Synthesis, crystal structure and antibacterial activity of 5-bromonicotinic acid [1-(4-Chlorophenyl)methylidene]hydrazide monohydrate methanol solvate

Article abstract of DOI:10.1007/s10870-008-9501-0

The compound 5-bromonicotinic acid [1-(4-chlorophenyl)methylidene]hydrazide monohydrate methanol solvate, derived from the condensation reaction of 5-bromonicotinic acid hydrazide with 4-chlorobenzaldehyde in a methanol solution, was synthesized and chara

Full text of DOI:10.1007/s10870-008-9501-0

J Chem Crystallogr (2009) 39:449–452
DOI 10.1007/s10870-008-9501-0
ORIGINAL PAPER
Synthesis, Crystal Structure and Antibacterial Activity
of 5-Bromonicotinic Acid [1-(4-Chlorophenyl)methylidene]
hydrazide Monohydrate Methanol Solvate
Wen-Hui Li
Received: 2 November 2007 / Accepted: 24 October 2008 / Published online: 11 November 2008
Ó Springer Science+Business Media, LLC 2008
Abstract The compound 5-bromonicotinic acid [1-(4-
chlorophenyl)methylidene]hydrazide monohydrate metha-
nol solvate, derived from the condensation reaction of 5-
bromonicotinic acid hydrazide with 4-chlorobenzaldehyde
in a methanol solution, was synthesized and characterized by
elemental analysis, IR spectrum, 1H NMR and X-ray single
crystal determination. The compound crystallizes in the
triclinic space group P - 1 with unit cell dimensions
Hydrazones possessing the azomethine –NHN=CH–
groups, have been demonstrated to possess antibacterial,
anticonvulsant, antitubercular, and antitumor activities [5–
7]. Recently, a pair of hydrazones derived from 3-hy-
droxybenzohydrazide and 3-alkoxysalicylaldehyde with
antibacterial activities have been reported [8]. The results
indicate that such compounds show potent antimicrobial
activities against Staphylococcus aureus, Escherichia coli,
Salmonella typhi and Pseudomonas aeruginosa. As a
continuous work, in this paper, the author reports the
synthesis, crystal structure and antibacterial activity of a
new Schiff base compound, 5-bromonicotinic acid [1-(4-
chlorophenyl)methylidene]hydrazide monohydrate metha-
nol solvate (see the following Scheme).
˚
˚
˚
a = 6.9360(14) A, b = 10.070(2) A, c = 12.267(3) A, a =
´
3
˚
84.39(3)°, b = 86.10(3)°, c = 80.50(3)°, V = 839.8(3) A ,
Z = 2, R1 = 0.0724, and wR2 = 0.1720. X-ray structure
determination reveals that the compound has a trans config-
uration with respect to the C=N double bond or C–N single
bond. In the crystal structure, molecules are linked through
intermolecular O–HÁÁÁN, O–HÁÁÁO, and C–HÁÁÁO hydrogen
bonds, forming layers parallel to the ab plane. The pre-
liminary biological tests show that the compound has
excellent antibacterial activity.
O
N
N
N
H
Cl
Br
Keywords Synthesis Á Crystal structure Á Schiff base Á
Hydrogen bonds Á Antibacterial activity
CH3OH
H2O
Introduction
Experimental
The condensation reaction of aromatic aldehydes with
primary amines has been shown to offer an easy and
inexpensive way of forming a variety of Schiff base
compounds. These Schiff base compounds exhibit a wide
range of biological activities and applications [1–4].
Materials and Measurements
All the starting materials and reagents were obtained
commercially and were used as received. Elemental anal-
yses were determined on an Elemental Vario EL III
elemental analyzer. Infrared spectra were measured as KBr
pellets on a Nicolet Magna 750 FT-IR spectrophotometer
W.-H. Li (&)
in the range 4,000–400 cm-1. The H NMR spectra were
1
Department of Chemical Engineering, Jingchu University
of Technology, 448000 Jingmen, People’s Republic of China
e-mail: liwh066@163.com
recorded on a Bruker AVANCE 500 MHz spectrometer
with tetramethylsilane as the internal reference.
123

450
J Chem Crystallogr (2009) 39:449–452
Synthesis of 5-Bromonicotinic Acid [1-(4-Chlorophenyl)
methylidene]hydrazide Monohydrate Methanol Solvate
Table 1 Crystal data and refinement parameters for the compound
CCDC
665052
C14H15BrClN3O3
Molecular formula
Molecular weight
Crystal system
Space group
5-Bromonicotinic acid hydrazide (1.0 mmol, 216.0 mg)
and 4-chlorobenzaldehyde (1.0 mmol, 140.6 mg) were
dissolved in a methanol solution (80 ml). The mixture was
stirred at room temperature for 10 min to give a clear
yellow solution. Yellow needle-like crystals of the com-
pound, suitable for X-ray single crystal structural deter-
mination, were formed at the bottom of the vessel on slow
evaporation of the solvent in air for a week. The crystals
were isolated, washed three times with methanol and dried
in air. Yield 317.0 mg (81.7%). Analysis calculated for
C14H15BrClN3O3: C, 43.27; H, 3.89; N, 10.81%; found: C,
43.03; H, 3.96; N, 10.72%. Selected IR data (KBr, cm-1):
3,582 (w), 3,437 (w), 3,065 (w), 2,931 (w), 2,862 (w),
1,645 (s), 1,635 (s), 1,280 (s), 755 (s). 1H NMR data
(DMSO-d6, ppm): d = 7.53 (s, 1H), 7.55 (s, 1H), 7.78
(s, 1H), 7.93 (s, 1H), 8.42 (s, 1H), 8.49 (s, 1H), 8.92 (d,
1H), 9.03 (d, 1H), 12.11(s, 1H).
388.65
Triclinic
P - 1
Temperature (K)
´
298(2)
˚
a (A)
6.9360(14)
10.070(2)
12.267(3)
84.39(3)
86.10(3)
80.50(3)
839.8(3)
2
´
˚
b (A)
´
˚
c (A)
a (°)
b (°)
c (°)
´
3
˚
V (A )
Z
Dcalc (g cm-3
Crystal dimensions (mm); colour
)
1.537
0.27 9 0.23 9 0.22; yellow
2.621
Absorption coefficient (mm-1
)
´
˚
Radiation k
Mo Ka (0.71073 A)
Tmin/Tmax
0.538/0.596
Reflections measured
Range/indices (h, k, l)
h limit (°)
6,870
Crystallography
-8, 8; -12, 12; -15, 15
1.67–26.49
X-ray single crystal diffraction measurement was carried
out at 298(2) K on a Bruker Smart 1000 CCD area dif-
fractometer equipped with a graphite-monochromatic Mo
Total no. of unique data
3,437 [Rint = 0.0479]
No. of observed data, I [ 2r(I)
No. of variables
1,714
210
´
˚
Ka radiation (k = 0.71073 A) for data collection. The unit
No. of restraints
4
cell dimensions were obtained with the least-squares
refinements and the structure was solved by direct methods
with SHELXTL-97 package [9]. The final refinement was
performed by full-matrix least-squares methods with
anisotropic thermal parameters for the non-hydrogen atoms
on F2. Atoms H1, H2A and H2B were located in a dif-
ference Fourier map and refined isotropically, with the
Goodness of fit on F2
R1, wR2 [I C 2r(I)]a
R1, wR2 (all data)a
0.916
0.0724, 0.1720
0.1398, 0.2069
P
P
P
P
a
R1 = ||Fo| - |Fc||/ |Fo|, wR2 = [ w(F2o - F2c)2/ w(Fo2)2]1/2
2
˚
iso(H) values fixed at 0.08 A , and with N–H distance
University. A standard inoculum was introduced onto the
surface of sterile agar plates, and a sterile glass spreader
was used for even distribution of the inoculum. The discs
measuring 7.0 mm in diameter were sterilized by dry heat
at 140 °C for 1 h. The sterile discs previously soaked in a
known concentration (5,000 lg/cm3 in DMSO) of the
compound were placed in nutrient agar medium. Solvent
and growth controls were maintained. The plates were
inverted and incubated for 24 h at 37 °C. Ciprofloxacin
was used as a standard. The inhibition zones were mea-
sured and compared with the control. Minimum inhibitory
concentration (MIC) was determined by broth dilution
technique. The nutrient broth, which contained logarithmic
serially twofold diluted amount of the compound and the
control, was inoculated with approximately 1 9 106 CFU/
cm3 of actively dividing bacterial cells. The cultures were
incubated for 24 h at 37 °C and the growth was monitored
visually and spectrophotometrically.
U
restrained to 0.90(1) A, O–H distances restrained to
˚
˚
˚
0.85(1) A, and HÁÁÁH distance restrained to 1.37(2) A.
Other H atoms were placed in the calculated positions and
constrained to ride on their parent atoms. Multi-scan
absorption correction was applied by using the SADABS
program [10]. The crystallographic data for the complex
are summarized in Table 1. Selected bond lengths and
bond angles are listed in Table 2. Hydrogen bonding
interactions are listed in Table 3. Crystallographic data for
the complex has been deposited with the Cambridge
Crystallographic Data Centre (CCDC 665052).
Antibacterial Tests
The bacterial subcultures for E. coli, P. aeruginosa, S. ty-
phi and S. aureus were obtained from the Dalian Medical
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J Chem Crystallogr (2009) 39:449–452
451
´
˚
Table 2 Bond distances (A) and angles (°) for the compound
Bond distances
Br1–C3
O1–C6
1.879(6)
1.226(7)
1.355(7)
1.270(7)
1.332(7)
1.392(8)
1.375(8)
1.464(8)
1.395(8)
1.374(9)
1.397(8)
Cl1–C11
O3–C14
N1–N2
N3–C4
C1–C2
1.753(6)
1.363(10)
1.389(6)
1.327(8)
1.389(8)
1.496(8)
1.381(8)
1.389(8)
1.399(8)
1.349(9)
N1–C6
N2–C7
N3–C5
C1–C5
C1–C6
C2–C3
C3–C4
C7–C8
C8–C9
C8–C13
C9–C10
C11–C12
Fig. 1 Molecular structure of the compound. Displacement ellipsoids
are drawn at the 30% probability level and H atoms are shown as
small spheres of arbitrary radii; numbering according to Table 2
C10–C11
C12–C13
Bond angles
C6–N1–N2
C4–N3–C5
C2–C1–C6
C3–C2–C1
C2–C3–Br1
N3–C4–C3
O1–C6–N1
N1–C6–C1
C9–C8–C13
C13–C8–C7
C11–C10–C9
C12–C11–Cl1
C11–C12–C13
Crystal Structure Description
118.5(5)
117.5(5)
126.1(5)
118.6(5)
121.4(5)
122.6(6)
122.3(5)
116.7(5)
118.6(5)
119.4(6)
119.4(6)
119.3(5)
119.0(6)
C7–N2–N1
C2–C1–C5
C5–C1–C6
C2–C3–C4
C4–C3–Br1
N3–C5–C1
O1–C6–C1
N2–C7–C8
C9–C8–C7
C8–C9–C10
C12–C11–C10
C10–C11–Cl1
C8–C13–C12
115.1(5)
117.3(5)
116.7(5)
119.8(6)
118.7(4)
124.2(6)
121.1(5)
121.9(6)
122.0(5)
120.0(6)
122.1(6)
118.6(5)
121.0(6)
Figure 1 gives perspective view of the compound with the
atomic labeling system. The compound consists of a Schiff
base molecule, a lattice methanol molecule and a lattice
water molecule. The Schiff base molecule is nearly
˚
coplanar, with mean deviation from plane of 0.0323 A. The
dihedral angle between the benzene ring and the pyridine
ring is 3.0(5)°. All the bond lengths in the compound are
within normal ranges [11], and comparable to those of the
similar compounds [8, 12, 13]. The C7=N2 bond length of
˚
1.270(7) A confirms it as a double bond. The C6–N1 bond
˚
length of 1.355(7) A and the N1–N2 bond length of
˚
1.389(6) A are relatively short, suggesting some degree of
delocalization in the acetohydrazide system. The torsion
angles C8–C7–N2–N1, C7–N2–N1–C6, and N2–N1–C6–
C1 are 0.4(5), 0.1(5), and 1.5(5)°, respectively.
In the crystal structure of the compound, the lattice
water molecules are linked to the Schiff base molecules
through the intermolecular hydrogen bonds of O2–
H2AÁÁÁN2, O2–H2AÁÁÁO1, O2–H2BÁÁÁN3 and C9–H9ÁÁÁO2.
The methanol molecules are linked to the Schiff base
molecules through the intramolecular hydrogen bonds of
Results and Discussion
The compound was obtained in high yield as air stable
yellow needle-like crystals from the methanol solution. It is
soluble in methanol, ethanol, acetonitrile, and DMSO,
insoluble in water and chloroform.
˚
Table 3 Distances (A) and angles (°) involving hydrogen bonding of the compound
˚
D(D–H) (A)
˚
˚
D–HÁÁÁA
D(HÁÁÁA) (A)
D(DÁÁÁA) (A)
\(D–HÁÁÁA) (°)
O2–H2AÁÁÁN2#1
O2–H2AÁÁÁO1#1
N1–H1ÁÁÁO3
0.85(5)
0.85(5)
0.90(5)
0.85(3)
0.82
2.37(4)
2.19(4)
1.96(5)
2.01(4)
1.87
3.099(7)
2.889(6)
2.862(7)
2.865(7)
2.685(8)
3.220(8)
2.761(8)
3.374(8)
3.447(8)
145(6)
139(5)
173(7)
175(7)
173
O2–H2BÁÁÁN3#2
O3–H3ÁÁÁO2
C2–H2ÁÁÁO3
0.93
2.32
162
C5–H5ÁÁÁO1
0.93
2.41
102
C7–H7ÁÁÁO3
0.93
2.59
142
C9–H9ÁÁÁO2#1
0.93
2.56
159
Symmetry transformations used to generate the equivalent atoms: #1 1 - x, 1 - y, 1 - z; #2 x, 1 ? y, z
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J Chem Crystallogr (2009) 39:449–452
Fig. 2 Molecular packing of
the compound, viewed along the
a axis. Hydrogen bonds are
shown as dashed lines
Acknowledgment The author greatly acknowledges Jingchu Uni-
versity of Technology for financial support.
N1–H1ÁÁÁO3, C2–H2ÁÁÁO3 and C7–H7ÁÁÁO2. The lattice
water and methanol molecules are linked together by
intramolecular hydrogen bonds of O3–H3ÁÁÁO2. All the
hydrogen bonds link the molecules forming layers parallel
to the ab plane (Fig. 2).
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graphic data for this paper. The data can be obtained free of
charge at http://www.ccdccam.ac.uk/const/retrieving.html
or from the Cambridge Crystallographic Data Centre
(CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax:
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