Convenient synthesis and characterization of pyrazolones and schiff bases

Article abstract of DOI:10.1080/00397911.2011.576323

A series of Schiff bases containing the pyrazolylpyrazole moiety has been synthesized in a convenient method at room temperature with good yields. All the compounds were well characterized by spectral and analytical data.

Full text of DOI:10.1080/00397911.2011.576323

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Convenient Synthesis and
Characterization of Pyrazolones and
Schiff Bases
K. S. Girisha a & Balakrishna Kalluraya a
a Department of Chemistry, Mangalore University, Mangalagangotri,
Karnataka, India
Accepted author version posted online: 10 Jan 2012.Version of
record first published: 21 Jun 2012.
To cite this article: K. S. Girisha & Balakrishna Kalluraya (2012): Convenient Synthesis and
Characterization of Pyrazolones and Schiff Bases, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 42:20, 3097-3102
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Synthetic Communications1, 42: 3097–3102, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.576323
CONVENIENT SYNTHESIS AND CHARACTERIZATION
OF PYRAZOLONES AND SCHIFF BASES
K. S. Girisha and Balakrishna Kalluraya
Department of Chemistry, Mangalore University, Mangalagangotri,
Karnataka, India
GRAPHICAL ABSTRACT
Abstract A series of Schiff bases containing the pyrazolylpyrazole moiety has been synthe-
sized in a convenient method at room temperature with good yields. All the compounds were
well characterized by spectral and analytical data.
Keywords Knoevenagel condensation; pyarzoles; pyrazolones; Schiff bases
INTRODUCTION
Pyrazoles and their derivaires are important molecules because they possess
anti-inflammatory,[1] selective COX-2 inhibitiory,[2] antiparasitic,[3] and antiviral[4]
activities. 5-Amino- and 5-anilinopyrazoles are important molecules from both
synthetic and biological points of view.[5] Generally these 5-aminopyrazoles are
synthesized by the reaction of hydrazine hydrate and methylenenitriles.[6] Other
important methods are the reduction of the 5-azidopyrazoles[7] and the reaction of
5-chloropyrazoles with ammonium hydroxide at higher temperature.[8] In recent years
the 5-amino pyrazoles and their derivatives have been synthesized in solid phase.[9]
Similarly 5-anilinopyrazoles are synthesized by the Ullmann reaction of 5-aminopyr-
azoles and bromo=chlorobenzene[5] or by the reaction of benzyolthioacetanilide with
substituted hydrazenes.[10] Schiff bases also show various biological activities such as
anti-inflammatory, analgesic, and antimicrobial[9c] activities. Keeping in mind these
Received January 1, 2011.
Address correspondence to Balakrishna Kalluraya, Department of Chemistry, Mangalore
University, Mangalagangotri 574 199, Karnataka, India. E-mail: bkalluraya@gmail.com
3097

3098
K. S. GIRISHA AND B. KALLURAYA
properties of pyrazole and Schiff bases and in continuation of our research work on
pyrazoles,[11] here we report a series of Schiff bases carrying the pyrazolylpyrazole
moiety.
RESULTS AND DISCUSSION
The Knoevenagel condensation of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-
4-carboxaldehyde 1 with ethylcyanoacetate at 0 ꢀC results in the formation of
ethyl-2-cyano-3-(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)propionate 2. This
propionate, when treated with hydrazine hydrate at room temperature, yielded
5-amino-4-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylidine]-2,4-dihydro-
3H-pyrazol-3-one 3. When aminopyrazoles are treated with suitably substituted
benzldehyde in the presence of a catalytic amount of acetic acid, 5-chloro-3-
methyl-4-methylidene[(31-substitutedbenzylidineamino)pyrazole-51-one]-1-phenyl-1-
H-pyrazole 4 is obtained. The 5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-carboxal-
dehyde 1 was synthesized following the literature procedure[11b] (Scheme 1).
The
formation
of
5-chloro-3-methyl-4-methylidene[(31-substituted
benzylidineamino)pyrazole-51-one]-1-phenyl-1H-pyrazole 4 was confirmed by spec-
tral and analytical data. All the newly synthesized compounds show the molecular
ion peak in accordance with the proposed structure, which confirms the stability
of the compounds. The infrared (IR) spectra of the Schiff bases shows absorption
bands at 3300–3450 cmꢁ1 for the amide –NH group, 1620–1680 cmꢁ1 for the
carbonyl group, and 1575–1605 cmꢁ1 for the imine group. Absence of peak in the
range of 3362 cmꢁ1 confirms the absence of an –NH2 group. The formation of these
compounds are further confirmed by the 1H NMR spectra, which show two singlets
at d, 8.55–8.73 integrating for one proton each, assigned to the imine proton and
alkene proton. The signal from the amide –NH proton is not observed because of
the exchange with D2O of the solvent as the spectra were recorded in CDCl3.
CONCLUSION
In conclusion, this is a convenient method for the preperation of Schiff bases
containing the pyrazole moiety. The reactions occur at room temperature in a short
Scheme 1. Synthetic scheme for the reaction of the pyrazolone Schiff’s bases.

PYRAZOLONES AND SCHIFF BASES
3099
time with good yield. However, the reported procedure[12] of Knoevenagel conden-
sation is carried out at high temperature. Further, at high temperature this Knoeve-
nagel condensation resulted in the formation of bispyrazoles, whereas at room
temperature it gave amino derivatives. It can be concluded that this reaction is highly
temperature sensitive.
EXPERIMENTAL
Melting points were determined in open capillary tubes and are uncorrected.
The purity of the compounds was confirmed by thin-layer chromatography (TLC)
using silica-gel plates in a petroleum ether–ethylacetate (9:1) system as mobile phase.
1H NMR spectra were recorded on a Bruker Avance-II 400-MHz NMR spec-
trometer using CDCl3 as solvent. Tetramethylsilane (TMS) was employed as internal
standard. Chemical shift values are expressed in d scale down field from TMS. The
infrared (IR) spectra were obtained in KBr disc on a Shimadzu-8400 FTIR spectro-
photometer. The mass spectra were recorded on a Waters Micromass Q-Tof Micro
LC mass spectrometer. CHN analysis was performed on a Vario-El-Elementar III
model analyzer.
Ethyl-2-cyano-3-(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-
yl)propionate 2
5-Chloro-3-methyl-1-phenyl-1H-pyrazol-4-carboxaldehyde 1 (0.1 mol) was dis-
solved in 10 mL of ethanol by heating. Ethylcyanoacetate (0.1 mol) was added to
this, and the reaction mixture was cooled to 0 ꢀC in an ice–salt mixture. Sodium
ethoxide (0.1 mol) in 5 mL ethanol was added to the cold reaction mixture with stir-
ring, and temperature was maintained at 0–5 ꢀC for another 2 h. The solid product
was filtered, separated by suction, washed with cold ethanol, dried, and recrystallized
from aqueous ethanol. Yield: 87%, mp 74–76 ꢀC (lit.[12] 75–78 ꢀC). CHN: found
(cal.): C, 60.75 (60.86); H, 4.58 (4.47); N, 13.24 (13.31). IR: 1516 cmꢁ1 (C N),
=
ꢁ1
1731.46 cmꢁ1 (C O), 2224.08 cm (-CN), 2991 cmꢁ1, 2935 cmꢁ1, 3064 cmꢁ1 for
=
alkyl group. Mass: e=z, 316=318 (3:1) (Mþ þ 1)=(Mþ þ 3). 1H NMR (400 MHz)
DMSO-d6: d, 1.29–1.33 (t, 3H, ester CH3), 2.44 (s, 3H, CH3 of pyrazole),
=
4.30–4.36 (q, 2H, -CH2- of ester), 7.56–7.62 (m, 5H, Ar-H), 8.18 (s, 1H, CH C).
5-Amino-4-[(5-chloro-3-methyl-1-phenyl-1h-pyrazol-4-
yl)methylene]-2,4-dihydro-3H-pyrazol-3-one 3
The ethyl-2-cyano-3-(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)propionate
2 (0.1 mol) was dissolved in 10 mL ethanol. Hydrazine hydrate (0.1 mol) was added
to this solution with stirring. The reaction mixture was stirred at room temperature
for 4 h. The solid was separated, filtered, washed with cold ethanol, dried, and recrys-
tallized from ethanol. Yield: 85.48%, mp 98–100 ꢀC. CHN: found (cal.): C, 55.7ꢁ9
(55.73); H, 4.16 (4.06); N, 23.11 (23.21). IR: 1528 cmꢁ1, 1600 cmꢁ1 (C N), 1628 cm
=
(amideC O), 2959 cm (-CH3), 3202 cmꢁ1 (-NH), 3362 cmꢁ1 (-NH2). Mass: e=
1
ꢁ1
=
z, 302=304 (3:1) (Mþ þ 1)=(Mþ þ 3). H NMR (400 MHz) CDCl3: d, 2.64 (s, 3H,
1
=
-CH3), 7.44–7.60 (m, 5H, Ar-H), 8.67 (s, 1H, CH C). The signals due to -NH2

3100
K. S. GIRISHA AND B. KALLURAYA
and –NH protons are not observed possibly because of the D2O exchange with the
solvent.
5-Chloro-3-methyl-4-methylidene[(31-substitutedbenzylidineamino)
pyrazole-51-one]-1-phenyl-1H-pyrazole 4
The 5-amino-4-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene]-2,4--
dihydro-3H-pyrazol-3-one 3 (0.1 mol) was taken in 10 mL ethanol. Suitably substi-
tuted benzaldehyde (0.1 mol) and a catalytic amount of acetic acid were added.
The reaction mixture was stirred at room temperature for 6 h. The separated product
was filtered, washed with alcohol, dried, and recrystallized from an ethanol–DMF
mixture. The characterization data of all the newly synthesized compounds are
summerized in Table 1.
Spectral Data of Some of the Other Represented Compounds
Compound 4b. Mass: e=z, 356=358 (Mþ þ 1)=(Mþ þ 3). IR (KBr pellet):
ꢁ1
1679 cmꢁ1 (NH-Cꢁ1O), 3326 cm (-NH), 2922 cmꢁ1 (alkyl streching), 1602 cmꢁ1
=
=
(N CH), 1523 cm (pyrazole N CH).
=
Compound 4c. Mass: e=z, 386=388 (Mþ þ 1)=(Mþ þ 3). 1H NMR (400 MHz)
(DMSO-d6): d, 2.51 (s, 3H, pyrazole-CH3), 3.84 (s, 3H, -OCH3), 7.05–7.07
(d, J ¼ 8.64 Hz, 2H, ortho protons of p-anisyl), 7.55–7.61 (m, 5H, Ar-H),
=
7.84–7.86 (d, J ¼ 8.6 Hz, 2H, meta protons of p-anisyl), 8.59 (s, 1H, CH C),
=
8.6673 (s, 1H, N CH).
Table 1. Characterization data of 5-chloro-3-methyl-4-methylidene[(31-substitutedbenzylidineamino)
pyrazole-51-one]-1-phenyl-1H-pyrazole 4
CHN analysis found (Calc.)
Mol.
wt
Yield
(%)
Mp
(ꢀC)
Compound
R
Mol. formula
21H16ClN5O
C
H
N
4a
4b
4c
4d
4e
4f
H
4-CH3
C
389.5
403.5
419.5
449.5
405.5
424
79
78
89
93
91
96
76
99
80
96
69
92
89
141–144 67.66 (64.7) 4.25 (4.14) 17.82 (17.96)
218–220 65.35 (65.43) 4.56 (4.49) 17.79 (17.39)
222–225 62.66 (62.93) 4.18 (4.32) 16.42 (16.68)
227–230 61.59 (61.40) 4.30 (4.48) 15.63 (15.57)
226–227 62.34 (62.15) 4.13 (3.97) 17.14 (17.26)
214–215 59.61 (59.45) 3.25 (3.56) 16.78 (16.51)
222–226 61.88 (61.85) 3.68 (3.71) 17.12 (17.17)
146–148 53.76 (53.81) 3.36 (3.23) 14.82 (14.94)
223–224 59.54 (59.45) 3.23 (3.56) 16.42 (16.51)
208–212 55.07 (54.98) 3.00 (3.08) 15.08 (15.27)
225–226 53.92 (53.81) 3.46 (3.23) 14.88 (14.94)
179–183 58.13 (58.00) 3.24 (3.48) 19.54 (19.33)
225–227 58.04 (58.00) 3.39 (3.48) 19.46 (19.33)
C22H18ClN5O
C22H18ClN5O2
3,4-dimethoxy C23H20ClN5O3
4-OCH3
4-OH
4-Cl
C
21H16ClN5O2
21H15Cl2N5O
C
4g
4h
4i
4-F
4-Br
C21H15ClFN5O 407.5
C21H15BrClN5O 468.5
2-Cl
3,4-Dichloro
3-Br
C21H15Cl2N5O
21H14Cl3N5O
C21H15BrClN5O 468.5
424
4j
C
458.5
4k
4l
4-NO2
3-NO2
C21H15ClN6O3
C21H15ClN6O3
434.5
434.5
4m
Note. Solvent for recrystallization: 1:1 mixture of ethanol–DMF.

PYRAZOLONES AND SCHIFF BASES
3101
Compound 4d. Mass: eꢁ=1z, 416=418 (Mþ þ 1)=(Mþ þ 3). IR (KBr pellet):
ꢁ1
1629 cm (NH-C O), 3305 cm (-NH), 2920 cmꢁ1 & 2958 cmꢁ1 (alkyl streching),
=
ꢁ1
1597 cmꢁ1 (N CH), 1569 cm (pyrazole N CH).
=
=
Compound 4f. Mass: e=z, 390=392=394 (Mþ þ 1)=(Mþ þ 3)=(Mþ þ 5). IR
ꢁ1
(KBr pellet): 1627 cmꢁ1 (NHꢁ-C1 O), 3388 cm (-NH), 2936 cmꢁ1 (alkyl streching),
=
1577 cmꢁ1 (N CH), 1529 cm (pyrazole N CH).
=
=
Compound 4h. Mass: e=z, 435=437 (Mþ þ 1)=(Mþ þ 3). 1H NMR (400 MHz)
(DMSO-d6): d, 2.65 (s, 3H, pyrazole-CH3), 7.45–7.61 (m, 7H, Ar-H & 2 ortho pro-
tons of p-bromophenyl), 7.71–7.73 (d, J ¼ 8.4 Hz, 2H, meta protons of p-bromo phe-
=
=
nyl), d, 8.62 (s, 1H, CH C), 8.697 (s, 1H, N CH).
Compound 4l. Mass: e=z, 401=403 (Mþ þ 1) = (Mþ þ 3). 1H NMR (400 MHz)
(DMSO-d6): d, 2.64 (s, 3H, pyrazole-CH3), d, 7.464–7.6058 (m, 5H, Ar-H),
8.014–8.036 (d, J ¼ 8.7 Hz, 2H, ortho protons of p-nitro phenyl), 8.31–8.334 (d,
=
J ¼ 8.7 Hz, 2H, meta protons of p-nitro phenyl), 8.7239 (s, 1H, CH C), 8.7360 (s,
ꢁ1
ꢁ1
ꢁ1
=
=
1H, N CH). IR (KBr pellet): 1631 cm (NH-Cꢁ1O), 3452 cm (-NH), 2976 cmꢁ1
(alkyl streching), 1577 cmꢁ1 (N CH), 1529 cm
=
=
(pyrazole N CH), 1567 cm
(NO2 assymmetric), 1419 cmꢁ1 (NO2 symmetric).
ACKNOWLEDGMENTS
The authors are thankful to the director, SAIF, Punjab University, for infra-
red, mass, and NMR spectra and the chairman, Department of Chemistry, Manga-
lore University, for providing the CHN analysis. One of the author (G. K. S.) is
thankful to the University Grants Commission, New Delhi, for the financial assist-
ance under the UGC-RFSMS scheme.
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