Synthesis, spectral studies and structure of 2-hydroxyacetophenone nicotinic acid hydrazone

Article abstract of DOI:10.1016/S0022-2860(02)00563-X

2-Hydroxyacetophenone nicotinic acid hydrazone (H₂ApNH) was synthesized as a part of our work, in search for non-linear optical crystal based on hydrazones, and studied spectroscopically. Complete NMR assignments for the hydrazone was made usin

Full text of DOI:10.1016/S0022-2860(02)00563-X

Journal of Molecular Structure 645 (2003) 221–226
www.elsevier.com/locate/molstruc
Synthesis, spectral studies and structure of 2-hydroxyacetophenone
nicotinic acid hydrazone
a
a
a
a,
*
P.B. Sreeja , A. Sreekanth , Chandini R. Nayar , M.R. Prathapachandra Kurup ,
A. Usmanb, I.A. Razakb, S. Chantraprommab,1, H.K. Funb
aDepartment of Applied Chemistry, Cochin University of Science and Technology, Kochi 682022, Kerala, India
bX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
Received 14 August 2002; revised 18 October 2002; accepted 23 October 2002
Abstract
2-Hydroxyacetophenone nicotinic acid hydrazone (H2ApNH) was synthesized as a part of our work, in search for non-linear
optical crystal based on hydrazones, and studied spectroscopically. Complete NMR assignments for the hydrazone was made
using COSY homonuclear and HMQC heteronuclear correlation techniques. Solid state reflectance was also studied in order to
understand the electronic structure of the synthesized compound. The crystal and molecular structures of H2ApNH were
determined. The compound crystallizes into an orthorhombic lattice with a non-centrosymmetric space group Pca21 with two
crystallographically unique molecules of in an asymmetric unit. The geometry reveals quasi co planarity in the whole molecular
skeleton with localization of the double bonds in the CyN–N–CyO with an E-configuration.
q 2002 Elsevier Science B.V. All rights reserved.
Keywords: Hydrazone; 1H NMR; 13C NMR; HMQC; COSY; Crystal studies
1. Introduction
metals [1–4]. Copper(II) complex of salicylaldehyde
benzoylhydrazone was shown to be a potent inhibitor
of DNA synthesis and cell growth. This hydrazone
also has mild bacteriostatic activity and a range of
analogues has been investigated as potential oral iron
chelating drugs for genetic disorders such as thalas-
semia [5–8]. There are also some reports on the
catalytic activities of their nickel complexes [9–12].
Hydrazones have been the subject of extensive
investigation due to their versatile chelating behavior
in particular those derived from pyridoxal phosphate
and isonicotinic acid [13,14], but those having the side
chain at 2- position of the heteroaromatic ring have
received much less attention. The corresponding
nicotinic acid hydrazones have not been as much
Chemistry of Schiff bases has been intensively
investigated in recent years, owing their coordination
properties and diverse applications. Schiff base
hydrazones are widely used in analytical chemistry
as a selective metal extracting agent as well as in
spectroscopic determination of certain transition
*
Corresponding author. Tel.: þ91-484-575-804; fax: þ91-484-
577-595.
E-mail address: mrp@cusat.ac.in (M.R. Prathapachandra
Kurup).
1
Permanent Address: Department of Chemistry, Faculty of
Science, Prince of Songkla University, Hat Yai, Songkhla 90112,
Thailand.
0022-2860/03/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved.
PII: S0022-2860(02)00563-X

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P.B. Sreeja et al. / Journal of Molecular Structure 645 (2003) 221–226
Table 1
Summary of crystal data and structure refinement for H2ApNH
Empirical formula
Formula weight
Color; shape
C14H14N3O2
256.28
Greenish brown; block
213(2) K
Measured temperature
Crystal system
Orthorhombic
Pca21
Space group
˚
Unit cell dimensions
a ¼ 8.2221(1)(5)A, a ¼ 908
˚
b ¼ 11.3743(1)A, b ¼ 908
˚
c ¼ 26.3962(4)A, g ¼ 908
Fig. 1. Structure of H2ApNH.
3
Volume V (A )
˚
2468.59(5)
Z
8
investigated and to the best of our knowledge and
there are no reports on 2-hydroxyacetophenone
nicotinic acid hydrazone (H2ApNH) (Fig. 1). In this
paper we discuss the structural and spectroscopic
studies of H2ApNH.
Dx (g cm23
)
1.379
m (mm21
)
0.095
Absorption correction
F(000)
Empirical
1080
u range (8)
Completeness to u
h; k; l
3.06–28.278
92.2%
210/10, 215/12, 231/34
14083
Reflections collected
Reflections unique
2. Experimental
5588
Tmax/Tmin
0.9831 and 0.9540
Number of parameters
GoF
345
2.1. Materials
1.004
Final R indices ½I $ 2sðIÞꢀ
R1 ¼ 0:0995; wR2 ¼ 0:2415
2-Hydroxyacetophenone (CDH) and nicotinic acid
hydrazide (Fluka) were used as received. 2-Hydro-
xyacetophenone nicotinic acid hydrazone (H2ApNH)
was prepared by refluxing 1:1 molar methanolic
solution of 2-hydroxyacetophenone and nicotinic acid
hydrazide for 6 h. On cooling the reactant medium,
pale yellow needle like crystals were separated out,
which were isolated by filtration and recrystallised
from methanol. The melting point of the compound,
H2ApNH is found to be 180–182 8C. The empirical
formula given for the compound C14H13N3O2 was
confirmed by elemental analysis. Found C, 66.12; H,
5.20; N, 16.95%. Calculated C, 65. 87; H, 5.13; N,
16.46%. The 1H NMR, 13C NMR, COSY and HMQC
spectra were recorded by using Bruker DRX500,
using DMSO-d6 as solvent and TMS as standard. IR
spectrum was recorded on ECO2000 FTIR NICO-
LET, using KBr pellet. Solid state reflectance
spectrum was recorded on Ocean Optics, Inc.
SD2000 Fiber Optic Spectrometer.
23
˚
Residual highest peak and deepest 1.142 and 20.746 eA
hole
the
compound.
A
crystal,
of
size
0.18 £ 0.42 £ 0.52 mm3, was mounted on glass fiber
with epoxy cement for the X-ray crystallographic
study. A summary of the crystallographic data for the
title complex at 213 K is gathered in Table 1. The data
was collected with a 1-K SMART CCD diffractometer
using graphite-monochromated Mo Ka radiation with
a detector distance of 4 cm and swing angle of 2358.
A hemisphere of the reciprocal space was covered by
combination of three sets of exposures; each set had a
different of angle (0, 88, 1808) and each exposure of
30 s covered 0.38 in v. The structures were solved by
direct methods and refined by least-square on F20 using
the SHELXTL [15] software package. The selected
bond lengths and bond angles of H2ApNH are listed in
Table 2.
2.2. X-ray data collection, structure solution
and refinement
3. Results and discussion
Single crystals of the H2ApNH were obtained by
slow evaporation of a methanolic solution of
Solid state reflectance spectral data shows the p–
pp transition is at 31950 cm21
,
n–pp of

P.B. Sreeja et al. / Journal of Molecular Structure 645 (2003) 221–226
223
Table 2
Selected bond lengths (A) and bond angles (deg) of H2ApNH
Complete assignment of 13C–{1H} NMR spectra,
recorded at 125.76 MHz is given below. Assignment
of protonated carbons were made by two dimensional
heteronuclear-correlated experiment using delay
values which corresponds to 1J(C,H). The HMQC
experiment provides correlation between protons and
their attached heteronuclei through the heteronuclear
scalar coupling. This sequence is very sensitive
(compare to the older HETCOR) as it is based on
proton detection (instead of the detection of the least
sensitive low gamma heteronuclei). From (Fig. 3)
HMQC it is evident that C(5), C(6), C(7), C(8) and
C(9) are nonprotonated carbons. C(5) d ¼ 159.6, C(4)
d ¼ 119, C(3) d ¼ 133, C(2) d ¼ 119, C(1) d ¼ 129,
C(6) d ¼ 118, C(7) d ¼ 159.4, C(14) d ¼ 15, C(8)
d ¼ 164, C(9) d ¼ 120, C(10) d ¼ 129, C(11)
d ¼ 153, C(12) d ¼ 137, C(13) d ¼ 150.
˚
O(1)–C(8) 1.242(6)
O(2)–C(5) 1.355(6)
N(1)–C(7) 1.284(6)
N(1)–N(2) 1.382(5)
N(2)–C(8) 1.339(6)
N(3)–C(13) 1.362(7)
N(3)–C(9) 1.374(7)
C(1)–C(6) 1.387(6)
C(7)–N(1)–N(2) 117.7(4)
C(8)–N(2)–N(1) 120.8(4)
C(13)–N(3)–C(9) 122.7(5)
O(2)–C(5)–C(6) 124.1(4)
O(2)–C(5)–C(4) 115.8(4)
N(1)–C(7)–C(6) 116.3(4)
N(1)–C(7)–C(14) 123.6(5)
O(1)–C(8)–N(2) 123.9(5)
N(2)–C(8)–C(9) 114.7(5)
C(10)–C(9)–N(3) 119.8(6)
N(3)–C(9)–C(8) 120.5(5)
C(9)–C(8)–O(1) 121.4(6)
the azomethine is found at 29590 cm21 and n–pp of
carbonyl is at 26110 cm21 [16]. Significant IR bands
of the compound and their tentative assignments are
discussed here. A broad band obtained at 3432 cm21
is assigned to be due to the OH stretching. Other
major bands are at 3238, 1672 and 1603 cm21 which
are attributed to n(NH), n(CyO) and n(CyN),
respectively, [7,8].
3.1. Crystal structure of the compound H2ApNH
The molecule of H2ApNH crystallizes into an
orthorhombic lattice with a non-centrosymmetric
space group Pca21. There are two crystallographically
unique molecules of H2ApNH in the asymmetric unit.
The molecular structure showing 30% displacement
ellipsoids with atomic-numbering scheme is shown in
Fig. 4. The molecular packing of the molecule in a
unit cell is shown in Fig. 5.
The complete assignment of the 1H NMR spectra is
given here. The spectrum was recorded at 500 MHz.
The assignment is done on the basis of chemical
shifts, multiplicities and coupling constants. The
signals at d ¼ 13.28 ppm and d ¼ 11.56 ppm rep-
resent OH and NH, respectively. Upon addition of
D2O the intensities of both OH and NH protons
significantly decrease, confirming the assignment. We
got one more singlet at d ¼ 9.1, which is found to be
coupled with a proton of H(12) (d ¼ 8.3) from the
1H/1H correlation spectra. Hence it is assigned to be of
H(13), for which a doublet is expected. A singlet of
three protons at d ¼ 2.5 was attributed to the methyl
group protons which are chemically and magnetically
equivalent. At d ¼ 6.9 we got a quartet which is
assigned to be a merged form of one triplet and a
doublet corresponding to H(4) and H(2). OH
d ¼ 13.28(s), NH d ¼ 11.56(s), H(13) d ¼ 9.1(s),
H(11) d ¼ 8.8(d) J ¼ 3.5 Hz, H (12) dd ¼ 8.3(d)
J ¼ 8 Hz, H(10) d ¼ 7.6(dd) J ¼ 5 Hz, J ¼ 7.5 Hz,
H(1) d ¼ 7.7(d) J ¼ 8 Hz, H(3) d ¼ 7.3(t) J ¼ 8 Hz,
J ¼ 7.5 Hz, H(2) d ¼ 6.95(d) J ¼ 8.5 Hz, H(4)
d ¼ 6.90(d) J ¼ 7.5 Hz, H(14) d ¼ 2.5(s).
˚
The C8–O1 bond, which averages 1.242(6) A in
H2ApNH is longer than the CyO bond 1.236(4) in 3-
formylpyridine semicarbazone [16] indicating con-
siderable amount of the bond delocalisation with the
pyridyl ring. As expected the C7–N1 bond length is
˚
1.284(6) A is comparable to the corresponding bond
˚
length of 1.291 A reported for 2-hydroxyacetophe-
none thiosemicarbazone [17]. The O atom and the
hydrazinic N1 atom are trans with respect to C8–N2
bond. Structure of the compound reveals quasi
coplanarity of the whole molecular skeleton with
localization of the double bonds in the central –
CyN–N–CyO which has an E-configuration with
respect to the double bond of the hydrazone bridge. A
trans s-cis configuration is fixed around the N2–N1
˚
(1.382 A) single bond [18]. The phenolic ring
maintains coplanarity with the central chain. The
angle N2–C8–O1 (123.98) is significantly greater
than C9–C8–O1 (121.48) possibly in order to relive
repulsion between lone pairs of electrons on atoms N1
Coupling between different protons are shown in
Fig. 2.

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P.B. Sreeja et al. / Journal of Molecular Structure 645 (2003) 221–226
1
Fig. 2. H/1H coupling observed in COSY of H2ApNH.
and O1. The central part of the molecule C7–N1–
N2–C8–C9, adopts a completely extended confor-
4. Supplementary data
˚
mation. The bond lengths C7–N1 (1.284 A) and C8–
˚
O1 (1.242 A) are typical of double bonds. So that the
Crystallographic data for the structural analysis has
been deposited with the Cambridge Crystallographic
Data Center, CCDC 190821 for compound H2ApNH.
Copies of this information maybe obtained free of
charge from The Director, CCDC, 12 Union Road,
chain is likely correspond to C7yN1–N2–C8yO1. A
similar observation was reported for a related
molecule, pyridoxal isonicotinoyl hydrazone [19].

P.B. Sreeja et al. / Journal of Molecular Structure 645 (2003) 221–226
225
Fig. 3. 13C–1H HMQC spectrum of the H2ApNH.
Fig. 4. Perspective view of the two crystallographically unique molecules H2ApNH with atom numbering scheme with atom numbering
schemes and displacement ellipsoids at 50% probability level. Hydrogen atoms are shown as small spheres of arbitrary radii.

226
P.B. Sreeja et al. / Journal of Molecular Structure 645 (2003) 221–226
Fig. 5. Packing diagram of the compound H2ApNH.
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