Syntheses, characterization, and antibacterial activities of four new schiff base compounds derived from 1-phenyl-3-methyl-4-benzoyl-2-pyrazolin-5-one

Article abstract of DOI:10.1002/jhet.874

Four new Schiff bases were designed and synthesized. 5-Methyl-4-(4- aminophenylamino-phenyl-methylene)-2-phenyl-2,4-dihydro-pyrazol-3-one (compound 1) and 5-methyl-4-(2-aminophenylamino-phenyl-methylene)-2-phenyl-2,4-dihydro- pyrazol-3-one (compound 2) we

Full text of DOI:10.1002/jhet.874

July 2012
Syntheses, Characterization, and Antibacterial Activities of Four
New Schiff Base Compounds Derived from 1-Phenyl-3-methyl-4-
benzoyl-2-pyrazolin-5-one
839
a
a
a
a
*
Chong‐Bo Liu, Yuan Chen, Liu‐Shui Yan, De‐He Huang,
and Zhi‐Qiang Xiongb
aDepartment of Applied Chemistry, School of Environment and Chemical Engineering, Nanchang
Hangkong University, Nanchang 330063, People’s Republic of China
bCenter for Analysis and Testing, Nanchang Hangkong University, Nanchang 330063, People’s
Republic of China
*
E-mail: cbliu2002@163.com
Received December 11, 2010
DOI 10.1002/jhet.874
View this article online at wileyonlinelibrary.com.
Four new Schiff bases were designed and synthesized. 5‐Methyl‐4‐(4‐aminophenylamino‐phenyl‐
methylene)‐2‐phenyl‐2,4‐dihydro‐pyrazol‐3‐one (compound 1) and 5‐methyl‐4‐(2‐aminophenylamino‐
phenyl‐ methylene)‐2‐ phenyl‐2,4‐ dihydro‐pyrazol‐3‐ one (compound 2) were synthesized by interaction of
1‐ phenyl ‐3‐ methyl ‐ 4‐ benzoyl‐2‐ pyrazolin ‐5‐ one (PMBP) with o ‐ and p‐phenylenediamine, respectively;
4,4′‐ (1,2 ‐ phenylenebis(azanediyl)bis(phenylmethanylylidene))bis(3 ‐ methyl ‐1‐ phenyl ‐1H ‐ pyrazol ‐ 5(4H) ‐
one) (compound 3) and 5 ‐ methyl ‐ 4 ‐ (phenyl(2‐ ((3‐ phenylallylidene)amino)phenylamino)methylene)‐2‐
phenyl‐2,4‐dihydro‐pyrazol‐3‐one (compound 4) were synthesized by interaction of compound 2 with PMBP
and cinnamaldehyde in an ethanolic medium, respectively. The molecular structures of the title compounds were
first characterized by single‐crystal X‐ray diffraction, mass spectrometry, and elemental analysis. The title com-
pounds were tested for antibacterial activity (Escherichia coli, Staphylococcus aureus, and Bacillus subtilis) by
disk diffusion method.
J. Heterocyclic Chem., 49, 839 (2012).
INTRODUCTION
from PMBP and their metal complexes have been widely stud-
ied in pharmaceutical activity and catalysis [18–22], although
Schiff bases with PMBP and diamine were ignored. Taking
into consideration all the features described above, we report
the syntheses, structural characterization, and antibacterial ac-
tivities of four new Schiff base compounds derived from
PMBP and phenylenediamines (o‐ or p‐phenylenediamine) in
this work, the reaction sequence is outlined in Scheme 1.
Schiff bases are well known not only for thermochromism
and photochromism in the solid state [1] but also for their phar-
macological properties as antibacterial agents, antifungal bioac-
tivities, and antitumor and inhibitory activities against viruses
[2–12]. In particular, much attention has been paid on heterocy-
clic Schiff base because of its super biological activity [13,14].
1‐Phenyl‐3‐methyl‐4‐benzoyl‐2‐pyrazolin‐5‐one (PMBP) is a
representative nitrogen heterocyclic diketone chelating agent
[15], which has been extensively applied in the extraction of
lanthanides, actinides, and radioactive chemical separation
analysis early years [16,17]. Recently, Schiff bases derived
RESULTS AND DISCUSSION
Crystal structure of compounds 1–4. The molecular
structures of four compounds were determined from single‐
© 2012 HeteroCorporation

840
C.-B. Liu, Y. Chen, L.-S. Yan, D.-H. Huang, and Z.-Q. Xiong
Vol 49
Scheme 1. Syntheses of compounds 1–4.
crystal X‐ray studies. Experimental details for X-ray data
collection of compounds 1–4 are presented in Table 1. Oak
Ridge Thermal-Ellipsoid Plot Program (ORTEP) diagrams
of compounds 1–4 with the atom numbering schemes are
shown in Figure 1. In compound 1, rings a, b, and c adopt
“three lobe motorfan”‐like conformation, the C7 atom is the
“axis”, and rings a, b, and c are “lobes”, as shown in Figure
1(I). The following data may be responsible for the
“motorfan” conformation. The angles of N3 C7 C14,
C14 C7 C8, and N3 C7 C8 are 119.6°, 120.1°, and 120.2°,
respectively, which are all close to 120°. In addition, the
dihedrals between rings a and b, rings a and c, and rings b
and c are 62.0°, 57.4°, and 62.1°, respectively, which are
very similar. Two kinds of intramolecular hydrogen bonding
interactions (N3—H3A···O1 and C23—H23···O1) exist in
the molecule of compound 1 [Fig. 1(I) and Table 2], which
favor the “motorfan” conformation. Similar to compound 1,
rings a, b, and c in compound 2 also adopt “three lobe
motorfan”‐like conformation with three angles all close to
120° (∠N2C7C8 = 120.0°, ∠N2C7C14 = 118.2°, and
∠C14C7C8 = 121.8°), and three dihedrals very similar (∠ab
= 65.7°, ∠bc = 65.4°, and ∠ac = 63.6°). There are two
intramolecular hydrogen bonding interactions within the
molecule of compound 2 [Fig. 1(III) and Table 2], which
favor the “motorfan” conformation. Compared with
compounds 1 and 2, neither rings a, b, and c nor rings a, b′,
and c′ in compound 3 form a “three lobe motorfan”
conformation with very different dihedrals of ∠ab = 65.2°,
∠bc = 63.4°, ∠ac = 89.5°; ∠ab′ = 78.1°, ∠b′c′ = 76.0°,
∠ac′ = 21.8°. There exists one kind of intramolecular
C—H···O hydrogen bonding interaction and two kinds of
intramolecular N—H···O hydrogen bonding interactions in
compound 3, the data are listed in Table 2. Compound 4
crystallizes in the P2/n space group with two
crystallographically unique molecules in the asymmetric
unit. The same as compound 3, the molecules in compound
4 do not form “three lobe motorfan”‐like conformation as
the dihedrals of ∠ab, ∠bc, and ∠ac in molecule A with
77.8°, 78.1°, and 45.4°, respectively, and the dihedrals of ∠a
′b′, ∠b′c′, and ∠a′c′ in molecule B with 72.7°, 71.7°, and
49.7°, respectively, are very different, as shown in Figure 1
(V). The molecules A and B are associated in pair by two
kinds of C—H···O hydrogen bonds [Fig. 1(V)], the data of
hydrogen bonding geometries are compiled in Table 2.
That acyl pyrazolone schiff bases often exist in different
tautomeric forms such as inime‐one, anime‐ol, and anime‐
one forms (Scheme 2) in solid state, and thus, many studies
have been made to establish the geometry of these deriva-
tives [23–25]. The C—N distances of the imine moiety of
compounds 1–4 except C23 N4 and C55 N8 in compound
4 are in the range 1.332–1.346 Å, which are significantly
longer than the C═N distances of 1.298 Å [26] and 1.292
Å [27] in pyrazolone compounds, and comparable to
C—N (1.342 Å) distance observed in similar pyrazolone
compound [28]; and the bond length of C7—C14 in com-
pound 1 and 2, C10—C8 and C32—C30 in compound 3
and C10—C8 and C42—C38 in compound 4 are in the
range 1.374–1.402 Å, which fall into the normal range of
C═C double bond; in addition the C—O distances in the
pyrazol moiety of compounds 1–4 are in the range
1.240–1.251 Å, which are significantly shorter than the dis-
tances found for C—O in some pyrazolone derivatives,
Journal of Heterocyclic Chemistry
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July 2012
Syntheses, Characterization, and Antibacterial Activities of Four New Schiff Base
Compounds Derived from 1-Phenyl-3-methyl-4-benzoyl-2-pyrazolin-5-one
841
Figure 1. I, III, IV, and V: molecular structures of compounds 1–4 showing the atom numbering scheme, dashed lines indicate hydrogen bonds, H atoms not
involved in hydrogen bonding have been omitted for clarity; II: scheme of three lobe motorfan conformation. [Color figure can be viewed in the online issue, which
is available at wileyonlinelibrary.com.]
1.341, 1.346 Å [29], and 1.331 Å [30], however, they are
close to the distances found for C O in similar compounds,
1.262 Å [29] and 1.254 Å [27]. All the above data prove
that compounds 1–4 exist in amine‐one form.
Testing of biological activities. The biological activity
of a particular substance relies on a complex sum of
individual properties including compound structure,
affinity for the target site, survival in the medium of
application, survival within the biological system,
transport properties, and state of the target organism [7].
In this study, we focused our attention on the structure–
activity relationship.
The data of antibacterial activities are summarized in
Table 3, which indicate that the synthesized compounds
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

842
C.-B. Liu, Y. Chen, L.-S. Yan, D.-H. Huang, and Z.-Q. Xiong
Vol 49
Table 1
Crystal data for compounds 1–4.
Compound
Empirical formula
Formula weight
T (K)
1
2
3
4
C
23H20N4O
368.43
296(2)
C23H20N4O
368.43
296(2)
C40H32N6O2
628.72
296(2)
C64H52N8O2
965.14
296(2)
Crystal system
Space group
A (Å)
Monoclinic
Cc
9.944(3)
16.960(3)
11.172(4)
90
99.635(4)
90
1857.5(9)
4
Monoclinic
P2(1)/c
9.203(2)
21.683(5)
9.611(2)
90
97.880(3)
90
1899.7(8)
4
Triclinic
PÀ1
Monoclinic
P2/n
17.097(2)
11.5033(14)
26.830(3)
90
96.028(2)
90
5247.5(11)
4
10.871(2)
11.584(3)
13.574(3)
88.757(3)
75.521(3)
82.029(3)
1638.9(6)
2
b (Å)
c (Å)
a (ꢀ)
b (ꢀ)
g (ꢀ)
V (Å3)
Z
F (0 0 0)
776
1.317
0.987
776
1.288
1.048
660
1.274
0.995
2032
1.222
1.121
Dc (mg mÀ3
)
Goodness-of-fit on F2
Data/restraints/parameters
Final R indices [I > 2sigma(I)]
3915/2/255
R1 = 0.0503
wR2 = 0.0806
R1 = 0.1416
wR2 = 0.1074
8121
3517/0/254
R1 = 0.0394
wR2 = 0.0995
R1 = 0.0535
wR2 = 0.1102
13,995
6060/0/435
R1 = 0.0409
wR2 = 0.0695
R1 = 0.0861
wR2 = 0.0777
12,796
9239/37/670
R1 = 0.0590
wR2 = 0.0667
R1 = 0.2080
wR2 = 0.0901
38,240
R indices (all data)
No. data collected
No. unique data
3915
0.174 and À0.179
3517
0.297 and À0.205
6060
0.177 and À0.179
9239
0.184 and À0.157
Largest diff. peak and hole (e ÅÀ3
)
display antibacterial activities against the tested bacteria
and the higher concentration of test samples, the more
active against the tested bacteria. Compound 1 has more
active against the tested bacteria than isomeric compound
2, owing to amino group at different locations. As can be
seen from Table 3 that symmetrical bis‐Schiff base com-
pound 3 is more active against the tested bacteria than com-
pound 2‐single‐Schiff base and compound 4‐asymmetrical
bis‐Schiff base. Compound 3 contains two pyrazole rings,
and compounds 2 and 4 both have one pyrazole ring, which
indicated that the activity of compounds against bacterial
strains decreased when the number of pyrazole ring
decreased. The results implied that N-heterocycle were
helpful in the antibacterial activity of the compounds.
CONCLUSIONS
In this study, four new compounds derived from PMBP
were prepared and mainly structural characterized by X‐ray
diffraction. The molecular structures of the title com-
pounds and intramolecular hydrogen bonding interactions
were studied. Biological testing showed that the synthe-
sized Schiff‐base compounds displayed antibacterial activ-
ities to the three bacteria, and antibacterial activity
increased with the increase of concentration. The study
on structure–activity relationships of these Schiff base indi-
cated that spatial position and the sum of N‐heterocycle
had influence on antibacterial activities of compounds 1–4.
EXPERIMENTAL
Table 2
Physical measurements. All reagents were commercially
available and used without further purification. Melting points
Hydrogen-bonding geometries (Å,ꢀ) for the title compounds.
Compound D–H⋯A
D–H H⋯A D–H⋯A ∠D–H⋯A
Scheme 2. Tautomeric forms of acyl pyrazolone derivatives.
1
2
3
N3–H3a⋯O1 0.86 2.16 2.796(4)
C23–H23⋯O1 0.93 2.39 2.960(5)
N2–H2d⋯O1 0.86 2.07 2.735(2)
C19–H19⋯O1 0.93 2.28 2.912(2)
N3–H3a⋯O1 0.86 2.02 2.689(2)
131
120
133
125
135
144
125
139
137
127
164
N6–H6⋯O2
C1–H1⋯O1
0.86 1.92 2.659(2)
0.93 2.25 2.891(3)
4
N3–H3a⋯O1 0.86 2.03 2.733(4)
N7–H7⋯O2 0.86 2.05 2.741(4)
C18–H18⋯O2 0.93 2.59 3.230(5)
C44–H44⋯O1 0.93 2.39 3.293(6)
Journal of Heterocyclic Chemistry
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July 2012
Syntheses, Characterization, and Antibacterial Activities of Four New Schiff Base
Compounds Derived from 1-Phenyl-3-methyl-4-benzoyl-2-pyrazolin-5-one
843
Table 3
1626, 1595, 1585, 1505, 1384, 1050, 850, 790, 750, 695, 650, 590
cm−1. MS (ES+) m/z 483.3678 [M+H]. Anal. calcd. for
C32H26N4O: C, 79.64; H, 5.43; N, 11.61. Found: C, 79.46; H,
5.25; N, 11.87.
Antibacterial activities data of compounds 1–4.
1
2
3
4
Crystallographic measurement. Single‐crystal diffraction
data were measured at room temperature in the ω/2θ mode on
the Bruker APEX II area detector diffractometer using the
graphite‐monochromated Mo Kα radiation.
Antibacterial testing. Preliminary in vitro tests for antibacterial
activity of all compounds have been carried out by disk diffusion
method. Antibacterial activities of compounds 1–4 against
Escherichia coli, Staphylococcus aureus, and Bacillus subtilis have
been investigated at the dosages of 1, 10, 15, 20, and 25 mg mL−1,
respectively, with the solvent of DMF. The disks with tested
substances and the blank (solvent) were added onto Petri dishes
inoculated with the tested bacterial strains. After 24‐h cultivation at
37°C, diameters of zones of inhibition were determined, DMF was
inactive under the applied conditions.
Escherichia coli
1
5
10
15
20
25
0.83
1.21
1.29
1.34
1.40
1.43
0.68
0.74
0.80
0.82
0.83
0.90
0.72
0.91
1.10
1.15
1.20
1.23
−
−
0.62
0.64
0.74
0.83
Staphylococcus aureus
1
1.1
À
0.63
1.21
1.32
1.48
1.55
1.62
À
5
1.15
1.28
1.47
1.51
1.57
0.62
0.74
0.80
0.97
1.01
À
10
15
20
25
0.75
1.01
1.13
1.19
Bacillus subtilis
Supplementary material.
X‐ray crystallographic files
1
5
À
0.63
0.70
0.85
0.90
1.21
1.30
0.80
1.21
1.32
1.41
1.54
1.61
À
(CIF) have been deposited with the Cambridge Crystallographic
Data Center, CCDC Nos. 803599–803602 for compound 1–4,
respectively. Copies of this information may be obtained free of
charge from The Director, CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK (fax: +44‐1223‐336‐033; email: deposit@ccdc.
cam.ac.uk or www:http://www.ccdc.cam. ac.uk).
+
À
10
15
20
25
1.15
1.27
1.35
1.40
0.67
0.70
0.73
0.81
were determined on a Micromelting point apparatus and were not
corrected. IR spectra were measured as KBr disks on a Nicolet
Avatar 5700 FT‐IR spectrometer. Elemental analyses were
performed with an Elementar Vario EL analyzer. Mass spectra
were taken on an Agilent Liquid chromatography–mass
spectrometry 6340 series instrument in the electrospray
ionization (positive electrospray ionization) mode.
Compound 1. PMBP (0.834 g, 3.0 mmol) and p‐
phenylenediamine (0.378 g, 3.5 mmol) were dissolved in ethanol
(40 mL) and the solution was heated under reflux for several hours.
The solvent was removed and yellow crystals obtained upon
recrystallization from ethanol in about 78% yield. m.p. 209–212 °C.
IR (KBr): 3430, 3042, 1626, 1599, 1475, 1421, 1362, 1300, 1250,
1185, 815, 750, 620, 570, 500 cm−1. MS (ES+) m/z 369.1866
[M+H]. Anal. calcd. for C23H20N4O: C, 74.98; H, 5.47; N, 15.21.
Found: C, 74.84; H, 5.22; N, 15.46.
Compound 2. The same synthetic procedure as that for
compound 1 was used except p‐phenylenediamine was replaced by
o‐phenylenediamine. The color of product is orange. Yield: 83%.
m.p. 229–231 °C. IR (KBr): 3403, 1626, 1583, 1567, 1502, 1395,
1310w, 1050, 850, 750, 700, 660, 590 cm−1. MS (ES+)
m/z 369.2342 [M+H]. Anal. calcd. for C23H20N4O: C, 74.98; H,
5.47; N, 15.21. Found: C, 74.93; H, 5.35; N, 15.39.
Compound 3. Compound 2 (0.368 g, 1.0 mmol) and PMBP
(0.417 g, 1.5 mmol) were dissolved in ethanol (30 mL) and the
solution stirred under room temperature for several hours. The
solvent volatilized under the temperature of about 5 °C and the
yellow crystals were obtained in about 30% yield after 2 months.
m.p. 197–199°C. IR (KBr): 3409, 1617, 1590, 1500, 1390, 1290,
1200, 1080, 1000, 750, 700, 670, 600 cm−1. MS (ES+) m/z
629.4896 [M+H]. Anal. calcd. for C40H32N6O2: C, 76.41; H, 5.13;
N, 13.37. Found: C, 76.56; H, 5.42; N, 13.14.
Acknowledgments. This work was supported by the Natural Sci-
ence Foundation of China (Grant No. 20961007), the Aviation
Fund (Grant No. 2010ZF56023), and Young Science Foundation
of Jiangxi province (Grant No. 2008DQ00600).
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