NEW PYRAZOLINE DERIVATIVES

Full text of DOI:10.1135/cccc19940247

New Compounds
247
NEW PYRAZOLINE DERIVATIVES
a
a
a
F. M. ABD EL LATIF , A. S. MAGHRABY , M. A. BARSY ,
a
b
M. Z. A. BADR and D. DOPP
a Department of Chemistry,
Aswan Faculty of Science, Aswan, Egypt
b Department of Chemistry,
Duisburg University, Duisburg, Germany
Received October 5, 1992
Accepted February 12, 1993
The biological activity of azoles, pyrimidines as well as pyrazolines are of interest1 – 5
.
Formation of pyrazolines and related compounds from hydrazine derivatives and
α,β-unsaturated carbonyl compounds in very common6. Pyrazoline fused with different
heterocyclic nuclei at position 4 and 5 have been reported7. Here we report the syn-
thesis of some new monocyclic or fused azoles and pyrimidinones linked to C-4 or
5-chloro-3-methyl-1-phenylpyrazoline.
EXPERIMENTAL
All melting points are uncorrected. Elemental analyses were carried out at Microanalytical Center,
Cairo University, IR spectra (KBr) on Perkin–Elmer infrared 127B spectrophotometer. 1H NMR
spectra were obtained on Varian EM 360 (60 MHz) in CDCl3 and mass spectra (Mat 311 A, 70 eV)
were performed at Chemistry Department, Duisburg University, Germany.
Preparation of α,β-Unsaturated Ketones II – IV; General Procedure
Equimolar portions (0.1 mol l−1) of formyl compound8 I and 3-methyl-1-phenylpyrazol-5-one or 2-
methyloxazolone, respectively, were dissolved in ethanol (50 ml), then 0.5 ml of piperidine was
added. The reaction mixture was allowed to reflux for 8 – 12 h, filtered hot, evaporated to one third
of its volume, cooled, acidified with few drops of acetic acid and the product (II or III, respectively)
precipitated on dilution with water. It was collected, washed by water and crystallized from appropri-
ate solvents.
The above method has been applied to preparation of the ketones (IVa – IVc) by condensation of
the formyl compound I with acetophenone derivatives; alcohol potassium hydroxide solution (0.15
mol l−1) has been used as a basic catalyst. The structure of ketones II, III and IVa – IVc was con-
firmed on the basis of analytical and spectral data (Tables I and II).
Reaction of α,β-Unsaturated Ketones II – IV with Hydrazine Derivatives; General Procedure
Equimolar amounts of ketones II – IV and the hydrazine hydrate in boiling ethanol in presence of
drops of acetic acid, phenylhydrazine with catalytic amount of piperidine (0.5 ml), hydroxylamine
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248
Abd El Latif, Maghraby, Barsy, Badr, Dopp:
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

New Compounds
249
TABLE I
Physical characteristics of ketones II – IV
Calculated/Found
M. p., °C
Formula
Compound
Yield, %
(M. w.)
% C
% H
% Cl
% N
IIa
185 – 187
C21H17ClN4O
(376.5)
66.93
66.91
4.52
4.85
9.43
9.40
14.87
14.85
80
IIIb
190 – 193
C15H12ClN3O2
(301.5)
59.70
59.61
3.98
3.89
11.77
11.65
13.93
13.82
75
IVac
IVbc
IVcc
115 – 117
C19H15ClN2O
(322.5)
70.70
70.62
4.65
4.50
11.01
10.88
8.68
8.53
75
180 – 183
C19H14ClN3O3
(367.5)
62.04
61.93
3.81
3.69
9.66
9.53
11.43
11.30
80
160 – 164
C20H17ClN2O2
(352.5)
68.09
67.97
4.82
4.70
10.07
9.98
7.94
7.82
65
Crystallized from a DMF, b methanol, c ethanol.
TABLE II
1
IR and H NMR data for the ketones II – IV
Compound
IRa, cm−1
1H NMR, ppm
II
1 730
1 725
1 730
1.29 s, 6 H (2 CH3); 4.8 s, 1 H (ylidene); 7.1 – 7.8 m, 10 H (2 ArH)
1.28 s, 3 H (CH3); 4.75 s, 1 H (ylidene); 7.1 – 7.8 m, 5 H (ArH)
III
IVa
1.3 s, 3 H (CH3); 6.15 d, 1 H (ylidene); 6.3 d, 1 H (ylidene); 7.1 – 7.8 m,
10 H (2 ArH)
IVb
IVc
1 735
1 735
1.3 s, 3 H (CH3); 6.1 d, 1 H (ylidene); 6.25 d, 1 H (ylidene); 7.1 – 7.8 m,
9 H (2 ArH)
1.3 s, 3 H (CH3); 3.1 s, 3 H (CH3−CO); 6.1 d, 1 H (ylidene); 6.2 d,
1 H (ylidene); 7.1 – 7.8 m, 9 H (2 ArH)
a
(C=O).
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Abd El Latif, Maghraby, Barsy, Badr, Dopp:
TABLE III
Physical characteristics of compounds V – XIV
Calculated/Found
M. p., °C
Yield, %
Formula
(M. w.)
Compound
% C
% H
% Cl
% N
Vaa
200 – 203
80
C23H21ClN6O
(432.5)
63.82
63.69
4.86
4.73
8.21
8.12
19.42
19.30
Vba
160 – 162
70
C27H23ClN6
(466.5)
69.45
69.34
4.93
4.81
7.61
7.53
18.01
17.87
Vca
205 – 207
50
C21H18ClN5O
(391.5)
64.37
64.15
4.60
4.47
9.07
8.98
17.88
17.74
VIab
VIbb
VIIaa
VIIba
VIIca
VIIIab
VIIIbb
IXaa
IXba
IXca
Xaa
230 – 233
70
C22H19ClN6O
(418.5)
63.08
62.97
4.54
4.42
8.48
8.41
20.07
19.95
210 – 212
73
C22H19ClN6S
(434.5)
60.76
60.68
4.37
4.25
8.17
8.12
19.33
19.21
220 – 223
80
C17H16ClN5O2
(357.5)
57.06
56.97
4.48
4.37
9.93
9.84
19.58
19.51
185 – 188
85
C21H18ClN5O
(391.5)
64.37
64.26
4.60
4.51
9.07
8.96
17.88
17.76
215 – 217
50
C15H13ClN4O2
(316.5)
56.87
56.78
4.11
4.02
11.22
11.08
17.69
17.58
235 – 238
60
C16H14ClN5O2
(343.5)
55.90
55.81
4.08
3.99
10.33
10.20
20.38
29.29
245 – 247
60
C16H14ClN5OS
(359.5)
53.41
53.37
3.89
3.76
9.87
9.82
19.47
19.40
140 – 142
70
C21H19ClN4O
(378.5)
66.58
66.47
5.02
4.88
9.38
9.30
14.80
14.68
130 – 132
75
C25H21ClN4
(412.5)
72.73
72.69
5.09
4.97
8.61
8.52
13.58
13.46
160 – 162
60
C19H16ClN3O
(337.5)
67.56
67.43
4.74
4.62
10.52
10.44
12.44
12.35
140 – 143
60
C20H17ClN4O
(364.5)
65.84
65.74
4.66
4.52
9.74
9.70
15.36
15.29
Xba
C20H17ClN4S
(380.5)
160 – 163
60
63.07
62.89
59.50
59.41
4.47
4.36
4.25
4.11
9.33
9.12
8.38
8.29
14.72
14.60
16.53
16.47
XIaa
C21H18ClN5O3
(423.5)
165 – 168
70
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New Compounds
251
TABLE III
(Continued)
Calculated/Found
M. p., °C
Yield, %
Formula
(M. w.)
Compound
% C
% H
% Cl
% N
XIba
120 – 123
C25H20ClN5O2
(457.5)
65.57
65.43
4.37
4.25
7.76
7.66
15.30
15.18
60
XIcb
210 – 212
C19H15ClN4O3
(382.5)
59.61
59.48
3.92
3.78
9.28
9.17
14.64
14.57
75
XIIac
XIIbc
XIIIac
XIIIbb
XIIIcc
XIVab
XIVba
160 – 163
C20H16ClN5O3
(409.5)
58.61
58.47
3.91
3.80
8.67
8.56
17.09
16.98
45
170 – 172
C20H16ClN5O2S
(425.5)
56.40
56.32
3.76
3.64
8.34
8.31
16.45
16.37
50
180 – 183
C22H21ClN4O2
(408.5)
64.63
64.51
5.14
5.03
8.69
8.57
13.71
13.58
70
210 – 213
C26H23ClN4O
(442.5)
70.51
70.38
5.20
5.12
8.02
7.93
12.66
12.53
60
175 – 177
C20H18ClN3O2
(367.5)
65.31
65.22
4.90
4.78
9.66
9.52
11.42
11.31
62
232 – 234
C21H19ClN4O2
(394.5)
63.88
63.75
4.82
4.67
9.00
8.89
14.20
14.07
74
185 – 187
C21H19ClN4OS
(410.5)
61.39
61.27
4.63
4.52
8.64
8.49
13.64
13.55
60
Crystallized from: a ethanol, b DMF, c methanol.
hydrochloride in 0.3 M alcoholic sodium hydroxide solution and urea or thiourea in presence of 0.05 M
hydrochloric acid, were refluxed for 5 – 10 h. The product of N-acetyl pyrazoline derivatives has
been obtained upon adding drops of cooled water to the concentrated solution, filtered, washed by
diluted ethanol and then recrystallized.
The reaction mixture containing N-phenylpyrazoline, isoxazoline or pyrimidinone derivatives was
concentrated and neutralized with acetic acid, hydrochloric acid and sodium hydroxide, respectively.
The solid product was collected by filtration, washed with cooled water, dried and then crystallized
from proper solvents. Most of these compounds have a brown to brownish orange colour, soluble in
1
most polar solvents. Physical characteristics and selected IR and H NMR data for these compounds
are presented in Tables III and IV.
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Abd El Latif, Maghraby, Barsy, Badr, Dopp:
TABLE IV
Spectral data for compounds V, VI and IX
Compound
IR, cm−1
1 690a
1H NMR, ppm
Va
1.2 s, 6 H (2 CH3); 2.2 s, 3 H (CH3−CO); 5.1 – 5.3 d, 2 H
(pyrazoline); 7.2 – 7.9 m, 10 H (2 ArH)
Vb
1 610b
1 615b
1.2 s, 6 H (2 CH3); 5.9 – 6.2 d, 2 H (pyrazoline); 7.1 – 7.9 m,
15 H (3 ArH)
Vc
1.2 s, 6 H (2 CH3); 5.1 – 5.2 d, 2 H (pyrazoline); 7.1 – 7.8 m,
10 H (2 ArH)
VIa
VIb
IXa
1 740a
1.2 s, 6 H (2 CH3); 3.4 b, 1 H (NH); 7.1 – 7.9 m, 12 H (2 ArH and
3 400 – 3 300c
pyrimidine H-3, H-4)
1 213d
3 400 – 3 300c
1.2 s, 6 H (2 CH3); 3.4 b, 1 H (NH); 7.1 – 7.8 m, 12 H (2 ArH and
pyrimidine H-3, H-4)
1 720a
1.2 s, 3 H (CH3); 2.2 s, 3 H (CH3−CO); 5.1 – 5.15 d, 2 H
(pyrazoline H-4); 5.2 t, 1 H (pyrazoline H-5); 7.2 – 7.9 m,
10 H (2 ArH)
IXb
IXc
1 615b
1 610b
1.2 s, 3 H (CH3); 5.1 – 5.15 d, 2 H (pyrazoline H-4); 5.2 t, 1 H
(pyrazoline H-5); 7.1 – 7.8 m, 15 H (3 ArH)
1.2 s, 3 H (CH3); 5.1 – 5.15 d, 2 H (pyrazoline H-4); 5.2 t, 1 H
(pyrazoline H-5); 7.1 – 7.8 m, 10 H (2 ArH)
a
c
Bonds attributed as (C=O), b (C=C), (N−H), d (C=S).
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Collect. Czech. Chem. Commun. (Vol. 59) (1994)