Synthesis, crystal structure and characterization of (Z)-2-N′- hydroxyisonicotinamidine

Article abstract of DOI:10.1080/15421406.2013.875735

The compound (Z)-2-N′-hydroxyisonicotinamidine, (2) was synthesized and characterized by 1H NMR, FT-IR, FAB-Mass, UV-Visible Spectra, and elemental Analysis. Its molecular structure was solved by single crystal X-ray diffraction method. The title molecule, C₆H₇N₃O is crystallized in the orthorhombic crystal system with the space group Pna2 ₁ and with unit cell parameters a = 12.5664(8) ?, b = 8.8622(6) ?, c = 5.7953(4) A, α = 90°, β; = 90°, γ = 90°, and Z = 4. The molecular and crystal structure of the title molecule is stabilized by an intramolecular interaction of the type N.HEEEO, and the intermolecular interactions of types N-H?N and O-H?N.

Full text of DOI:10.1080/15421406.2013.875735

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Synthesis, Crystal Structure and
Characterization of (Z)-2-N′-
hydroxyisonicotinamidine
a
c
b
a
M. Prabhuswamy , Dinesha , K. J. Pampa , S. Madan Kumar , G. K.
c
a
Nagaraja & N. K. Lokanath
a
Department of Studies in Physics, University of Mysore, Mysore,
India
b
Department of Studies in Microbiology, University of Mysore,
Mysore, India
c
Department of Chemistry, Mangalore University, Mangalore, India
Published online: 27 May 2014.
To cite this article: M. Prabhuswamy, Dinesha, K. J. Pampa, S. Madan Kumar, G. K. Nagaraja
&
N. K. Lokanath (2014) Synthesis, Crystal Structure and Characterization of (Z)-2-N′-
hydroxyisonicotinamidine, Molecular Crystals and Liquid Crystals, 593:1, 243-252, DOI:
0.1080/15421406.2013.875735
1
To link to this article: http://dx.doi.org/10.1080/15421406.2013.875735
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Mol. Cryst. Liq. Cryst., Vol. 593: pp. 243–252, 2014
Copyright © Taylor & Francis Group, LLC
ISSN: 1542-1406 print/1563-5287 online
DOI: 10.1080/15421406.2013.875735
Synthesis, Crystal Structure and Characterization
ꢀ
of (Z)-2-N -hydroxyisonicotinamidine
1
3
2
M. PRABHUSWAMY, DINESHA, K. J. PAMPA,
1
3
S. MADAN KUMAR, G. K. NAGARAJA,
AND N. K. LOKANATH1
,∗
1
Department of Studies in Physics, University of Mysore, Mysore, India
Department of Studies in Microbiology, University of Mysore, Mysore, India
Department of Chemistry, Mangalore University, Mangalore, India
2
3
ꢀ
The compound (Z)-2-N -hydroxyisonicotinamidine, (2) was synthesized and character-
1
ized by H NMR, FT-IR, FAB-Mass, UV-Visible Spectra, and elemental Analysis. Its
molecular structure was solved by single crystal X-ray diffraction method. The title
molecule, C
group Pna2
6
H
7
N
3
O is crystallized in the orthorhombic crystal system with the space
1
and with unit cell parameters a = 12.5664(8) Å, b = 8.8622(6) Å, c =
◦
◦
◦
5
.7953(4) Å, α = 90 , β = 90 , γ = 90 , and Z = 4. The molecular and crystal structure
of the title molecule is stabilized by an intramolecular interaction of the type N—H···O,
and the intermolecular interactions of types N—H···N and O—H···N.
Keywords Amidoxime; characterization; crystal structure; inter-molecular interac-
tions
Introduction
Versatile heterocyclic compounds were synthesized from carbonitrile. The reaction of
carbonitrile with hydroxylamine hydrochloride gave amidoximes. Amidoximes are com-
pounds bearing both a hydroxyimino and an amino group at the same carbon atom.
Amidoximes are bifunctional molecules exhibiting a rich, diverse chemistry, and pro-
vides the intermediates for the preparation of heterocycles such as oxadiazoles. These are
less basic because of the introduction of the oxygen atom. A number of amidoximes has
already been used as drugs, or currently being in clinical trials. Amidoximes are absorbed
from the gastrointestinal tract and then reduced to the activity of amidines. So, they act as
prodrugs for the amidines [1, 2]. Their numerous pharmaceutical applications such as bac-
tericidal and fungicidal [3], local anesthetics [4], antitumor and antimalarial agents [5], and
their ability to release NO were clarified, giving a new insight to their mode of action and
allowing the design of new therapeutic agents [6]. Prompted by these observations, it was
ꢀ
contemplated to synthesis of the title compound (Z) -2-N -hydroxyisonicotinamidine and it
1
is well characterized by the single-crystal X-ray diffraction, H NMR, FT-IR, FAB-Mass,
UV-Visible Spectra, and elemental Analysis (Scheme 1).
∗
Address correspondence to N. K. Lokanath, Department of Studies in Physics, University of
Mysore, Mysore 570 006, India. E-mail: lokanath@physics.uni-mysore.ac.in
243

244
M. Prabhuswamy et al.
ꢀ
Scheme 1. Synthesis of Compound (Z)-2-N -hydroxyisonicotinamidine.
Experimental
Materials and Methods
Melting point was taken in an open capillary tube and was uncorrected. The purity of the
compound was confirmed by thin-layer chromatography using Merck silica gel 60 F254
coated aluminum plates. IR spectrum was recorded on Shimadzu-FTIR Infrared spectrom-
−1
1
eter in KBr (νmax in cm ). H NMR (400 MHz) spectrum was recorded on a Bruker Avance
II 400 spectrometer, with 5 mm PABBO BB-1H TUBES, using CDCl3 as a solvent and
TMS as internal standard (chemical shift in δ ppm). The FAB mass spectra were recorded
on a JEOL SX 102/DA-6000 spectrophotometer/Data system using Argon/Xenon (6 kV,
1
0 mA) FAB gas, at 70 eV. The UV-Vis spectrum was recorded in Shimadzu UV-2550
UV-Visible spectrophotometer. Elemental analysis was carried out by using VARIO EL-III
Elementar Analysensysteme GmBH).
(
ꢀ
Procedure for the Preparation of (Z)-2-N -hydroxyisonicotinamidine(2)
Sodium bicarbonate (70 mmol, 5.88 g) was added in portions to a solution of hydroxylamine
hydrochloride (70mmol, 4.79 g) in18mLof water. Asolutionof 4-cyanopyridine (35mmol,
3.64 g) in 34 mL of ethanol was then added, and the mixture stirred under reflux for 6 hr.
The precipitate formed was filtered off and recrystallized from ethanol. Yield 71%; m.p.
◦
2
07–209 C.
Figure 1. FT-IR spectrum.

ꢀ
Characterization of (Z)-2-N -hydroxyisonicotinamidine
245
Figure 2. 1H NMR spectra.
Results and Discussion
FT-IR Spectral Analysis
The FT-IR spectrum of the crystal structure was shown in Fig. 1. IR spectra showed strong
−1
absorption bands at 3311 and 3460 cm due to primary amine group and vibration band at
−
1
−
1
3
161 cm due to the hydroxyl group. The absorption peaks at 1600 and 1633 cm were
due to the stretching vibration corresponds to C C and C N groups.
Figure 3. FAB mass spectrum.

246
M. Prabhuswamy et al.
Figure 4. UV-visible spectrum.
1H NMR Spectral Analysis
1
1
The H NMR spectrum of the crystal structure was shown in Fig. 2. H NMR spectrum
showed sharp singlet at δ 5.49 and δ 10.0 ppm due to NH2 and O-H protons, respectively.
The four aromatic protons displayed two signals; a doublet of doublet at δ 7.63 ppm and δ
8.59 ppm with coupling constants of nearly 1.62 Hz and 4.54 Hz.
Fast Atom Bombardment Analysis
ꢀ
The formation of compound (Z)-2-N -hydroxyisonicotinamidine was confirmed by record-
ing its fast atom bombardment (FAB)-Mass spectrum and shown in Fig. 3. The compound
+
showed a molecular ion peak at m/z 138 (M+H) in agreement with the molecular formula
C6H7N3O. The base peak was seen at m/z 91 due to the formation of molecular ion radical
of 4-methylpyridine during fragmentation.
Table 1. Elemental analysis for C6H7N3O
Element
Experimental (%)
Calculated (%)
Carbon
Nitrogen
Hydrogen
52.47
30.55
5.09
52.55
30.64
5.14

ꢀ
Characterization of (Z)-2-N -hydroxyisonicotinamidine
247
Figure 5. ORTEP view of the title molecule with atom numbering scheme. The displacement ellip-
soids for nonhydrogen atoms are drawn at 50% probability level. Dashed line indicates intramolecular
hydrogen bond of the type N—H···O.
UV-Vis Spectral Analysis
Like FT-IR spectroscopy, UV spectroscopy also useful in the evaluation of the compounds.
On UV electronic spectrum compounds are analyzed based on the characteristic frequencies
corresponding to define groups and it is shown in Fig. 4. The UV-Vis spectrum was recorded
by using methanol as a solvent. From the graph, it was observed that the compound shows
∗
an absorption peak at 305 nm. The transmittance of the compound is due to the π-π
Figure 6. Packing of molecules when viewed down a-axis.

248
M. Prabhuswamy et al.
Figure 7. Packing of molecules when viewed down b-axis.
Figure 8. Packing of molecules when viewed down the c-axis.

ꢀ
Characterization of (Z)-2-N -hydroxyisonicotinamidine
249
Table 2. Crystal data and structure refinement
Parameter
Value
CCDC deposit No.
Empirical formula
Formula weight
945510
C6 H7 N3 O
137.15
Temperature
293(2) K
Wavelength
1.54178 Å
Crystal system, space group
Unit cell dimensions
Orthorhombic, Pna21
a = 12.5664(8) Å α = 90
◦
◦
b = 8.8622(6) Å β = 90
c = 5.7953(4) Å γ = 90
◦
3
Volume
645.4(7) Å
3
Z, Calculated density
Absorption coefficient
F(000)
4, 1.411 Mg/m
0.847 mm
288
−
1
Crystal size
Theta ranges for data collection
Limiting indices
0.21 × 0.19 × 0.18 mm
◦
6.11–64.59
−12 ≤ h ≤ 14, −10 ≤ k ≤ 10, −6 ≤ l ≤ 2
3875/786 [R (int) = 0.0313]
98.5%
Reflections collected/unique
◦
Completeness to theta = 64.59
2
Refinement method
Full-matrix least-squares on F
Data/restraints/parameters
786/1/92
1.092
Goodness-of-fit on F2
Final R indices [I > 2sigma(I)]
R indices (all data)
Absolute structure parameter
Extinction coefficient
R1 = 0.0279, wR2 = 0.0737
R1 = 0.0279, wR2 = 0.0737
0.3(4)
0.168(8)
−3
Largest diff. peak and hole
0.153 and −0.137 e. Å
transition of the constituent group. Hence, the material may be useful for optoelectronic
applications.
Elemental Analysis
In order to confirm the chemical composition of the synthesized compound Carbon (C),
Hydrogen (H), and Nitrogen (N) analysis was carried out. The experimental and calculated
percentages of C, H, and N were given in Table 1.The differences between experimental
and calculated percentages of C, H, and N were very close to each other and within
the experimental errors. This confirms the formation of the product in the stoichiometric
proportion.
Single Crystal X-Ray Diffraction Method
A colorless block-shaped single crystal of the suitable size of the title compound was
selected for data collection. X-ray intensity data were collected for the title compound at
temperature 293 K, on Bruker AXS Proteum2 CCD diffractometer with X-ray generator

250
M. Prabhuswamy et al.
Table 3. Selected bond lengths and angles (Å, )
◦
O(10)-N(9)
C(2)-N(1)
1.4183(19)
1.337(3)
N(9)-C(7)
1.293(2)
C(4)-C(7)
1.476(2)
N(1)-C(6)
1.342(3)
C(7)-N(8)
1.356(2)
N(1)-C(2)-C(3)
C(7)-N(9)-O(10)
C(2)-N(1)-C(6)
N(9)-C(7)-N(8)
N(9)-C(7)-C(4)
N(8)-C(7)-C(4)
N(1)-C(6)-C(5)
123.66(19)
108.29(13)
116.73(16)
123.60(16)
117.91(13)
118.41(16)
123.66(18)
operating at 45 kV and 10 mA, using CuKα radiation (λ = 1.54178 Å). Data were collected
◦
◦
◦
with different settings of φ (0 and 90 ), keeping the scan width of 0.5 , exposure time of
s, the sample to detector distance was 45.10 mm [7]. A complete data set is processed
5
using the software SAINT PLUS [8]. The structure was solved by direct methods and
2
refined by full-matrix least squares method on F using SHELXS and SHELXL programs
[9]. All nonhydrogen atoms were revealed in the first difference Fourier map itself. All
hydrogen atoms were positioned geometrically (C–H = 0.93 Å, N–H = 0.86 Å, O–H =
0
.82 Å) and refined using a riding model with Uiso(H) = 1.2 Ueq (C,N) and Uiso(H) =
1.5 Ueq (O). After several cycles of refinement, the final difference Fourier map showed
peaks of no chemical significance and the residual is saturated to 0.0279. The geometrical
calculations were carried out using the program PLATON [10]. The molecular and packing
diagrams were generated using the software MERCURY [11].
X-ray diffraction analysis revealed that the title compound is crystallized in the or-
thorhombic crystal system with the space group Pna21. The unit cell parameters are a =
◦
◦
◦
1
6
5
2.5664(8) Å, b = 8.8622(6) Å, c = 5.7953(4) Å, α = 90 , β = 90 , γ = 90 , and V =
3
45.4(7) Å . The ORTEP view of the title molecule with displacement ellipsoids drawn at
0% probability level is shown in Fig. 5.
◦
Table 4. Selected torsion angles ( )
N(1)-C(2)-C(3)-C(4)
C(3)-C(2)-N(1)-C(6)
O(10)-N(9)-C(7)-N(8)
O(10)-N(9)-C(7)-C(4)
C(3)-C(4)-C(7)-N(9)
C(5)-C(4)-C(7)-N(9)
C(3)-C(4)-C(7)-N(8)
C(5)-C(4)-C(7)-N(8)
C(4)-C(5)-C(6)-N(1)
0.0(3)
0.4(3)
−3.4(3)
179.83(14)
156.65(16)
−23.7(2)
−20.3(2)
159.40(17)
−0.6(3)

ꢀ
Characterization of (Z)-2-N -hydroxyisonicotinamidine
251
◦
Table 5. Hydrogen bond geometry (Å, )
D—H···A
d(D—H)
d(H···A)
2.18
2.29
1.97
d(D···A)
2.4990(2)
3.1247(2)
2.7578(2)
<(DHA)
∗
N8—H8A···O10
0.86
0.86
0.82
102
162
162
i
N8—H8B···N9
ii
O10—H10···N1
∗
Symmetry codes: (i) 1/2−x, −1/2+y, 1/2+z; (ii) −1/2+x, 1/2−y, −1+z; ( ) Intramolecular inter-
action.
The packing of molecules when viewed down a-axis, b-axis, and c-axis are given in
Figs. 6–8, respectively. The crystal data and structure refinement details are given in Table 2.
Bond lengths and bond angles are given in Table 3. Torsion angles and Hydrogen-bond
geometry are given in Tables 4 and 5, respectively.
The pyridine ring, N1/C2/C3/C4/C5/C6 lies in the axial position with respect to the
plane described by the amidxoime chain N8—C7—N9—O10, confirmed by the dihedral
◦
◦
angle 21.83(9) . A torsion angle of 156.65(16) about C3—C4—C7—N9 confirms that the
pyridine ring attached at C7 reflects Anti-Periplanar conformation. The overall geometry
of the title compound is similar to the molecule N’-Hydroxynicotinamidine [12].
An intramolecular interaction N8–H8A···O10 forms a five-membered planar ring
C7/N8/H8A/O10/N9 with amidoxime chain. The crystal structure exhibits N8–H8A···π
interaction (N8–H8A···Cg1 [where Cg1 is the centroid of the ring N1/C2/C3/C4/C5/C6
with a symmetry code 1/2–x, –1/2+y, –1/2+z] with a N—Cg distance of 3.2956(17) Å,
◦
N—H···Cg angle of 138 ) and the structure is stabilized by the intermolecular interactions
of types N—H···O, N—H···N, and O—H···N in the crystal lattice.
Conclusion
ꢀ
The compound (Z)-2-N -hydroxyisonicotinamidine, (2) was synthesized and characterized
1
by means of H NMR, FAB-Mass, FT-IR, and UV–visible spectroscopy data. The molecular
structure of this compound was determined by single crystal XRD method. The crystal
structure of the title compound reveals a potentially tautomeric amidoximes to be the
amino-oxime form and it adopts a nonplanar cis-syn configuration. Spectral data show that
the material may be useful for optoelectronic applications.
Acknowledgments
The authors thank the IOE X-ray diffraction facility, University of Mysore, Mysore for
collecting the data.
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