Synthesis of 1-substituted 3,5-diaryl-2-pyrazolines by the reaction of α,β-unsaturated ketones with hydrazines

Article abstract of DOI:10.1002/jhet.5570430117

1-Acetyl-, 1-propionyl- and 1-phenyl-3,5-diaryl-2-pyrazolines have been synthesized by the reaction of the appropriate α,β-unsaturated ketones with hydrazine or phenylhydrazine in hot acetic acid or propionic acid. Structures of all new 2-pyrazolines 16-4

Full text of DOI:10.1002/jhet.5570430117

Jan-Feb 2006
111
Synthesis of 1-Substituted 3,5-Diaryl-2-pyrazolines by the Reaction of
α,β-Unsaturated Ketones with Hydrazines
Albert Lévai [a]* and József Jekő [b]
[a] Department of Organic Chemistry, University of Debrecen, P.O.Box 20, H-4010 Debrecen, Hungary
[b] Department of Chemistry, College of Nyíregyháza, Sóstói u. 31/b, H-4400 Nyíregyháza, Hungary
Received June 14, 2005
1-Acetyl-, 1-propionyl- and 1-phenyl-3,5-diaryl-2-pyrazolines have been synthesized by the reaction of
the appropriate α,β-unsaturated ketones with hydrazine or phenylhydrazine in hot acetic acid or propionic
1
13
acid. Structures of all new 2-pyrazolines 16-40 have been elucidated by microanalyses, H and C nmr
spectroscopies.
J. Heterocyclic Chem., 43, 111 (2006).
Introduction.
aromatic rings of the α,β-unsturated ketones, used as start-
ing materials, on the formation of 2-pyrazolines on their
reaction with hydrazines. Electronic structures of the aro-
matic rings of starting materials 1-15 can also influence
the electron density of the α,β-unsaturated ketone units of
the molecules. Compounds 1-15 seem to be adequate
examples to investigate this effect, too.
Compounds 1-15 were allowed to react with hydrazine
hydrate in hot acetic acid or propionic acid to afford 1-
acetyl-3,5-diaryl-2-pyrazolines 16-28 or 3,5-diaryl-1-
Pyrazolines are important and useful five-membered
heterocyclic compounds and various procedures have been
worked out for their synthesis [1-5]. Several pyrazoline
derivatives were found to possess important bioactivities,
viz. antibacterial [6,7], antiviral [8], antifungal [9],
immunosuppressive [10], central nervous system [11],
molluscicidal [12,13], etc. activities. 1-Acetyl-3,5-diaryl-
2-pyrazolines have been found to inhibit the monoamine
oxidases [14]. On the other hand, 1,3,5-triaryl-2-pyrazo-
lines were utilized as scintillation solutes [15]. Recently, 3-
(2-pyridyl)-2-pyrazoline derivatives have been used as
novel fluorescent probes [16]. All these mentioned bioac-
tivities and other utilities stimulated the research in this
field. 2-Pyrazolines proved to be the most useful pyrazo-
line type compounds and various methods have been
developed for their synthesis [4,5,12-38]. A generally used
simple and convenient procedure is based on the reaction
of α,β-unsaturated aldehydes and ketones with hydrazines.
As a continuation of our studies on the synthesis of 2-pyra-
zolines [32,33,35,36,38] by this method, herein we
describe the synthesis of new 1-substituted 3,5-diaryl-2-
pyrazolines bearing polycyclic aryl and/or heteroaryl moi-
eties by the reaction of α,β-unsaturated ketones with
hydrazines.
Results and Discussion.
Most of the α,β-unsaturated ketones used as starting
materials for the synthesis of 2-pyrazolines belong to the
substituted chalcones or exocyclic α,β-unsaturated
ketones. There are only sporadic literature data on the uti-
lization of α,β-unsaturated ketones bearing polycyclic aro-
matic rings [23,37], 2-furyl or 2-thienyl moieties
[22,27,29]. For this reason, the aim of our present study
was to investigate the influence of the space demand of the

112
A. Lévai and J. Jekő
Vol. 43
propionyl-2-pyrazolines 29-34 in good yields (70-89%)
(Scheme 1). It should be mentioned that only 1-acylated-
2-pyrazolines could be detected in the crude reaction
mixtures.
α,β-Unsaturated ketones 1,4-6,8 and 15 have also been
reacted with phenylhydrazine in hot acetic acid and 3,5-
diaryl-1-phenyl-2-pyrazolines were obtained in high yields
(74-90%) (Scheme 2). In the crude reaction mixtures no
by-produtcs were detected by chromatography.
the N-acetyl and N-propionyl groups have also been detected
in the C nmr spectra of compounds 16-28 and 29-34 (cf.
Experimental).
13
In summary, we have synthesized a series of new 1-substi-
tuted 3,5-diaryl-2-pyrazolines by the reaction of α,β-unsatu-
rated ketones with hydrazines in hot acetic acid or propionic
acid solution. This simple and convenient procedure made
available the preparation of 3,5-diaryl-2-pyrazolines even
with bulky aryl groups at positions 3 and 5. All these new 2-
pyrazolines are stable compounds which property makes
them useful substances in the drug research.
EXPERIMENTAL
Melting points were determined with a Koffler hot-stage appa-
1
13
ratus and are uncorrected. H and C nmr spectra were measured
on a Varian Gemini 200 spectrometer at 200/50 MHz in CDCl
3
(internal standard TMS, δ = 0.0 ppm) at room temperature.
Elemental analyses were measured in-house with a Carlo Erba
1106 EA instrument. The tlc was performed on Kieselgel 60 F
254
(Merck) layer using hexane:acetone (7:3 v/v) or toluene:ethyl
acetate (4:1 v/v) as eluents. Starting materials 1-15 were synthe-
sized according to known methods [37,39-43].
General Procedure for the Preparation of 2-Pyrazolines 16-40
A mixture of α,β-unsaturated ketone (1-15, 10.0 mmoles),
hydrazine hydrate or phenylhydrazine (30.0 mmoles), acetic acid
(50 ml) (in the case of 2-pyrazolines 16-28 and 35-40) or propi-
onic acid (50 ml) (in the case of 2-pyrazolines 29-34) was
refluxed for 3 hours, then poured onto crushed ice. The precipi-
tate was separated by filtration, washed with water and crystal-
lized from methanol to afford 2-pyrazolines (Scheme 1).
Our experimental results prove that this simple procedure
is extremely convenient for the preparation of such kind of
1-substituted 3,5-diaryl-2-pyrazolines. Both the space
demand and the electronic structure of the aryl groups are
almost without influence on the formation of the 2-pyrazo-
line ring. Even such bulky groups as 1- or 2-naphthyl, 9-
anthryl and 9-phenanthryl can easily be accomodated at the
C-3 and C-5 atoms of a 2-pyrazoline molecule. This is cor-
roborated by the fact that these 2-pyrazolines are very sta-
ble compounds which can be stored at room temperature
for a long time without the risk of decomposition.
1-Acetyl-5-(2-naphthyl)-3-phenyl-2-pyrazoline (16).
This compound was obtained as white needles in 70% yield,
1
mp 144-145°; H nmr (CDCl ): δ 2.46 (3H, s, Me), 3.24 (1H, dd,
3
J = 4.7, 17.7 Hz, 4-H
), 3.81 (1H, dd, J = 11.8, 17.7 Hz, 4-
trans
H
), 5.76 (1H, dd, J = 4.7, 11.8 Hz, 5-H), 7.25-7.81 (m, 12 arom.
cis
Structures of the synthesized 2-pyrazolines 16-40 have
13
H); C nmr (CDCl ): δ 21.8, 42.3, 60.1, 123.6, 124.7, 126.0,
126.4, 126.7, 127.8, 128.1, 128.9, 129.2, 130.5, 131.6, 133.5,
139.3, 154.0, 168.1.
3
1
13
been elucidated by microanalyses, H and C nmr spectro-
1
scopies. In the H nmr spectra of compounds 16-40, the three
Anal. Calcd. for C
Found: C, 80.39; H, 5.81; N, 8.78.
H N O: C, 80.23; H, 5.77; N, 8.91.
hydrogen atoms attached to the C-4 and C-5 carbon atoms of
the 2-pyrazoline skeleton gave an ABX spin system. The 2-
pyrazoline structure are unequivocally proved both by the
chemical shift data and by the coupling constant values (cf.
Experimental). Characteristic singlet signal of the N-acetyl
group of the 1-acetyl-2-pyrazolines 16-28 were detected in
21 18 2
1-Acetyl-5-(9-anthryl)-3-(4-bromophenyl)-2-pyrazoline (17).
This substance was prepared as white needles in 84% yield,
1
mp 272-273°; H nmr (CDCl ): δ 2.36 (3H, s, Me), 3.46 (1H, dd,
3
J = 9.8, 18.0 Hz, 4-H
), 3.87 (1H, dd, J = 13.0, 18.0 Hz, 4-
trans
1
each H nmr spectrum. Triplet and quartet signals of the
H
), 6.82 (1H, dd, J = 9.8, 13.0 Hz, 5-H), 7.24-8.48 (m, 13 arom.
cis
13
ethyl part of the N-propionyl group of compounds 29-34
were observed in each case. Owing to the steric interaction
between the N-1 phenyl group and the two 4-H atoms, the
trans-4-H is shielded and the cis-4-H is deshielded. Signals
H); C nmr (CDCl ): δ 21.7, 41.5, 56.2, 122.8, 123.2, 124.7,
3
124.9, 125.0, 126.3, 126.8, 128.2, 128.4, 128.8, 129.6, 130.3,
130.6, 131.4, 131.6, 132.1, 132.2, 153.0, 169.9.
Anal. Calcd. for C
H BrN O: C, 67.73; H, 4.32; N, 6.32.
25 19 2
Found: C, 67.61; H, 4.37; N, 6.20.
13
of the aromatic protons are highly overlapped. In the C nmr
1-Acetyl-5-(9-anthryl)-3-(1-naphthyl)-2-pyrazoline (18).
This compound was obtained as white plates in 79% yield, mp
spectra of compounds 16-40, chemical shift data of carbon
atoms C-3 (151-154 or 146-148 ppm), C-4 (41-44 ppm) and
C-5 (56-65 ppm) confirm the 2-pyrazoline structure deduced
1
251-252°; H nmr (CDCl ): δ 2.39 (3H, s, Me), 3.76 (1H, dd, J =
3
1
13
8.6, 17.8 Hz, 4-H
), 4.12 (1H, dd, J = 12.7, 17.8 Hz, 4-H ),
from the H nmr measurements. C nmr chemical shifts of
trans
cis

Jan-Feb 2006
Synthesis of 1-Substituted 3,5-Diaryl-2-pyrazolines
113
6.92 (1H, dd, J = 8.6, 12.7 Hz, 5-H), 7.12-8.37 (m, 16 arom. H);
Anal. Calcd. for C H N O: C, 82.39; H, 5.53; N, 7.68.
25 20 2
Found: C, 82.29; H, 5.59; N, 7.79.
13
C nmr (CDCl ): δ 20.3, 44.4, 56.8, 123.0, 123.3, 124.7, 125.0,
3
125.5, 125.9, 126.0, 126.6, 126.8, 127.2, 127.9, 128.0, 128.4,
128.7, 128.9, 129.1, 129.6, 130.3, 130.7, 131.4, 134.6, 137.2,
151.4, 172.9.
1-Acetyl-5-(9-anthryl)-3-(2-naphthyl)-2-pyrazoline (24).
This compound was isolated as white plates in 77% yield, mp
1
217-218°; H nmr (CDCl ): δ 2.43 (3H, s, Me), 3.62 (1H, dd, J =
Anal. Calcd. for C
H N O: C, 84.03; H, 5.35; N, 6.75.
3
29 22 2
9.3, 18.0 Hz, 4-H
), 4.02 (1H, dd, J = 13.1, 18.0 Hz, 4-H ),
Found: C, 84.17; H, 5.30; N, 6.84.
trans
cis
6.92 (1H, dd, J = 9.3, 13.1 Hz, 5-H), 7.24-8.53 (m, 16 arom. H);
1-Acetyl-5-(4-methoxyphenyl)-3-(2-naphthyl)-2-pyrazoline
(19).
13
C nmr (CDCl ): δ 21.8, 41.7, 56.1, 123.1, 123.3, 123.6, 124.7,
3
125.0, 126.3, 126.7, 126.9, 127.3, 128.0, 128.5, 128.7, 129.2,
129.6, 130.3, 131.6, 131.7, 132.1, 133.2, 134.4, 154.2, 169.9.
This material was prepared as white needles in 81% yield, mp
1
151-152°; H nmr (CDCl ): δ 2.48 (3H, s, Me), 3.29 (1H, dd, J =
Anal. Calcd. for C
H N O: C, 84.03; H, 5.35; N, 6.75.
3
29 22 2
4.6, 17.6 Hz, 4-H
), 3.79 (3H, s, MeO), 3.81 (1H, dd, J = 11.7,
Found: C, 84.14; H, 5.39; N, 6.65.
trans
17.6 Hz, 4-H ), 5.60 (1H, dd, J = 4.6, 11.7 Hz, 5-H), 6.85-8.11
cis
1-Acetyl-3-(2-phenanthryl)-5-phenyl-2-pyrazoline (25).
This substance was prepared as white needles in 83% yield,
13
(m, 11 arom. H); C nmr (CDCl ): δ 21.9, 42.1, 55.2, 59.5,
3
114.2, 123.2, 126.7, 126.9, 127.1, 127.8, 128.3, 128.4, 129.0,
132.9, 134.1, 153.8, 158.9, 168.7.
1
mp 190-191°; H nmr (CDCl ): δ 2.51 (3H, s, Me), 3.30 (1H, dd,
3
J = 4.7, 17.6 Hz, 4-H
), 3.86 (1H, dd, J = 11.7, 17.6 Hz, 4-
Anal. Calcd. for C
H N O : C, 76.72; H, 5.85; N, 8.13.
trans
22 20 2 2
H
), 5.65 (1H, dd, J = 4.7, 11.7 Hz, 5-H), 7.26-8.70 (m, 14
Found: C, 76.84; H, 5.79; N, 8.21.
cis
13
arom. H); C nmr (CDCl ): δ 21.9, 42.3, 60.1, 122.8, 123.2,
124.0, 125.5, 126.7, 126.9, 127.2, 127.8, 128.6, 128.8, 129.4,
129.8, 131.3, 131.7, 132.4, 141.8, 153.6, 168.8.
3
1-Acetyl-5-(3,4-methylenedioxyphenyl)-3-(2-naphthyl)-2-pyra-
zoline (20).
This compound was prepared as white needles in 83% yield,
Anal. Calcd. for C
Found C, 82.49; H, 5.48; N, 7.59.
H N O: C, 82.39; H, 5.53; N, 7.68.
25 20 2
1
mp 198-199°; H nmr (CDCl ): δ 2.49 (3H, s, Me), 3.28 (1H, dd,
3
J = 4.6, 17.7 Hz, 4-H
), 3.83 (1H, dd, J = 11.7, 17.7 Hz, 4-
trans
1-Acetyl-3-(9-phenanthryl)-5-phenyl-2-pyrazoline (26).
This compound was prepared as white plates in 76% yield, mp
H
), 5.57 (1H, dd, J = 4.6, 11.7 Hz, 5-H), 6.72-8.10 (m, 10 arom.
cis
13
H); C nmr (CDCl ): δ 22.0, 42.3, 59.8, 101.1, 106.0, 108.5,
3
1
204-205°; H nmr (CDCl ): δ 2.54 (3H, s, Me), 3.47 (1H, dd, J =
119.1, 123.2, 126.7, 127.1, 127.8, 128.3, 128.5, 128.9, 132.9,
134.1, 135.9, 147.0, 148.1, 153.8, 168.8.
3
4.6, 17.4 Hz, 4-H
), 4.06 (1H, dd, J = 11.8, 17.4 Hz, 4-H ),
trans
cis
5.62 (1H, dd, J = 4.6, 11.8 Hz, 5-H), 7.27-9.41 (m, 14 arom. H);
Anal. Calcd. for C
Found: 73.62; H, 5.09; N, 7.92.
H N O : C, 73.73; H, 5.06; N, 7.81.
22 18 2 3
13
C nmr (CDCl ): δ 22.1, 44.9, 58.8, 122.8, 123.1, 125.8, 126.8,
3
127.2, 127.6, 127.8, 128.4, 129.1, 129.2, 129.3, 130.5, 130.7,
131.1, 131.3, 142.1, 154.4, 169.1.
1-Acetyl-5-(4-chlorophenyl)-3-(2-naphthyl)-2-pyrazoline (21).
This substance was obtained as white needles in 89% yield, mp
Anal. Calcd. for C
Found: C, 82.48; H, 5.58; N, 7.76.
H N O: C, 82.39; H, 5.53; N, 7.68.
25 20 2
1
152-153°; H nmr (CDCl ): δ 2.48 (3H, s, Me), 3.27 (1H, dd, J =
3
4.7, 17.6 Hz, 4-H
), 3.88 (1H, dd, J = 11.2, 17.6 Hz, 4-H ),
trans
cis
1-Acetyl-5-(4-bromophenyl)-3-(2-furyl)-2-pyrazoline (27).
This material was isolated as white needles in 83% yield, mp
5.61 (1H, dd, J = 4.7, 11.2 Hz, 5-H), 7.19-8.09 (m, 11 arom. H);
13
C nmr (CDCl ): δ 21.9, 42.1, 59.4, 123.2, 126.8, 127.1, 127.3,
3
1
162-163°; H nmr (CDCl ): δ 2.40 (3H, s, Me), 3.04 (1H, dd, J =
128.3, 128.5, 129.0, 132.9, 133.4, 134.1, 140.3, 153.7, 168.8.
3
5.6, 17.4 Hz, 4-H
), 3.70 (1H, dd, J = 11.3, 17.4 Hz, 4-H ),
Anal. Calcd. for C
H ClN O: C, 72.31; H, 4.91; N, 8.03.
trans
cis
21 17 2
5.51 (1H, dd, J = 5.6, 11.3 Hz, 5-H), 6.51-7.57 (m, 7 arom. H);
Found: C, 72.22; H, 4.95; N, 7.92.
13
C nmr (CDCl ): δ 21.8, 41.8, 58.9, 111.9, 112.6, 121.3, 131.9,
3
1-Acetyl-5-(2,4-dichlorophenyl)-3-(2-naphthyl)-2-pyrazoline (22).
This compound was prepared as white plates in 79% yield, mp
140.5, 144.8, 145.4, 146.6, 168.7.
Anal. Calcd. for C
H BrN O : C, 54.07; H, 3.93; N, 8.40.
15 13 2 2
1
183-184°; H nmr (CDCl ): δ 2.52 (3H, s, Me), 3.18 (1H, dd, J =
Found.: C, 54.15; H, 3.98; N, 8.32.
3
5.1, 17.3 Hz, 4-H
), 3.96 (1H, dd, J = 11.9, 17.3 Hz, 4-H ),
trans
cis
1-Acetyl-5-(9-anthryl)-3-(2-furyl)-2-pyrazoline (28).
This compound was prepared as pale yellow needles in 81%
5.91 (1H, dd, J = 5.1, 11.9 Hz, 5-H), 7.03-8.08 (m, 10 arom. H);
13
C nmr (CDCl ): δ 21.9, 41.2, 57.5, 123.1, 126.8, 127.0, 127.2,
3
1
yield, mp 242-243°; H nmr (CDCl ): δ 2.34 (3H, s, Me), 3.45
127.4, 127.6, 127.9, 128.4, 128.6, 129.8, 132.5, 132.9, 133.9,
134.2, 137.3, 154.1, 168.9.
3
(1H, dd, J = 9.4, 18.1 Hz, 4-H
), 3.86 (1H, dd, J = 13.1, 18.1
trans
Hz, 4-H ), 6.54 (1H, dd, J = 9.4, 13.1 Hz, 5-H), 6.75-8.50 (m, 12
Anal. Calcd. for C
Found: C, 65.72; H, 4.26; N, 7.21.
H Cl N O: C, 65.81; H, 4.21; N, 7.30.
cis
21 16 2 2
13
arom. H); C nmr (CDCl ): δ 21.7, 41.3, 55.6, 112.1, 112.8,
3
122.9, 123.1, 124.7, 124.9, 126.3, 126.7, 128.4, 128.7, 129.5,
130.3, 131.2, 131.5, 132.0, 145.0, 147.1, 153.8, 169.8.
1-Acetyl-3,5-di(2-naphthyl)-2-pyrazoline (23).
This material was obtained as white plates in 88% yield, mp
Anal. Calcd. for C
H N O : C, 77.95; H, 5.12; N, 7.90.
23 18 2 2
1
238-239°; H nmr (CDCl ): δ 2.49 (3H, s, Me), 3.39 (1H, dd, J =
Found: C, 77.84; H, 5.16; N, 7.98.
3
4.8, 17.6 Hz, 4-H
), 3.83 (1H, dd, J = 11.7, 17.6 Hz, 4-H ),
trans
cis
5-(1-Naphthyl)-3-phenyl-1-propionyl-2-pyrazoline (29).
This substance was obtained as white needles in 89% yield, mp
5.81 (1H, dd, J = 4.8, 11.7 Hz, 5-H), 7.26-8.12 (m, 14 arom. H);
13
H nmr (CDCl ): δ 22.0, 42.3, 60.2, 123.3, 123.4, 124.5, 125.9,
3
1
164-165°; H nmr (CDCl ): δ 1.31 (3H, t, J = 7.6 Hz, CH CH ),
126.2, 126.7, 127.1, 127.2, 127.6, 127.8, 127.9, 128.4, 129.0,
132.9, 133.3, 134.1, 139.1, 153.9, 168.9.
3
2
3
2.98 (2H, q, J = 7.6 Hz, CH CH ), 3.16 (1H, dd, J = 8.1, 17.7 Hz, 4-
2
3

114
A. Lévai and J. Jekő
Vol. 43
H
), 3.93 (1H, dd, J = 11.8, 17.7 Hz, 4-H ), 6.36 (1H, dd, J =
2.94 (2H, q, J = 7.5 Hz, CH CH ), 3.18 (1H, dd, J = 5.2, 17.8 Hz,
2 3
trans
cis
13
8.1, 11.8 Hz, 5-H), 7.19-8.06 (m, 12 arom. H); C nmr (CDCl ): δ
8.9, 27.5, 41.8, 57.4, 112.4, 121.7, 123.0, 125.7, 125.8, 126.4,
126.7, 128.2, 128.8, 129.3, 130.4, 131.7, 134.5, 136.6, 154.4, 172.7.
4-H
), 3.95 (1H, dd, J = 11.9, 17.8 Hz, 4-H ), 5.92 (1H, dd, J
3
trans
cis
13
= 5.2, 11.9 Hz, 5-H), 7.04-8.09 (m, 10 arom. H); C nmr
(CDCl ): δ 8.8, 27.4, 40.8, 57.4, 123.3, 126.9, 127.2, 127.3,
3
Anal. Calcd. for C
H
N O: C, 80.46; H, 6.14; N, 8.53.
127.8, 128.0, 128.5, 128.7, 128.9, 129.0, 129.9, 133.1, 134.3,
137.7, 154.1, 172.7.
22 20
2
Found: C, 80.57; H, 6.18; N, 8.61.
Anal. Calcd. for C
Found: C, 66.60; H, 5.52; N, 7.12.
H Cl N O: C, 66.51; H, 4.57; N, 7.05.
22 18 2 2
5-(2-Naphthyl)-3-phenyl-1-propionyl-2-pyrazoline (30).
This material was isolated as white plates in 86% yield, mp
1,3-Diphenyl-5-(2-naphthyl)-2-pyrazoline (35).
This compound was prepared as pale yellow needles in 83%
1
133-134°; H nmr (CDCl ): δ 1.21 (3H, t, J = 7.4 Hz, CH CH ),
3
2
3
2.83 (2H, q, J = 7.4 Hz, CH CH ), 3.21 (1H, dd, J = 4.8, 17.8 Hz,
2
3
1
4-H
), 3.80 (1H, dd, J = 11.8, 17.8 Hz, 4-H ), 5.72 (1H, dd, J
yield, mp 145-146°; H nmr (CDCl ): δ 3.22 (1H, dd, J = 7.4,
trans
cis
3
13
= 4.8, 11.8 Hz, 5-H), 7.28-7.84 (m, 12 arom. H); C nmr
17.2 Hz, 4-H
), 3.95 (1H, dd, J = 12.6, 17.2 Hz,
4-H ),
trans
cis
(CDCl ): δ 8.8, 27.5, 42.0, 60.2, 123.6, 124.7, 126.0, 126.3,
5.42 (1H, dd, J = 7.4, 12.6 Hz, 5-H), 6.79-7.86 (m, 17 arom. H);
3
13
126.7, 127.8, 128.1, 129.1, 130.4, 131.7, 133.1, 133.5, 139.5,
153.7, 172.6.
C nmr (CDCl ): δ 43.5, 64.8, 112.4, 113.6, 119.3, 123.9, 124.8,
3
125.9, 126.1, 126.5, 127.9, 128.0, 128.7, 128.8, 129.0, 129.5,
132.9, 133.1, 133.7, 140.2, 145.2, 147.0.
Anal. Calcd. for C
H N O: C, 80.46; H, 6.14; N, 8.53.
22 20 2
Found: C, 80.38; H, 6.09; N, 8.47.
Anal. Calcd. for C H N : C, 86.18; H, 5.78; N, 8.04. Found:
25 20 2
C, 86.29; H, 5.84; N, 8.13.
3-(2-Naphthyl)-5-phenyl-1-propionyl-2-pyrazoline (31).
This compound was obtained as white plates in 81% yield, mp
1,5-Diphenyl-3-(2-naphthyl)-2-pyrazoline (36).
1
144-145°; H nmr (CDCl ): δ 1.29 (3H, t, J = 7.5 Hz, CH CH ),
This substance was obtained as yellow plates in 90% yield, mp
3
2
3
1
2.90 (2H, q, J = 7.5 Hz, CH CH ), 3.30 (1H, dd, J = 4.8, 17.0 Hz,
225-226°; H nmr (CDCl ): δ 3.23 (1H, dd, J = 7.2, 17.1 Hz, 4-
trans
2
3
3
4-H
), 3.84 (1H, dd, J = 11.9, 17.0 Hz, 4-H ), 5.65 (1H, dd, J
H
), 3.92 (1H, dd, J = 12.6, 17.1 Hz, 4-H ), 5.31 (1H, dd, J =
trans
cis
cis
13
13
= 4.8, 11.9 Hz, 5-H), 7.21-8.09 (m, 12 arom. H); C nmr
7.2, 12.6 Hz, 5-H), 6.75-8.18 (m, 17 arom. H); C nmr (CDCl ):
3
(CDCl ): δ 8.8, 27.5, 41.9, 60.2, 123.4, 125.7, 126.9, 127.1,
δ 43.5, 64.6, 113.4, 119.2, 123.5, 125.0, 126.3, 126.4, 127.6,
127.8, 128.1, 128.9, 129.2, 130.4, 133.3, 133.4, 142.6, 144.7,
146.8.
3
127.3, 127.7, 128.0, 128.5, 128.6, 129.0, 129.3, 133.2, 134.3,
142.3, 153.8, 172.6.
Anal. Calcd. for C
H
N O: C, 80.46; H, 6.14; N, 8.53.
Anal. Calcd. for C H N : C, 86.18; H, 5.78; N, 8.04. Found:
22 20
2
25 20 2
Found: C, 80.53; H, 6.18; N, 8.63.
C, 86.08; H, 5.71, N, 7.93.
5-(3,4-Methylenedioxyphenyl)-3-(2-naphthyl)-1-propionyl-2-
5-(4-Methoxyphenyl)-3-(2-naphthyl)-1-phenyl-2-pyrazoline
pyrazoline (32).
(37).
This substance was prepared as white plates in 74% yield, mp
This compound was prepared as yellow plates in 77% yield,
1
1
143-144°; H nmr (CDCl ): δ 1.26 (3H, t, J = 7.5 Hz, CH CH ),
mp 176-177°; H nmr (CDCl ): δ 3.11 (1H, dd, J = 6.9, 17.1 Hz,
3
2
3
3
2.89 (2H, q, J = 7.5 Hz, CH CH ), 3.27 (1H, dd, J = 4.7, 17.6 Hz,
4-H
), 3.69 (3H, s, MeO), 3.74 (1H, dd, J = 12.3, 17.1 Hz, 4-
2
3
trans
4-H
), 3.82 (1H, dd, J = 11.8, 17.6 Hz, 4-H ), 5.53 (1H, dd, J
H
), 5.15 (1H, dd, J = 6.9, 12.3 Hz, 5-H), 6.70-8.10 (m, 16
trans
cis
cis
13
= 4.7, 11.8 Hz, 5-H), 5.91 (2H, s, CH ), 6.73-8.11 (m, 10 arom.
arom. H); C nmr (CDCl ): δ 43.4, 55.2, 64.0, 113.6, 114.6,
123.6, 124.8, 125.1, 126.1, 126.5, 127.2, 127.8, 128.2, 128.4,
129.0, 129.1, 130.2, 133.6, 134.8, 144.9, 146.9, 159.2.
2
3
13
H); C nmr (CDCl ): δ 8.7, 27.5, 41.9, 59.9, 101.1, 106.1, 108.6,
3
119.2, 123.4, 126.9, 127.1, 127.3, 127.9, 128.5, 128.6, 129.3,
133.1, 134.3, 136.3, 147.2, 148.3, 153.7, 172.6.
Anal. Calcd. for C
H N O: C, 82.51; H, 5.86; N, 7.39.
26 22 2
Anal. Calcd. for C
H
N O : C, 74.18; H, 5.41; N, 7.52.
Found: C, 82.62; H, 5.91; N, 7.28.
23 20
2 3
Found: C, 74.28; H, 5.46; N, 7.60.
5-(3,4-Methylenedioxyphenyl)-3-(2-naphthyl)-1-phenyl-2-pyra-
5-(4-Chlorophenyl)-3-(2-naphthyl)-1-propionyl-2-pyrazoline
zoline (38).
(33).
This material was prepared as yellow needles in 82% yield, mp
1
This compound was prepared as white needles in 82% yield,
192-193°; H nmr (CDCl ): δ 3.24 (1H, dd, J = 7.1, 17.1 Hz, 4-
3
1
mp 192-193°; H nmr (CDCl ): δ 1.23 (3H, t, J = 7.5 Hz,
H
), 3.92 (1H, dd, J = 12.7, 17.1 Hz, 4-H ), 5.25 (1H, dd, J =
3
trans cis
CH CH ), 2.89 (2H, q, J = 7.5 Hz, CH CH ), 3.39 (1H, dd, J =
7.1, 12.7 Hz, 5-H), 5.92 (2H, s, CH ), 6.81-8.20 (m, 15 arom. H);
2
3
2
3
2
13
4.9, 17.7 Hz, 4-H
), 3.90 (1H, dd, J = 11.9, 17.7 Hz, 4-H ),
C nmr (CDCl ): δ 21.3, 44.2, 63.7, 116.4, 116.7, 120.5, 121.5,
trans
cis
3
5.60 (1H, dd, J = 4.9, 11.9 Hz, 5-H), 7.19-8.10 (m, 11 arom. H);
123.8, 123.9, 124.4, 128.7, 134.4, 134.5, 138.7, 139.4, 140.3,
140.7, 141.7, 143.6, 144.3, 145.1, 145.7, 148.6.
13
C nmr (CDCl ): δ 8.7, 27.4, 41.8, 59.6, 123.4, 126.9, 127.2,
3
127.3, 128.0, 128.5, 128.7, 129.1, 129.2, 133.1, 133.6, 134.6,
134.3, 140.8, 153.7, 172.6.
Anal. Calcd. for C H N O : C, 79.57; H, 5.14; N, 7.13.
26 20 2 2
Found: C, 79.44; H, 5.18; N, 7.22.
Anal. Calcd. for C
Found: C, 72.91, H, 5.33; N, 7.81.
H ClN O: C, 72.82; H, 5.28; N, 7.72.
22 19 2
5-(4-Chlorophenyl)-3-(2-naphthyl)-1-phenyl-2-pyrazoline (39).
This substance was obtained as pale yellow needles in 74%
5-(2,4-Dichlorophenyl)-3-(2-naphthyl)-1-propionyl-2-pyrazoline
(34).
1
yield, mp 160-161°; H nmr (CDCl ): δ 3.23 (1H, dd, J = 7.1,
3
17.0 Hz, 4-H
), 3.97 (1H, dd, J = 12.3, 17.0 Hz,
4-H ),
trans
cis
This substance was isolated as white needles in 71% yield, mp
5.80 (1H, dd, J = 7.1, 12.3 Hz, 5-H), 6.79-8.20 (m, 16 arom. H);
1
13
195-196°; H nmr (CDCl ): δ 1.29 (3H, t, J = 7.5 Hz, CH CH ),
C nmr (CDCl ): δ 43.4, 63.9, 113.5, 119.4, 123.4, 125.1, 125.4,
3
2
3
3

Jan-Feb 2006
Synthesis of 1-Substituted 3,5-Diaryl-2-pyrazolines
115
[13] N. Mishriky, Y. A. Ibrahim, A. S. Girgis and N. G. Fawzy,
Pharmazie, 54, 738 (1999).
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Befani, P. Turini, B. Mondovi, S. Alcaro and A. Tafi, Bioorg. Med. Chem.
Lett., 12, 3629 (2002).
126.5, 127.3, 127.8, 128.1, 128.2, 128.8, 129.0, 129.4, 129.9,
130.2, 133.3, 133.5, 141.0, 144.5, 146.8.
Anal. Calcd. for C
H ClN : C, 78.42; H, 5.01; N, 7.31.
25 19 2
Found: C, 78.53; H, 5.06; N, 7.42.
3,5-Di(2-naphthyl)-1-phenyl-2-pyrazoline (40).
This compound was prepared as yellow plates in 81% yield,
[15] R. H. Wiley, C. H. Jarboe, F. N. Hayes, E. Hansbury, J. T.
Nielsen, P. X. Callahan and M. Sellars, J. Org. Chem., 23, 732 (1958).
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(1909).
1
mp 205-206°; H nmr (CDCl ): δ 3.34 (1H, dd, J = 7.4, 17.1 Hz,
3
4-H
), 4.04 (1H, dd, J = 11.3, 17.1, 4-H ), 5.50 (1H, dd, J =
trans
cis
13
7.4, 11.3 Hz, 5-H), 6.81-8.20 (m, 19 arom. H); C nmr (CDCl ):
3
δ 43.5, 64.9, 113.5, 119.3, 122.2, 123.5, 123.8, 124.7, 125.1,
125.9, 126.4, 126.8, 127.8, 128.1, 128.2, 128.9, 129.4, 130.4,
132.9, 133.3, 133.4, 133.5, 140.0, 144.8, 146.9.
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(1933).
[19] L. C. Raiford and W. J. Peterson, J. Org. Chem., 1, 544
(1936).
Anal. Calcd. for C
H N : C, 87.41; H, 5.56; N, 7.03. Found:
29 22 2
[20] L. C. Raiford and G. V. Gundy, J. Org. Chem., 3, 265 (1938).
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Chem., 100, 1924 (1969).
C, 87.52; H, 5.61; N, 7.12.
Acknowledgements.
The present study was sponsored by the Hungarian Scientific
Research Fund (Grant No. OTKA T049468) for which our grati-
tude is expressed. Thechnical assistance of Mrs. M. Nagy is
highly appreciated.
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