Synthesis, vibrational, NMR, quantum chemical and structure-activity relation studies of 2-hydroxy-4-methoxyacetophenone

Article abstract of DOI:10.1016/j.saa.2014.03.121

The stable geometry of 2-hydroxy-4-methoxyacetophenone is optimised by DFT/B3LYP method with 6-311++G^* and cc-pVTZ basis sets. The structural parameters, thermodynamic properties and vibrational frequencies of the optimised geometry have been determined. The effects of substituents (hydroxyl, methoxy and acetyl groups) on the benzene ring vibrational frequencies are analysed. The vibrational frequencies of the fundamental modes of 2-hydroxy-4-methoxyacetophenone have been precisely assigned and analysed and the theoretical results are compared with the experimental vibrations. ¹H and ¹³C NMR isotropic chemical shifts are calculated and assignments made are compared with the experimental values. The energies of important MO's, the total electron density and electrostatic potential of the compound are determined. Various reactivity and selectivity descriptors such as chemical hardness, chemical potential, softness, electrophilicity, nucleophilicity and the appropriate local quantities are calculated.

Full text of DOI:10.1016/j.saa.2014.03.121

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Synthesis, vibrational, NMR, quantum chemical and structure-activity
relation studies of 2-hydroxy-4-methoxyacetophenone
b
a
c
d
V. Arjunan a, , L. Devi , R. Subbalakshmi , T. Rani , S. Mohan
⇑
a Department of Chemistry, Kanchi Mamunivar Centre for Post-Graduate Studies, Puducherry 605 008, India
b Research and Development Centre, Bharathiar University, Coimbatore 641 046, India
c Department of Chemistry, Rajiv Gandhi College of Engineering and Technology, Puducherry 605 402, India
d School of Sciences and Humanities, Vel Tech University, Avadi, Chennai 600 062, India
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
ꢀ
ꢀ
2-Hydroxy-4-methoxyacetophenone
has only one stable geometry.
Intramolecular hydrogen bond of the
type OAHꢁ ꢁ ꢁO is present with
O7AO11 is (2.56 Å).
ꢀ
ꢀ
ꢀ
The extreme limits of the electrostatic
potential is 1.082e ꢂ 10ꢃ2
.
The C@O carbon shows downfield
shift at 202.60 ppm.
The nO
strong stabilisation of
40.31 kcal molꢃ1
?
p⁄
interaction has
C1AC2
.
a r t i c l e i n f o
a b s t r a c t
Article history:
The stable geometry of 2-hydroxy-4-methoxyacetophenone is optimised by DFT/B3LYP method with
6-311++G⁄⁄ and cc-pVTZ basis sets. The structural parameters, thermodynamic properties and vibrational
frequencies of the optimised geometry have been determined. The effects of substituents (hydroxyl,
methoxy and acetyl groups) on the benzene ring vibrational frequencies are analysed. The vibrational
frequencies of the fundamental modes of 2-hydroxy-4-methoxyacetophenone have been precisely
assigned and analysed and the theoretical results are compared with the experimental vibrations. 1H
and 13C NMR isotropic chemical shifts are calculated and assignments made are compared with the
experimental values. The energies of important MO’s, the total electron density and electrostatic
potential of the compound are determined. Various reactivity and selectivity descriptors such as chemical
hardness, chemical potential, softness, electrophilicity, nucleophilicity and the appropriate local
quantities are calculated.
Received 13 December 2013
Received in revised form 8 March 2014
Accepted 29 March 2014
Available online 16 April 2014
Keywords:
FTIR
FT-Raman
2-Hydroxy-4-methoxyacetophenone
NMR
DFT
Ó 2014 Elsevier B.V. All rights reserved.
Introduction
resins of acetophenone with formaldehyde and base resulting
polymers used as components of coatings, adhesives and inks.
Acetophenone occurs naturally in many foods including apple,
cheese, apricot, banana and cauliflower. Commercially significant
Acetophenone is used to create fragrances that correspond to
almond, cherry, honeysuckle, jasmine and strawberry. It is used
in medicine; it was marketed as a hyptonic and anticonvulsant
under the brand name hypnone. Chloroacetophenone is primarily
used as a riot-control agent (tear gas) and in Chemical Mace
[1,2]. Hydroxyacetophenone is used as a building block for the
⇑
Corresponding author. Tel.: +91 413 2211111, mobile: +91 9442992223; fax:
+91 413 2251613.
E-mail address: varjunftir@yahoo.com (V. Arjunan).
http://dx.doi.org/10.1016/j.saa.2014.03.121
1386-1425/Ó 2014 Elsevier B.V. All rights reserved.

V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
165
synthesis of rubbers, plastics, pharmaceuticals, agrochemicals,
flavour and fragrances. In pharmaceuticals hydroxyacetophenone
is employed as an intermediate for the synthesis of medicine
named as propafenone which is used for curing arrhythmia [3].
2-Hydroxy-4-methoxyacetophone is a major component of
Moutan cortex, which has been used as a tranquillizer and an anti-
hypertensive [4]. It has analgesic, antipyretic and antibacterial
properties and finds use in the treatment of arthritis and suppress
ADP or collagen-induced human blood platelet aggregation in a
dose-dependent manner [5]. It has also been shown to possess
anti-inflammatory properties and to have a diuretic action [6].
2-Hydroxy-4-methoxyacetophenone is a major active component
of Chinese herbal medicines such as Cynanchi Paniculati Radix
(CPR, Xuchangqing in Chinese) [7,8] and Moutan Cortex (Mudanpi
in Chinese) [9,10]. Pharmacological evaluation revealed that
paeonol possesses cardio protective [11] and anti-diabetic [12]
effects, inhibits the anaphylactic reaction [13] and is beneficial in
the treatment of cardiovascular disorders [14] and colitis [15].
More importantly, it posses extensive pharmacological activity,
such as anti-atherosclerosis, anti-tumor, promoting blood circula-
tion and strengthening the immune system [16–19]. Furthermore,
paeonol has a good effect in curing rheumatic pain, stomach pain,
eczema and so on [20]. 2-Hydroxy-4-methoxyacetophenone can
improve blood flow, down-regulate transcription factors NF-kB
and AP-1 [15,21].
The FTIR spectrum is recorded by KBr pellet method on a Bruker
IFS 66V spectrometer equipped with a Globar source, Ge/KBr beam
splitter, and a TGS detector in the range of 4000–400 cmꢃ1. The
spectral resolution was 2 cmꢃ1. The FT-Raman spectrum is also
recorded in the range 4000–50 cmꢃ1 using the same instrument
with FRA106 Raman module equipped with Nd:YAG laser source
operating at 1.064 lm with 200 mW powers. A liquid nitrogen
cooled-Ge detector is used. The frequencies of all sharp bands are
accurate to 2 cmꢃ1. A total of 256 scans are used with a scanning
.
speed of 30 cmꢃ1 minꢃ1 The 1H (400 MHz; CDCl3) and 13C
(100 MHz; CDCl3) nuclear magnetic resonance (NMR) spectra were
recorded on a Brucker HC400 instrument. Chemical shifts for pro-
tons are reported in parts per million scales (d scale) downfield
from tetramethylsilane.
Computational details
The compound 2H4MAP was subjected to DFT calculation to
find the optimised geometrical parameters, thermodynamic prop-
erties, the charges of the atoms and vibrational frequencies. The
LCAO-MO-SCF restricted DFT-B3LYP correlation functional
calculations have been performed with Gaussian-09 [28] program,
invoking gradient geometry optimisation. The gradient corrected
density functional theory (DFT) [29] with the three-parameter
hybrid functional (B3) [30,31] for the exchange part and the
Lee–Yang–Parr (LYP) [32] correlation functional [33,34] with the
standard cc-pVTZ and high level 6-311++G⁄⁄ basis sets have been
used for the computation of molecular properties. The optimised
parameters of the compound 2H4MAP are used for harmonic
vibrational frequency calculations resulting in IR and Raman fre-
quencies together with intensities and Raman depolarisation
ratios. The force constants obtained from the B3LYP/6-311++G⁄⁄
method have been utilised in the normal coordinate analysis by
Wilson’s FG matrix method [35–37]. The potential energy distribu-
tions corresponding to each of the observed frequencies were
calculated with the program of Fuhrer et al. [38].
The vibrational spectral analysis were carried out by FTIR and
FT-Raman spectroscopy for 2,4-difluoroacetophenone [22],
3-methoxy acetophenone [23], acetophenone and 4-methoxyace-
tophenone adsorbed on silica–alumina catalyst [24], acetophe-
none, acetophenone-methyl-d3, and 4-methoxyacetophenone
[25], acetophenone,
a-fluoroacetophenone and propiophenone
have been subjected to ab initio conformational analysis [26] and
acetophenone and their deuterated analogues (d3, d5, d8) in the
liquid-phase [27].
Vibrational spectra and electronic structure properties of
2-hydroxy-4-methoxyacetophenone (2H4MAP) have not been
studied. Since the carbonyl group plays a vital role in determining
the physical and chemical properties of a molecule due to its high
permanent dipole moment, the spectral data for this compound is
of special interest. Thus, the experimental and theoretical studies
of 2H4MAP molecule, an important conjugated compound of indus-
trial and biological interest [4–21], have been reported in this inves-
tigation. The results are compared to the available experimental
data, in order to extract further information on the description
of molecular properties. The effect of AOH and AOCH3 groups
on the keto CAO group and the skeletal vibrations have been
discussed.
Isoelectronic molecular electrostatic potential surfaces (MEP)
and electron density surfaces [39] were calculated using
6-311++G⁄⁄ basis set. The molecular electrostatic potential (MEP)
at a point r in the space around a molecule can be expressed as:
Z
0
0
X
~
ZA
q
ðr Þdr
VðrÞ ¼
ꢃ
0
~
~
~
jr ꢃ rj
~
jRA ꢃ rj
A
where ZA is the charge on nucleus A, located at RA and
q
(r0) is the
electronic density function for the molecule. The first and second
terms represent the contributions to the potential due to nuclei
and electrons, respectively. V(r) is the resultant electric potential
at each point r, which is the net electrostatic effect produced at
the point r by both the electrons and nuclei of the molecule. The
molecular electrostatic potential (MEP) serves as a useful quantity
to explain hydrogen bonding, reactivity and structure-activity rela-
tionship of molecules including biomolecules and drugs. Structures
resulting from the plot of electron density surface mapped with
electrostatic potential surface depict the shape, size, charge density
distribution and the site of chemical reactivity of a molecule.
GaussView 5.0.8 visualisation program [40] has been utilised to
construct the MEP surface, the shape of highest occupied molecular
orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)
orbitals. The energy distribution of the molecular orbitals and
HOMO–LUMO energy gap have also been calculated by B3LYP/
6-311++G⁄⁄ method.
Experimental
Synthesis of 2-hydroxy-4-methoxyacetophenone
A mixture of 2,4-dihydroxyacetophenone (6 g, 39.5 mmol),
dimethyl sulfate (4.1 ml, 43.4 mmol) and potassium carbonate
(8.2 g, 59.2 mmol) in 100 ml acetone was stirred at room temper-
ature for 6 h. After completion of the reaction as indicated by
TLC, the solid was filtered off and the solvent was evaporated.
The residue was chromatographed over silica gel column using
petroleum ether/ethylacetate (9:1) as mobile phase to yield
2-hydroxy-4-methoxyacetophenone (5.2 g, 80%) as white solid.
Molecular weight: 166.17 g/mol. Melting point: 48–50 °C.
1H NMR (DMSOꢃd6) d: 12.73 (s, 1H), 7.61 (d, J = 8.9 Hz, 1H),
6.43 (dd, J = 8.9, 2.5 Hz, 1H), 6.41 (d, J = 2.5 Hz, 1H), 3.83 (s, 3H),
2.54 (s, 3H). 13C NMR (DMSOꢃd6) d: 202.60, 166.15, 165.28,
132.35, 113.93, 107.51, 100.91, 55.52, 26.12.
The Raman scattering activities (Si) calculated by Gaussian 03 W
program were suitably converted to relative Raman intensities (Ii)
using the following relationship derived from the basic theory of
Raman scattering [41].

166
V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
P
n
4
determined by using the relation xga
¼
k¼1xak where, n is the
fðm0
ꢃ
miÞ Si
Ii ¼
number of atoms coordinated to the reactive atom and xak is the
local electrophilicity of the atom k.
mi½1 ꢃ expðꢃhc i=kTÞꢄ
m
where v vi is the vibrational wave-
0 is the exciting frequency (cmꢃ1),
number of the ith normal mode, h, c and k are universal constants,
and f is the suitably chosen common scaling factor for all the peak
intensities.
Results and discussion
Conformational analysis
The isotropic chemical shifts are frequently used as an aid in
identification of organic compounds and accurate predictions of
molecular geometries are essential for reliable studies of magnetic
properties. The B3LYP-GIAO method is one of the best methods for
including electron correlation and allows calculating the nuclear
magnetic shielding tensors with accuracy [42,43]. The 1H and 13C
NMR isotropic shielding are calculated using the GIAO method
using the optimised parameters obtained from B3LYP/6-311++G⁄⁄
method. The isotropic shielding values are used to calculate
the isotropic chemical shifts d with respect to tetramethylsilane
The conformational analysis is carried out by potential surface
scan with B3LYP method using 6-31G⁄⁄ basis set in order to ascer-
tain the most stable geometry. During the scan, all the geometrical
parameters are simultaneously relaxed while the dihedral angle
C3AC2AO7AH22 is varied in steps of 15° ranging from 0° to
360°. The energy profile as a function of angle of rotation with
respect to the dihedral angle derived from potential energy surface
scan is shown in Fig. 1. All the possible conformers are optimised to
find out the energetically and thermodynamically most stable
configuration of the compound. The compound 2H4MAP has three
different conformers. The stability of the conformer is in the order
I > II > III. The energy profile obtained from DFT method shows a
true minima (I) at 0° and 360° while two more possible conformers
(II and III) are also obtained corresponding to the rotation on the
dihedral angle (C3AC2AO7AH22) 90° and 180°, respectively. The
conformer III with an angle of rotation 90° is the transition struc-
ture. The presence of large bulky groups in 2H4MAP leads to a very
high energy barrier to internal rotation and can be locked into one
most stable configuration (I).
(TMS). diso(X) =
r
TMS(X) ꢃ
riso(X), where diso – isotropic chemical
shift and riso – isotropic shielding. The electronic properties such
as HOMO and LUMO energies are determined by time-dependent
DFT (TD-DFT) approach, while taking solvent effect into account
[44–47].
Various reactivity and selectivity descriptors such as chemical
hardness, chemical potential, softness, electrophilicity, nucleophi-
licity and the appropriate local quantities employing natural
population analysis (NPA) scheme are calculated. Both the global
and local reactivity descriptors are determined using finite differ-
ence approximation to reveal the intramolecular reactivity of the
molecule. The vertical ionisation potential (I), electron affinity (A)
and the electron populations are determined on the basis of
B3LYP/6-311++G⁄⁄ method. The energy of the N electron species
of the 2H4MAP has been determined by restricted B3LYP method
while N ꢃ 1 and N + 1 electronic species are done by restricted
open B3LYP method using the geometry optimised with B3LYP/6-
311++G⁄⁄ method. The site-selectivity of a chemical system can
be determined by using Fukui function [48,49] which can be inter-
From the potential energy surface scan three conformers I, II
and III with relative energies 0.0, 12.25 and 18.93 kcal molꢃ1
,
respectively have been shortlisted. The optimised geometry,
scheme of atom numbering and the possible conformers of the
compound are shown in Fig. 2. Thus, the optimised structure (I)
corresponds to 0° and 360° in the PES surface belongs to the most
stable geometry of 2H4MAP molecule. In the conformer I, the car-
bonyl group (CAO) and the hydroxyl group (OAH) are within reach
to form CAOꢁ ꢁ ꢁHAO hydrogen bond while in the conformer II these
two groups are away from each other and there is no possibility of
intramolecular hydrogen bond. The relative energies indicate that
the conformer I is more stable due to the presence of intramolecu-
preted either as the change of electron density
q(r) at each point r
when the total number of electrons are changed or as the sensitiv-
ity of chemical potential (
l
) of a system to an external perturbation
at a particular point r.
lar hydrogen bonding than II and III by 12.25 and 18.93 kcal molꢃ1
respectively.
,
ꢀ
ꢁ
ꢀ
ꢁ
@
q
@N
ðrÞ
d
v
l
ðrÞ
fðrÞ ¼
¼
The most stable conformer (I) is exactly planar, where the
dihedral angles C2AC1AC10AO11, C3AC2AO7AH22 and
C1AC2AO7AH22 are 0°, 180° and 0°, respectively. Similarly, the
d
v
ðrÞ
N
Yang and Parr introduced local softness s(r) to predict the
reactivity [50]. The s(r) describes the sensitivity of the chemical
potential of the system to the local external perturbation and is
obtained by simply multiplying Fukui function f(r) with global
softness S. The local softness values are generally used in
predicting electrophilic, nucleophilic and free radical reactions,
regioselectivity, etc.
ꢀ
ꢁ
@
q
ðrÞ
sðrÞ ¼
and sðrÞ ¼ fðrÞS
@
l
v
ðrÞ
where S is the global softness which is inversely related to global
hardness ( ).
The generalised philicity descriptor,
g
x
(r) contains almost all
informations about hitherto known different global and local reac-
tivity and selectivity descriptors, in addition to the information
regarding electrophilic/nucleophilic power of a given atomic site
in a molecule [46]. The local quantity called philictiy associated
with a site k in a molecule can be calculated as xka
¼
x
fka, where
x
¼
l
2=2
g
and a = +, ꢃ and 0 represents local philic quantities
describing nucleophilic, electrophilic and radical attacks respec-
tively. The condensed philicity summed over a group of relevant
atoms which is defined as the group philicity [51] can also be
Fig. 1. Conformational energy profile of 2-hydroxy-4-methoxyacetophenone.

V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
167
Fig. 2. The structure, atom numbering scheme and the possible conformations of 2-hydroxy-4-methoxyacetophenone.
stable conformer (II) is also perfectly planar, where the dihedral
angles C2AC1AC10AO11, C3AC2AO7AH22 and C1AC2AO7AH22
are 180°, 180° and 0°, respectively. In the conformer III, the
acetyl (ACOCH3) group takes up the plane perpendicular to
the benzene ring and thus it is non-planar. The dihedral angle
C2AC1AC10AO11 of this conformer is 87.1°. The AOH group also
lie 2.2° (mean torsional angle of the oxygen atom) out of plane
from the benzene ring and the hydroxyl group leaning towards
the carbonyl group. The conformer III is the transition structure
between the conformers I and II. The barrier for the conversion
of the second stable conformer II to the most stable conformer I
The geometry in the 2H4MAP is dominated by hydrogen bond
involving the hydroxyl group and the oxygen atom of the carbonyl
group. The carbonyl and hydroxyl groups involves in the formation
of intramolecular hydrogen bond of the type OAHꢁ ꢁ ꢁO. The bond
distances of the OAHꢁ ꢁ ꢁO intramolecular hydrogen bond are
O7AH22 is (0.99 Å), H22ꢁ ꢁ ꢁO11 is (1.67 Å) and O7AO11 is (2.56
Å) respectively. These values are well agreed with the literature
[55]. In the case 4-hydroxy 3-methoxyacetophenone the groups
attached to the aromatic ring deviates slightly from coplanarity
with the ring [52]. But in the case 2H4MAP the orientations of
the carbonyl, methyl and methoxy groups with respect to the
aromatic ring are perfectly planar. This is confirmed by the
dihedral angle, C12AC10AC1AC2;180°, C12AC10AC1AC6;0°,
O8AC4AC3AC2;180°, O8AC4AC5AC6;180°, O11AC10AC1AC2;0°,
O11AC10AC1AC6;180°.
through the transition structure III is only 6.68 kcal molꢃ1
.
Structural properties
The optimised stable geometry and the scheme of atom num-
bering of the compound 2H4MAP are represented in Fig. 2. The
optimised structural parameters bond length, bond angle and the
dihedral angle for the more stable geometry of 2H4MAP
determined at B3LYP with 6-311++G⁄⁄ and cc-pVTZ basis sets are
presented in Table 1. The influence of the substituent on the
molecular parameters, particularly in the CAC bond distance of
ring carbon atoms seems to be small. The mean bond length
of aromatic ring is 1.40 Å. The longer bond length (1.46 Å) of
C1AC10 is due to the absence of delocalisation of carbonyl lone
pair of electrons towards the ring. Similarly, the bond C10AC12
has 1.51 Å because of the hyperconjugative effect of the methyl
group and the due to the partial ionic character of the CAO group,
decreases in force constant and increase in bond length. The bond
length of C10AO11 and C10AC12 are 1.24 and 1.51 Å, respectively
shows an excellent results with the bond length of 4-hydroxy
3-methoxyacetophenone [52].
The molecular geometry in the 2H4MAP is determined in order
to study the geometric distortions in the substituted benzene ring
and to investigate the possibilities for intramolecular hydrogen
bonding. Intramolecular hydrogen bonding has little effect on the
length of the CAO bond of the participating phenol group of
2H4MAP and four different CAO bond lengths are found in the
molecule: e.g. C2AO7 is 1.34 Å, C4AO8 is 1.35 Å, C9AO8 is 1.43
Å and C10AO11 is 1.24 Å. The bond length C4AO8 (1.35 Å) is con-
siderably shortened in relation to the CAO bond distance (1.381 Å)
of phenol [53]. While the bond length C10AO11 (1.24 Å) of
2H4MAP is elongated with respect to acetophenone (CAO; 1.216
Å) [54]. This is due to the existence of keto-enol tautomerism.
Analysing the bond angle of aromatic ring of 2H4MAP, one can
observe that the geometry of the benzene ring is seen to be rela-
tively perturbed due to the presence of different substituents. With
the electron donating and withdrawing substituents on the benzene
ring, the symmetry of the ring is distorted, yielding variation in bond
angles at the point of substitution and at the ortho and meta posi-
tions as well. The studies indicated that the interior bond angle, at
the carbon to which a methyl, hydroxyl or amino group is attached,
is invariably smaller than that normally adopted as the interior
bond angle of the benzene ring [56,57]. On the other hand, the inte-
rior bond angle at the carbon to which a nitro group is attached
invariably exceeds the normal 120° [58]. The bond angle C2AC1AC6
is 117.6° where the ACOCH3 group is attached while at ortho posi-
tions the bond angle C1AC2AC3 is found to be 120.6° while the
bond angle C1AC6AC5 is 122.1°. This indicates that the inner bond
angle is less than 120° where the electron withdrawing acetyl group
attached while the inner ortho bond angles are more than 120°. This
is also due to the predominance of the partial ionic nature of the
carbonyl group. Similarly, the bond angle C1AC2AC3 and
C3AC4AC5 where the electron donating hydroxyl and methoxy
groups attached are more than 120°. These are determined by
B3LYP/6-311++G⁄⁄ method as 120.6° and 120.5°, respectively.
Thermodynamic analysis
The thermodynamic parameters of the compound have also
been computed and presented in Table 2, in order to get reliable
data from which the relations among energy, structure and

168
V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
Table 1
Table 1 (continued)
Structural parameters of 2-hydroxy-4-methoxyacetophenone calculated byB3LYP/6-
Structural
parameters
B3LYP/6-
311G++⁄⁄
B3LYP/cc- Experimentala Experimentalb
pVTZ
311G++⁄⁄ and B3LYP/cc-pVTZ methods.
Structural
parameters
B3LYP/6-
311G++⁄⁄
B3LYP/cc- Experimentala Experimentalb
pVTZ
C2AC3AC4AO8
H13AC3AC4AC5
H13AC3AC4AO8
C3AC4AC5AC6
C3AC4AC5AH14
O8AC4AC5AC6
O8AC4AC5AH14
C3AC4AO8AC9
C5AC4AO8AC9
C4AC5AC6AC1
C4AC5AC6AH15
H14AC5AC6AC1
H14AC5AC6AH15
C4AO8AC9AH19
C4AO8AC9AH20
C4AO8AC9AH21
C1AC10AC12AH16
C1AC10AC12AH17
C1AC10AC12AH18
ꢃ180.0
ꢃ180.0
0.0
ꢃ180.0
ꢃ180.0
0.0
179.05
Bond distance (Å)
C1@C2
C1AC6
C1AC10
C2AC3
C2AO7
1.42
1.41
1.46
1.40
1.34
1.39
1.08
1.41
1.35
1.37
0.99
1.43
1.09
1.24
1.51
1.67
1.09
1.42
1.41
1.46
1.40
1.33
1.39
1.08
1.41
1.35
1.37
0.99
1.42
1.09
1.24
1.51
1.65
1.09
1.40
1.40
1.49
1.39
1.35
1.38
1.42
1.40
1.47
1.40
1.34
1.38
0.0
0.0
180.0
180.0
0.0
180.0
180.0
0.0
179.5
179.5
0.0
0.0
C3@C4
ꢃ180.0
ꢃ180.0
CAH (ring)c
C4AC5
0.0
0.0
1.38
1.37
1.38
1.40
1.38
ꢃ180.0
180.0
0.0
180.0
ꢃ61.2
61.2
ꢃ180.0
180.0
0.0
180.0
ꢃ61.2
61.2
C4AO8
C5@C6
O7AH22
O8AC9
1.43
C9AHc
C10@O11
C10AC12
O11ꢁ ꢁ ꢁH22
C12AHc
1.23
1.50
1.23
1.51
ꢃ59.8
ꢃ59.7
59.8
59.8
180.0
180.0
120.2
ꢃ120.3
0.0
O11AC10AC12AH16 120.2
O11AC10AC12AH17 ꢃ120.2
O11AC10AC12AH18
0.0
Bond angle (°)
C2AC1AC6
C2AC1AC10
C6AC1AC10
C1AC2AC3
C1AC2AO7
C3AC2AO7
C2AC3AC4
C2AC3AH13
C4AC3AH13
C3AC4AC5
C3AC4AO8
C5AC4AO8
C4AC5AC6
C4AC5AH14
C6AC5AH14
C1AC6AC5
C1AC6AH15
C5AC6AH15
C2AO7AH22
C4AO8AC9
O8AC9AH19
O8AC9AH20
O8AC9AH21
HAC9AHc
C1AC10AO11
C1AC10AC12
O11AC10AC12
C10AC12AH16
C10AC12AH17
C10AC12AH18
HAC12AH
117.6
119.8
122.6
120.6
122.0
117.3
119.8
117.5
122.6
120.5
124.1
115.3
119.3
118.8
121.9
122.1
119.2
118.6
106.6
119.0
105.7
111.2
111.2
109.6
121.0
120.2
118.8
111.0
111.0
108.5
108.7
117.6
119.3
118.7
a
b
c
Values taken from Ref. [52].
Values taken from Ref. [55].
Mean value.
119.7
122.7
120.6
121.8
117.6
119.9
117.6
122.5
120.5
124.1
115.4
119.3
118.8
121.8
122.1
119.2
118.6
106.1
118.9
105.9
111.3
111.3
109.5
121.2
120.2
118.6
111.0
111.0
108.6
108.7
119.0
121.7
119.6
122.0
118.4
120.2
119.8
121.5
120.0
122.1
118.0
120.6
Table 2
The thermodynamic parameters calculated by B3LYP method with 6-311++G and
cc-pVTZ basis sets-energies of frontier molecular orbitals and global reactivity
descriptors of 2-hydroxy-4-methoxyacetophenone.
120.0
125.9
114.0
120.2
119.4
121.5
119.8
Thermodynamic parameters (298 K)
B3LYP/
B3LYP/
cc-pVTZ
6-311++G⁄⁄
SCF energy (a.u)
ꢃ574.822043 ꢃ574.870715
Total energy (thermal) – Etotal (kcal molꢃ1
Heat capacity at const. volume – Cv
)
116.47
42.28
116.80
41.84
(cal molꢃ1 Kꢃ1
)
120.6
116.8
Entropy – S (cal molꢃ1 Kꢃ1
)
103.29
114.70
109.45
102.44
115.02
109.87
Vibrational energy – Evib (kcal molꢃ1
Zero-point vibrational energy – E0
)
(kcal molꢃ1
)
Rotational constants (GHz)
A
B
C
2.15
0.56
0.45
2.16
0.56
0.45
119.9
120.1
120.1
120.3
120.0
119.7
Dipolemoment (Debye)
lx
ly
lz
ꢃ2.12
ꢃ2.03
ꢃ2.20
ꢃ2.04
0.00
0.00
ltotal
3.06
2.88
ELUMO+1 (eV)
ELUMO (eV)
EHOMO (eV)
EHOMOꢃ1 (eV)
ELUMO (eV) ꢃ EHOMO (eV)
Ionisation potential – I (eV)
Electron affinity – A (eV)
ꢃ0.4800
ꢃ1.8131
ꢃ6.4366
ꢃ6.9949
4.6235
8.1530
ꢃ0.1377
4.0076
ꢃ4.0076
1.9373
4.1453
0.1206
10.0902
2.0750
ꢃ0.2797
ꢃ1.6526
ꢃ6.3074
ꢃ6.8756
4.6548
Dihedral angle (°)
C6AC1AC2AC3
C6AC1AC2AO7
C10AC1AC2AC3
C10AC1AC2AO7
C2AC1AC6AC5
C2AC1AC6AH15
C10AC1AC6AC5
C10AC1AC6AH15
C2AC1AC10AO11
C2AC1AC10AC12
C6AC1AC10AO11
C6AC1AC10AC12
C1AC2AC3AC4
C1AC2AC3AH13
O7AC2AC3AC4
O7AC2AC3AH13
C1AC2AO7AH22
C3AC2AO7AH22
C2AC3AC4AC5
0.0
180.0
180.0
0.0
0.0
180.0
180.0
0.0
0.0
0.0
ꢃ180.0
ꢃ180.0
0.0
ꢃ180.0
ꢃ180.0
0.0
Electronegativity (
Chemical potential (
Electrophilicity (
Hardness (
Softness (S)
v)
l
179.5
173.0
)
x)
0.0
0.0
g
)
ꢃ180.0
ꢃ180.0
0.0
ꢃ180.0
ꢃ180.0
0.0
Electrofugality (
Nucleofugality (
D
D
Ee)
En)
0.0
0.0
ꢃ180.0
ꢃ180.0
0.0
0.0
180.0
0.0
ꢃ180.0
ꢃ180.0
0.0
0.0
180.0
0.0
ꢃ179.3
reactivity characteristics of the molecule can be obtained.
Knowledge of permanent dipole moment of a molecule provides
wealth of information. It can allow us to determine a molecule’s

V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
169
Fig. 3. (a) The total electron density mapped with electrostatic potential surface and (b) the electrostatic potential contour map of 2-hydroxy-4-methoxyacetophenone.
is due to the inductive influence of the hydroxyl and methoxy
groups, and become relatively more important as its mesomeric
influence is reduced by steric factors [59].
Analysis of molecular electrostatic potential
Molecular electrostatic potential (MEP) mapping is very useful
in the investigation of the molecular structure with its physio-
chemical property relationships [39,60–62]. Total SCF electron
density surface mapped with molecular electrostatic potential
(MEP) of 2H4MAP determined by B3LYP/6-311++G⁄⁄ method is
shown in Fig. 3(a) while the contour map of the molecular electro-
static potential is given in Fig. 3(b). The MEP surface displays the
molecular shape, size and electrostatic potential values.
The colour scheme for the MEP surface is red-electron rich or
partially negative charge; blue-electron deficient or partially
positive charge; light blue-slightly electron deficient region; yel-
low-slightly electron rich region, respectively. The oxygen atoms
have more negative potentials and the hydrogen atoms have more
positive potentials. The extreme limits of the electron density
observed in 2H4MAP is 4.279e ꢂ 10ꢃ2. The MEP of 2H4MAP
clearly indicates the electron rich centres of oxygen atoms. The
Molecular electrostatic potential surface of 2H4MAP determined
by B3LYP/6-311++G⁄⁄ method is shown in the supplementary
Fig. S1. The minimum and maximum limits of the electrostatic
potential observed in 2H4MAP are 1.082e ꢂ 10ꢃ2
.
Frontier molecular orbitals
Highest occupied molecular orbital (HOMO) and lowest unoc-
cupied molecular orbital (LUMO) are very important parameters
for quantum chemistry. The energies of HOMO, LUMO, LUMO+1
and HOMOꢃ1 and their orbital energies are calculated using
B3LYP/6-311++G⁄⁄ method and the pictorial illustration of the
frontier molecular orbitals are shown in Fig. 4. Molecular orbitals
provide insight into the nature of reactivity and some of the
structural and physical properties of molecules. The positive and
negative phase is represented in red and green colour, respectively.
The plots reveal that the region of HOMO spread over the entire
molecule of 2H4MAP while in the case of LUMO it is spread over
the entire molecule except on acetyl group. The calculated energy
Fig. 4. The frontier molecular orbitals of 2-hydroxy-4-methoxyacetophenone.
conformation. The total thermal energies, vibrational energy
contribution to the total energy, the rotational constants and the
dipole moment values obtained from DFT/B3LYP methods are well
agreed with the literature. The dipole moment of 2H4MAP (3.06 D)

170
V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
Table 3
Bond orbital analysis of 2-hydroxy-4-methoxyacetophenone.
Bond orbital
Occupancy
1.9760
Atom
Contribution from parent NBO (%)
Co-efficiency
Atomic hybrid contributions (%)
C1AC2
C1
50.77
49.23
61.75
38.25
51.20
48.80
52.14
47.86
49.86
50.14
34.22
65.78
50.20
49.80
57.80
42.20
61.18
38.82
50.67
49.33
33.16
66.84
50.07
49.93
54.24
45.76
60.91
39.09
60.24
39.76
67.54
32.46
59.65
40.35
59.11
40.89
59.11
40.89
34.59
65.41
29.14
70.86
48.52
51.48
60.75
39.25
60.75
39.25
61.40
38.60
0.7125
0.7016
0.7858
0.6185
0.7155
0.6986
0.7221
0.6918
0.7061
0.7081
0.5850
0.8110
0.7085
0.7057
0.7603
0.6496
0.7822
0.6230
0.7118
0.7024
0.5759
0.8175
0.7076
0.7066
0.7365
0.6765
0.7804
0.6252
0.7761
0.6306
0.8218
0.5698
0.7723
0.6352
0.7689
0.6394
0.7689
0.6394
0.5881
0.8088
0.5398
0.8418
0.6966
0.7175
0.7794
0.6265
0.7794
0.6265
0.7836
0.6213
s(32.76) + p2.05 (67.11)
s(36.66) + p1.73 (63.28)
s(0.00) + p1.00 (99.96)
s(0.00) + p1.00 (99.95)
s(35.02) + p1.85 (64.90)
s(35.32) + p1.83 (64.59)
s(32.19) + p2.10 (67.70)
s(35.97) + p1.78 (63.98)
s(36.28) + p1.75 (63.65)
s(35.23) + p1.83 (64.63)
s(27.03) + p2.70 (72.91)
s(33.60) + p1.97 (66.07)
s(35.47) + p1.81 (64.37)
s(37.78) + p1.65 (62.15)
s(0.00) + p1.00 (99.91)
s(0.00) + p1.00 (99.95)
s(29.20) + p2.42 (70.72)
s(99.97) + p0.00 (0.03)
s(36.05) + p1.77 (63.89)
s(33.94) + p1.94 (65.94)
s(26.12) + p2.82 (73.75)
s(33.26) + p2.00 (66.64)
s(37.03) + p1.70 (62.87)
s(36.86) + p1.71 (63.03)
s(0.00) + p1.00 (99.93)
s(0.00) + p1.00 (99.95)
s(28.99) + p2.45 (70.92)
s(99.92) + p0.00 (0.06)
s(27.78) + p2.60 (72.15)
s(99.93) + p0.00 (0.06)
s(27.46) + p2.64 (72.44)
s(22.96) + p3.35 (76.89)
s(25.29) + p2.95 (74.64)
s(99.90) + p0.00 (0.08)
s(25.95) + p2.85 (73.98)
s(99.91) + p0.00 (0.08)
s(25.95) + p2.85 (73.98)
s(99.91) + p0.00 (0.08)
s(30.71) + p2.25 (69.21)
s(39.82) + p1.50 (59.69)
s(0.00) + p1.00 (99.83)
s(0.00) + p1.00 (99.67)
s(33.34) + p2.00 (66.60)
s(28.74) + p2.48 (71.19)
s(23.43) + p3.27 (76.50)
s(99.91) + p0.00 (0.07)
s(23.43) + p3.27 (76.50)
s(99.91) + p0.00 (0.07)
s(24.34) + p3.11 (75.59)
s(99.91) + p0.00 (0.07)
C2
C1
C2
C1
C6
C1
C10
C2
C3
C2
O7
C3
C4
C3
C4
C3
H13
C4
C5
C4
O8
C5
C6
C5
C6
C5
H14
C6
H15
O8
C9
C9
H19
C9
H20
C9
C1@C2
1.5894
1.9749
1.9804
1.9767
1.9934
1.9820
1.6919
1.9730
1.9737
1.9903
1.9795
1.7544
1.9744
1.9742
1.9913
1.9896
1.9941
1.9941
1.9946
1.9752
1.9893
1.9732
1.9732
1.9879
C1AC6
C1AC10
C2AC3
C2AO7
C3AC4
C3@C4
C3AH13
C4AC5
C4AO8
C5AC6
C5@C6
C5AH14
C6AH15
O8AC9
C9AH19
C9AH20
C9AH21
C10AO11
C10@O11
C10AC12
C12AH16
C12AH17
C12AH18
H21
C10
O11
C10
O11
C10
C12
C12
H16
C12
H17
C12
H18
gap of HOMO–LUMO’s explains the ultimate charge transfer
interface within the molecule.
such as type of bond orbital, their occupancies, the natural atomic
hybrids of which the NBO is composed, giving the percentage of
the NBO on each hybrid, the atom label and a hybrid label showing
the hybrid orbital (spx) composition (the amount of s-charac-
ter, p-character, etc.) of 2-hydroxy-4-methoxyacetophenone
determined by B3LYP/6-311++G⁄⁄ method. The occupancies of
NBOs reflecting their exquisite dependence on the chemical
environment. The Lewis structure that is closest to the optimised
structure is determined.
The energies of the frontier molecular orbitals of 2-hydroxy-
4-methoxyacetophenone employing B3LYP method using
6-311++G⁄⁄ and cc-pVTZ basis sets are given in Table 2. The fron-
tier orbital energy gap calculated by B3LYP/cc-pVTZ method
(ELUMO ꢃ EHOMO) in case of 2H4MAP is found to be is 4.6548 eV.
Natural bond orbital (NBO) analysis
For example, the bonding orbital for C1AC2 with 1.976 elec-
trons has 50.77% C1 character in a sp2.05 hybrid and has 49.23%
C2 character in a sp1.73 hybrid orbital. In the case of C10AO11
bonding orbital with 1.9752 electrons has 29.14% C10 character
and has 70.86% O11 character. A bonding orbital for C4AO8 with
1.9903 electrons has 33.16% C4 character in a sp2.82 hybrid and
has 66.84% O8 character in a sp2.00 orbital. The O8AC9 with
1.9913 electrons has 67.54% O8 character in a sp2.64 hybrid and
has 32.46% C9 character in a sp3.35 orbital. The CAC bonds of the
aromatic ring posses more p character than s character. This is
The analysis of the bond orbitals of 2H4MAP by B3LYP/6-
311++G⁄⁄ method is carried out to provide the occupancy,
contribution to the parent NBO and mainly on the percentage
contributions of the atoms present in the bond. NBO analysis of
molecules illustrate the deciphering of the molecular wavefunction
in terms Lewis structures, charge, bond order, bond type, hybrid-
isation, resonance, donor–acceptor interactions, charge transfer
and resonance possibility. Table 3 depicts the bonding concepts

V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
171
Table 4
[63–66]. This energy represents the estimate of the off-diagonal
NBO Fock matrix element. The stabilisation energy E(2) associated
with i (donor) ? j (acceptor) delocalisation is estimated from the
second-order perturbation approach as given below
Second order perturbation theory analysis of Fock matrix of 2-hydroxy-4-methoxy-
acetophenone using NBO analysis.
Donor (i) ꢃ Acceptor
(j) interaction
E(2)a
E(j) ꢃ E(i)b
F(i ꢃ j)e
(kcal molꢃ1
)
(a.u.)
(a.u.)
F2ði; jÞ
p
p
p
p
r
p
p
r
r
r
p
(C1AC2) ? p⁄ (C1AC2)
(C1AC2) ? p⁄ (C3AC4)
(C1AC2) ? p⁄ (C5AC6)
4.32
12.27
24.85
0.26
0.27
0.28
0.25
1.07
0.28
0.29
1.02
1.03
0.96
0.27
0.28
1.03
1.05
1.02
1.03
0.91
0.52
0.030
0.052
0.077
0.082
0.065
0.080
0.054
0.061
0.059
0.057
0.054
0.074
0.064
0.060
0.062
0.062
0.058
0.047
Eð2Þ ¼ q
i ej
ꢃ
ei
(C1AC2) ? p⁄ (C10AO11) 30.26
where qi is the donor orbital occupancy, ei and ej are diagonal
elements (orbital energies) and F(i, j) is the off-diagonal Fock matrix
element.
The different types of donor–acceptor interactions and their
stabilisation energy are determined by second order perturbation
analysis of Fock matrix of 2H4MAP. The stabilisation energy of
all lone pair–bond pair interactions and only bond pair–bond pair
interactions are listed in Table 4. In 2H4MAP molecule, the lone
(C2AC3) ? r⁄ (C4AO8)
(C3AC4) ? p⁄ (C1AC2)
(C3AC4) ? p⁄ (C5AC6)
(C3AH13) ? r⁄ (C1AC2)
(C3AH13) ? r⁄ (C4AC5)
(C4AC5) ? r⁄ (O8AC9)
(C5AC6) ? p⁄ (C1AC2)
(C5AC6) ? p⁄ (C3AC4)
(C5AH14) ? r⁄ (C1AC6)
(C5AH14) ? r⁄ (C3AC4)
(C6AH15) ? r⁄ (C1AC2)
(C6AH15) ? r⁄ (C4AC5)
(C9AH19) ? r⁄ (C4AO8)
(C12AH16) ? p⁄
4.88
26.79
12.40
4.51
4.27
4.24
11.99
22.98
4.94
4.32
4.70
p
r
r
r
r
r
r
pair donor orbital, nO
?
p⁄CC interaction between the O(7) lone pair
and the C1AC2 antibonding orbital gives a strong stabilisation of
40.31 kcal molꢃ1. The n ? r⁄ stabilisation energy of lone pair of
electrons present in the oxygen atom (O8) to the antibonding orbital
4.72
4.59
4.91
(C10AO11)
(
r⁄) of (C3AC4) is 34.68 kcal molꢃ1. The bond pair donor orbital,
r
(C12AH17) ? p⁄
4.90
0.52
0.047
pCC
rCC
?
?
p⁄CO interactions give more stabilisation than pCC
r⁄CC interactions.
?
p⁄CC and
(C10AO11)
r
(C12AH18) ? r⁄ (C1AC10) 4.53
0.95
1.08
0.32
0.98
1.10
0.34
0.67
0.67
1.13
0.75
0.66
0.059
0.088
0.109
0.076
0.086
0.102
0.057
0.057
0.073
0.087
0.104
n[LP(1)] (O7) ? r⁄ (C1AC2)
n[LP(2)] (O7) ? p⁄ (C1AC2)
n[LP(3)] (O7) ? r⁄ (C2AC3)
n[LP(1)] (O8) ? r⁄ (C3AC4)
8.95
40.31
5.77
NMR spectral studies
8.36
n[LP(2)] (O8) ? r⁄ (C3AC4) 34.68
n[LP(2)] (O8) ? r⁄ (C9AH20) 5.50
n[LP(2)] (O8) ? r⁄ (C9AH21) 5.50
n[LP(1)] (O11) ? r⁄ (C1AC10) 5.88
n[LP(2)] (O11) ? r⁄ (C1AC10) 12.01
NMR spectroscopy has proved to be an exceptional tool to elu-
cidate structure and molecular conformation. Density functional
theory (DFT) shielding calculations are rapid and applicable to
large systems. The ‘‘gauge independent atomic orbital’’ (GIAO)
method [67–70] has proven to be quite accepted and accurate.
To provide an explicit assignment and analysis of 13C and 1H
NMR spectra, theoretical calculations on chemical shift of the title
compound are carried out by GIAO method at B3LYP/6-311++G⁄⁄
level [71] with CHCl3 solvent. The 1H and 13C NMR spectra of
2H4MAP are illustrated in the supplementary Figs. S2 and S3,
respectively.
n[LP(2)] (O11) ? r⁄
(C10AC12)
19.39
LP – Lone pair.
a
Stabilisation (delocalisation) energy.
Energy difference between i(donor) and j(acceptor) NBO orbitals.
Fock matrix element i and j NBO orbitals.
b
e
The 1H and 13C theoretical and experimental chemical shifts,
isotropic shielding tensors and the chemical shift assignments
are presented in Table 5. The hydrogen atoms are mostly localised
on periphery of the molecules and their chemical shifts would be
more susceptible to intermolecular interactions as compared to
that for other heavier atoms. Unsaturated carbons give signals in
overlapped areas of the spectrum with chemical shift values from
100 to 200 ppm [72]. 13C NMR spectra exhibit signals somewhat
downfield of 200 ppm depending on the structure. Such signals
are typically weak due to the absence of nuclear Overhauser
effects. The external magnetic field experienced by the carbon
nuclei is affected by the electronegativity of the atoms attached
to them. The effect of this is that the chemical shift of the carbon
increases if the carbon is attached to an electronegative atom.
clearly indicates the delocalisation of
carbon atoms. Similarly C10AO11 bond has also posses more p
character.
p electrons among all the
Natural bond orbital (NBO) analysis is
a useful tool for
understanding delocalisation of electron density from occupied
Lewis-type (donor) NBOs to properly unoccupied non-Lewis type
(acceptor) NBOs within the molecule. The stabilisation of orbital
interaction is proportional to the energy difference between
interacting orbitals. Therefore, the interaction having strongest
stabilisation takes place between effective donors and effective
acceptors. This bonding–antibonding interaction can be quantita-
tively described in terms of the NBO approach that is expressed
by means of second-order perturbation interaction energy E(2)
Table 5
The experimental and calculated 1H and 13C isotropic chemical shifts (diso – ppm) with respect to TMS and isotropic magnetic shielding tensors (
r
iso) of 2-hydroxy-4-
methoxyacetophenone.
Assignment
riso (1H)
Cal. (diso
)
Expt. (d)
Assignment
riso
(
13C)
Cal. (diso
)
Expt. (d)
H13
H14
H15
H16
H17
H18
H19
H20
H21
H22
25.23
25.10
23.79
28.80
28.80
29.68
27.57
27.88
27.88
18.17
6.74
6.87
8.18
3.17
3.17
2.29
4.40
4.09
4.09
13.80
6.41
6.43
7.61
2.54
2.54
2.54
3.83
3.83
3.83
12.73
C1
C2
C3
C4
C5
C6
C9
C10
C12
66.33
8.63
82.33
9.27
71.24
45.31
126.76
ꢃ25.52
155.63
118.2
175.9
102.2
175.26
113.29
139.22
57.77
210.05
28.90
113.93
165.28
100.91
166.15
107.51
132.35
55.52
202.60
26.12

172
V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
Thus, the carbonyl carbon atom C10 in 2H4MAP show very
downfield effect and the corresponding observed chemical shift
is 202.60 ppm.
The more electronegative character of the oxygen atoms ren-
ders a positive charge to the carbon and thus C2 and C4 chemical
shifts are observed in the more downfield shift at 165.28 and
166.15 ppm. The chemical shift values of other carbon atoms of
2H4MAP are observed at 132.35, 113.93 and 107.51 ppm and are
attributed to C6, C1 and C5, respectively. The methyl carbon atom
(C9) connected to the O8 oxygen atom of 2H4MAP give signal in
the upfield chemical shift at 55.52 ppm.
The 1H chemical shifts of 2H4MAP are obtained by complete
analysis of their NMR spectra and interpreted critically in an
attempt to quantify the possible different effects acting on the
shielding constant and in turn to the chemical shift of protons.
The hydrogen atom H13, H14 and H15 attached with the aromatic
carbons of 2H4MAP shows three peaks at 6.41, 6.43 and 7.61 ppm,
respectively. The hydrogen atom H19, H20 and H21 attached with
the methyl carbon of 2H4MAP are in the same chemical environ-
ment and shows one peak at 3.83 ppm. The linear correlation
between the experimental and theoretical 1H and 13C NMR
chemical shifts are represented in the supplementary Fig. S4.
Vibrational analysis
The geometry of the molecule is possessing Cs point group
symmetry. The 60 fundamental modes of vibrations are span into
41 in-plane modes of A0 and 19 out of plane bending vibrations
of A00 species. All the vibrations are active in both IR and Raman.
The observed FTIR and FT-Raman spectra of 2H4MAP are shown
in Figs. 5 and 6. The observed FTIR and FT-Raman wavenumbers
along with the theoretical infrared and Raman frequencies of along
Fig. 6. (a) Experimental FT-Raman, (b) theoretical B3LYP/cc-pVTZ and (c) B3LYP/
6-311++G⁄⁄ simulated Raman spectra of 2-hydroxy-4-methoxyacetophenone.
with their relative intensities and probable assignments are
summarised in Table 6.
Scale factors
A better agreement between the computed and experimental
frequencies can be obtained by using different scale factors for
different types of fundamental vibrations. To determine the scale
factors, the procedure used previously [73–82] have been followed
that minimises the residual separating experimental and theoreti-
cally predicted vibrational frequencies. The optimum scale factors
for vibrational frequencies were determined by minimising the
residual
N
ꢂ
ꢃ
X
2
D
¼
k
xTi heor
ꢃ
mEi xpt
i
where xiTheo and miExpt are the ith theoretical harmonic frequency
and ith experimental fundamental frequency (in cmꢃ1), respectively
and N is the number of frequencies included in the optimisation
qffiffi
D
N
which leads to RMS ¼
.
In B3LYP/6-311++G⁄⁄ method a scaling factor 0.98 for OAH
stretching and 0.95 for all other fundamental modes have been uti-
lised to obtain the scaled frequencies and compared with the
experimentally observed frequencies. But in B3LYP/cc-pVTZ
method the scale factors 0.99, 0.95, 0.97 and 0.98 are used for
OAH stretching, CAH stretching, the fundamental modes up to
1300 cmꢃ1 and all others, respectively. The resultant scaled
frequencies are listed in Table 6. The correlation diagram for the
calculated and the experimental frequencies of 2H4MAP are shown
Fig. 5. (a) Experimental FTIR, (b) theoretical B3LYP/cc–pVTZ and (c) B3LYP/
6-311++G⁄⁄ simulated infrared spectra of 2-hydroxy-4-methoxyacetophenone.

Table 6
The observed FTIR-FT-Raman and calculated frequencies using B3LYP/6-311++G⁄⁄ and B3LYP/cc-pVTZ methods with their relative intensities and probable assignments of 2-hydroxy-4-methoxyacetophenonea.
Species Observed wavenumber
B3LYP/6-311++G⁄⁄ calculated wavenumber
Depolarisation ratio B3LYP/cc-pVTZ calculated wavenumber
Depolarization Assignment %PED
ratio
(cmꢃ1
FTIR
)
FTR
Unscaled
Scaled
IR
Raman
Unscaled (cmꢃ1
)
Scaled (cmꢃ1
)
IR intensity Raman
intensity
(cmꢃ1
)
(cmꢃ1
)
intensity
Intensity
A0
A0
A0
A0
A0
A0
A00
A00
A0
A0
3208 w
3058 w
3266
3220
3207
3188
3144
3142
3097
3080
3038
3016
3201
3059
3047
3029
2987
2985
2942
2926
2886
2865
367.49
0.58
3.08
2.98
7.27
19.22
6.65
28.96
2.30
45.43
40.48
70.69
21.90
50.13
70.31
26.01
28.94
100.00
91.56
0.14
0.26
0.19
0.67
0.56
0.46
0.75
0.75
0.02
0.03
3224
3210
3208
3189
3144
3137
3097
3076
3041
3016
3192
3050
3048
3030
2987
2980
2942
2922
2889
2865
356.89
8.47
21.11
1.90
5.79
19.99
6.63
28.96
2.19
45.90
48.80
52.28
59.59
23.91
55.79
76.36
27.93
31.22
100.00
95.19
0.25
0.13
0.26
0.65
0.56
0.46
0.75
0.75
0.02
0.03
m
m
m
m
m
m
m
m
m
m
OH
CH
CH
CH
85mOH
89mCH
90mCH
92mCH
3057 w
2998 w
3007 m
aCH3(keto) 86mCH
aCH3(O) 87mCH
aCH3(keto) 85mCH
aCH3(O) 83mCH
sCH3(keto) 85mCH
2960 m
2908 w
2957 vw
2907 w
2822 w
2676 vw
2556 vw
2391 vw
2024 vw
1631 vs
1622 vs
1578 s
2830 vw
47.69
sCH3(O)
89mCH
2 ꢂ 1334
2 ꢂ 1286
2 ꢂ 1209
2 ꢂ 1023
A0
A0
A0
A0
A0
A00
A00
A0
A0
A0
A0
A0
A0
A0
A0
A0
A0
A0
A00
A0
A0
A00
A0
A0
A0
A0
A00
A0
A0
A0
A00
A00
A00
A00
A0
A0
A0
1632 m
1618 s
1573 w
1670
1659
1607
1537
1503
1492
1482
1477
1474
1460
1429
1398
1362
1333
1287
1259
1233
1196
1167
1153
1083
1045
1042
987
958
955
859
844
810
749
721
710
661
593
584
580
1637
1626
1575
1506
1473
1462
1452
1447
1445
1431
1400
1370
1335
1306
1261
1234
1208
1172
1144
1130
1061
1024
1021
967
939
936
842
827
794
734
707
696
648
581
572
568
526.83
193.41
128.50
86.37
39.97
10.38
11.81
37.83
11.59
16.14
102.47
134.62
140.57
5.81
86.76
8.27
5.84
1.82
5.07
7.54
4.79
2.63
4.80
6.36
2.02
10.30
59.71
1.54
4.19
8.23
4.28
1.55
1.39
1.13
13.37
4.31
0.01
0.25
0.10
7.00
0.28
0.04
0.00
15.93
0.01
5.87
0.30
3.36
0.40
0.37
2.14
0.35
0.68
0.41
0.23
0.57
0.75
0.75
0.35
0.75
0.50
0.16
0.37
0.28
0.47
0.12
0.23
0.42
0.36
0.75
0.74
0.20
0.06
0.75
0.14
0.75
0.19
0.75
0.75
0.75
0.09
0.75
0.13
0.75
0.75
0.39
0.75
0.16
1679
1663
1614
1545
1506
1495
1483
1481
1477
1464
1438
1399
1367
1340
1290
1266
1240
1200
1173
1158
1087
1050
1049
992
972
957
900
870
821
752
749
713
671
597
591
586
1629
1613
1566
1499
1461
1450
1439
1437
1433
1420
1395
1357
1326
1300
1264
1241
1215
1176
1150
1135
1065
1029
1028
972
953
938
882
853
805
737
734
699
658
585
579
574
453.20
179.74
160.73
85.93
34.62
8.27
9.14
42.65
5.58
18.42
98.19
128.86
128.46
4.92
396.84
19.76
158.95
6.68
74.18
5.95
3.08
2.67
4.73
7.17
5.43
2.60
5.93
5.55
0.75
9.34
59.07
0.83
3.26
6.81
3.67
1.43
0.93
1.35
11.92
0.08
3.50
0.19
0.01
6.85
0.44
0.15
0.23
16.27
0.08
5.63
0.14
3.66
0.32
0.38
1.92
0.34
0.63
0.58
0.33
0.64
0.75
0.75
0.36
0.73
0.40
0.69
0.40
0.28
0.75
0.19
0.22
0.45
0.47
0.75
0.74
0.25
0.75
0.10
0.11
0.75
0.17
0.75
0.75
0.75
0.11
0.75
0.15
0.75
0.74
0.75
0.33
0.20
m
m
m
m
C@O
CC
CC
CC
92mC@O
86mCC
79mCC
84mCC
72dCH3 + 15bCAO
69dCH3 + 12bCAO
70dCH3 + 14bC@O
67dCH3 + 14bCAO
65dCH3 + 20bC@O
79mCC
66bOH + 16bCCC
70dCH3 + 19bC@O
77mCC
79mCC
82mCO
79mCC
74mCO
56bCH + 18bCCC
62xCH3 + 20cC@O
52bCH + 20bCCC
72mCC
1505 s
1465 m
1460 w
daCH3(O)
daCH3(O)
daCH3(keto)
dsCH3(O)
daCH3(keto)
mCC
bOH
dsCH3(keto)
1440 m
1419 m
1370 vs
1334 s
1420 w
1380 w
1336 vs
1283 w
1255 w
1231 s
m
m
m
m
m
CC
CC
CAO(CH3)
CC
CAO(H)
1286 s
1258 vs
1230 m
1209 vs
1167 m
1154 m
1140 s
431.31
11.66
160.93
9.34
1211 w
1160 vw
bCH
x
bCH
0.64
1.02
CH3
99.66
34.45
29.31
1.61
41.33
0.59
40.46
28.71
116.97
11.86
0.83
1.28
8.80
5.10
8.63
44.22
1.11
2.68
101.38
32.38
2.45
29.10
37.07
0.34
41.82
62.74
46.37
25.17
1.05
1.27
7.23
4.04
8.53
45.09
1.07
2.64
1072 m
1071 s
1039 w
m
CC
CH3
OAC(H3)
bCCC
x
54xCH3 + 25cCAO
69mOC
49bCCC + 24bCH
65mOC
1023 m
987 m
960 s
m
997 vw
961 m
mCOACH3
bCH
55bCH + 18bCCC
860 m
823 m
815 s
735 vw
706 w
663 w
621 w
590 m
574 s
870 vw
832 vw
c
OH
56
cOH + 20cCCC
bC@O
q
q
60bC@O + 18bCC
CH3
CH3
51
53
48
45
57
54
q
q
CH3 + 19bC@O
CH3 + 22bCAO
737 s
711 m
c
c
c
c
CH
CH
C@O
CH
c
c
c
c
CH + 28cCCC
CH + 29cCCC
C@O + 21cCC
CH + 25cCCC
613 m
592 w
bCC
bCC
bCCC
49bCC + 27bC@O
48dCC + 22bCH
42bCCC + 25bCH
511 vw
518 w
522
512
525
515
(continued on next page)

174
V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
in Fig. S5. The RMS deviation between the observed and the
theoretical wavenumber is only 12 cmꢃ1 in both the methods.
Skeletal stretching vibrations
The carbon–carbon vibrations are more interesting if the double
bond is in conjugation with the ring. The actual positions of the
CAC stretching modes are determined not so much by the nature
of substituents but by the form of the substitution around the ring
[83,84]. The CAC bands which indicate aromatic properties of
benzene derivatives mainly occur within the range of 1640–
1200 cmꢃ1. The strong bands observed in the infrared spectrum
at 1622, 1578, 1505, 1334 and 1286 cmꢃ1 and in Raman the
medium lines observed at 1618, 1573, 1336 and 1283 cmꢃ1 are
assigned to the CAC stretching modes of 2H4MAP. The modes
observed at 987 and 997 cmꢃ1 in infrared and Raman spectra are
assigned to the CCC in-plane ring trigonal bending vibration. The
other in-plane bending vibrations are assigned to the modes at
574, 456 and 417 cmꢃ1. The CCC out of plane bending modes are
attributed to the low Raman frequencies [85].
CAH vibrations
The aromatic CAH stretching vibrations are normally found
between 3100 and 3000 cmꢃ1 [86]. In this region the bands are
not affected appreciably by the nature of substituents. The
aromatic CAH stretching vibrations present in the benzene ring
of 2H4MAP are seen as weak bands at 3058 and 3007 cmꢃ1. The
aromatic CAH in-plane bending modes of benzene and its deriva-
tives are observed in the region 1300–1000 cmꢃ1. The peaks seen
at 1167 and 1140 cmꢃ1 in IR spectrum belongs to the aromatic
CAH in-plane bending vibrations. The CAH out of plane bending
mode of benzene derivatives are observed in the region
1100–600 cmꢃ1. The aromatic CAH out of plane bending vibrations
of 2H4MAP are seen in the infrared spectrum at 706, 663 and
590 cmꢃ1and in the Raman spectrum at 711 and 592 cmꢃ1
.
Methoxy (AOCH3) group vibrations
In methoxy group, the asymmetric stretching mode of the ACH3
group would be expected to be depolarised. The s(CH3) stretching
frequency is established at 2822 cmꢃ1 and the asymmetric methyl
stretching modes
a(CH3) are assigned at 2908 cmꢃ1 in the IR and
m
m
at 2907 in the Raman spectra. The asymmetrical methyl deforma-
tion mode, da(CH3) is observed at 1465 cmꢃ1. The symmetrical
methyl deformational mode is obtained at 1440 cmꢃ1 in IR
spectrum. The
m
(CAOMe) stretching frequency is established at
1258 cmꢃ1 while the
m
(OACH3) mode is assigned at 1023 cmꢃ1
.
The presence of the strong band in Raman at 737 cmꢃ1 is attributed
to the ACH3 rocking. These assignments are substantiated by the
reported literature [87,88]. The presence of weak band in Raman
at 1039 cmꢃ1 is attributed to the ACH3 wagging mode.
Hydroxyl (AOH) group vibrations
The OAH group gives rise to three vibrations namely (stretch-
ing, in-plane and out-of plane bending vibrations). The OAH group
vibrations are likely to be the most sensitive to the environment, so
they show pronounced shifts in the spectra of the hydrogen
bonded species. Bands due to OAH stretching are of medium to
strong intensity in the infrared spectrum, although it may be
broad. In Raman spectra the band is generally weak. Unassociated
hydroxyl groups absorbs strongly in the region 3670-3580 cmꢃ1
.
The band due to the free hydroxyl group is sharp and its intensity
increases. For solids, liquids and concentrated solutions a broad
band of less intensity is normally observed [74,74]. A broad

V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
175
stretching of OAHꢁꢁꢁA also indicates the presence of intramolecular
hydrogen bonding [74]. The observed band due to OAH stretching
is very broad in this case indicates the intramolecular hydrogen
bonding between the OAH and CAO groups of the type OAHꢁꢁꢁO
hydrogen bonding. The compound under investigation shows a
weak and broad stretching of hydroxyl group at 3208 cmꢃ1 in the
infrared spectrum. The in-plane and out of plane OAH bending
vibrations are assigned at 1419 and 860 cmꢃ1, respectively in the
infrared spectrum.
A band of medium-to-strong intensity in IR due to the CH3
deformation vibrations are observed at 1390–1340 cmꢃ1
For methyl groups adjacent to the carbonyl groups, the CH3 sym-
.
metrical deformation has
a lower frequency in the region
1360–1355 cmꢃ1. The asymmetrical methyl deformation mode,
da(CH3) is theoretically determined at 1452 and 1445 cmꢃ1. The
symmetrical methyl deformational mode is obtained at
1370 cmꢃ1 in IR spectrum [86].
A band of medium-to-strong intensity due to the CAC stretching
vibration is found at 1225–1075 cmꢃ1 for aromatic ketones. Thus,
the bands observed at 1230 and 1072 cmꢃ1 are assigned to the
CAC stretching vibration of the CACOAC group. Aromatic methyl
ketones generally have a strong absorption at 600A580 cmꢃ1 which
is due to the in-plane bending vibration of the CACOAC group. In
Carbonyl group (C@O) vibrations
The carbonyl group is contained in a large number of different
classes of compounds, e.g. aldehydes, ketones, carboxylic acids,
esters, amides, acid anhydrides, acid halides, etc., for which a
strong absorption band due to the CAO stretching vibration is
observed in the region 1850–1550 cmꢃ1. Because of its intensity
in the infrared and the relatively interference free region in which
it occurs, this band is reasonably easy to recognise. In Raman
spectra, the CAO stretching band is much less intense than in
infrared. The frequency of this carbonyl stretching is dependent
on various factors: (i) The more electronegative an atom or group
directly attached to a carbonyl group the greater is the frequency.
this case it is observed at 574 cmꢃ1
.
Analysis of structure-activity descriptors
Natural bond orbital (NBO) methods enable fundamental bond-
ing concepts by studying hybridisation and covalency effects in
polyatomic wave functions. The atomic charges of 2H4MAP calcu-
lated by NBO analysis using the B3LYP method with 6-311++G⁄⁄
basis set are presented in Table 7. Among the ring carbon atoms
C2, C4 and C10 of 2H4MAP have positive charges. The positive
charge on these carbon atoms is due to the attachment of electro-
negative oxygen atom to it. In 2H4MAP compound the other
carbon atoms and oxygen atoms have negative charge. The corre-
lation of the atomic charges of 2H4MAP is depicted in Fig. 7.
The understanding of chemical reactivity and site selectivity of
the molecular systems have been effectively handled by the
(ii) Unsaturation in the
a, b-position tend to decrease the
frequency except for amides which are little influenced, by
15–40 cmꢃ1 from that expected without conjugation. (iii) Hydro-
gen bonding to the CAO results in a decrease in the frequency of
40–60 cmꢃ1, this being independent of whether the hydrogen
bonding is inter- or intramolecular. (iv) The physical state of the
sample. In the solid phase, the frequency of the vibration is slightly
decreased compared with that in dilute non-polar solutions [72].
o-Hydroxy aryl ketones exhibit a strong band in the region
1655–1610 cmꢃ1 due to the carbonyl stretching vibration. The
presence of intramolecular hydrogen bonding causes this fre-
quency to be lower than might otherwise be expected. The mCAO
stretching frequency shows very strong band at 1631 cmꢃ1 in IR
spectrum and a medium band at 1632 cmꢃ1 in the Raman spec-
trum. The bCAO in-plane bending frequency is assigned to
823 cmꢃ1 in infrared and
cCAO out of plane bending frequency
to 613 cmꢃ1 in Raman spectrum.
A band of medium-to-strong intensity in both IR and Raman
due to the CH3 symmetric stretching vibration is found at
2940–2840 cmꢃ1 for methyl ketones. A band of medium-to-weak
intensity in the infrared and strong-to-medium intensity in Raman
spectra due to the CH3 asymmetric stretching vibrations are found
at 3045–2965 and 3020–2930 cmꢃ1 for methyl ketones. In the
present case, the
ms(CH3) stretching frequency is calculated at
2886 cmꢃ1 and the asymmetric methyl stretching modes
ma(CH3)
are assigned at 2998 and 2957 cmꢃ1 in the Raman spectrum.
Fig. 7. The correlation of atomic charges of 2-hydroxy-4-methoxyacetophenone.
Table 7
Calculated local reactivity properties (f) of 2-hydroxy-4-methoxyacetophenone using B3LYP/6-311++G⁄⁄ method for natural population analysis (NPA) derived charges.
+
ꢃ
0
Atom
Neutral
Anion
Cation
0.1290
0.2537
ꢃ0.1837
0.2000
fk
fk
fk
Df(k)
C1
C2
C3
C4
C5
C6
O7
O8
C9
C10
O11
C12
ꢃ0.2732
0.4143
ꢃ0.2530
0.3560
ꢃ0.4022
0.1606
0.0202
ꢃ0.1910
0.0512
0.4224
ꢃ0.2189
0.1547
ꢃ0.0583
ꢃ0.0295
ꢃ0.1290
ꢃ0.0092
ꢃ0.1085
ꢃ0.0546
ꢃ0.0328
0.0113
ꢃ0.3679
ꢃ0.3974
ꢃ0.1842
ꢃ0.1069
0.3636
0.2346
0.1636
0.0173
ꢃ0.2926
ꢃ0.2839
ꢃ0.1302
ꢃ0.6572
ꢃ0.4774
ꢃ0.2235
0.5749
ꢃ0.2931
ꢃ0.2387
ꢃ0.7118
ꢃ0.5102
ꢃ0.2122
0.3740
0.1653
ꢃ0.4492
0.0076
ꢃ0.4611
ꢃ0.3401
ꢃ0.1022
0.3168
ꢃ0.2292
ꢃ0.0505
ꢃ0.2579
ꢃ0.1865
ꢃ0.0455
0.0580
0.4400
ꢃ0.1378
ꢃ0.1961
ꢃ0.1373
ꢃ0.1213
0.2581
ꢃ0.1161
0.4065
0.3073
0.1135
ꢃ0.2009
ꢃ0.1403
0.0218
ꢃ0.5177
ꢃ0.6146
ꢃ0.7549
ꢃ0.1960
ꢃ0.4186
ꢃ0.2795
0.2783
ꢃ0.6759
ꢃ0.6541
ꢃ0.3401
ꢃ0.3358
ꢃ0.1570
0.3576

176
V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
Table 8
Calculated local reactivity properties (s and
x
), relative electrophilicity and nucleophilicity of 2-hydroxy-4-methoxyacetophenone using B3LYP/6-311++G⁄⁄ method.
+
ꢃ
0
+
ꢃ
0
Atom
sk
sk
sk
Dsk
xk
xk
xk
Dxk
Electro philicity
Nucleo philicity
C1
C2
C3
C4
C5
C6
O7
O8
C9
C10
O11
C12
0.0024
ꢃ0.0485
0.0194
ꢃ0.0230
0.0062
0.0509
0.0391
ꢃ0.1129
ꢃ0.0572
ꢃ0.2499
ꢃ0.0178
ꢃ0.2102
ꢃ0.1058
ꢃ0.0635
0.0219
ꢃ0.7792
0.3111
ꢃ0.3700
0.0991
0.8183
ꢃ0.0495
ꢃ0.3608
0.1622
ꢃ20.2083
ꢃ2.7714
6.1667
ꢃ1.2628
49.2727
ꢃ0.0687
8.4242
10.2500
ꢃ8.7857
ꢃ1.5785
2.9882
ꢃ0.0070
ꢃ0.0036
ꢃ0.0156
ꢃ0.0011
ꢃ0.0131
ꢃ0.0066
ꢃ0.0040
0.0014
ꢃ0.0264
0.0187
ꢃ0.0353
0.0531
ꢃ0.0140
0.0490
0.0371
0.0137
ꢃ0.0624
0.0336
0.0431
ꢃ0.4241
0.2997
ꢃ0.5669
0.8524
ꢃ0.2249
0.7875
0.5953
0.2199
ꢃ1.0029
0.5392
0.6928
ꢃ0.0222
ꢃ0.0129
ꢃ0.3569
ꢃ0.2070
0.0197
0.0021
0.3169
0.0335
ꢃ0.7919
ꢃ0.0542
0.0009
ꢃ0.0556
ꢃ0.0410
ꢃ0.0123
0.0382
ꢃ0.0276
ꢃ0.0061
ꢃ0.0311
ꢃ0.0225
ꢃ0.0055
0.0070
ꢃ0.8702
0.0147
ꢃ0.8933
ꢃ0.6589
ꢃ0.1980
0.6137
ꢃ0.4440
ꢃ0.0977
ꢃ0.4995
ꢃ0.3612
ꢃ0.0881
0.1123
0.0203
ꢃ14.5556
0.1187
0.0976
ꢃ0.1138
ꢃ0.6335
0.3347
ꢃ0.0642
ꢃ0.0242
ꢃ0.0169
0.0026
ꢃ0.3892
ꢃ0.2718
0.0422
ꢃ0.0505
ꢃ0.0337
ꢃ0.8110
ꢃ0.5414
ꢃ0.0405
ꢃ0.0189
ꢃ0.6505
ꢃ0.3042
ꢃ15.5769
conceptual density functional theory (DFT) [89]. Chemical poten-
tial, global hardness, global softness, electronegativity and electro-
philicity are global reactivity descriptors, highly successful in
predicting global chemical reactivity trends. The global parameters
such as ionisation potential (I), electron affinity (A), electrophilicity
(iv) The carbonyl and hydroxyl groups involves in the formation
of intramolecular hydrogen bond of the type OAHꢁ ꢁ ꢁO. The
bond distances of the OAHꢁ ꢁ ꢁO intramolecular hydrogen
bond are O7AH22 is (0.99 Å), H22ꢁ ꢁ ꢁO11 is (1.67 Å) and
O7AO11 is (2.56 Å) respectively.
(
x
), electronegativity (
v
), hardness (
g
), and softness (S) of the mol-
(v) The total dipole moment of the molecule determined by
B3LYP/6-311++G⁄⁄ method is 3.06 D reveals the high polarity
of the molecule.
ecule are determined and displayed in Table 2. The site-selectivity
of a chemical system, cannot, however, be studied using the global
descriptors of reactivity.
(vi) The maximum and minimum observed total electron den-
Fukui functions and local softness are extensively applied to
probe the local reactivity and site selectivity. The formal defini-
tions of all these descriptors and working equations for their com-
putation have been described [89–92]. The Fukui functions of the
individual atoms of the neutral, cationic and anionic species of
2H4MAP calculated by B3LYP/6-311++G⁄⁄ method are presented
in Table 7. The molecule under investigation mainly gives substitu-
tion reactions. It is clearly understood that the atoms C1, C3, C5,
O7, O8, C9, O11 and C12 are favourable for nucleophilic attack.
The other atoms are favourable for electrophilic attack.
sity of the molecule is 4.279e ꢂ 10ꢃ2 while the extreme
limits of the electrostatic potential is 1.082e ꢂ 10ꢃ2
.
(vii) The LUMO–HOMO energy gap of 2-hydroxy-4-methoxyace-
tophenone determined by B3LYP/cc-pVTZ method is
4.6548 eV.
(viii) The strong bands observed in the infrared spectrum at 1622,
1578, 1505, 1334 and 1286 cmꢃ1 and in Raman the medium
lines observed at 1618, 1573, 1336 and 1283 cmꢃ1 are
assigned to the CAC stretching modes of 2H4MAP.
(ix) The
1631 cm
1632 cmꢃ1 in the Raman spectrum.
m
CAꢃO1 stretching frequency shows very strong band at
The local softness, relative electrophilicity (sþk =skꢃ) and relative
in IR spectrum and medium band at
a
nucleophilicity (sꢃk =skþ) indices, the dual local softness
D
sk and the
k) have also been determined to
predict the reactive sites of the molecule and are summarised in
Table 8. From the dual local softness sk and the multiphilicity
descriptors ( k) one can understand that the atoms C1, C3, C5,
multiphilicity descriptors (
D
x
(x) The compound under investigation shows a weak and broad
stretching of hydroxyl group at 3208 cmꢃ1 in the infrared
spectrum. The in-plane and out of plane OAH bending vibra-
tions are assigned at 1419 and 860 cmꢃ1, respectively in the
infrared spectrum.
(xi) The carbonyl carbon atom C10 in 2H4MAP shows very
downfield effect and the corresponding observed chemical
shift is 202.60 ppm. The more electronegative character of
the oxygen atoms renders a positive charge to the carbon
and thus C2 and C4 chemical shifts are observed in the more
downfield shift at 165.28 and 166.15 ppm.
D
D
x
O7, O8, C9, O11 and C12 are favourable for nucleophilic attack.
The other atoms are favourable for electrophilic attack. The local
reactivity descriptors of the individual atoms of the molecule
sak ¼ fkaS; xak
¼
x
fka and fka where, a = +, ꢃ and 0 are presented in
Tables 7 and 8. These are the local philicity quantities describing
for nucleophilic, electrophilic and free radical attack, respectively
which clearly express the electron rich/deficient nature of the indi-
vidual atoms.
(xii) The methyl carbon atom (C9) connected to the O8 oxygen
atom of 2H4MAP give signal in the upfield chemical shift
at 55.52 ppm.
Conclusions
(xiii) The hydrogen atom H13, H14 and H15 attached with the
aromatic carbons of 2H4MAP shows three peaks at 6.41,
6.43 and 7.61 ppm, respectively. The hydrogen atom H19,
H20 and H21 attached with the methyl carbon of 2H4MAP
are in the same chemical environment and shows one peak
at 3.83 ppm.
The following observations are made from the current investi-
gations of 2-hydroxy-4-methoxyacetophenone.
(i) The presence of large bulky groups in 2H4MAP leads to a
very
high
energy
barrier
to
internal
rotation
(18.93 kcal molꢃ1) and can be locked into only one most sta-
ble configuration (I).
(xiv) In 2-hydroxy-4-methoxyacetophenone molecule, the lone
pair donor orbital, nO
?
p⁄CC interaction between the O(7) lone
(ii) The benzene ring and the substituents hydroxyl, methoxy
and acetyl groups are planar, without any twist in the
molecule.
(iii) All the dihedral angles of the compound are either 180° or
0°. This reveals that all the atoms of 2-hydroxy-4-methoxy-
acetophenone lie in the molecular plane which confirms the
planarity of the molecule.
pair and the C1AC2 antibonding orbital gives a strong stabili-
sation of 40.31 kcal molꢃ1. The n ? r⁄ stabilisation energy of
lone pair of electrons present in the oxygen atom (O8) to the
antibonding orbital (r⁄) of (C3AC4) is 34.68 kcal molꢃ1
.
(xv) From the dual local softness
descriptors ( k) one can understand that the atoms C1, C3,
C5, O7, O8, C9, O11 and C12 are favourable for nucleophilic
Dsk and the multiphilicity
D
x

V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177
177
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The order of nucleophilic and electrophilic attack is
C5 > C1 > O7 > C12 > O8 > O11 > C3 > C9 and vice versa.
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