Available online at WSN 36 (2016) EISSN

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1 Available online at WSN 36 (2016) EISSN Synthesis, spectral, molecular structure, HOMO- LUMO and NLO analysis of some (E)-N -(3,3- dimethyl-2,6-diarylpiperidin-4-ylidene)-4- methoxybenzohydrazide G. Sundaraselvan and S. Darlin Quine* Department of Chemistry, Government Arts College, C. Mutlur, Chidambaram , India * address: sdarlinquine@gmail.com ABSTRACT (E)-N -(3,3-dimethyl-2,6-diarylpiperidin-4-ylidene)-4-methoxybenzohydrazide (DDMs) have been synthesized and their IR and 1 H spectra were recorded. The optimized geometric parameters (bond lengths, bond angles and dihedral angles) were in good agreement with the corresponding experimental values. In addition, HOMO-LUMO, MEP and atomic charges of carbon, nitrogen and oxygen were calculated using B3LYP/6-311G(d,p) level theory. The polarizability and first order hyperpolarizability of the title molecule were calculated and interpreted. Keywords: piperidin-4-one; DFT; HOMO LUMO energies; NLO 1. INTRODUCTION The piperidone and its derivatives are a class of nitrogen containing heterocycles that have received much attention because of their wide range of biological activities 1-5 as well as properties useful from the technological point of view 6,7. Pipeeridin-4-ones were also used as corrosion and oxidation inhibitors 8. Regardless of this fact, studies regarding the investigation

2 of their molecular structure and their electronic structure by computational techniques are lacking in the chemical literature Density functional theory (DFT) calculations are the excellent alternative methods in the design of NLO molecules and it helps to predict properties of the new materials, such as molecular dipole moments, polarizabilities, and hyperpolarizabilities 12. The present work reports the results of a systematic study of the geometrical and electronic structure, electrostatic potential surfaces and molecular hyperpolarizability based on their density functional theory computations. 2. EXPERIMENTAL DETAILS Synthesis of 3,3-Dimethyl-2,6-diarylpiperidin-4-ones ( 1-5) Dry ammonium acetate (100 mmol), 3-methyl-2-butanone (100 mmol) and appropriate substituted benzaldehyde (200 mmol) in ethanol were just heated to boil and allowed to stand at room temperature overnight. The reaction mixture was diluted with ether (100 ml) and treated with Conc. HCl (20 ml). The precipitated hydrochloride was washed with ethanol ether. The hydrochloride was suspended in acetone and neutralized with aqueous ammonia. Dilution with water gave the free base which was recrystallized from ethanol. Synthesis of ethyl 4-methoxybezoate (6) and 4-methoxybezo hydrazide (7) Ethyl 4-methoxybezoate (6) and 4-methoxybezo hydrazide (7) were synthesized as per the procedure described in literature 13. Synthesis of (E)-N -(3,3-dimethyl-2,6-diarylpiperidin-4-ylidene)-4-methoxybenzohydrazide (8-12) A mixture of 3,3-Dimethyl-2,6-diarylpiperidin-4-ones (1 mmol), 4-methoxybezo hydrazide (1.5 mmol) in ethanol and a few drops of acetic acid was added and refluxed for 2 4 h. On completion of the reaction time, a solid mass was formed, which was then cooled to room temperature. The precipitate was filtered off and washed with ice-cooled water ethanol mixture. The crude product was recrystallized from ethanol. Synthetic routes of compounds are given in scheme 1. (E)-N -(3,3-dimethyl-2,6-diphenylpiperidin-4-ylidene)-4-methoxybenzohydrazide (8) Pale Yellow solid; Yield 65%., M.P: 191 C, MF: C 27 H 29 N 3 O 2 ; elemental analysis: Calcd (%): C, 75.85; H, 6.84; N, 9.83; O, 7.48; found (%): C, 75.74; H, 6.86; N, 9.79; IR (KBr, cm -1 ): 3464 (N-H), 3068 (Ar-C-H), 2935 (AliC-H), 1647 (C=O); 1 H-NMR (CDCl 3 ) (m, Ar-H), 2.14 (1H, N-H), 7.26 (1H, N-H), 3.01 (1H, H5ax,), 3.13 (1H, H5eq), 3.88 (1H, H2), 3.54 (1H, H6), 3.50 (3H, OCH 3 ), 1.62 (3H, CH 3 ); Mass (m/z): 426 (M+), 350, 265, 164, 107, 96, 77. (E)-N -(2,6-bis(4-fluorophenyl)-3,3-dimethyl-2,6-diphenylpiperidin-4-ylidene)-4- methoxybenzohydrazide (9) Yellow solid; Yield 63%., M.P: 204 C, MF: C 27 H 27 F 2 N 3 O 2 ; elemental analysis: Calcd (%): C, 69.96; H, 5.87; F, 8.20; N, 9.07; O, 6.90; found (%): C, ; H, 5.83; N, -28-

3 9.03; IR (KBr, cm -1 ): 3477 (N-H), 3064 (Ar-C-H), 2920 (AliC-H), 1674 (C=O); 1 H-NMR (CDCl 3 ) (m, Ar-H), 2.14 (1H, N-H), 7.28 (1H, N-H), 2.18 (1H, H5ax,), 2.54 (1H, H5eq), 4.36 (1H, H2), 4.00 (1H, H6), 3.91 (3H, OCH 3 ), 1.61 (3H, CH 3 ); Mass (m/z): 462 (M+), 368, 328, 273, 150, 107. (E)-N -(2,6-bis(4-chlorophenyl)-3,3-dimethyl-2,6-diphenylpiperidin-4-ylidene)-4- methoxybenzohydrazide (10) Pale Yellow solid; Yield 66%., M.P: 189 C, MF: C 27 H 27 Cl 2 N 3 O 2 ; elemental analysis: Calcd (%): C, 65.32; H, 5.48; Cl, 14.28; N, 8.46; O, 6.45; found (%): C, ; H, 5.45; N, 8.43; IR (KBr, cm -1 ): 3427 (N-H), 3059 (Ar-C-H), 2927 (AliC-H), 1653 (C=O); 1 H-NMR (CDCl 3 ) (m, Ar-H), 1.97 (1H, N-H), 7.28 (1H, N-H), 2.37 (1H, H5ax,), 2.54 (1H, H5eq), 3.19 (1H, H2), 4.78 (1H, H6), 3.68 (3H, OCH 3 ), 1.66 (3H, CH 3 ); Mass (m/z): 458 (M+), 444, 352, 324, 282, 135, 93. (E)-N -(3, 3-dimethyl-2,6-di-p-tolylpiperidin-4-ylidene)-4-methoxybenzohydrazide (11) Pale Yellow solid; Yield 60%., M.P: 214 C, MF: C 29 H 33 N 3 O 2 ; elemental analysis: Calcd (%): C, 76.45; H, 7.30; N, 9.22; O, 7.02; found (%): C, 76.30; H, 7.29; N, 9.12; IR (KBr, cm -1 ): 3464 (N-H), 3068 (Ar-C-H), 2918 (AliC-H), 1597 (C=O); 1 H-NMR (CDCl 3 ) (m, Ar-H), 2.15 (1H, N-H), 6.75 (1H, N-H), 2.48 (1H, H5ax,), 2.66 (1H, H5eq), 3.65 (1H, H2), 3.65 (1H, H6), 3.45 (3H, OCH 3 ), 1.62 (3H, CH 3 ); Mass (m/z): 454 (M+), 440, 349, 329, 293, 135. (E)-I -(2,6-bis(4-methoxyphenyl)-3,3-dimethyl-2,6-diphenylpiperidin-4-ylidene)-4- methoxybenzohydrazide (12) Pale Yellow solid; Yield 61%., M.P: 231 C, MF: C 29 H 33 N 3 O 4 ; elemental analysis: Calcd (%): C, 71.44; H, 6.82; N, 9.22; O, 13.13; found (%): C, 71.43; H, 6.70; N, 9.12; IR (KBr, cm -1 ): 3462 (N-H), 3070 (Ar-C-H), 2920 (AliC-H), 1656 (C=O); 1 H-NMR (CDCl 3 ) (m, Ar-H), 2.17 (1H, N-H), 6.90 (1H, N-H), 2.70(1H, H5ax,), 3.06 (1H, H5eq), 3.82 (1H, H2), 3.44 (1H, H6), 3.88 (3H, OCH 3 ), 1.68 (3H, CH 3 ); Mass (m/z): 486 (M+), 472, 456, 380, 352, 349, 164, 111. Spectral measurements The FT-IR spectrum of the synthesized DDMs was measured in the range cm -1 on a AVATAR-330 FT-IR spectrometer (Thermo Nicolet) using KBr (pellet form). 1 H NMR spectrum was recorded at 400 MHz on a BRUKER model using CDCl 3 as solvent. Tetramethylsilane (TMS) was used as internal reference for all NMR spectra, with chemical shifts reported in δ units (parts per million) relative to the standard. Computational studies Structure optimizations of DDMs were performed at the Density Functional Theory (DFT) level employing B3LYP/6-311G(d,p) functional as implemented in the Gaussain 03W 14. To investigate the reactive sites of the title molecules, the Mulliken and molecular electrostatic potential were evaluated. -29-

4 Scheme 1. Synthetic routes of compounds (8-12). -30-

5 Moreover, in order to show nonlinear optical (NLO) activity of studied molecules, the dipole moment, linear polarizability and first order hyperpolarizability were obtained from molecular polarizabilities based on theoretical calculations. Also, the HOMO-LUMO on optimized structures is accomplished at B3LYP/6-311G(d,p) level computation. The electronegativity (χ) were reported by Iczkowski et al. 15 is performed as χ = (E HOMO + E LUMO )/2. The global electrophilicity 16 (ω) is also calculated following the expression ω = (μ 2 /2η), where μ is the chemical potential (μ (E HOMO + E LUMO ) / 2), and η is the chemical hardness (E LUMO E HOMO )/2) RESULTS AND DISCUSSION Molecular geometry The chair conformer of piperidine molecule is the most stable conformer 18,19. Therefore, we neglected other conformations i.e. boat, envelope or twist boat because of their high energy. Piperidine molecules show the equatorial disposition of N-H in chair conformer as the most stable one 20. Fig. 1. Numbering Pattern of DDMs. The optimized structural parameters such as bond lengths, bond and dihedral angles of DDMs were determined at B3LYP level theory with 6-311G(d,p) basis set and are presented in Table 1 in accordance with the atom numbering scheme of the molecule shown in Fig. 1. To the best of our knowledge, no single crystal X-ray crystallographic data of DDMs has yet been reported. However, the theoretical results obtained are almost comparable with closely related molecules such as E)- N -(3,3-Dimethyl-2,6-diphenylpiperidin- -31-

6 4-ylidene)isonicotinohydrazide 21. The C2-N1 and C6-N1 bond nearly Å by B3LYP, which is coincide with literature value Å 21. (8) (9) -32-

7 (10) (11) -33-

8 (12) Fig. 2. Optimized structures of DDMs. Table 1. Selected bond lengths, bond angles and dihedral angles of DDMs. Bond length (Å) XRD a C2-N N1-H C6-N C2-C C3-C C4-C C5-C C3-C C3-C C4-N N17-N

9 N18-H N18-C C19-O C Bond angle ( ) N1-C2-C N1-C6-C H1-N1-C H1-N1-C C2-C3-C C3-C4-C C4-C5-C C2-N1-C C3-C4-N C5-C4-N H18-N18-C N18-C19-O Dihedral ( ) N1-C2-C3-C N1-C6-C5-C C8-C3-C4-N C7-C3C4-N N1-C2-C9-C N1-C2-C9-C N1-C6-C13-C N1-C6-C13-C N17-N18-C19-C a- Values are taken from Ref. 21 Piperidine ring essentially adopts chair conformation, with all substituents equatorial as evident from the torsional angles [N1 C2 C3 C and and N1 C6 C5 C and by B3LYP and XRD, respectively. In the molecular optimized structure, the hydrazone analogue is nearly planar with the dihedral angle -35-

10 (N17-N18-C19-C20) around ~16.19 B3LYP and adopts an E configuration with respect to the C4=N4 bond 21. Form the result we concluded that the E configuration is more stable than the other possibilities. Mulliken analysis The calculation of Mulliken atomic charges plays an important role in the application of quantum mechanical calculations to molecular systems. The Mulliken atomic charges for the DDMs calculated at the B3LYP/6-31G(d,p) level in gas-phase are presented in Fig. 3 and Table 2. Results from Table 2 show that C7 has higher positive value than C8 in title compounds. This difference is due to the from that C7 experiences I effect from oxygen (N17) atom. The Table 2 for DDMs shows that the high positive charge in molecule is [H1, C4, C12, C16, H18, C19, C23]. The positive regions are related to nucleophilic reactivity. The negative regions are located around the oxygen (O19, O27) and nitrogen (N1, N1 and N18) atoms which are related to electrophilic reactivity 22. These data clearly show that DDMs are the most reactive towards substitution reactions. Table 2. Mulliken atomic charges of DDMs. Atom N H C C C C C C C C C R C C R

11 N N H C O C C O C R = H, F, O, C and O for 8, 9, 10, 11 and 12, respectivel. Fig. 3. Mulliken charges of DDMs -37-

12 Molecular electrostatic potential analysis (8) (9) -38-

13 (10) (11) -39-

14 (12) Fig. 4. MEP diagram of DDMs. Molecular electrostatic potential (MEP) is a helpful descriptor used to visualize the electrophilic or nucleophilic reactive sites of molecules 22, and to show the electrostatic potential regions in terms of color grading. In MEP map (Fig. 4), different values of the electrostatic potential are represented by different colors: red and blue represents the regions of the most negative and positive electrostatic potential whereas green represents the region of zero potential. Potential increases in the order of: red < orange < yellow < green < blue. The positive regions are placed around all hydrogen atoms attached with the nitrogen, which are related to nucleophilic reactivity 22. The negative regions are located around the oxygen and nitrogen atoms. As shown in Fig. 4, the negative potential sites are around the electronegative (oxygen and nitrogen) atoms and the positive potential sites are hydrogen and carbon atoms, while the remaining species are surrounded by orange, yellow and green. As we conclude from this our title molecules are ready for both electrophilic and nucleophilic reactions. Frontier molecular orbital analysis The frontier molecular orbitals play an important role in the electric and optical properties, as well as in chemical reactions, UV Vis and fluorescence spectra 23,24. The contour surfaces of the frontier molecular orbitals for each molecule drawn in Fig. 5. In the DDMs, the electron cloud distribution in HOMO is piperidine ring and hydrazone unit, but the contribution of molecular fragment to LUMO are mainly from the hydrazone unit. The difference of the charge separation between the HOMO and LUMO of those structure play important role in the internal charge transfer (ICT). -40-

15 Furthermore, the difference on the values of ΔE of compounds 8-12 was observed, which has different substituent at 12 & 16- sites of the phenyl core. Table 3. Calculated energy values (ev) of DDMs in gas phase. DFT/B3LYP/6-311G(d,p) E HOMO E LUOMO ELUMO-HOMO E HOMO E LUOMO E (LUMO+1)- (HOMO-1) Electrinegativity(χ) Hardness(η) Electrophilicity index(ψ) Softness(s) For a system lower value of ΔE makes it more reactive or less stable and also has a direct influence on the electron density difference for the stabilizing ICT process. In this sense, it seems that the selection of a methoxy containing substituent has a beneficial effect among the designed candidate. As a result, the trend of ΔE gap of inspected compounds becomes 12 > 10 > 11 > 9 > 8. We can observe from this Table 3, the introduction of different substituent at 12 & 16- sites of the phenyl core significantly change the ΔE value. Chemical hardness is related with the stability and reactivity of a chemical system, it measures the resistance to change in the electron distribution or charge transfer. In this sense, chemical hardness corresponds to the gap between the HOMO and LUMO. The larger the HOMO LUMO energy gap, the harder and more stable/less reactive the molecule. The higher value of ΔE represents more hardness or less softness of a compound, thus compound 8 referred as hard molecule when compared to Another global reactivity descriptor electrophilicity index (ψ) describes the electron accepting ability of the systems quite similar to hardness and chemical potential. High values of electrophilicity index increases electron accepting abilities of the molecules. Thus, electron accepting abilities of compounds 8-12 are arranged in following order: 9 > 8 > 10 > 11 >

16 Fig. 5. Molecular orbitals and energies for the HOMO and LUMO in gas phase. -42-

17 Non-linear optical activity NLO is important property providing key for areas such as telecommunications, signal processing and optical interactions 26,27. A large variety of NLO switches exhibiting large changes in the first order hyperpolarizability (β), the molecular second-order NLO response. In this context, the design of NLO switches, that is, molecules computed for their first hyperpolarizability by alternate their substitution at 12 and 16- sites in phenyl core. The total static dipolemoment (μ), the Mean polarizabilty (α), Anisotropy of the polarisabiltiy (Δα) and the first order hyperpolarizability (β 0 ) using the x, y, z components are calculated using the following equations. μ = (μ x 2 + μ y 2 + μ z 2 ) 1/2 [( ) ( ) ( ) ( )] ) ( ) ( ) ( Table 4. Non-linear optical properties of DDMs calculated using B3LYP method using 6-311G(d,p) basis set. NLO behavior Dipole moment (μ) D Mean polarizabilty (α) x10-23 esu Anisotropy of the Polarisabiltiy (Δα) x10-24 esu First order polarizabilty (β 0 ) x10-30 esu As the results mentioned previously 10,28,29, hydrazones may have significance nonlinear optical property. In this sense a series of new molecules possessing nonlinear optical property are designed which includes S, F, OH, CH 3 and OCH 3 groups at 12 & 16- sites of the phenyl core. According to Table 4, all values of each mentioned molecules are greater than their urea 30 values. Therefore, NLO properties of our compounds are better than urea. -43-

18 Results from Table 4, the general ranking of NLO properties should be as follows: 12 > 10 > 8 > 11 > 9. With results in hand, molecule 5 is the best candidate for NLO properties. To sum up, it can be concluded that the presence of an electron donating group (methoxy) in the para position at the phenyl ring contributes to decrease the dipole moments, mean polarisability and first order hyperpolarizability of the DDMs probably because of an inductive competition between the methoxy and the electronic density available in the molecule. When it is compared with similar compounds in the literature, the β 0 value tittle compounds are high than that of 3t-pentyl-2r,6c-diphenylpiperidin-4-one semicarbazone (β 0 = 0.65 x10-30 esu) 28 and 3t-pentyl-2r,6c-diphenylpiperidin-4-one thiosemicarbazone (β 0 = 1.28 x10-30 esu) 29. The above results show that DDMs can be best material for NLO applications 4. CONCLUSIONS Results from in hand, piperidone ring adopts chair conformation with equatorial orientation of substituent at C2, C3, C6 and hyzrazone analogue adopts an E configuration with respect to C4=N17. In addition, Mulliken charge and MEP analysis predicts the most reactive parts in the molecule. The result of molecular orbital composition analysis revealed for DDMs, that the ΔE gap could be lowered upon modifying the 12 & 16- sites of the phenyl core. Among this, compound 12 is the best candidate for the stabilizing ICT process. Another conclusion of the paper is the calculated first hyperpolarizability is comparable with reported values of similar derivatives and the 12 is a strong candidate for future studies of nonlinear optics. References [1] C. Ramalingam, Y.T. Park, S. Kabilan, Eur. J. Med. Chem., 41 (2006) 683. [2] S. Balasubraanian, G. Aridoss, P. Parthiban, Biol. Pharm. Bull., 29 (2006) 125. [3] S. Murugesan, S. Perumal, S. Selvaraj, Chem. Pharm. Bull., (Tokyo) 54 (2006) 795. [4] M.X. Li, C.L. Chen, C.S. Ling, J. Zhou, B.S. Ji, Y.J. Wu, J.Y. Niu, Bioorg. Med. Chem. Lett., 19 (2009) [5] Sethukumar, C. Udhaya Kumar, R. Agilandeshwari, B. Arul Prakasam, J. Mol. Struct., 1047 (2013) 237. [6] J. Jayabharathi, V. Thanikachalam, M. Padamavathy, N. Srinivasan, Spectrochim. Acta, Part A 81 (2011) 380. [7] J. Jayabharathi, V. Thanikachalam, M. Padamavathy, M. Venkatesh Perumal, J. Fluoresc., 22 (2012) 269. [8] L. Ravikumar, G. Rathika, R. Punitha, Int. J. Eng. Res. Tech., 2 (2013) [9] S. Subashchandrabose, H. Saleem, Y. Erdogdu, G. Rajarajan, V. Thanikachalam, Spectrochim. Acta, Part A 82 (2011)

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