Synthesis of new bis-3,5-diphenylpyrazolines derivatives linked with alkyl chains

Article abstract of DOI:10.1002/jhet.5570450547

(Chemical Equation Presented) New bis-3,5-diphenylpyrazoline derivatives have been synthesized according to Elway [1] (1999) and Sangwan's [2] (1992) methodology. Most of them were obtained in good yields, from the reaction between an alkyl linked bis-cha

Full text of DOI:10.1002/jhet.5570450547

Sep-Oct 2008
1521
Synthesis of New Bis-3,5-diphenylpyrazolines Derivatives Linked
with Alkyl Chains
Braulio Insuasty,a* Henry Martinez,a Jairo Quiroga,a Rodrigo Abonía,a
Manuel Noguerasb* and Justo Cobob
aGrupo de Investigación de Compuestos Heterocíclicos, Department of Chemistry,
Universidad del Valle, A. A. 25360 Cali, Colombia
bDepartment of Inorganic and Organic Chemistry, Universidad de Jaén, 23071 Jaén, Spain.
Received February 27, 2008
COCH3
N
O
N
R
R
R
O
O
N2H4
(CH2)n
O
(CH2)n
O
AcOH
R
O
N
N
COCH3
New bis-3,5-diphenylpyrazoline derivatives have been synthesized according to Elway [1] (1999) and
Sangwan’s [2] (1992) methodology. Most of them were obtained in good yields, from the reaction between
an alkyl linked bis-chalcones and hydrazine in acetic acid. The activity of some bis-pyrazolines was
evaluated against Helicobacter pylori.
J. Heterocyclic Chem., 45, 1521 (2008).
INTRODUCTION
catalytic amounts of sodium hydroxide [8]. All bis-
chalcones were obtained in good yields.
Recently, considerable interest has been focused on
pyrazoline system, specially, 3,5-diarylpyrazoline
derivatives, which have displayed a tremendous spectrum
of biological activity; for example, antitumoral activity
[3], human Acyl-CoA inhibitors (anti-atherosclerosis) [4]
with an important activity (MIC50 between 14.7-164.3
μM), anti-depressant agents [5] or as bactericide (anti-
Helicobacter pylori, with MIC90 between 8-64 μg/mL)
[6]. With respect to the anti-depressant activity, the
authors [5] found that the presence of 4-chlorophenyl
group at position 3 of the pyrazoline system increased the
anti-depressant activity. More recently Azam and co-
workers [7] reported the synthesis of bis-pyrazolines with
a great activity as inhibitors of the growth of Entamoeba
The synthesis of the bis-pyrazolines was carried out
with hydrazine, and acetic acid as a solvent, obtaining the
N-acetylated final products (Scheme 1), consistent with a
previous work [2].
The spacers of methylenes chains that liked both
pyrazolines were varied in order to analyze any possible
influence on biological activity.
The structure of new bis-chalcones 3a-f were
established by usual analytical and spectroscopic methods
(1D and 2D-NMR mainly, MS and elemental analysis, see
experimental section). The IR spectra of compounds 3a-f
showed a strong C=O stretching band at interval 1659 and
1668 cm-1, as usual for this kind highly conjugated C=O.
The 1H NMR spectra of compounds 3a-f showed the
aromatic protons between 6.84-7.84 ppm, two doublets at
7.40-7.93 ppm (J=15.6–15.7 Hz) corresponding to the
trans vinyl protons of the ꢀ,ꢁ-unsaturated system.
Additionally, proton signals of -O-(CH2)n-O- fragment
appear at 4.10-4.28 and 1.96-2.35 ppm for the CH2-groups
connected to the oxygen and for the interior CH2-groups
respectively.
histolytica,
a
potent pathogen, which causes
approximately 100,000 deaths annually.
The bis-pyrazolines 4a-f were prepared using
a
previous methodology reported by Elway [1] and
Sangwan [2] by the reaction of bis-chalcones 3a-f with
hydrazine in acetic acid. For some of them its anti- H.
Pylori activity was evaluated.
RESULTS AND DISCUSSION
The structures of 4a-f were established by the usual
analytical and spectroscopic methods given above.
Where, the IR spectra of compounds 4a-f showed a strong
stretching band at interval 1660-1666 cm-1, that resulted
The bis-chalcones derivatives 3a-f were obtained
according to Claisen-Schmidt reaction by treating
diketone 1 and aromatic aldehydes 2 in ethanol with

1522
B. Insuasty, H. Martinez, J. Quiroga, R. Abonía
M. Nogueras and J. Cobo.
Vol 45
Scheme 1
COCH3
N
HX
O
N
O
R
CH3
R
HM
HA
CHO
O
O
O
i
ii
(CH2)n
O
(CH2)n
O
2
(CH2)n
O
+
R
HM
HA
R
CH3
R
2
O
N
HX
COCH3
O
N
4a-f
3a-f
1
i) EtOH/NaOH, rt; ii) N2H4/CH3COOH/Reflux
Comp.
3a/4a
3b/4b
3
3c/4c
3
3d/4d
3e/4e
4
3f/4f
n
3
4
4
R
3,4,5-Tri-OMe
8/28
4-OMe
10/32
4-CF3
9/25
3,4,5,Tri-OMe
7/27
4-OMe
9/28
4-CF3
8/26
t. r. (hours)
1
the C=O amide type (acetyl group). The H NMR spectra
of compounds 4a-f showed aromatic protons at interval
6.42-7.60 ppm, three doublet of doublets corresponding to
an AMX system characteristic of pyrazolines, where HA
appear at interval 3.12–3.40 ppm, HM at interval 3.66–
3.75 ppm and HX at interval 5.50–5.62 ppm, with three
coupling constants around JAM(gem)=17.7 Hz, JAX(trans)=4.7
Hz and JMX(cis)=11.8Hz.
activity of pyrazolines and bis-pyrazolines warrants
further study of other biological activities and small
chemical modifications over these new compounds, in
order to find an improvement in the activity.
EXPERIMENTAL
Melting points were taken on a Stuart SMP3 melting point
apparatus and were not corrected. IR spectra were recorded on a
As recorded previously, Helicobacter Pylori, an S-
shaped spiral microaerophilic, Gram-negative bacterium
first isolated in human gastric mucosa in 1982, is
considered to be the major causative agent of several
gastric pathologies, such as chronic gastritis, peptic ulcer
disease and gastric cancer [6]. Due to these different
biological activities, the compounds 4a, 4d, 4e and
metronidazole were evaluated with against 20 H. pylori
strains, including metronidazole resistant strains. But
unfortunately those compounds did not show an important
biological activity compare with metronidazole. There
was not significant difference between spacers of 3 and 4
methylenes.
1
Shimadzu FTIR-8400 using KBr discs. The H- and 13C NMR
spectras were run on a BRUKER AVANCE spectrometer
operating at 400 MHz and 100 MHz respectively in DMSO-d6
using TMS as internal Standard (belong to the Servicios
Técnicos de Investigación, Universidad de Jaén, STIUJA). The
mass spectra were recorded on SHIMADZU GCMS201, by
electronic impact operating at 70 eV. The elemental analyses
have been obtained using a LECO CHNS-900 and an Thermo
Finnigan FlashEA1112 CHNS-O (STIUJA) elemental analyzers.
Diketones 1 were obtained according to methodology described
in work [8].
General procedure for the synthesis of bis-chalcones 3a-f.
To a solution of diketone 1 (1 mmol) and aromatic aldehyde 2 (2
mmol) in absolute ethanol (10 mL), a catalytic amount of
sodium hydroxide (0.100 g) was added, and the reaction mixture
was stirred at room temperature until the precipitate formation.
The precipitate was isolated by filtration and washed with hot
ethanol.
1,3-Bis(4-((3,4,5-(trimethoxy)phenyl)-acryloyl)phenoxy)-
propane 3a. This compound was obtained according to general
procedure as a yellow solid; Yield 93%; m.p: 146-148 ºC. IR
(KBr) cm-1: (C=O) 1665; EIMS: m/z (70 eV): 668 (20, M+), 490
(78), 459 (100), 457 (58). 1H NMR (400 MHz, DMSO-d6, ppm):
2.33 (m, 2H), 4.26 (t, 4H), J=6.3 Hz, 6.88 (s, 4H), 3.90 (s, 6H),
3.92 (s, 12H), 8.04 (d, 4H), 6.98 (d, 4H), J=8.9 Hz., 7.42 (d,
2H), 7.71 (d, 2H), J=15.6Hz. 13C NMR (DMSO-d6, ppm): 188.6
In summary, the alkyl spacers bis-chalcones 3 were
obtained by
a Claisen-Schmidt reaction with
arylaldehyde, a diketone, and catalytic amounts of sodium
hydroxide, in high yields, which were used to provide
new 1,3 and 1,4 bis-(4-((aryl)-N-acetyl-pyrazolin-5-
yl)phenoxy)alkyl derivatives
hydrazine, in good to excellent yields.
4
by reaction with
The anti-H. pylori activity was evaluated for some of
those bis-pyrazolines, however low biological activity
was obtained (MIC90 ꢀ 128 μg/mL). Even though, the
activity against H. Pyroli was not successful, the great

Sep-Oct 2008
Synthesis of New Bis-3,5-diphenylpyrazolines Derivatives Linked with Alkyl Chains
1523
(C1), 162.6 (Cp’), 153.5 (Cm), 144.2 (C3), 140.4 (Cp), 131.3 (Ci’),
130.8 (Co’), 130.5 (Ci), 121.2 (C2), 114.3 (Cm’), 105.7 (Co), 64.5
(OCH2), 61.0 (OCH3(p)), 56.3 (OCH3(m)), 29.1 (CH2). Elem.
Anal. for C39H40O10, Calculated (%): C, 70.05; H, 6.03; found: C,
70.17; H, 5.97.
1.96 (m, 4H), 4.21 (t, 4H), J=5.8 Hz, 7.74 (s, 4H), 7.99 (d, 4H),
J=8.1 Hz, 8.07 (d, 4H), 7.07 (d, 4H), J=8.7 Hz, 7.67 (d, 2H),
7.86 (d, 2H), J=15.7 Hz. 13C NMR (DMSO-d6, ppm): 187.1 (C1),
162.2 (Cp’), 125.0 (Cm), 140.1 (C3), 138.4 (Cp), 131.9 (Ci’), 130.2
(Co’), 129.9 (Ci), 124.8 (C2), 114.1 (Cm’), 124.7 (Co), 122.1
(CF3), 67.3 (OCH2), 24.7 (CH2). Elem. Anal. for C36H28F6O4,
Calculated (%): C, 67.71; H, 4.42; found: C, 67.82; H, 4.41.
General procedure for the synthesis of bis- pyrazolines
4a-f. A solution of bis-chalcone 3 (1 mmol) and hydrazine-
hydrate (2 mmol) in 70 mL (aprox) of acetic acid was refluxed
during 25-32 hours. The solution was cooled to room
temperature, and then water was added until the formation of
precipitate. A white solid was isolated by filtration, washed with
cold ethanol and recrystallized from ethanol. In cases 4c, 4e and
4f chromatographical purification has been donde using silicagel
60 (0063-0.200 mm), eluent chloroform-acetate, 10:1.
1,3-Bis(4-((4-(methoxy)phenyl)-acryloyl)phenoxy)propane
3b. This compound was obtained according to general procedure
as yellow solid; Yield 95 %; m.p: 139-141 ºC. IR (KBr) cm-1:
(C=O) 1675; EIMS: m/z (70 eV): 548 (80, M+), 386 (100), 253
1
(53), 161 (90). H NMR (400 MHz, DMSO-d6, ppm): 2.25 (m,
2H), 4.24 (t, 4H), J=6.2 Hz, 3.84 (s, 6H), 7.77 (d, 4H), 6.98 (d,
4H), J=8.7 Hz, 8.08 (d, 4H), 7.08 (d, 4H), J=8.0 Hz, 7.63 (d,
2H), 7.56 (d, 2H), J=15.3 Hz. 13C NMR (100 MHz, DMSO-d6,
ppm): 188.5 (C1), 143.5 (C3), 120.7 (C2), 162.8 (Cp’), 131.6 (Ci’),
131.0 (Co’), 115.2 (Cm’), 55.9 (OCH3), 161.9 (Cp), 130.7 (Co),
128.1 (Ci), 115.1 (Co), 65.5 (OCH2), 30.8 (CH2). Elem. Anal. for
C35H32O6, Calculated (%): C, 76.62; H, 5.88; found: C, 76.59; H,
5.93.
1,3-Bis(4-((3,4,5-(trimethoxy)phenyl)-N-acetyl-pyrazolin-
5-yl)phenoxy)-propane 4a. This compound was obtained
according to general procedure as white solid; Yield 89%; m.p:
120-121 ºC. IR (KBr) cm-1: (C=O) 1662; EIMS: m/z (70 eV):
1,3-Bis(4-((4-(trifluoromethyl)phenyl)-acryloyl)phenoxy)-
propane 3c. This compound was obtained according to general
procedure as light yellow solid; Yield 90%; m.p: 189-190 ºC. IR
(KBr) cm-1: (C=O) 1659; EIMS: m/z (70 eV): 624 (23, M+), 584
1
780 (4, M+), 737 (19), 528 (38), 487 (15), 43 (100). H NMR
(400 MHz, CDCl3, ppm): 2.32 (m, 2H), 4.22 (t, 4H), J=6.0 Hz,
6.96 (d, 4H), 7.67 (d, 4H), J=8.89 Hz, 3.48 (dd, 2H), 3.66 (dd,
2H), Jgem=17.62 Hz, 5.51 (dd, 2H), Jcis=11.75 Hz, Jtrans=4.75 Hz,
6.42 (s, 4H), 2.35 (s, 6H), 3.82 (s, 12H), 3.79 (s, 6H). 13C NMR
(CDCl3, ppm): 64.4 (OCH2), 29.1 (CH2), 124.1 (Ci’), 128.2 (Co’),
114.7 (Cm’), 160.6 (Cp’), 137.3 (Ci), 102.4 (Co), 153.7 (Cm),
137.8 (Cp), 153.6 (C1), 42.6 (C2), 60.7 (C3), 168.8 (C4), 21.9
(C5), 56.1 (OCH3(m)), 60.0 (OCH3(p)). Elem. Anal. for
C43H48N4O10, Calculated (%): C, 66.14; H, 6.20; N, 7.17; found:
C, 66.19; H, 6.13; N, 6.98.
1
(20), 333 (28), 199 (100). ). H NMR (400 MHz, DMSO-d6,
ppm): 2.35 (m, 2H), 4.28 (t, 4H), J=5.8 Hz, 7.67 (d, 4H), 7.69
(d, 4H), J=7.9 Hz, 8.02 (d, 4H), 6.99 (d, 4H), J=8.5 Hz, 7.42 (d,
2H), 7.75 (d, 2H), J=15.7 Hz. 13C NMR (DMSO-d6, ppm): 188.2
(C1), 163.0 (Cp’), 125.7 (Co), 141.9 (C3), 138.6 (Cp), 132.0 (Ci’),
131.0 (Co’), 131.7 (Ci), 124.3 (C2), 114.3 (Cm’), 125.9 (Cm),
122.7 (CF3), 65.0(OCH2), 29.2 (CH2). Elem. Anal. for
C35H26F6O4, Calculated (%): C, 67.31; H, 4.20; found: C, 67.39;
H, 4.18.
1,4-Bis(4-((3,4,5-(trimethoxy)phenyl)-acryloyl)phenoxy)-
butane 3d. This compound was obtained according to general
procedure as yellow solid; Yield 95%; m.p: 196-197 ºC. IR
(KBr) cm-1: (C=O) 1668; EIMS: m/z (70 eV): 682 (25, M+), 651
(95), 121 (100), 473 (48). 1H NMR (400 MHz, DMSO-d6, ppm):
2.05 (m, 4H), 4.12 (t, 4H), J=4,8 Hz, 6.87 (s, 4H), 3.92 (s, 12H),
3.90 (s, 6H) 8.04 (d, 4H), 6.99 (d, 4H), J=8.9 Hz, 7.40 (d, 2H),
7.73 (d, 2H), J=15.6 Hz. 13C NMR (DMSO-d6, ppm): 188.6 (C1),
162.8 (Cp’), 153.5 (Cm), 144.2 (C3), 140.4 (Cp), 131.2 (Ci’), 130.6
(Co’), 130.6 (Ci), 121.2 (C2), 114.3 (Cm’), 105.7 (Co), 65.9
(OCH2), 61.00 (OCH3(p)), 56.3 (OCH3(m)), 25.9 (CH2). Elem.
Anal. for C40H42O10, Calculated (%): C, 70.37; H, 6.20; found: C,
70.48; H, 6.29.
1,4-Bis(4-((4-(methoxy)phenyl)-acryloyl)phenoxy)butane
3e. This compound was obtained according to general procedure
as yellow solid; Yield 96 %; m.p: 137-138 ºC. IR (KBr) cm-1:
(C=O) 1677; EIMS: m/z (70 eV): 562 (35, M+), 444 (72), 400
(100), 161 (72). 1H NMR (400 MHz, DMSO-d6, ppm): 1.96 (m,
4H), 4.20 (t, 4H), J=5.5 Hz, 3.83 (s, 6H), 7.72 (d, 4H), 7.00 (d,
4H), J=8.7 Hz, 8.04 (d, 4H), 7.06 (d, 4H), J=8.7 Hz, 7.57 (d,
2H), 7.64 (d, 2H), J=15.7 Hz. 13C NMR (100 MHz, DMSO-d6,
ppm): 187.2 (C1), 142.0 (C3), 120.0 (C2), 161.8 (Cp’), 130.6 (Ci’),
129.8 (Co’), 114.1 (Cm’), 54.8 (OCH3), 160.8 (Cp), 129.5 (Co),
127.2 (Ci), 114.0 (Co), 67.3 (OCH2), 24.8 (CH2). Elem. Anal. for
C36H34O6, Calculated (%): C, 76.85; H, 6.09; found: C, 76.84; H,
6.11.
1,3-Bis(4-((4-(methoxy)phenyl)-N-acetyl-pyrazolin-5-yl)-
phenoxy)propane 4b. This compound was obtained according
to general procedure as white solid; Yield 56%; m.p: 125-126
ºC. IR (KBr) cm-1: (C=O) 1660; EIMS: m/z (70 eV): 660 (15,
1
M+), 645 (12), 627 (100). H NMR (400 MHz, CDCl3, ppm):
2.34 (m, 2H), 4.25 (t, 4H), J=6.0 Hz, 6.94 (d, 4H), 7.61 (d, 4H),
J=8.7 Hz, 3.20 (dd, 2H), 3.67 (dd, 2H), Jgem=17.7 Hz, 5.50 (dd,
2H), Jcis=11.7 Hz, Jtrans=4.5 Hz, 7.28 (d, 4H), 6.84 (d, 4H), J=8.8
Hz, 2.37 (s, 6H), 3.85 (s, 18H), 13C NMR (CDCl3, ppm): 65.4
(OCH2), 23.4 (CH2), 124.1 (Ci’), 127.9 (Co’), 114.6 (Cm’), 159.8
(Cp’), 134.2 (Ci), 126.9 (Co), 114.5 (Cm), 158.8 (Cp), 153.6 (C1),
42.3 (C2), 59.3 (C3), 167.9 (C4), 21.4 (C5), 56.2 (OCH3). Elem.
Anal. for C39H40N4O6, Calculated (%): C, 70.89; H, 6.10; N,
8.48; found: C, 70.84; H, 6.02; N, 8.26.
1,3-Bis(4-((4-(trifluoromethyl)phenyl)-N-acetyl-pyrazolin-
5-yl)phenoxy)-propane 4c. This compound was obtained
according to general procedure as white solid. Yield 59%; m.p:
103-104 ºC. IR (KBr) cm-1: (C=O) 1663; EIMS: m/z (70 eV):
1
736 (5, M+), 693 (100), 634 (29), 464 (36). H NMR (400 MHz,
CDCl3, ppm): 2.31 (m, 2H), 4.20 (t, 4H), J=5.8 Hz, 6.97 (d, 4H),
7.66 (d, 4H), J=8.9 Hz, 3.12 (dd, 2H), 3.75 (dd, 2H), Jgem=17.7
Hz, 5.62 (dd, 2H), Jcis=11.8 Hz, Jtrans=4.7 Hz, 7.33 (d, 4H), 7.60
(d, 4H), J=8.2 Hz, 2.42 (s, 6H). 13C NMR (CDCl3, ppm): 65.5
(OCH2), 29.1 (CH2), 123.9 (Ci’), 128.2 (Co’), 114.7 (Cm’), 160.7
(Cp’), 145.8 (Ci), 126.0 (Co), 125.9 (Cm), 130.0 (Cp), 153.5 (C1),
122.6 (CF3), 42.2 (C2), 59.5 (C3), 168.8 (C4), 21.8 (C5). Elem.
Anal. for C39H34F6N4O4, Calculated (%): C, 63.58; H, 4.65; N,
7.60; found: C, 63.51; H, 4.58; N, 7.47.
1,4-Bis(4-((4-(trifluoromethyl)phenyl)-acryloyl)phenoxy)-
butane 3f. This compound was obtained according to general
procedure as light yellow solid; Yield 90%; m.p: 192-194 ºC. IR
(KBr) cm-1: (C=O) 1662; EIMS: m/z (70 eV): 638 (6, M+), 347
(100), 305 (45), 199 (32). 1H NMR (400 MHz, DMSO-d6, ppm):
1,4-Bis(4-((3,4,5-(trimethoxy)phenyl)-N-acetyl-pyrazolin-5-
yl)phenoxy)-butane 4d. This compound was obtained
according to general procedure as white solid; Yield 92%; m.p:

1524
B. Insuasty, H. Martinez, J. Quiroga, R. Abonía
M. Nogueras and J. Cobo.
Vol 45
188-190 ºC. IR (KBr) cm-1: (C=O) 1666; EIMS: m/z (70 eV):
4H), 7.59 (d, 4H), J=8.3 Hz, 2.42 (s, 6H). 13C NMR (CDCl3,
ppm): 65.8 (OCH2), 25.9 (CH2), 122.7 (Ci’), 125.7 (Co’), 114.9
(Cm’), 160.9 (Cp’), 145.8 (Ci), 126.9 (Co), 128.2 (Cm), 130.0 (Cp),
153.5 (C1), 122.6 (CF3), 42.3 (C2), 59.4 (C3), 168.8 (C4), 21.8
(C5). Elem. Anal. for C40H36F4N4O4, Calculated (%): C, 64.00;
H, 4.83; N, 7.46; found: C, 64.09; H, 4.75; N, 7.23.
1
794 (5, M+), 751 (15), 542 (39), 251 (84), 44 (100). H NMR
(400 MHz, CDCl3, ppm): 2.04 (m, 4H), 4.13 (t, 4H), J=5.8 Hz,
6.95 (d, 4H), 7.69 (d, 4H), J=8.9 Hz, 3.15 (dd, 2H), 3.70 (dd,
2H), Jgem=17.7 Hz, 5.51 (dd, 2H), Jcis=11.7 Hz, Jtrans=4.7 Hz, 6.43
(s, 4H), 2.55 (s, 6H), 3.82 (s, 12H), 3.80 (s, 6H). 13C NMR
(CDCl3, ppm): 65.8 (OCH2), 25.9 (CH2), 123.9 (Ci’), 128.2 (Co’),
114.6 (Cm’), 160.8 (Cp’), 137.3 (Ci), 102.4 (Co), 153.8 (Cm),
137.8 (Cp), 153.6 (C1), 42.6 (C2), 60.7 (C3), 168.8 (C4), 21.9
(C5), 56.1 (OCH3(m)), 60.0 (OCH3(p)). Elem. Anal. for
C44H50N4O10, Calculated (%): C, 66.48; H, 6.34; N, 7.05; found:
C, 66.54; H, 6.23; N, 6.92.
1,4-Bis(4-((4-(methoxy)phenyl)-N-acetyl-pyrazolin-5-yl)-
phenoxy)butane 4e. This compound was obtained according to
general procedure as white solid, Yield 86%; m.p: 139-140 ºC.
IR (KBr) cm-1: (C=O) 1660; EIMS: m/z (70 eV): 674 (25M+),
659 (19), 631 (100), 84 (69). 1H NMR (400 MHz, CDCl3, ppm):
2.01 (m, 4H), 4.09 (t, 4H), J=5.7 Hz, 6.94 (d, 4H), 7.66 (d, 4H),
J=8.7 Hz, 3.13 (dd, 2H), 3.68 (dd, 2H), Jgem=17.7 Hz, 5.53 (dd,
2H), Jcis=11.7 Hz, Jtrans=4.4 Hz, 7.16 (d, 4H), 6.85 (d, 4H), J=8.9
Hz, 2.39 (s, 6H), 3.78 (s, 6H), 13C NMR (CDCl3, ppm): 67.6
(OCH2), 25.9 (CH2), 124.1 (Ci’), 128.3 (Co’), 114.6 (Cm’), 160.7
(Cp’), 134.2 (Ci), 126.9 (Co), 114.2 (Cm), 158.9 (Cp), 153.6 (C1),
42.3 (C2), 59.3 (C3), 168.6 (C4), 21.9 (C5), 56.2 (OCH3). Elem.
Anal. for C40H42N4O6, Calculated (%): C, 71.20; H, 6.27; N,
8.30; found: C, 71.29; H, 6.19; N, 8.16.
Acknowledgements. To The Colombian Institute for Science
and Research (COLCIENCIAS), Universidad del Valle, the
Spanish “Consejería de Innovación, Ciencia y Empresa, Junta de
Andalucía” and “Servicios Técnicos de Investigación de la
Universidad de Jaén” for financial support. Also to Dr. Bruna
Bizzarri, Dipartimento di Studi di Chimica e Tecnología delle
Sostanze Biológicamente Attive, Università “La Sapienza”, Italy
for the anti H-Pylori activity evaluation.
REFERENCES
[1] Elway, A. J. Chem.. Res. (S) 1999, 602-603.
[2] Sangwan, N. K.; Verma, B. S.; Dhindsa, K. S. Indian J.
Chem., 1992, 31B, 590-594.
[3] Manna, F.; Chimeti, F.; Fioravanti, R.; Bolasco, A.; Secci,
D.; Chimenti, P.; Ferlini, C.; Scambia, G. Bioorg. Med. Chem. Lett.
2005, 15, 4632-4635.
[4] Jeong, T.; Kim, K. S.; Lee, S.; An, S.; Cho, K.; Lee W. S.
Bioorg. Med. Chem. Lett. 2004, 14, 2715-2717.
[5] Palaska, E.; Aytemir, M.; Uzbay, T.; Erol, D. J. Med. Chem.,
2001, 36, 539-543.
[6] Chimenti, F.; Manna, F.; Bolasco, A.; Secci, D.; Chimenti,
P.; Granese, A.; Rivanera, D.; Lilli, D.; Scaltrito, M. M.; Brenciaglia, M.
I. Bioorg. Med. Chem. Lett. 2005, 15, 603-607.
[7] Bhat, A. R.; Athar, F.; Azam, A. Eur. J. Med. Chem. 2007,
doi:10.1016/j.ejmech.2007.11.005. In press.
1,4-Bis(4-((4-(trifluoromethyl)phenyl)-N-acetyl-pyrazolin-
5-yl)phenoxy)-butane 4f. This compound was obtained
according to general procedure as white solid; Yield 55%; m.p:
110-112 ºC. IR (KBr) cm-1: (C=O) 1664; EIMS: m/z (70 eV):
750 (6, M+), 707 (100), 689 (22.), 648 (27). 1H NMR (400
MHz, CDCl3, ppm): 2.04 (m, 4H), 4.09 (t, 4H), J=5.8 Hz, 6.95
(d, 4H), 7.61 (d, 4H), J=8.9 Hz, 3.13 (dd, 2H), 3.72 (dd, 2H),
Jgem=17.7 Hz, 5.62 (dd, 2H), Jcis=11.8 Hz, Jtrans=4.8 Hz, 7.33 (d,
[8] Al-Smadi, M.; Hanold, N.; Meier, H. J. Heterocyclic Chem.,
1997, 34, 605-611.