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

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177

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Synthesis, vibrational, NMR, quantum chemical and structure-activity relation studies of 2-hydroxy-4-methoxyacetophenone V. Arjunan a,⇑, L. Devi b, R. Subbalakshmi a, T. Rani c, S. Mohan d a

Department of Chemistry, Kanchi Mamunivar Centre for Post-Graduate Studies, Puducherry 605 008, India 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 b

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 OAH  O is present with O7AO11 is (2.56 Å).  The extreme limits of the electrostatic potential is ±1.082e  102.  The C@O carbon shows downfield shift at 202.60 ppm. ⁄  The nO ? p C1AC2 interaction has strong stabilisation of 40.31 kcal mol1.

a r t i c l e

i n f o

Article history: 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

a b s t r a c t 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. Ó 2014 Elsevier B.V. All rights reserved.

Introduction Acetophenone occurs naturally in many foods including apple, cheese, apricot, banana and cauliflower. Commercially significant ⇑ Corresponding author. Tel.: +91 413 2211111, mobile: +91 9442992223; fax: +91 413 2251613. E-mail address: [email protected] (V. Arjunan). http://dx.doi.org/10.1016/j.saa.2014.03.121 1386-1425/Ó 2014 Elsevier B.V. All rights reserved.

resins of acetophenone with formaldehyde and base resulting polymers used as components of coatings, adhesives and inks. 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

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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 antihypertensive [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 circulation 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 vibrational spectral analysis were carried out by FTIR and FT-Raman spectroscopy for 2,4-difluoroacetophenone [22], 3-methoxy acetophenone [23], acetophenone and 4-methoxyacetophenone adsorbed on silica–alumina catalyst [24], acetophenone, 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 industrial and biological interest [4–21], have been reported in this investigation. 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.

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 temperature 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. 1 H NMR (DMSOd6) 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 (DMSOd6) d: 202.60, 166.15, 165.28, 132.35, 113.93, 107.51, 100.91, 55.52, 26.12.

165

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 cm1. The spectral resolution was 2 cm1. The FT-Raman spectrum is also recorded in the range 4000–50 cm1 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 cm1. A total of 256 scans are used with a scanning speed of 30 cm1 min1. 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 protons 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 properties, 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 frequencies 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 distributions corresponding to each of the observed frequencies were calculated with the program of Fuhrer et al. [38]. 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:

VðrÞ ¼

X

ZA

A

RA  ~ rj j~



Z

qð~r0 Þdr0 j~ r0  ~ rj

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 relationship 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. 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].

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f ðm0  mi Þ4 Si Ii ¼ mi ½1  expðhcmi =kTÞ where v0 is the exciting frequency (cm1), vi is the vibrational wavenumber 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. 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 (TMS). diso(X) = rTMS(X)  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, nucleophilicity and the appropriate local quantities employing natural population analysis (NPA) scheme are calculated. Both the global and local reactivity descriptors are determined using finite difference 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  1 and N + 1 electronic species are done by restricted open B3LYP method using the geometry optimised with B3LYP/6311++G⁄⁄ method. The site-selectivity of a chemical system can be determined by using Fukui function [48,49] which can be interpreted either as the change of electron density q(r) at each point r when the total number of electrons are changed or as the sensitivity of chemical potential (l) of a system to an external perturbation at a particular point r.

f ðrÞ ¼

    @ qðrÞ dl ¼ @N v ðrÞ dv 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.

sðrÞ ¼

  @ qðrÞ @ l v ðrÞ

P determined by using the relation xag ¼ nk¼1 xak where, n is the number of atoms coordinated to the reactive atom and xak is the local electrophilicity of the atom k. Results and discussion Conformational analysis The conformational analysis is carried out by potential surface scan with B3LYP method using 6-31G⁄⁄ basis set in order to ascertain 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 structure. 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). From the potential energy surface scan three conformers I, II and III with relative energies 0.0, 12.25 and 18.93 kcal mol1, 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 carbonyl group (CAO) and the hydroxyl group (OAH) are within reach to form CAO  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 intramolecular hydrogen bonding than II and III by 12.25 and 18.93 kcal mol1, respectively. The most stable conformer (I) is exactly planar, where the dihedral angles C2AC1AC10AO11, C3AC2AO7AH22 and C1AC2AO7AH22 are 0°, 180° and 0°, respectively. Similarly, the

and sðrÞ ¼ f ðrÞS

where S is the global softness which is inversely related to global hardness (g). The generalised philicity descriptor, x(r) contains almost all informations about hitherto known different global and local reactivity 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 xak ¼ xfka , where x ¼ l2 =2g and a = +,  and 0 represents local philic quantities describing nucleophilic, electrophilic and radical attacks respectively. 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 through the transition structure III is only 6.68 kcal mol1. Structural properties The optimised stable geometry and the scheme of atom numbering 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 considerably 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.

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 OAH  O. The bond distances of the OAH  O intramolecular hydrogen bond are O7AH22 is (0.99 Å), H22  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°. Analysing the bond angle of aromatic ring of 2H4MAP, one can observe that the geometry of the benzene ring is seen to be relatively 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 positions 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 interior 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 positions 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

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Table 1 Structural parameters of 2-hydroxy-4-methoxyacetophenone calculated byB3LYP/6311G++⁄⁄ and B3LYP/cc-pVTZ methods. Structural parameters Bond distance (Å) C1@C2 C1AC6 C1AC10 C2AC3 C2AO7 C3@C4 CAH (ring)c C4AC5 C4AO8 C5@C6 O7AH22 O8AC9 C9AHc C10@O11 C10AC12 O11  H22 C12AHc 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

B3LYP/6311G++⁄⁄ 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

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

Table 1 (continued)

B3LYP/cc- Experimentala Experimentalb pVTZ 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

117.6 119.7 122.7 120.6 121.8 117.6 119.9 117.6 122.5 120.5 124.1 115.4 119.3 118.8 121.8 122.1 119.2 118.6 106.1 118.9 105.9 111.3 111.3 109.5 121.2 120.2 118.6 111.0 111.0 108.6 108.7

1.40 1.40 1.49 1.39 1.35 1.38

1.42 1.40 1.47 1.40 1.34 1.38

1.38 1.37 1.38

1.40 1.38

1.43 1.23 1.50

1.23 1.51

119.3 119.0 121.7 119.6 122.0 118.4 120.2

118.7 119.8 121.5 120.0 122.1 118.0 120.6

120.0 125.9 114.0 120.2

119.4

120.6

119.8

121.5

116.8

119.9 120.1 120.1

120.3 120.0 119.7

a b c

Structural parameters

B3LYP/6311G++⁄⁄

B3LYP/cc- Experimentala Experimentalb pVTZ

C2AC3AC4AO8 H13AC3AC4AC5 H13AC3AC4AO8 C3AC4AC5AC6 C3AC4AC5AH14 O8AC4AC5AC6 O8AC4AC5AH14 C3AC4AO8AC9 C5AC4AO8AC9 C4AC5AC6AC1 C4AC5AC6AH15 H14AC5AC6AC1 H14AC5AC6AH15 C4AO8AC9AH19 C4AO8AC9AH20 C4AO8AC9AH21 C1AC10AC12AH16 C1AC10AC12AH17 C1AC10AC12AH18 O11AC10AC12AH16 O11AC10AC12AH17 O11AC10AC12AH18

180.0 180.0 0.0 0.0 180.0 180.0 0.0 0.0 180.0 0.0 180.0 180.0 0.0 180.0 61.2 61.2 59.8 59.8 180.0 120.2 120.2 0.0

180.0 180.0 0.0 0.0 180.0 180.0 0.0 0.0 180.0 0.0 180.0 180.0 0.0 180.0 61.2 61.2 59.7 59.8 180.0 120.2 120.3 0.0

0.0 180.0 180.0 0.0 0.0 180.0 180.0 0.0 0.0 180.0 180.0 0.0 0.0 180.0 180.0 0.0 0.0 180.0 0.0

0.0 180.0 180.0 0.0 0.0 180.0 180.0 0.0 0.0 180.0 180.0 0.0 0.0 180.0 180.0 0.0 0.0 180.0 0.0

179.5

179.5

Values taken from Ref. [52]. Values taken from Ref. [55]. Mean value.

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. Thermodynamic parameters (298 K)

B3LYP/ 6-311++G⁄⁄

B3LYP/ cc-pVTZ

SCF energy (a.u) Total energy (thermal) – Etotal (kcal mol1) Heat capacity at const. volume – Cv (cal mol1 K1) Entropy – S (cal mol1 K1) Vibrational energy – Evib (kcal mol1) Zero-point vibrational energy – E0 (kcal mol1)

574.822043 116.47 42.28

574.870715 116.80 41.84

Rotational constants (GHz) A B C

103.29 114.70 109.45

102.44 115.02 109.87

2.15 0.56 0.45

2.16 0.56 0.45

2.12 2.20 0.00 3.06 0.4800 1.8131 6.4366 6.9949 4.6235 8.1530 0.1377 4.0076 4.0076 1.9373 4.1453 0.1206 10.0902 2.0750

2.03 2.04 0.00 2.88 0.2797 1.6526 6.3074 6.8756 4.6548

Dipolemoment (Debye)

lx ly lz ltotal

Dihedral angle (°) C6AC1AC2AC3 C6AC1AC2AO7 C10AC1AC2AC3 C10AC1AC2AO7 C2AC1AC6AC5 C2AC1AC6AH15 C10AC1AC6AC5 C10AC1AC6AH15 C2AC1AC10AO11 C2AC1AC10AC12 C6AC1AC10AO11 C6AC1AC10AC12 C1AC2AC3AC4 C1AC2AC3AH13 O7AC2AC3AC4 O7AC2AC3AH13 C1AC2AO7AH22 C3AC2AO7AH22 C2AC3AC4AC5

179.05

179.5

173.0

ELUMO+1 (eV) ELUMO (eV) EHOMO (eV) EHOMO1 (eV) ELUMO (eV)  EHOMO (eV) Ionisation potential – I (eV) Electron affinity – A (eV) Electronegativity (v) Chemical potential (l) Electrophilicity (x) Hardness (g) Softness (S) Electrofugality (DEe) Nucleofugality (DEn)

179.3

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

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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 physiochemical 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 electrostatic 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; yellow-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  102. 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  102.

Frontier molecular orbitals

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)

Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are very important parameters for quantum chemistry. The energies of HOMO, LUMO, LUMO+1 and HOMO1 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

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Table 3 Bond orbital analysis of 2-hydroxy-4-methoxyacetophenone. Bond orbital

Occupancy

Atom

Contribution from parent NBO (%)

Co-efficiency

Atomic hybrid contributions (%)

C1AC2

1.9760

C1@C2

1.5894

C1AC6

1.9749

C1AC10

1.9804

C2AC3

1.9767

C2AO7

1.9934

C3AC4

1.9820

C3@C4

1.6919

C3AH13

1.9730

C4AC5

1.9737

C4AO8

1.9903

C5AC6

1.9795

C5@C6

1.7544

C5AH14

1.9744

C6AH15

1.9742

O8AC9

1.9913

C9AH19

1.9896

C9AH20

1.9941

C9AH21

1.9941

C10AO11

1.9946

C10@O11

1.9752

C10AC12

1.9893

C12AH16

1.9732

C12AH17

1.9732

C12AH18

1.9879

C1 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 H21 C10 O11 C10 O11 C10 C12 C12 H16 C12 H17 C12 H18

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)

gap of HOMO–LUMO’s explains the ultimate charge transfer interface within the molecule. The energies of the frontier molecular orbitals of 2-hydroxy4-methoxyacetophenone employing B3LYP method using 6-311++G⁄⁄ and cc-pVTZ basis sets are given in Table 2. The frontier orbital energy gap calculated by B3LYP/cc-pVTZ method (ELUMO  EHOMO) in case of 2H4MAP is found to be is 4.6548 eV.

Natural bond orbital (NBO) analysis The analysis of the bond orbitals of 2H4MAP by B3LYP/6311++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, hybridisation, resonance, donor–acceptor interactions, charge transfer and resonance possibility. Table 3 depicts the bonding concepts

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-character, 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. For example, the bonding orbital for C1AC2 with 1.976 electrons 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

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V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177 Table 4 Second order perturbation theory analysis of Fock matrix of 2-hydroxy-4-methoxyacetophenone using NBO analysis. Donor (i)  Acceptor ( j) interaction

E(2)a (kcal mol1)

E( j)  E(i)b (a.u.)

F(i  j)e (a.u.)

p (C1AC2) ? p⁄ (C1AC2) p (C1AC2) ? p⁄ (C3AC4) p (C1AC2) ? p⁄ (C5AC6) p (C1AC2) ? p⁄ (C10AO11) r (C2AC3) ? r⁄ (C4AO8) p (C3AC4) ? p⁄ (C1AC2) p (C3AC4) ? p⁄ (C5AC6) r (C3AH13) ? r⁄ (C1AC2) r (C3AH13) ? r⁄ (C4AC5) r (C4AC5) ? r⁄ (O8AC9) p (C5AC6) ? p⁄ (C1AC2) p (C5AC6) ? p⁄ (C3AC4) r (C5AH14) ? r⁄ (C1AC6) r (C5AH14) ? r⁄ (C3AC4) r (C6AH15) ? r⁄ (C1AC2) r (C6AH15) ? r⁄ (C4AC5) r (C9AH19) ? r⁄ (C4AO8) r (C12AH16) ? p⁄

4.32 12.27 24.85 30.26 4.88 26.79 12.40 4.51 4.27 4.24 11.99 22.98 4.94 4.32 4.70 4.72 4.59 4.91

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

4.90

0.52

0.047

4.53 8.95 40.31 5.77 8.36 34.68 5.50 5.50 5.88 12.01 19.39

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

(C10AO11)

r (C12AH17) ? p⁄ (C10AO11) r (C12AH18) ? r⁄ (C1AC10) n[LP(1)] (O7) ? r⁄ (C1AC2) n[LP(2)] (O7) ? p⁄ (C1AC2) n[LP(3)] (O7) ? r⁄ (C2AC3) n[LP(1)] (O8) ? r⁄ (C3AC4) n[LP(2)] (O8) ? r⁄ (C3AC4) n[LP(2)] (O8) ? r⁄ (C9AH20) n[LP(2)] (O8) ? r⁄ (C9AH21) n[LP(1)] (O11) ? r⁄ (C1AC10) n[LP(2)] (O11) ? r⁄ (C1AC10) n[LP(2)] (O11) ? r⁄ (C10AC12)

LP – Lone pair. a Stabilisation (delocalisation) energy. b Energy difference between i(donor) and j(acceptor) NBO orbitals. e Fock matrix element i and j NBO orbitals.

clearly indicates the delocalisation of p electrons among all the carbon atoms. Similarly C10AO11 bond has also posses more p character. 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 quantitatively 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 methoxyacetophenone.

13

[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

Eð2Þ ¼ qi

F 2 ði; jÞ ej  ei

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 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 mol1. 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 mol1. The bond pair donor orbital, pCC ? p⁄CO interactions give more stabilisation than pCC ? p⁄CC and rCC ? r⁄CC interactions. NMR spectral studies NMR spectroscopy has proved to be an exceptional tool to elucidate 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. 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.

C isotropic chemical shifts (diso – ppm) with respect to TMS and isotropic magnetic shielding tensors (riso) of 2-hydroxy-4-

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 25.52 155.63

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

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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 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. 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 environment 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 theoretically predicted vibrational frequencies. The optimum scale factors for vibrational frequencies were determined by minimising the residual

D¼

N  2 X kxTheor  mExpt i i i

where xTheo and mExpt are the ith theoretical harmonic frequency i i and ith experimental fundamental frequency (in cm1), respectively and N is the number of frequencies included in the optimisation qffiffiffi which leads to RMS ¼ ND.

Fig. 5. (a) Experimental FTIR, (b) theoretical B3LYP/cc–pVTZ and (c) B3LYP/ 6-311++G⁄⁄ simulated infrared spectra of 2-hydroxy-4-methoxyacetophenone.

In B3LYP/6-311++G⁄⁄ method a scaling factor 0.98 for OAH stretching and 0.95 for all other fundamental modes have been utilised 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 cm1 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

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

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

B3LYP/6-311++G⁄⁄ calculated wavenumber

FTIR

FTR

Unscaled (cm1)

Scaled (cm1)

IR intensity

Raman Intensity

3208 w 3058 w

3057 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 47.69

45.43 40.48 70.69 21.90 50.13 70.31 26.01 28.94 100.00 91.56

3007 m 2998 w 2960 m 2908 w

2957 vw 2907 w

2822 w 2676 vw 2556 vw 2391 vw 2024 vw 1631 vs 1622 vs 1578 s 1505 s 1465 m

2830 vw

1632 m 1618 s 1573 w 1460 w

1440 m

1419 m 1370 vs 1334 s 1286 s 1258 vs 1230 m 1209 vs 1167 m 1154 m 1140 s 1072 m 1023 m 987 m 960 s

1420 1380 1336 1283 1255 1231 1211 1160

w w vs w w s w vw

1071 s 1039 w 997 vw 961 m

860 m 823 m 815 s 735 vw 706 w 663 w 621 w 590 m 574 s

870 vw 832 vw

511 vw

518 w

737 s 711 m 613 m 592 w

1670 1659 1607 1537 1503 1492 1482 1477 1474 1460 1429 1398 1362 1333 1287 1259 1233 1196 1167 1153 1083 1045 1042 987 958 955 859 844 810 749 721 710 661 593 584 580 522

1637 1626 1575 1506 1473 1462 1452 1447 1445 1431 1400 1370 1335 1306 1261 1234 1208 1172 1144 1130 1061 1024 1021 967 939 936 842 827 794 734 707 696 648 581 572 568 512

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 5.81 431.31 11.66 160.93 9.34 0.64 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

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

Depolarisation ratio

0.14 0.26 0.19 0.67 0.56 0.46 0.75 0.75 0.02 0.03

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

B3LYP/cc-pVTZ calculated wavenumber Unscaled (cm1)

Scaled (cm1)

IR intensity

Raman intensity

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

1679 1663 1614 1545 1506 1495 1483 1481 1477 1464 1438 1399 1367 1340 1290 1266 1240 1200 1173 1158 1087 1050 1049 992 972 957 900 870 821 752 749 713 671 597 591 586 525

1629 1613 1566 1499 1461 1450 1439 1437 1433 1420 1395 1357 1326 1300 1264 1241 1215 1176 1150 1135 1065 1029 1028 972 953 938 882 853 805 737 734 699 658 585 579 574 515

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 1.02 101.38 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

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

Depolarization ratio

Assignment

%PED

0.25 0.13 0.26 0.65 0.56 0.46 0.75 0.75 0.02 0.03

mOH mCH mCH mCH maCH3(keto) maCH3(O) maCH3(keto) maCH3(O) msCH3(keto) msCH3(O)

85mOH 89mCH 90mCH 92mCH 86mCH 87mCH 85mCH 83mCH 85mCH 89mCH

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

2  1334 2  1286 2  1209 2  1023 mC@O mCC mCC mCC daCH3(O) daCH3(O) daCH3(keto) dsCH3(O) daCH3(keto) mCC bOH dsCH3(keto) mCC mCC mCAO(CH3) mCC mCAO(H) bCH xCH3 bCH mCC xCH3 mOAC(H3) bCCC mCOACH3 bCH cOH bC@O qCH3 qCH3 cCH cCH cC@O cCH bCC bCC bCCC

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 54xCH3 + 25cCAO 69mOC 49bCCC + 24bCH 65mOC 55bCH + 18bCCC 56cOH + 20cCCC 60bC@O + 18bCC 51qCH3 + 19bC@O 53qCH3 + 22bCAO 48cCH + 28cCCC 45cCH + 29cCCC 57cC@O + 21cCC 54cCH + 25cCCC 49bCC + 27bC@O 48dCC + 22bCH 42bCCC + 25bCH

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A0 A0 A0 A0 A0 A0 A00 A00 A0 A0

Observed wavenumber (cm1)

V. Arjunan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 130 (2014) 164–177

%PED

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 cm1. The strong bands observed in the infrared spectrum at 1622, 1578, 1505, 1334 and 1286 cm1 and in Raman the medium lines observed at 1618, 1573, 1336 and 1283 cm1 are assigned to the CAC stretching modes of 2H4MAP. The modes observed at 987 and 997 cm1 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 cm1. The CCC out of plane bending modes are attributed to the low Raman frequencies [85].

bCCC bCCC bCCC bCAOCH3 bOACH3 cCCC cCCC cCCC cCCC cCAC cCAC cOACH3 cCAOCH3

Assignment

131 w

166 w

IR intensities – (km/mole); Raman intensities – (Å)4/(a.m.u). a m – stretching; b – in-plane bending; d – deformation; q – rocking; c – out of plane bending; x – wagging and s – twisting- wavenumbers (cm1).

0.27 0.59 1.68 0.90 0.66 3.20 0.31 0.43 0.20 0.02 0.26 0.10 0.02 3.05 2.14 1.61 5.58 0.44 0.63 0.00 0.00 6.02 0.04 3.83 0.63 2.52 461 456 410 342 290 256 243 199 184 146 132 105 65 0.47 0.25 1.91 0.87 0.31 3.11 0.23 0.49 0.18 0.18 0.25 0.09 0.03 2.19 4.19 1.52 6.44 0.84 0.66 0.02 0.01 6.64 0.02 4.33 0.52 2.94 453 448 407 335 281 254 237 194 183 139 123 101 61 462 457 415 342 287 259 242 198 187 142 126 103 62 446 426 318 304 456 vw 417 vw A0 A0 A0 A0 A0 A00 A00 A00 A00 A00 A00 A00 A00

FTIR

FTR

w w w w

Unscaled (cm1)

Scaled (cm1)

IR intensity

Raman Intensity

0.75 0.75 0.60 0.13 0.75 0.25 0.75 0.75 0.35 0.75 0.75 0.75 0.75

470 465 418 349 296 261 248 203 188 149 135 107 66

Unscaled (cm1)

Scaled (cm1)

IR intensity

Raman intensity

0.75 0.75 0.61 0.13 0.75 0.29 0.75 0.75 0.34 0.75 0.75 0.75 0.75

Depolarization ratio B3LYP/cc-pVTZ calculated wavenumber Depolarisation ratio B3LYP/6-311++G⁄⁄ calculated wavenumber Observed wavenumber (cm1) Species

Table 6 (continued)

in Fig. S5. The RMS deviation between the observed and the theoretical wavenumber is only 12 cm1 in both the methods.

49dCCC + 21bCH 44bCCC + 28bCAO 45bCCC + 26bCAO 49bCO + 25bCCC 42bCO + 21bCAO 46cCCC + 20cCH 42cCCC + 24cCH 45cCCC + 28cCH 47cCCC + 25cCH 41cCC + 24cCH 42cCC + 26cCH 47cCO + 28cCCC 43cCO + 24cCCC

174

CAH vibrations The aromatic CAH stretching vibrations are normally found between 3100 and 3000 cm1 [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 cm1. The aromatic CAH in-plane bending modes of benzene and its derivatives are observed in the region 1300–1000 cm1. The peaks seen at 1167 and 1140 cm1 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 cm1. The aromatic CAH out of plane bending vibrations of 2H4MAP are seen in the infrared spectrum at 706, 663 and 590 cm1and in the Raman spectrum at 711 and 592 cm1. Methoxy (AOCH3) group vibrations In methoxy group, the asymmetric stretching mode of the ACH3 group would be expected to be depolarised. The ms(CH3) stretching frequency is established at 2822 cm1 and the asymmetric methyl stretching modes ma (CH3) are assigned at 2908 cm1 in the IR and at 2907 in the Raman spectra. The asymmetrical methyl deformation mode, da (CH3) is observed at 1465 cm1. The symmetrical methyl deformational mode is obtained at 1440 cm1 in IR spectrum. The m(CAOMe) stretching frequency is established at 1258 cm1 while the m(OACH3) mode is assigned at 1023 cm1. The presence of the strong band in Raman at 737 cm1 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 cm1 is attributed to the ACH3 wagging mode. Hydroxyl (AOH) group vibrations The OAH group gives rise to three vibrations namely (stretching, 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 cm1. 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

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stretching of OAHA 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 OAHO hydrogen bonding. The compound under investigation shows a weak and broad stretching of hydroxyl group at 3208 cm1 in the infrared spectrum. The in-plane and out of plane OAH bending vibrations are assigned at 1419 and 860 cm1, respectively in the infrared spectrum.

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 cm1. 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. (ii) Unsaturation in the a, b-position tend to decrease the frequency except for amides which are little influenced, by 15–40 cm1 from that expected without conjugation. (iii) Hydrogen bonding to the CAO results in a decrease in the frequency of 40–60 cm1, 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 cm1 due to the carbonyl stretching vibration. The presence of intramolecular hydrogen bonding causes this frequency to be lower than might otherwise be expected. The mCAO stretching frequency shows very strong band at 1631 cm1 in IR spectrum and a medium band at 1632 cm1 in the Raman spectrum. The bCAO in-plane bending frequency is assigned to 823 cm1 in infrared and cCAO out of plane bending frequency to 613 cm1 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 cm1 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 cm1 for methyl ketones. In the present case, the ms(CH3) stretching frequency is calculated at 2886 cm1 and the asymmetric methyl stretching modes ma (CH3) are assigned at 2998 and 2957 cm1 in the Raman spectrum.

A band of medium-to-strong intensity in IR due to the CH3 deformation vibrations are observed at 1390–1340 cm1. For methyl groups adjacent to the carbonyl groups, the CH3 symmetrical deformation has a lower frequency in the region 1360–1355 cm1. The asymmetrical methyl deformation mode, da (CH3) is theoretically determined at 1452 and 1445 cm1. The symmetrical methyl deformational mode is obtained at 1370 cm1 in IR spectrum [86]. A band of medium-to-strong intensity due to the CAC stretching vibration is found at 1225–1075 cm1 for aromatic ketones. Thus, the bands observed at 1230 and 1072 cm1 are assigned to the CAC stretching vibration of the CACOAC group. Aromatic methyl ketones generally have a strong absorption at 600A580 cm1 which is due to the in-plane bending vibration of the CACOAC group. In this case it is observed at 574 cm1. Analysis of structure-activity descriptors Natural bond orbital (NBO) methods enable fundamental bonding concepts by studying hybridisation and covalency effects in polyatomic wave functions. The atomic charges of 2H4MAP calculated 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 electronegative oxygen atom to it. In 2H4MAP compound the other carbon atoms and oxygen atoms have negative charge. The correlation 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

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. Atom

Neutral

Anion

Cation

fk+

fk

fk0

Df(k)

C1 C2 C3 C4 C5 C6 O7 O8 C9 C10 O11 C12

0.2732 0.4143 0.3679 0.3636 0.2839 0.1302 0.6572 0.4774 0.2235 0.5749 0.6146 0.6759

0.2530 0.3560 0.3974 0.2346 0.2931 0.2387 0.7118 0.5102 0.2122 0.3740 0.7549 0.6541

0.1290 0.2537 0.1837 0.2000 0.1653 0.1378 0.1961 0.1373 0.1213 0.2581 0.1960 0.3401

0.4022 0.1606 0.1842 0.1636 0.4492 0.0076 0.4611 0.3401 0.1022 0.3168 0.4186 0.3358

0.0202 0.0583 0.0295 0.1290 0.0092 0.1085 0.0546 0.0328 0.0113 0.2009 0.1403 0.0218

0.1910 0.0512 0.1069 0.0173 0.2292 0.0505 0.2579 0.1865 0.0455 0.0580 0.2795 0.1570

0.4224 0.2189 0.1547 0.2926 0.4400 0.1161 0.4065 0.3073 0.1135 0.5177 0.2783 0.3576

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Table 8 Calculated local reactivity properties (s and x), relative electrophilicity and nucleophilicity of 2-hydroxy-4-methoxyacetophenone using B3LYP/6-311++G⁄⁄ method. Atom

sk+

sk 

sk0

Dsk

xk+

x k

xk0

Dxk

Electro philicity

Nucleo philicity

C1 C2 C3 C4 C5 C6 O7 O8 C9 C10 O11 C12

0.0024 0.0070 0.0036 0.0156 0.0011 0.0131 0.0066 0.0040 0.0014 0.0242 0.0169 0.0026

0.0485 0.0194 0.0222 0.0197 0.0542 0.0009 0.0556 0.0410 0.0123 0.0382 0.0505 0.0405

0.0230 0.0062 0.0129 0.0021 0.0276 0.0061 0.0311 0.0225 0.0055 0.0070 0.0337 0.0189

0.0509 0.0264 0.0187 0.0353 0.0531 0.0140 0.0490 0.0371 0.0137 0.0624 0.0336 0.0431

0.0391 0.1129 0.0572 0.2499 0.0178 0.2102 0.1058 0.0635 0.0219 0.3892 0.2718 0.0422

0.7792 0.3111 0.3569 0.3169 0.8702 0.0147 0.8933 0.6589 0.1980 0.6137 0.8110 0.6505

0.3700 0.0991 0.2070 0.0335 0.4440 0.0977 0.4995 0.3612 0.0881 0.1123 0.5414 0.3042

0.8183 0.4241 0.2997 0.5669 0.8524 0.2249 0.7875 0.5953 0.2199 1.0029 0.5392 0.6928

0.0495 0.3608 0.1622 0.7919 0.0203 14.5556 0.1187 0.0976 0.1138 0.6335 0.3347 0.0642

20.2083 2.7714 6.1667 1.2628 49.2727 0.0687 8.4242 10.2500 8.7857 1.5785 2.9882 15.5769

conceptual density functional theory (DFT) [89]. Chemical potential, global hardness, global softness, electronegativity and electrophilicity are global reactivity descriptors, highly successful in predicting global chemical reactivity trends. The global parameters such as ionisation potential (I), electron affinity (A), electrophilicity (x), electronegativity (v), hardness (g), and softness (S) of the molecule are determined and displayed in Table 2. The site-selectivity of a chemical system, cannot, however, be studied using the global descriptors of reactivity. Fukui functions and local softness are extensively applied to probe the local reactivity and site selectivity. The formal definitions of all these descriptors and working equations for their computation 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 substitution 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.  The local softness, relative electrophilicity (sþ k =sk ) and relative þ nucleophilicity (s =s ) indices, the dual local softness Dsk and the k k multiphilicity descriptors (Dxk) have also been determined to predict the reactive sites of the molecule and are summarised in Table 8. From the dual local softness Dsk and the multiphilicity descriptors (Dxk) one can understand 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. The local reactivity descriptors of the individual atoms of the molecule sak ¼ fka S; xak ¼ xfka and fka where, a = +,  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 individual atoms. Conclusions The following observations are made from the current investigations 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 mol1) and can be locked into only one most stable configuration (I). (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-methoxyacetophenone lie in the molecular plane which confirms the planarity of the molecule.

(iv) The carbonyl and hydroxyl groups involves in the formation of intramolecular hydrogen bond of the type OAH  O. The bond distances of the OAH  O intramolecular hydrogen bond are O7AH22 is (0.99 Å), H22  O11 is (1.67 Å) and O7AO11 is (2.56 Å) respectively. (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. (vi) The maximum and minimum observed total electron density of the molecule is ±4.279e  102 while the extreme limits of the electrostatic potential is ±1.082e  102. (vii) The LUMO–HOMO energy gap of 2-hydroxy-4-methoxyacetophenone 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 cm1 and in Raman the medium lines observed at 1618, 1573, 1336 and 1283 cm1 are assigned to the CAC stretching modes of 2H4MAP. (ix) The mCAO stretching frequency shows very strong band at 1631 cm1 in IR spectrum and a medium band at 1632 cm1 in the Raman spectrum. (x) The compound under investigation shows a weak and broad stretching of hydroxyl group at 3208 cm1 in the infrared spectrum. The in-plane and out of plane OAH bending vibrations are assigned at 1419 and 860 cm1, 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. (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. (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. (xiv) In 2-hydroxy-4-methoxyacetophenone molecule, the lone 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 mol1. 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 mol1. (xv) From the dual local softness Dsk and the multiphilicity descriptors (Dxk) one can understand that the atoms C1, C3, C5, O7, O8, C9, O11 and C12 are favourable for nucleophilic

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