Synthesis, characterization and crystal structures of hydrazone compounds derived from isonicotinohydrazide

Article abstract of DOI:10.4314/bcse.v32i1.11

New isonicotinohydrazone compounds, N’-(3-bromobenzylidene)isonicotinohydrazide (1) and N’-(2,3-difluorobenzylidene)isonicotinohydrazide (2), were prepared and structurally characterized by elemental analysis, IR, UV and¹H NMR spectra, and sing

Full text of DOI:10.4314/bcse.v32i1.11

Bull. Chem. Soc. Ethiop. 2018, 32(1), 125-132.
2018 Chemical Society of Ethiopia and The Authors
DOI: https://dx.doi.org/10.4314/bcse.v32i1.11
ISSN 1011-3924
Printed in Ethiopia

SYNTHESIS, CHARACTERIZATION AND CRYSTAL STRUCTURES OF
HYDRAZONE COMPOUNDS DERIVED FROM ISONICOTINOHYDRAZIDE
1
1*
1
1
1
Meng-Ting Zhu , Xiao-Yang Qiu , Shu-Juan Liu , Ling-Yan He , Deng-Zhu Xu , and
2
*
Zhonglu You
1
College of Science & Technology, Ningbo University, Ningbo, 315212, China
Department of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian
16029, China
2
1
(Received October 18, 2014; Revised January 24, 2018; Accepted January 31, 2018)
ABSTRACT. New isonicotinohydrazone compounds, N’-(3-bromobenzylidene)isonicotinohydrazide (1) and
N’-(2,3-difluorobenzylidene)isonicotinohydrazide (2), were prepared and structurally characterized by elemental
1
analysis, IR, UV and H NMR spectra, and single crystal X-ray determination. Compound 1 crystallizes in the
monoclinic space group P2
01.748(2)º, V = 1218.7(4) Å , Z = 4, R
space group P-1 with unit cell dimensions a = 7.6241(6) Å, b = 11.3937(9) Å, c = 14.335(1) Å, α = 79.664(1)º, β
1
/n with unit cell dimensions a = 7.600(2) Å, b = 11.365(2) Å, c = 14.412(2) Å, β =
3
1
1 2
= 0.0335, and wR = 0.0745. Compound 2 crystallizes in the triclinic
3
=
75.990(1)º, γ = 71.159(1)º, V = 1136.5(2) Å , Z = 4, R
1 2
= 0.0345, and wR = 0.0940. Structures of both
compounds are stabilized by hydrogen bonds and π···π interactions.
KEY WORDS: Isonicotinohydrazone, Crystal structure, Hydrogen bonds, X-ray diffraction
INTRODUCTION
Isonicotinohydrazide is a well known anti-tuberculosis drug. It can react with aldehydes to form
isonicotinohydrazones, which show interesting biological activities [1-4]. Moreover,
isonicotinohydrazone compounds usually possess three or more donor atoms, which can readily
form complexes with various metal atoms [5-12]. Recently, we found that halido-substituted
hydrazones have potential antimicrobial activities [13]. Study on the synthesis and structures of
such compounds are important for medicinal chemistry. In the present work, two new
isonicotinohydrazone compounds, N’-(3-bromobenzylidene)isonicotinohydrazide (1) and N’-
(
2,3-difluorobenzylidene)isonicotinohydrazide (2), were prepared and structurally characterized.
EXPERIMENTAL
Materials and measurements
Starting materials, reagents and solvents were purchased from commercial suppliers and used as
received. Elemental analyses were performed on a Perkin-Elmer 240 Celemental analyzer. IR
–
1
spectra were recorded on a Jasco FT/IR-4000 spectrometer as KBr pellets in the 4000-400 cm
1
13
region. UV spectra were recorded on a Lambda 900 spectrometer. H NMR and C NMR data
were recorded on a Bruker 300MHz and 75 MHz instrument. HRMS data was obtained with
ESI (electrospray ionization) mode.
_
*
_________
Corresponding author. E-mail:xiaoyang_qiu@126.com, youzhonglu@126.com
This work is licensed under the Creative Commons Attribution 4.0 International License

126
Meng-Ting Zhu et al.
Synthesis of N’-(3-bromobenzylidene)isonicotinohydrazide
1). 3-Bromobenzaldehyde (1.0 mmol, 0.185 g) andisonicotinohydrazide (1.0 mmol, 0.137 g)
(
were mixed in methanol, and stirred at room temperature for 1 h. The solvent was evaporated by
distillation to give colorless solid, which was washed with methanol. Yield: 87%. Single crystals
of the compound suitable for X-ray diffraction were obtained by recrystallization of the product
in methanol. Anal. calcd. for C13
H10BrN O: C, 51.3; H, 3.3; N, 13.8; found: C, 51.5; H, 3.3; N,
3
+
1
3.7%. HRMS (ESI): m/z calcd for C13
H10BrN
3
O [M + H] 305.0762; found: 305.0765. IR data
-
1
(
KBr, cm ): 3197 (w), 1682 (s), 1620 (m), 1546 (s), 1411 (w), 1349 (w), 1268 (s), 1216 (w),
1
1
136 (w), 1062 (w), 946 (w), 847 (w), 787 (w), 745 (w), 682 (m), 635 (w). UV (λ, ε): 300 nm,
4 -1 -1 1 6
.07 × 10 L mol cm . H NMR (300 MHz, d -DMSO): δ 12.31 (s, 1H, NH), 8.85 (d, 2H, py-
1
3
6
H), 8.46 (s, 1H, CH=N), 8.0-7.4 (m, 6H, ArH). C NMR (75 MHz, d -DMSO): δ 161.5, 151.5,
51.3, 146.3, 140.0, 134.5, 132.3, 131.9, 130.2, 128.7, 122.5, 121.6, 121.5.
1
Synthesis of N’-(2,3-difluorobenzylidene)isonicotinohydrazide
2). 2,3-Difluorobenzaldehyde (1.0 mmol, 0.142 g) and isonicotinohydrazide (1.0 mmol, 0.137
(
g) were mixed in methanol, and stirred at room temperature for 1 h. The solvent was evaporated
by distillation to give colorless solid, which was washed with methanol. Yield: 95%.Single
crystals of the compound suitable for X-ray diffraction were obtained by recrystallization of the
product in methanol. Anal. calcd. For C13
H F N O: C, 59.8; H, 3.5; N, 16.1; found: C, 60.0; H,
9 2 3
+
3
.4; N, 15.9%. HRMS (ESI): m/z calcd for C13
H
9
F
2
N
3
O [M + H] 262.0786; found: 262.0780.
-
1
IR data (KBr, cm ): 3190 (w), 1687 (s), 1618 (w), 1555 (s), 1480 (s), 1406 (m), 1288 (s), 1208
(
×
8
1
w), 1141 (w), 1089 (w), 1062 (w), 995 (m), 853 (w), 786 (w), 685 (w). UV (λ, ε): 300 nm, 2.20
4
-1
-1
1
6
10 L mol cm . H NMR (300 MHz, d -DMSO): δ 12.27 (s, 1H, NH), 8.81 (d, 2H, py-H),
13 6
.70 (s, 1H, CH=N),7.9-7.3 (m, 5H, ArH). CNMR (75 MHz, d -DMSO): δ 161.7, 151.6, 151.5,
50.4, 148.4, 148.2, 140.7, 125.3, 125.2, 121.6, 121.5, 118.9, 118.7.
Data collection, structural determination and refinement
Diffraction intensities for the compounds were collected at 298(2) K using a Bruker D8
VENTURE PHOTON diffractometer with MoKα radiation (λ = 0.71073 Å). The collected data
were reduced using the SAINT program [14], and multi-scan absorption corrections were
performed using the SADABS program [15]. The structures were solved by direct methods and
2
refined against F by full-matrix least-squares methods using the SHELXTL [16]. All of the
non-hydrogen atoms were refined anisotropically. The amino H atoms were located in
difference Fourier maps and refined isotropically with N–H distances restrained to 0.90(1) Å.
All other H atoms were placed in idealized positions and constrained to ride on their parent
atoms. The crystallographic data for the compounds are summarized in Table 1. Hydrogen
bonding information is given in Table 2.
Table 1. Crystallographic and experimental data for the compounds.
Compound
Formula
1
C
2
C
13
H
10BrN
3
O
13 9 2 3
H F N O
Mr
T (K)
304.1
298(2)
261.2
298(2)
Crystal shape/color
Crystal size (mm )
Crystal system
Space group
a (Å)
block/colorless
0.270.270.26
Monoclinic
block/colorless
0.180.180.15
Triclinic
P-1
7.6241(6)
3
P2
1
/n
7.600(2)
Bull. Chem. Soc. Ethiop. 2018, 32(1)

Crystal structures of hydrazone compounds derived from isonicotinohydrazide
127
b (Å)
c (Å)
α (º)
β (º)
γ (º)
11.365(2)
14.412(2)
90
101.748(2)
90
1218.7(4)
4
1.658
11.3937(9)
14.335(1)
79.664(1)
75.990(1)
71.159(1)
1136.4(2)
4
3
V (Å )
Z
–3
D

c
(g cm )
(Mo-K) (mm )
1.527
0.123
-1
3.363
F(000)
608
536
Reflections collected
Unique reflections
Observed reflections (I 2(I))
Parameters
11803
2311
1695
166
5956
4176
3618
350
Restraints
1
2
Min. and max. transmission
0.4637, 0.4751
1.032
0.0335, 0.0745
0.9782, 0.9818
1.046
0.0345, 0.0940
0.0404, 0.1002
2
Goodness-of-fit on F
a
R
R
1
, wR
, wR
2
[I 2(I)]
(all data)
a
1
2
0.0566, 0.0847
a
2
2
2 2 1/2
R
1
= F
o c o 2 o o
–F /F , wR = [w(F –Fc )/w(F ) ] .
Table 2. Hydrogen bond distances (å) and bond angles (°) for the compounds.
D–H∙∙∙A
1
O1–H1∙∙∙N3
2
d(D–H)
d(H∙∙∙A)
d(D∙∙∙A)
Angle (D–H∙∙∙A)
i
0.90(1)
2.30(1)
3.158(3)
162(3)
N2–H2∙∙∙N6
N5–H5∙∙∙N3
0.90(1)
0.90(1)
2.23(1)
2.29(1)
3.101(2)
3.162(2)
165(2)
165(2)
ii
Symmetry codes: i)1 – x, –1 –y, –z; ii)x, 1 +y, z.
RESULTS AND DISCUSSION
Chemistry
Compounds 1 and 2 were readily synthesized by reaction of 1:1 molar ratio of
isonicotinohydrazide with 3-bromobenzaldehyde and 2,3-dichlorobenzaldehyde, respectively, in
methanol at room temperature, with high yields (over 90%) and purity (Scheme 1). Single
crystals suitable for X-ray diffraction were obtained by slow evaporation of the methanol
solutions containing the compounds in air. The compounds have been characterized by various
physico-chemical methods. Structures of the compounds were further confirmed by single
crystal X-ray crystallography.
N
O
CHO
X
H
N
NH2
+
N
H
N
O
N
X
Y
Y
Scheme 1. The synthetic procedure of the compounds. 1: X = H, Y = Br; 2: X = Y = F.
Bull. Chem. Soc. Ethiop. 2018, 32(1)

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Meng-Ting Zhu et al.
Structure description of the compounds
Figures 1 and 2 give perspective views of compounds 1 and 2, respectively, with atomic
labeling systems. X-ray crystallography reveals that the molecules of the compounds adopt E
configuration with respect to the methylidene units. The distances of the C7-N1 bonds in both
compounds, and the C20-N4 bond in 2, ranging from 1.26 to 1.27 Å, confirm them as typical
double bonds. The shorter distances of the C–N bonds and the longer distances of the C=O
bonds for the –C(O)–NH– units than usual, suggests the presence of conjugation effects in the
molecules. The remaining bond lengths in the compounds are comparable to each other, and
within normal values [17, 18]. The dihedral angles between the benzene and pyridine rings are
5
.3(3)° for 1, and 4.9(3)° and 1.1(3)° for 2. The crystal structures of the compounds are
stabilized by hydrogen bonds and π···π interactions (Table 3, Figures 3 and 4).
Figure 1. A perspective view of the molecular structure of 1 with the atom labeling scheme.
Thermal ellipsoids are drawn at the 30% probability level.
Figure 2. A perspective view of the molecular structure of 2 with the atom labeling scheme.
Thermal ellipsoids are drawn at the 30% probability level.
Bull. Chem. Soc. Ethiop. 2018, 32(1)

Crystal structures of hydrazone compounds derived from isonicotinohydrazide
129
Figure 3. Molecular packing diagram of 1. Hydrogen bonds are shown as dashed lines.
Figure 4. Molecular packing diagram of 2. Hydrogen bonds are shown as dashed lines.
Bull. Chem. Soc. Ethiop. 2018, 32(1)

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Meng-Ting Zhu et al.
Table 3. Parameters among planes for the compounds.
Cg
Distance
between ring angle (º)
centroids (Å)
Dihedral Perpendicular Perpendicular
Beta
of angle (º) angle (º)
on Cg(J) on Cg(I)
Gamma
distance of distance
Cg(I)
Cg(J) (Å)
(Å)
1
iii
iv
Cg(1)-Cg(2)
Cg(2)-Cg(1)
2
3.854
4.783
5
55
-3.598
-1.970
-3.461
4.666
26.1
12.7
21.0
65.7
v
Cg(3)-Cg(4)
Cg(3)-Cg(4)
Cg(5)-Cg(6)
Cg(5)-Cg(6)
3.746
3.979
3.715
3.939
5
5
1
1
-3.358
3.528
-3.490
3.442
-3.451
3.541
-3.503
3.468
22.9
27.2
19.4
28.3
26.3
27.5
20.1
29.1
vi
vii
viii
Symmetry codes: iii) – x, 1 –y, 1 –z; iv) 1/2 + x, 1/2–y, –1/2 +z; v) – x, –y, 1 –z; vi) 1 – x, –y, 1 –z; vii) 1 – x, 1 –y,
z; viii) 2 – x, 1 –y, –z. Cg(1) and Cg(2) are the centroids of N3-C11-C10-C9-C13-C12 and C1-C6 of 1; Cg(3),
–
Cg(4),Cg(5)and Cg(6) are the centroids of N3-C11-C10-C9-C13-C12, C1-C6, N6-C24-C23-C22-C26-C25, and
C14-C19 of 2.
Spectra description
In the FT-IR spectra of the compounds, the vibrations of the hydrogen-bonded NH protons are
-
1
-1
shown as sharp and weak bands at 3197 and 3190 cm . The intense bands at 1682 cm for 1 and
-
1
-1
1
1
687 cm for 2 are generated by ν(C=O) vibrations, whereas the bands at 1620 cm for 1 and
618 cm for 2 are generated by the ν(C=N) vibrations.
-1
UV spectra of the compounds are shown in Figure 5. Both compounds have single bands
centered at 300 nm, which can be assigned to the π→π* transitions.
1
13
6
1
The H and C NMR of the compounds were run in d -DMSO. In the H NMR spectra of the
compounds, the singlet at about 12.3 ppm can be attributed to the proton of the –NH groups.
The protons of the azomething groups are shown at 8.46 and 8.70 ppm as a singlet for 1 and 2,
respectively. The multiplets in the 8.0–7.3 ppm range can be assignable to the protons of the
benzene rings. The doublet peaks in the 8.9–8.8 ppm range can be assignable to the protons of
1
3
the pyridine rings. In the spectra of the C NMR, the resonances at 162 ppm may be assigned to
the carbon atoms of the CH=N groups. The aromatic carbon atoms are shown in the 118–152
ppm range.
1.00
0.75
0.50
0.25
0.00
300 nm
1
2
250
300
350
400

(nm)
Figure 5. UV spectra of the compounds in methanol solutions.
Bull. Chem. Soc. Ethiop. 2018, 32(1)

Crystal structures of hydrazone compounds derived from isonicotinohydrazide
131
CONCLUSION
Two isonicotinohydrazone compounds N’-(3-bromobenzylidene)isonicotinohydrazide and N’-
2,3-difluorobenzylidene)isonicotinohydrazide were prepared and structurally characterized.
(
The crystal structures of the compounds are detailed described. Structures of both compounds
are stabilized by hydrogen bonds and π···π interactions.
ACKNOWLEDGMENTS
This work was financially supported by K.C. Wong Magna Fund in Ningbo University, Ningbo
Natural Science Foundation (Project No. 201701HJ-B01019) and the College Students of
Science and Technology Innovation Projects in Zhejiang Province (Project No.2017R405008).
Supporting information
CCDC–1012074 for 1, and 1012075 for 2 contain the supplementary crystallographic data for
this
paper.
These
data
can
be
obtained
free
of
charge
at
http://www.ccdc.cam.ac.uk/const/retrieving.html or from the Cambridge Crystallographic Data
Centre (CCDC), 12 Union Road, CambridgeCB2 1EZ, UK; fax: +44(0)1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk.
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