcd. for C H N O : C, 72.48; H, 5.87; N, 11.66.
29 28
4 3
Found: C, 72.50; H, 5.95; N, 11.45.
TsOH•H O, 25 mmol) in a mortar in the absence of solvent and
2
allowed to stand for 1 hour at room temperature. After comple-
tion of the reaction (TLC), water (30 ml) was added to the reac-
tion mixture and the slurry was extracted twice with chloroform
(20 and 10 ml). The organic solution was washed with saturated
Bis[1-(2,3-dimethyl-1-phenyl-3-pyrazolin-5-one)]-4-phenyl-
phenylmethane (3f).
This compound was obtained as a white powder; mp 224-226
-1
1
°C; IR (KBr) 1672 (C=O) cm ; H nmr (deuteriochloroform) δ
NaHCO and then water, dried over NaSO , and evaporated
3
4
7.06-7.73 (m, 19H), 5.20 (s, 1H), 3.49 (s, 6H), 2.67 (s, 6H).
under reduced pressure.
Anal. Calcd. for C H N O : C, 77.75; H, 5.97; N, 10.36.
35 32
4 2
Bis[1-(2,3-dimethyl-1-phenyl-3-pyrazolin-5-one)]phenyl-
methane (3a).
Found: C, 67.70; H, 6.11; N, 10.31.
REFERENCES AND NOTES
Author to whom correspondence should be addressed.
This compound was obtained as a white powder; mp 203-205
-1
1
°C (from ethyl acetate); IR (KBr) 1664 (C=O) cm ; H nmr
(deuteriochloroform) δ 7.18-7.46 (m, 15H), 5.30 (s, 1H), 3.03 (s,
6H), 2.13 (s, 6H).
*
[1] Reactivity in Molecular Crystals, Y. Ohashi, Ed.; VCH,
Kodansha, Tokyo, 1993.
[2] Organic Solid State Chemistry, G. R. Desiraju, Ed.,
Elsevier, Amsterdam, 1987.
Anal. Calcd. for C H N O : C, 74.97; H, 6.08; N, 12.06.
29 28
4 2
Found: C, 75.07; H, 6.10; N, 12.05.
Bis[1-(2,3-dimethyl-1-phenyl-3-pyrazolin-5-one)]-2-nitro-
[3] T. Tanaka and F. Toda, Chem. Rev. , 100, 1025 (2000).
[4] P. T. Anastas, J. C. Warner, Green Chemistry: Theory and
Practice, Oxford University Press, New York, 1998.
[5] Meng, J.-B.; Wang, W.-G.; Xiong, G.-X.; Wang, Y.-M.;
Fu, D.-C.; Du, D.-M.; Wang, R.-J.; Wang, H.-G.; Koshima, H.;
Matsuura, T. J. Photochem. Photobiol. A: Chem., 74, 43 (1993).
[6] Wang, Y.-M.; Meng, J.-B.; Matsuura, T. Trends in
Heterocyclic Chem., 6, 21 (1999).
phenylmethane (3b).
This compound was obtained as a yellow powder; mp 186-187
-1
1
°C (from ethyl acetate); IR (KBr) 1632 (C=O) cm ; H nmr
(deuteriochloroform) δ 7.32-8.13 (m, 14H), 6.28 (s, 1H), 3.10 (s,
6H), 2.21 (s, 6H).
Anal. Calcd. for C H N O : C, 68.34; H, 5.34; N, 13.74.
Found: C, 68.51; H, 5.39; N, 13.60.
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5 4