Synthesis of 1-substituted 5-aryl-3-(3-coumarinyl)-2-pyrazolines by the reaction of 3-aryl-1-(3-coumarinyl)propen-1-ones with hydrazines

Article abstract of DOI:10.1002/jhet.5570420633

1-Acetyl- and 1-propionyl-2-pyrazolines 11-27 have been synthesized by the reaction of (3-coumarinyl)chalcones 1-10 with hydrazine in hot acetic acid or propionic acid. While 5-aryl-3-(3-coumarinyl)-1-phenyl-2-pyrazolines 28-35 have been prepared by the r

Full text of DOI:10.1002/jhet.5570420633

Sep-Oct 2005
1231
Synthesis of 1-Substituted 5-Aryl-3-(3-coumarinyl)-2-pyrazolines
by the Reaction of 3-Aryl-1-(3-coumarinyl)propen-1-ones
with Hydrazines
Albert Lévai [a],* József Jekő [b] and D. I. Brahmbhatt [c]
[a] Department of Organic Chemistry, University of Debrecen, P.O.Box 20, H-4010 Debrecen, Hungary
[b] ICN Hungary Co. Ltd., H-4440 Tiszavasvári, Hungary
[c] Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388 120, Gujarat, India
Received April 4, 2005
th
Dedicated to Professor Dr. Fritz Sauter on the occasion of his 75 birthday
1-Acetyl- and 1-propionyl-2-pyrazolines 11-27 have been synthesized by the reaction of (3-
coumarinyl)chalcones 1-10 with hydrazine in hot acetic acid or propionic acid. While 5-aryl-3-(3-
coumarinyl)-1-phenyl-2-pyrazolines 28-35 have been prepared by the reaction of (3-coumarinyl)chalcones
1,3,5-10 with phenylhydrazine in hot pyridine. Structures of all new compounds have been elucidated by
1
13
microanalyses, H and C nmr spectroscopies.
J. Heterocyclic Chem., 42, 1231 (2005).
Introduction.
Results and Discussion.
As described in the introduction, both the coumarins and
the 2-pyrazolines possess important bioactivities which
render them useful substances in drug research. On this
basis, it appeared expedient to synthesize new heterocyclic
compounds bearing both a coumarinyl moiety and a 2-
pyrazoline unit. Reaction of (3-coumarinyl)chalcones, as
easily available α,β-unsaturated ketones, with hydrazines
seemed to be a convenient route to fulfil this aim.
3-Aryl-1-(3-coumarinyl)propen-1-ones 1-10 were
allowed to react with hydrazine hydrate in hot acetic acid
or propionic acid to afford 1-acetyl-2-pyrazolines 11-20
and 1-propionyl-2-pyrazolines 21-27 in good yields (67-
80%) (Scheme 1). Substitution pattern of the aromatic ring
was almost without influence either on the course of the
reaction or on the yields of the isolated products. It is
worth mentioning that only one reaction product, viz. the
1-acylated-2-pyrazoline was detected or isolated under
these reaction conditions. This outcome of the reaction is
advantageous since the 1-acylated-2-pyrazolines are stable
compounds, which can be used for biological trials without
the risk of unwanted decompositions.
Coumarins are natural oxygen heterocyclic compounds
found in various plants [1-3]. Because of their well known
bioactivities, viz. antibacterial and antifungal [4], anticoag-
ulant [5,6], etc. activities, natural, semisynthetic and syn-
thetic coumarins possess a prominent place in drug
research. Their utility stimulated the development of new
synthetic procedures for the preparation of coumarin type
substances. Some of these compounds can be used as use-
ful intermediates for the synthesis of valuable heterocyclic
ring systems. Among others, the 3-cinnamoyl coumarins
synthesized by the reaction of 3-acetyl coumarins with
aromatic aldehydes [6-12] proved to be especially impor-
tant. 3-Cinnamoyl coumarins have been used for the syn-
thesis of pyridines [6], isoxazolines [12], 1,5-benzodi-
azepines [13] and 1,5-benzothiazepines [14,15] and other
nitrogen-containing heterocyclic compounds.
Pyrazolines are important nitrogen-containing five-
membered heterocyclic compounds. Several pyrazoline
derivatives were found to show considerable biological
activities, e.g. antimicrobial [16], central nervous sys-
tem [17] and immunosuppressive [18] activities. 2-
Pyrazolines became the most frequently studied pyrazo-
line type compounds and various methods have been
worked out for their synthesis [19-21]. Since the mile-
stone work of Fischer and Knövenagel published in the
late nineteenth century [22], the reaction of α,β-unsatu-
rated aldehydes and ketones with hydrazines became a
generally used simple and convenient procedure for the
preparation of 2-pyrazolines [23-42]. As a consequence,
numerous substituted 2-pyrazolines have been synthe-
sized for various purposes. To continue our previous
studies in this field [31-33,37,38,40-42], herein we
describe the synthesis of 1-substituted 5-aryl-3-(3-
coumarinyl)-2-pyrazolines by the reaction of (3-
coumarinyl)-chalcones and hydrazines.

1232
A. Lévai, J. Jekő and D. I. Brahmbhatt
Vol. 42
Elemental analyses were measured in-house with a Carlo Erba
instrument, model 1106 EA. The tlc was performed on Kieselgel
The reaction of (3-coumarinyl)chalcones with phenyl-
hydrazine was carried out in hot acetic acid, leading to
multicomponent reaction mixtures as shown by tlc moni-
toring. We have not tried to separate the products detected
by tlc in the crude reaction mixtures. To overcome this dif-
ficulty, 3-aryl-1-(3-coumarinyl)propen-1-ones 1,3,5-10
were allowed to react with phenylhydrazine in hot pyridine
as was the case with other α,β-unsaturated ketones
[31,37,38,41] and 5-aryl-3-(3-coumarinyl)-1-phenyl-2-
pyrazolines 28-35 (Scheme 2) were obtained as sole
isolable products in good yields (68-74%).
60 F
(Merck) layer using toluene:ethyl acetate (4:1 v/v) or
254
hexane:acetone (7:3 v/v) as eluents. Starting materials 1-10 were
synthesized according to known procedures [6-12].
General Procedure for the Preparation of 1-Acetyl- (11-20) and 1-
Propionyl-2-pyrazolines (21-27).
A mixture of (3-coumarinyl)chalcones (1-10 or 1,3,4,7-10, 5.0
mmoles), hydrazine hydrate (15.0 mmoles), acetic acid (25 ml) or
propionic acid (25 ml) was refluxed for 3 hours, then poured into
water. The precipitate was separated by filtration, washed with
water and crystallized from methanol to obtain 2-pyrazolines 11-
27 (Scheme 1).
1-Acetyl-3-(3-coumarinyl)-5-phenyl-2-pyrazoline (11).
This compound was obtained as white needles in 68% yield,
1
mp 225-226°; H nmr (CDCl ): δ 2.43 (s, 3H, Me), 3.40 (dd, 1H,
3
J = 4.8, 19.0 Hz, 4-H
), 3.96 (dd, 1H, J = 11.9, 19.0 Hz, 4-
trans
H
), 5.59 (dd, 1H, J = 4.8, 11.9 Hz, 5-H), 7.17-7.64 (m, 9 arom.
cis
13
H), 8.45 (s, 1H, 4'-H); C nmr (CDCl ): δ 21.8, 44.2, 60.3,
116.7, 118.9, 119.8, 125.0, 125.6, 127.8, 128.8, 128.9, 132.9,
140.9, 141.6, 150.8, 154.3, 169.1.
3
Anal. Calcd. for C H N O : C, 72.28; H, 4.85; N, 8.42.
20 16
2 3
Found: C, 72.41; H, 4.89; N, 8.46.
1-Acetyl-3-(3-coumarinyl)-5-(3-methylphenyl)-2-pyrazoline
(12).
Structures of all new 1-substituted 2-pyrazolines 11-35
This material was prepared as pale yellow needles in 72%
yield, mp 191-192°; H nmr (CDCl ): δ 2.32 (s, 3H, Me), 2.43 (s,
3H, Me), 3.40 (dd, 1H, J = 4.8, 19.0 Hz, 4-H
= 12.0, 19.0 Hz, 4-H ), 5.56 (dd, 1H, J = 4.8, 12.0 Hz, 5-H),
6.98-7.63 (m. 8 arom. H), 8.43 (s, 1H- 4'-H); C nmr (CDCl ): δ
21.4, 21.9, 44.3, 60.4, 116.6, 118.8, 119.8, 122.4, 124.9, 126.1,
128.4, 128.7, 132.7, 138.5, 140.7, 141.5, 150.7, 154.1, 168.8.
Anal. Calcd. for C H N O : C, 72.82; H, 5.24; N, 8.08.
1
13
have been elucidated by elemental analyses, H and
C
1
3
1
nmr spectroscopic measurements. In the H nmr spectra of
substances 11-35, the three protons attached to the C-4 and
C-5 carbon atoms of the 2-pyrazoline unit gave an ABX
spin system. Both the chemical shifts and the coupling
constant values (cf. Experimental) unequivocally prove the
), 3.97 (dd, 1H, J
trans
cis
13
3
1
2-pyrazoline structure. In the H nmr spectra of the 1-
21 18
2 3
Found: C, 72.91; H, 5.28; N, 8.15.
acetyl-2-pyrazolines 11-20 a singlet signal between 2.4
and 2.5 ppm refers to an N-acetyl group. While the triplet
and the quartet signals of an N-propionyl moiety were
1-Acetyl-3-(3-coumarinyl)-5-(4-methylphenyl)-2-pyrazoline
(13).
1
assigned in the H nmr spectra of 1-propionyl-2-pyrazo-
This substance was obtained as pale yellow needles in 67%
yield, mp 200-201°; H nmr (CDCl ): δ 2.30 (s, 3H, Me), 2.43 (s,
3H, Me), 3.40 (dd, 1H, J = 4.7, 18.0 Hz, 4-H
13
1
lines 21-27. In the C nmr spectra of compounds 11-35,
3
the chemical shifts of carbon atoms C-3 (153-154 ppm), C-
), 3.95 (dd, 1H, J
trans
= 12.0, 18.0 Hz, 4-H ), 5.56 (dd, 1H, J = 4.7, 12.0 Hz, 5-H),
4 (43-45 ppm) and C-5 (59-64 ppm) corroborate the 2-
cis
13
1
13
7.12-7.63 (m, 8 arom. H), 8.43 (s, 1H, 4'-H); C nmr (CDCl ): δ
pyrazoline structure deduced from the H nmr data.
C
3
20.9, 21.8, 44.1, 60.2, 116.7, 118.9, 119.9, 125.1, 125.6, 128.9,
129.6, 132.9, 137.5, 138.8, 140.9, 150.8, 154.3, 160.1.
nmr chemical shift values of the N-acetyl and N-propionyl
13
groups have also been observed in the C nmr spectra of
Anal. Calcd. for C H N O : C, 72.82; H, 5.24; N, 8.08.
21 18
2 3
compounds 11-20 and 21-27 (cf. Experimental).
Found: C, 72.74; H, 5.19; N, 8.14.
In conclusion, we have synthesized new 1-substituted 5-
aryl-3-(3-coumarinyl)-2-pyrazolines by the reaction of (3-
coumarinyl)chalcones and hydrazines under simple and
convenient reaction conditions. These new heterocyclic
compounds may be beneficially used in drug reserach.
1-Acetyl-3-(3-coumarinyl)-5-(4-isopropylphenyl)-2-pyrazoline
(14).
This compound was isolated as white needles in 74% yield, mp
1
238-239°; H nmr (CDCl ): δ 1.22 (d, 6H, J = 6.9 Hz,
3
CH(CH ) ), 2.42 (s, 3H, Me), 2.85 (m, 1H, CH(CH ) ), 3.41 (dd,
3 2
3 2
1H, 4.6, 18.8 Hz, 4-H
), 3.98 (dd, 1H, J = 11.7, 18.8 Hz, 4-
trans
EXPERIMENTAL
H
), 5.59 (dd, 1H, J = 4.6, 11.7 Hz, 5-H), 7.16-7.62 (m, 8 arom.
cis
13
H), 8.44 (s, 1H, 4'-H); C nmr (CDCl ): δ 21.8, 23.7, 33.6, 44.1,
3
Melting points were determined with a Koffler hot-stage appa-
60.1, 116.8, 118.9, 125.1, 125.4, 125.6, 127.0, 128.9, 132.9,
138.9, 140.9, 148.4, 151.0, 154.4, 169.1.
1
13
ratus and are uncorrected. H and C nmr spectra were recorded
on a Varian Gemini 200 spectrometer at 200/50 MHz in CDCl
Anal. Calcd. for C H N O : C, 73.78; H, 5.92; N, 7.48.
3
23 22
2 3
(internal standard TMS, δ = 0.0 ppm) at ambient temperature.
Found: C, 73.90; H, 5.87; N, 7.54.

Sep-Oct 2005
Synthesis of 1-Substituted 5-Aryl-3-(3-coumarinyl)-2-pyrazolines
1233
1-Acetyl-3-(3-coumarinyl)-5-(2-methoxyphenyl)-2-pyrazoline
(15).
H
), 5.52 (dd, 1H, J = 4.7, 11.7 Hz, 5-H), 7.08-7.67 (m, 8 arom.
cis
13
H), 8.42 (s, 1H, 4'-H); C nmr (CDCl ): δ 21.7, 44.0, 59.9,
116.8, 118.9, 119.7, 121.7, 125.1, 125.4, 127.6, 128.9, 132.1,
132.7, 133.1, 1407, 141.2, 150.8, 154.4, 168.1.
3
This substance was prepared as pale yellow plates in 71% yield,
1
mp 118-119°; H nmr (CDCl ): δ 2.48 (s, 3H, Me), 3.25 (dd, 1H, J
3
Anal. Calcd. for C H BrN O : C, 58.41; H, 3.68; N, 6.81.
20 15
2 3
= 4.7, 18.9 Hz, 4-H
), 3.84 (s, 3H, MeO), 3.95 (dd, 1H, J =
trans
Found: C, 58.47; H, 3.74; N, 6.86.
11.6, 18.9 Hz, 4-H ), 5.82 (dd, 1H, J = 4.7, 11.6 Hz, 5-H), 6.96-
cis
13
7.62 (m, 8 arom. H), 8.41 (s, 1H- 4'-H); C nmr (CDCl ): δ 21.8,
43.3, 55.3, 56.4, 111.0, 116.7, 119.0, 120.2, 125.0, 125.7, 128.8,
128.9, 129.0, 132.8, 140.7, 151.7, 154.3, 156.3, 169.1.
3-(3-Coumarinyl)-5-phenyl-1-propionyl-2-pyrazoline (21).
3
This compound was obtained as pale yellow needles in 80%
1
yield, mp 221-222°; H nmr (CDCl ): δ 1.27 (t, 3H, J = 7.5 Hz,
CH CH ), 2.89 (dd, 2H, J = 7.5, 15.0 Hz, CH CH ), 3.42 (dd,
1H, J = 4.9, 18.0 Hz, 4-H
3
Anal. Calcd. for C H N O : C, 69.60; H, 5.01; N, 7.73.
21 18
2 4
2
3
2
3
Found: C, 69.71; H, 4.97; N, 7.76.
), 3.98 (dd, 1H, J = 8.1, 18.0 Hz, 4-
trans
1-Acetyl-3-(3-coumarinyl)-5-(3-methoxyphenyl)-2-pyrazoline (16).
This material was obtained as pale yellow plates in 74% yield,
H
), 5.59 (dd, 1H, J = 4.9, 8.1 Hz, 5-H), 7.21-8.17 (m, 9 arom.
cis
13
H), 8.48 (s, 1H, 4'-H); C nmr (CDCl ): δ 8.9, 27.6, 44.1, 60.6,
112.8, 116.7, 117.8, 118.9, 123.6, 125.5, 127.6, 128.4, 128.8,
130.9, 132.5, 140.7, 141.7, 150.4, 154.2, 172.3.
3
1
mp 183-184°; H nmr (CDCl ): δ 2.34 (s, 3H, Me), 3.19 (dd, 1H,
3
J = 4.2, 18.5, 4-H
), 3.73 (s, 3H, MeO), 3.89 (dd, 1H, J = 11.8,
trans
Anal. Calcd. for C H N O : C, 72.82; H, 5.24; N, 8.08.
21 18
2 3
18.5 Hz, 4-H ), 5.51 (dd, 1H, J = 4.7, 11.8 Hz, 5-H), 6.73-7.87
cis
Found: C, 72.94; H, 5.29; N, 8.17.
13
(m, 8 arom. H), 8.60 (s, 1H, 4'-H); C nmr (CDCl ): δ 21.6, 43.8,
55.0, 59.3, 111.5, 112.5, 116.2, 117.5, 118.9, 119.3, 125.1, 129.5,
130.0, 133.2, 142.1, 144.1, 151.1, 153.7, 159.8, 167.9.
3
3-(3-Coumarinyl)-5-(4-methylphenyl)-1-propionyl-2-pyrazoline
(22).
Anal. Calcd. for C H N O : C, 69.60; 5.01; N, 7.73. Found:
21 18
2 4
This material was prepared as yellow needles in 68% yield, mp
C, 69.51; H, 5.06; N, 7.69.
1
183-184°; H nmr (CDCl ): δ 1.21 (t, 3H, J = 7.4 Hz, CH CH ),
2.29 (s, 3H, Me), 2.80 (dd, 2H, J = 7.4, 14.8 Hz, CH CH ), 3.40
3
2
3
1-Acetyl-3-(3-coumarinyl)-5-(4-methoxyphenyl)-2-pyrazoline (17).
2
3
(dd, 1H, J = 4.7, 18.9 Hz, 4-H
), 3.92 (dd, 1H, J = 12.0, 18.9
This compound was prepared as yellow needles in 69%, mp
trans
1
Hz, 4-H ), 5.54 (dd, 1H, J = 4.7, 12.0 Hz, 5-H), 7.08-7.60 (m, 8
199-200°; H nmr (CDCl ): δ 2.42 (s, 3H, Me), 3.41 (dd, 1H, J =
cis
3
13
arom. H), 8.39 ( s, 1H, 4'-H); C nmr (CDCl ): δ 8.9, 21.0, 27.5,
44.0, 60.4, 116.6, 118.8, 119.9, 125.5, 128.7, 132.7, 138.8, 140.6,
150.4, 154.1, 159.1, 172.2.
4.8, 19.0 Hz, 4-H
), 3.78 (3, 3H, MeO), 3.94 (dd, 1H, J = 11.9,
3
trans
19.0 Hz, 4-H ), 5.54 (dd, 1H, J = 4.8, 11.9 Hz, 5-H), 6.83-7.62
cis
13
(m, 8 arom. H), 8.45 (s, 1H, 4'-H); C nmr (CDCl ): δ 21.8, 44.1,
55.2, 59.9, 114.3, 116.8, 118.9, 120.0, 125.1, 126.9, 127.1, 128.9,
132.9, 133.9, 140.9, 150.9, 154.4, 159.3, 169.1.
3
Anal. Calcd. for C H N O : C, 73.32; H, 5.59; N, 7.77.
22 20
2 3
Found: C, 73.46; H, 5.64; N, 7.68.
Anal. Calcd. for C H N O : C, 69.60; H, 5.01; N, 7.73.
Found: C, 69.68; H, 5.06; N, 7.68.
21 18
2 4
3-(3-Coumarinyl)-5-(4-isopropylphenyl)-1-propionyl-2-pyrazo-
line (23).
1-Acetyl-3-(3-coumarinyl)-5-(4-fluorophenyl)-2-pyrazoline
(18).
This substance was isolated as pale yellow plates in 67% yied,
1
mp 137-138°; H nmr (CDCl ): δ 1.23 (m, 9H, CH CH ,
3
2
3
CH(CH ) ), 2.85 (m, 3H, CH CH , CH(CH ) ), 3.40 (dd, 1H, J =
This compound was prepared as yellow needles in 76% yield,
3 2
2
3
3 2
1
4.7, 18.9 Hz, 4-H
), 3.93 (dd, 1H, J = 11.9, 18.9 Hz, 4-H ),
mp 193-194°; H nmr (CDCl ): δ 2.43 (s, 3H, Me), 3.41 (dd, 1H,
trans
cis
3
5.57 (dd, 1H, J = 4.7, 11.9 Hz, 5-H), 7.12-7.60 (m, 8 arom. H),
J = 4.9, 19.0 Hz, 4-H
), 3.97 (dd, 1H, J = 13.9, 19.0 Hz, 4-
trans
13
8.41 (s, 1H, 4'-H); C nmr (CDCl ): δ 8.9, 23.9, 27.6, 33,7, 44.0,
H
), 5.60 (dd, 1H, J = 4.9, 13.9 Hz, 5-H), 6.97-7.67 (m, 8 arom.
3
cis
13
60.3, 116.6, 118.9, 124.9, 125.5, 126.9, 128.7, 139,0, 140.6,
148.1, 150.5, 154.1, 159.1, 172.3.
H), 8.47 (s, 1H, 4'-H); C nmr (CDCl ): δ 21.9, 44.2, 59.8,
115.4, 116.7, 118.8, 119.6, 124.9, 127.3, 128.8, 132.9, 137.3,
140.9, 150.6, 154.1, 168.8.
3
Anal. Calcd. for C H N O : C, 74.21; H, 6.23; N, 7.21.
24 24
2 3
Found: C, 74.13; H, 6.27; N, 7.34.
Anal. Calcd. for C H FN O : C, 68.56; H, 4.32; N, 7.99.
20 15
2 3
Found: C, 68.64; H, 4.35; N, 8.06.
3-(3-Coumarinyl)-5-(4-methoxyphenyl)-1-propionyl-2-pyrazo-
line (24).
1-Acetyl-5-(4-chlorophenyl)-3-(3-coumarinyl)-2-pyrazoline (19).
This substance was isolated as yellow needles in 74% yield,
This compound was prepared as yellow needles in 71% yield,
mp 184-185°; H nmr (CDCl ): δ 1.21 (t, 3H, J 7.5 Hz, CH CH ),
2.81 (dd, 2H, J = 7.5, 15.0 Hz, CH CH ), 3.41 (dd, 1H, J = 4.7,
1
1
mp 208-209°; H nmr (CDCl ): δ 2.42 (s, 3H, Me), 3.38 (dd, 1H,
3
2
3
3
J = 5.1, 18.9 Hz, 4-H
), 3.96 (dd, 1H, J = 12.1, 18.9 Hz, 4-
2
3
trans
19.0 Hz, 4-H
), 3.79 (dd, 1H, J = 12.0, 19.0 Hz, 4-H ), 5.54
H
), 5.54 (dd, 1H, J = 5.1, 12.1 Hz, 5-H), 7.12-7.63 (m, 8 arom.
trans
cis
cis
13
(dd, 1H, J = 4.7, 12.0 Hz, 5-H), 6.82-7.61 (m, 8 arom. H), 8.39 (s,
H), 8.44 (s, 1H, 4'-H); C nmr (CDCl ): δ 21.7, 44.0, 59.8,
116.7, 118.8, 119.6, 125.1, 127.2, 128.9, 129.1, 133.0, 133.6,
140.1, 141.1, 150.8, 154.5, 159.4, 169.1.
3
13
1H, 4'-H); C nmr (CDCl ): δ 8.9, 27.6, 43.9, 55.3, 60.1, 114.3,
3
116.7, 124.9, 126.9, 128.7, 132.7, 140.6, 150.6, 054.4, 172.4.
Anal. Calcd. for C H N O : C, 70.20; H, 5.36; N, 7.44.
Anal. Calcd. for C H Cl N O : C, 65.49; H, 4.12; N, 7.63.
22 20
2 4
20 15
2 3
Found: C, 70.32; H, 5.31; N, 7.55.
Found: C, 65.58; H, 4.16; N, 7.67.
1-Acetyl-5-(4-bromophenyl)-3-(3-coumarinyl)-2-pyrazoline (20).
3-(3-Coumarinyl)-5-(4-fluorophenyl)-1-propionyl-2-pyrazoline
(25).
This compound was obtained as yellow plates in 74% yield,
1
mp 227-228°; H nmr (CDCl ): δ 2.41 (s, 3H, Me), 3.39 (dd, 1H,
This substance was obtained as yellow plates in 69% yield, mp
161-162°; H nmr (CDCl ): δ 1.23 (t, 3H, J = 7.5 Hz, CH CH ),
3
1
J = 4.7, 18.8 Hz, 4-H
), 3.96 (dd, 1H, J = 11.7, 18.8 Hz, 4-
trans
3
2
3

1234
A. Lévai, J. Jekő and D. I. Brahmbhatt
Vol. 42
2.87 (dd, 2H, J = 7.5, 15.0, CH CH ), 3.41 (dd, 1H, J = 4.9, 19.0
109.1, 113.7, 116.5, 119.8, 124.7, 125.5, 125.7, 127.9, 128.3,
128.7, 129.1, 129.8, 131.5, 137.5, 17.8, 138.1, 153.6.
2
3
Hz, 4-H
), 3.98 (dd, 1H, J = 12.0, 19.0 Hz, 4-H ), 5.57 (dd,
trans
cis
1H, 4.9, 12.0 Hz, 5-H), 7.02-7.61 (m, 8 arom. H), 8.45 (s, 1H, 4'-
Anal. Calcd. for C H N O : C, 78.93; H, 5.29; N, 7.36.
Found: C, 78.82; H, 5.35; N, 7.47.
25 20 2 2
13
H); C nmr (CDCl ): δ 8.8, 27.5, 43.9, 59.9, 115.9, 116.8, 118.8,
3
119.7, 124.9, 127.3, 127.5, 128.7, 132.8, 137.5, 140.8, 150.3,
154.1, 159.1, 172.3.
3-(3-Coumarinyl)-5-(2-methoxyphenyl)-1-phenyl-2-pyrazoline
(30).
Anal. Calcd. for C H FN O : C, 69.22; H, 4.70; N, 7.68.
21 17
2 3
This compound was prepared as yellow needles in 69% yield,
Found: C, 69.34; H, 4.65; N, 7.76.
1
mp 181-182°; H nmr (CDCl ): δ 3.29 (dd, 1H, J = 6.7, 18.4 Hz,
3
5-(4-Chlorophenyl)-3-(3-coumarinyl)-1-propionyl-2-pyrazoline
(26).
4-H
), 3.92 (s, 3H, MeO), 4.11 (dd, 1H, J = 12.6, 18.4 Hz, 4-
trans
H
), 5.70 (dd, 1H, 6.7, 12.6 Hz, 5-H), 6.79-7.60 (m, 13 arom.
cis
13
This material was isolated as yellow needles in 72% yield, mp
H), 8.39 (s, 1H, 4'-H); C nmr (CDCl ): δ 29.7, 43.9, 59.1,
3
1
191-192°; H nmr (CDCl ): δ 1.21 (t, 3H, J = 7.5 Hz, CH CH ),
110.4, 111.2, 113.4, 116.4, 119.5, 120.7, 123.8, 124.5, 125.3,
126.3, 127.2, 128.2, 128.9, 130.6, 131.3, 137.3, 137.7, 141.2,
153.5.
3
2
3
2.82 (dd, 2H, J = 7.5, 15.0 Hz, CH CH ), 3.39 (dd, 1H, J = 5.1,
2
3
18.9 Hz, 4-H
), 3.98 (dd, 1H, J = 12.1, 18.9 Hz, 4-H ), 5.56
trans
cis
(dd, 1H, J = 5.1, 12.1 Hz, 5-H), 7.16-7.62 (m, 8 arom. H), 8.43 (s,
Anal. Calcd. for C H N O : C, 75.74; H, 5.08; N, 7.06.
Found: C, 75.63; H, 5.12; N, 6.98.
25 20 2 3
13
1H, 4'-H); C nmr (CDCl ): δ 8.9, 27.5, 43.9, 60.0, 116.7, 118.8,
3
119.7, 124.9, 127.1, 128.7, 129.0, 132.9, 133.4, 140.2, 150.3,
154.1, 159.2, 172.3.
3-(3-Coumarinyl)-5-(3-methoxyphenyl)-1-phenyl-2-pyrazoline
(31).
Anal. Calcd. for C H ClN O : C, 66.23; H, 4.50; N, 7.35.
21 17
2 3
This material was isolated as yellow plates in 68% yield, mp
Found: C, 66.31; H, 4.55; N, 7.26.
1
179-180°; H nmr (CDCl ): δ 3.40 (dd, 1H, J = 7.4, 18.4 Hz, 4-
trans
3
5-(4-Bromophenyl)-3-(3-coumarinyl)-1-propionyl-2-pyrazoline
(27).
H
H
), 3.78 ( s, 3H, MeO), 4.11 (dd, 1H, J = 12.7, 18.4 Hz, 4-
), 5.31 (dd, 1H, J = 7.4, 12.7 Hz, 5-H), 6.80-7.68 (m, 13
cis
13
This compound was prepared as yellow plates in 74% yield,
arom. H), 8.41 (s, 1H, 4'-H); C nmr (CDCl ): δ 45.2. 55.2, 64.9,
3
1
mp 217-218°; H nmr (CDCl ): δ 1.21 (t, 3H, J = 7.5 Hz,
111.4, 112.8, 113.7, 116.4, 117.9, 119.5, 120.8, 123.6, 124.7,
125.2, 128.2, 128.9, 130.2, 131.5, 137.5, 143.0, 143.7, 144.1.
153.6, 160.2.
3
CH CH ), 2.87 (dd, 2H, J = 7.5, 14.9 Hz, CH CH ), 3.40 (dd,
2
3
2
3
1H, J = 5.1, 19.0 Hz, 4-H
), 3.98 (dd, 1H, J = 12.1, 19.0 Hz, 4-
trans
H
), 5.52 (dd, 1H, J = 5.1, 12.1 Hz, 5-H), 7.12-7.63 (m, 8 arom.
Anal. Calcd. for C H N O : C, 75.74; H, 5.08; N, 7.06.
Found: 75.85; H, 5.02; N, 7.11.
cis
25 20 2 3
13
H), 8.46 (s, 1H, 4'-H); C nmr (CDCl ): δ 8.8, 27.5, 43.8, 60.0,
116.6, 118.8, 119.6, 121.5, 124.9, 128.7, 131.9, 132.8, 140.8,
150.3, 154.1, 159.1, 172.3.
3
3-(3-Coumarinyl)-5-(4-methoxyphenyl)-1-phenyl-2-pyrazoline
(32).
Anal. Calcd. for C H BrN O : C, 59.31; H, 4.03; N, 6.58.
21 17
2 3
This compound was prepared as yellow plates in 74% yield,
Found: C, 59.41; H, 4.07; N, 6.67.
1
mp 169-170°; H nmr (CDCl ): δ 3.36 (dd, 1H, J = 7.2, 18.4 Hz,
3
General Procedure for the Synthesis of 5-Aryl-3-(3-coumarinyl)-
1-phenyl-2-pyrazolines (28-35)
4-H
), 3.76 (s, 3H, MeO), 4.08 (dd, 1H, J = 12.6, 18.4 Hz, 4-
trans
H
), 5.30 (dd, 1H J = 7.2, 12.6, 5-H), 6.87-7.61 (m, 13 arom.
cis
13
A mixture of 3-(3-coumarinyl)chalcones (1,3,5-10, 5.0
mmoles), phenylhydrazine (20.0 mmoles) and pyridine (30 ml)
was refluxed for 6 hours and then poured onto crushed ice. The
precipitate was separated by filtration, washed with water and
crystallized from methanol to afford compounds 28-35 (Scheme
2).
H), 8.41 (s, 1H, 4'-H); C nmr (CDCl ): δ 45.3, 55.3, 64.5,
3
113.7, 114.5, 116.4, 119.8, 124.7, 125.5, 126.9, 128.2, 128.9,
131.4, 134.2, 137.5, 142.8, 144.6, 153.1, 159.4.
Anal. Calcd. for C H N O : C, 75.74; H, 5.08; N, 7.06.
25 20
2 3
Found: C, 75.82; H, 5.13; N, 7.14.
3-(3-Coumarinyl)-5-(4-fluorophenyl)-1-phenyl-2-pyrazoline
3-(3-Coumarinyl)-1,5-diphenyl-2-pyrazoline (28).
(33).
This compound was prepared as white needles in 71% yield,
This substance was isolated as yellow plates in 70% yield, mp
1
1
mp 181-182°; H nmr (CDCl ): δ 3.40 (dd, 1H, J = 7.3, 18.4 Hz,
107-108°; H nmr (CDCl ): δ 3.39 (dd, 1H, J = 7.2, 18.4 Hz, 4-
3
3
4-H
), 4.11 (dd, 1H, J = 12.7, 18.4 Hz, 4-H ), 5.38 (dd, 1H, J
H
), 4.15 (dd, 1H, J = 12.6, 18.4 Hz, 4-H ), 5.36 (dd, 1H, J =
trans
cis
trans cis
= 7.3, 12.7 Hz, 5-H), 6.81-7.60 (m, 14 arom. H), 8.40 (s, 1H-4'-
7.2, 12.6 Hz, 5-H), 6.82-7.58 (m, 13 arom. H), 8.44 (s, 1H, 4'-H);
13
13
H); C nmr (CDCl ): δ 45.2, 64.9, 113.7, 116.4, 117.7, 119.5,
C nmr (CDCl ): δ 45.3, 64.3, 113.7, 115.8, 116.3, 117.4, 119.5,
3
3
120.4, 124.7, 125.3, 127.6, 128.2, 129.2, 130.9, 131.4, 132.5,
137.5, 142.1, 144.0, 153.6, 159.6.
120.0, 120.7, 121.1, 124.7, 127.5, 128.2, 129.3, 131.6, 137.8,
138.5, 143.0, 153.6.
Anal. Clacd. for C H N O : C, 78.67; H, 4.95; N, 7.64.
Anal. Calcd. for C H FN O : C, 74.98; H, 4.46; N, 7.28.
24 18
2
2
24 17 2 2
Found: C, 78.79; H, 4.89; N, 7.69.
Found: C, 74.87; H, 4.51; N, 7.36.
3-(3-Coumarinyl)-5-(4-methylphenyl)-1-phenyl-2-pyrazoline
5-(4-Chlorophenyl)-3-(3-coumarinyl)-1-phenyl-2-pyrazoline
(29).
(34).
This substance was obtained as yellow needles in 74% yield,
This compound was obtained as yellow needles in 73% yield,
1
1
mp 193-194°; H nmr (CDCl ): δ 2.31 (s, 3H, Me), 3.39 (dd, 1H,
mp 149-150°; H nmr (CDCl ): δ 3.39 (dd, 1H, J = 7.2, 18.4 Hz,
3
3
J = 7.2, 18.3 Hz, 4-H
), 4.11 (dd, 1H, J = 12.6, 18.3 Hz, 4-
4-H
), 4.12 (dd, 1H, J = 12.7, 18.4 Hz, 4-H ), 5.31 (dd, 1H, J
trans
trans cis
H
), 5.30 (dd, 1H, J = 7.2, 12.6 Hz, 5-H), 6.80-7.10 (m, 13
= 7.2, 12.7 Hz, 5-H), 6.89-7.58 (m, 13 arom. H), 8.41 (s, 1H, 4'-
cis
13
13
arom. H), 8.41 (s, 1H, 4'-H); C nmr (CDCl ): δ 21.1, 45.3, 64.8,
H); C nmr (CDCl ): δ 45.2, 64.3, 113.7, 116.5, 119.5, 120.1,
3
3

Sep-Oct 2005
Synthesis of 1-Substituted 5-Aryl-3-(3-coumarinyl)-2-pyrazolines
1235
[13]
(1990).
R. Djudjic and M. Trkovnik, Croat. Chem. Acta, 63, 13
120.7, 124.7, 127.2, 128.2, 129.1, 129.3, 131.6, 133.4, 137.8,
140.6, 143.8, 153.6.
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(2003).
Anal. Calcd. for C C ClN O : C, 71.91; H, 4.28; N, 6.98.
24 17
2 2
Found: C, 71.83; H, 4.33; N, 7.07.
5-(4-Bromophenyl)-3-(3-coumarinyl)-1-phenyl-2-pyrazoline
[16] K. Ramalingham, G. X. Thyvekikakath, K. D. Berlin, R. W.
Chesnut, R. A. Brown, N. N. Durham, A. E. Ealick and D. van der Helm,
J. Med. Chem., 20, 847 (1977).
[17] R. E. Brown and J. Shavrel, Jr., US Patent 3,624,102 (1972);
Chem. Abstr., 76, 59618 (1972).
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(1981).
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R. Katritzky, C. W. Rees and E. F. Scriven, eds., Pergamon Press, Oxfrod,
1996.
(35).
This substance was prepared as yellow plates in 68% yield, mp
1
205-206°; H nmr (CDCl ): δ 3.38 (dd, 1H, J = 7.2, 18.4 Hz, 4-
3
H
), 4.13 (dd, 1H, J = 12.7, 18.4 Hz, 4-H ), 5.34 (dd, 1H, J =
trans
cis
7.2, 12.7 Hz, 5-H), 6.88-8.12 (m, 13 arom. H), 8.40 (s, 1H, 4'-H);
13
C nmr (CDCl ): δ 45.1, 64.4, 113.7, 116.5, 119.5, 120.1, 124.7,
3
127.6, 128.2, 129.1, 131.6, 132.3, 137.8, 141.1, 143.1, 143.7,
153.5.
Anal. Calcd. for C H BrN O : C, 64.73; H, 3.85; N, 6.29.
Found: C, 64.84; H, 3.81; N, 6.40.
24 17
2 2
[20] A. Lévai, Khim. Geterotsikl. Soedin., 747 (1997).
[21] A. Lévai, J. Heterocyclic Chem., 39, 1 (2002).
[22] E. Fischer and O. Knövenagel, Ann. Chem., 239, 194 (1887).
Acknowledgements.
[23]
(1936).
L. C. Raiford and W. J. Peterson, J. Org. Chem., 1, 544
The present study was sponsored by the Hungarian National
Research Foundation (Grant No. OTKA T049468) for which our
gratitude is expressed. Technical assistance of Mrs. M. Nagy is
highly appreciated.
[24] W. Ried and G. Dankert, Chem. Ber., 57, 2707 (1957).
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