untitled European Journal of Chemistry 8 (4) (2017) 358‐366 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2017 Atlanta Publishing House LLC ‐ All rights reserved ‐ Printed in the USA http://dx.doi.org/10.5155/eurjchem.8.4.358-366.1632 European Journal of Chemistry Journal webpage: www.eurjchem.com Heteroaromatization with 4‐phenyldiazenyl‐1‐naphthol. Part III: One‐pot synthesis and DFT study of 4H‐naphthopyran derivatives Hany Mostafa Mohamed 1,2, Ashraf Hassan Fekry Abd El‐Wahab 1,2,* and Tarek Maamon El‐Gogary 1,3 1 Chemistry Department, Faculty of Science, Jazan University, 2097, Jazan, Kingdom Saudi Arabia 2 Chemistry Department, Faculty of Science, Al‐Azhar University, 11884, Nasr City, Cairo, Egypt 3 Chemistry Department, Faculty of Science (Domyat), Damietta University, 34517, Domyat Al‐Gideda, Egypt * Corresponding author at: Chemistry Department, Faculty of Science, Jazan University, 2097, Jazan, Kingdom Saudi Arabia. Tel.: +966.054.0963753. Fax: +966.017.3230028. E‐mail address: ash_abdelwahab@yahoo.com (A.H.F.A. El‐Wahab). ARTICLE INFORMATION ABSTRACT DOI: 10.5155/eurjchem.8.4.358-366.1632 Received: 21 July 2017 Received in revised form: 23 August 2017 Accepted: 04 September 2017 Published online: 31 December 2017 Printed: 31 December 2017   A one pot three component reaction of 4‐phenyldiazenyl‐1‐naphthol (1), p‐chloro benzaldehyde (2) and malononitrile or ethyl cyanoacetate (3) in ethanol/piperidine under reflux afforded 2‐amino‐4‐(p‐chlorophenyl)‐6‐phenyldiazenyl‐4H‐naphtho[1,2‐b]pyrano‐3‐ carbonitrile (4a) and ethyl 2‐amino‐4‐(p‐chlorophenyl)‐6‐phenyldiazenyl‐4H‐naphtho[1,2‐ b]pyrano ‐3‐carboxylate (4b). Structure of these compounds was established on the basis of IR, 1H NMR, 13C NMR, Mass and UV‐Vis spectra. Molecular geometry of compounds 4a and b was obtained at B3LYP/6‐31+G(d) level. Two tautomers and two conformers were geometrically optimized. The tautomers are separated by about 7.942 kcal/mol while rotational conformers are only separated by 0.511 kcal/mol. Molecular reactivity descriptors including global electrophilicity, hardness, softness and local condensed Fukui functions were computed and discussed. Frontier molecular orbitals (HOMO and LUMO) were also computed. KEYWORDS Malononitrile Fukui functions Ethyl cyanoacetate 4‐Phenyldiazenyl‐1‐naphthol 4H‐Naphthopyran derivatives Density Functional Theory (DFT) Cite this: Eur. J. Chem. 2017, 8(4), 358‐366 1. Introduction Synthetic azo compounds are widely used in different application fields, such as medicines, cosmetics, food, paints, plastics, shipbuilding, automobile industry and cable manufac‐ ture [1‐12]. Moreover, azo compounds are known for their antineoplastics [13], antidiabetics [14], antiseptics [15], antibacterial [16] and antitumor activities [17]. 4H‐Pyran nucleus is a fertile source of biologically important molecules possessing a wide spectrum of biological and pharmacological activities such as antimicrobial [18‐21], inhibitors of influenza virus sialidases [22,23], DNA strand‐breaking activity and mutagenicity [24], antiviral agent [25], antiproliferation agent [26], sex pheromone [27], antitumor [28,29] and central nervous system (CNS) activity [18‐30]. The synthesis of 4H‐ naphthopyrans involves a one‐pot three‐component coupling reaction of, p‐chlorobenzaldehyde, malononitrile or ethyl cyanoacetate and phenyldiazenyl‐1‐naphthol. Nowadays, multi‐component reactions (MCRs) provide significant advan‐ tages over normal linear step synthesis, in terms of easy work‐ up procedures and purification, short reaction time, energy and raw‐material consumption. The present work reports the results of molecular geometrical data for compound 2‐amino‐ 4‐(p‐chlorophenyl)‐6‐(phenyldiazenyl)‐4H‐naphtho[1,2‐b]py‐ ran‐3‐carbonitrile (4a) and ethyl 2‐amino‐4‐(p‐chlorophenyl)‐ 6‐(phenyldiazenyl)‐4H‐naphtho[1, 2‐b]pyran‐3‐carboxylate (4b) were computed using quantum density functional theory at B3LYP/6‐31G(d) and chemical reactivity descriptors were computed to explore the reactivity of compound 4a and 4b. 2. Experimental 2.1. Instrumentation Melting points were determined with a Stuart Scientific Co., Ltd. apparatus. UV spectra were measured on a Shimadzu UV‐1601PC UV‐Vis spectrophotometer. IR spectra were determined as KBr pellets on a Jasco FT/IR 460 plus spectro‐ photometer. 1H NMR and 13C NMR spectra were recorded using a Bruker AV 400 MHz spectrometer. Mass spectra were measured on a Shimadzu GC/MS‐QP5050A spectrometer. Elemental analyses were performed on a Perkin‐Elmer 240 microanalyser in the Faculty of Science, Cairo University, Egypt. Mohamed et al. / European Journal of Chemistry 8 (4) (2017) 358‐366 359 Scheme 1 2.2. Synthesis of 4H‐naphthopyran derivatives (4a and b) To a mixture of 4‐phenyldiazenyl‐1‐naphthol (2.48 g, 10 mmol), p‐chlorobenzaldehyde (1.40 g, 10 mmol) and malono‐ nitrile (0.66 g, 10 mmol) or ethylcyano acetate (1.13 g, 10 mmol) in absolute ethanol (30 mL) was added a catalytic amount of piperidine (0.5 mL). The reaction mixture was heated until complete precipitation occurred (Reaction times: 2 h for compound 4a; 5 h for compound 4b) (Scheme 1). The solid product formed which was collected by filtration and recrystallized from dioxane and ethanol/benzene mixture, respectively. 2‐Amino‐4‐(p‐chlorophenyl)‐6‐(phenyl diazenyl)‐4H‐napht ho[1,2‐b]pyran‐3‐carbonitrile (4a): Color: Yellow crystals. Yield: 90 %. M.p.: 245‐246 °C. FT‐IR (KBr, ν, cm‐1): 3417, 3327, 3207 (NH2), 3001, 2960, 2812 (CH str.), 2196 (CN), 1666 (C=C), 1510 (N=N). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.93‐ 7.24 (m, 14H, Ar‐H), 4.95 (s, 1H, CH‐Pyran), 4.84 (bs, 2H, NH2, exchangeable by D2O). 13C NMR (100 MHz, CDCl3, δ, ppm): 158.59 (C‐2), 152.94 (C‐6), 144.70, 142.63, 133.44, 131.41, 133.29, 129.45, 129.20, 129.14, 127.82, 127.43, 123.75, 123.71, 123.28, 123.17, 120.90 (Ar‐C), 116.98 (CN), 61.33 (C‐ 3), 40.74 (C‐4). MS (EI, m/z (%)): 438 (M++2, 0.1), 436 (M+, 20.4), 325 (75.8), 220 (59.9), 77 (100), 51 (18.2). UV/Vis (CH3COCH3, λmax, nm): 268.80. Anal. calcd for C26H17ClN4O: C, 71.48; H, 3.92; N, 12.82. Found: C, 71.01; H, 3.40; N, 12.39%. Ethyl 2‐amino‐4‐(p‐chlorophenyl)‐6‐(phenyl diazenyl)‐4H‐ naphtho[1,2‐b]pyran‐3‐carboxylate (4b): Color: Yellow crys‐ tals. Yield: 75 %. M.p.: 208‐209 °C. FT‐IR (KBr, ν, cm‐1): 3417, 3380, 3126 (NH2), 3060, 3010, 2960, (CH str.), 1675 (CO), 1629 (C=C), 1539 (N=N). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.92‐720 (m, 14H, Ar‐H), 6.54 (bs, 2H, NH2, exchangeable by D2O), 5.14 (s, 1H, CH‐Pyran), 4.11 (q, 2H, J = 7.0 Hz, CH2), 1.21 (t, 3H, J = 7.0 Hz, CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 169.15 (CO), 159.62 (C‐2), 153.08 (C‐6), 145.81, 145.79, 145.68, 144.26,132.05, 131.24, 131.02, 129.61, 129.37,129.13, 128.45,128.36, 127.32, 127.00, 126.40, 123.79, 123.61,123.11, 120.54, 112.76 (Ar‐C ), 79.01 (C‐3), 59.73 (CH2), 40.37 (C‐4), 14.37 (CH3). MS (EI, m/z (%)): 485 (M++2, 5.41), 483 (M+, 9.22), 372 (35.2), 268 (18.5), 181 (6.7), 91 (100), 75 (60.1), 51 (9.3). UV/Vis (CH3COCH3, λmax, nm): 267.58. Anal. calcd. for C28H22ClN3O3: C, 69.49; H, 4.58; N, 8.68. Found: C, 69.05; H, 4.12; N, 8.25%. 2.3. Computational details All computations were done using Gaussian09 suite of programs [31]. Molecular geometry of anthraquinone com‐ pounds were optimized in the gas phase at DFT, B3LYP/6‐ 31+G(d,p) level of theory. A frequency job was performed on the optimized geometry to confirm a minimum energy structure. Fukui functions were calculated using DMol module [32,33] employing B3LYP/DND method implemented in Material Studio program [34]. 3. Results and discussion 3.1. Synthesis In continuation of previous work for synthesis of naphtha‐ pyrans with arylidine skeleton [20,21,35‐40], we report herein the synthesis of naphthopyrans through three component condensation of aromatic aldehydes, malononitrile or ethyl cyanoacetate and naphthol. Thus, treatment of 4‐phenyldi azenyl‐1‐naphthol (1), p‐chlorobenzaldehyde (2) and malono‐ nitrile or ethyl cyanoacetate (3) in ethanol/piperidine under reflux afforded 2‐amino‐4‐(p‐chlorophenyl)‐6‐phenyldiazen yl‐4H‐naphtho[1,2‐b]pyrano‐3‐carbonitrile (4a) and ethyl 2‐ amino‐4‐(p‐chlorophenyl)‐6‐phenyldiazenyl‐4H‐naphtho[1,2‐ b]pyrano‐3‐carboxylate (4b), respectively (Scheme 1). Struc‐ ture of these compounds was established on the basis of IR, UV, 1H NMR, 13C NMR and MS data. A plausible mechanism for the formation of naphthopyran derivatives catalyzed by piperidine is shown in Scheme 2. The Knoevenagel reaction in the presence of piperidine occurs via an initial formation of 2‐(4‐chlorobenzylidene)malononitrile or ethyl‐3‐(4‐chlorophenyl)‐2‐cyanoacrylate, after removal of one molecule of water from the condensation of p‐chloro benzaldehyde and malononitrile or ethyl cyanoacetate. 4‐ Phenyldiazenyl‐1‐naphthol is converted to the enolate form after tautomerisation and attacks the of 2‐(4‐chloro benzyli‐ dene)malononitrile or ethyl‐3‐(4‐chlorophenyl)‐2‐cyano acrylate as Michael acceptor, to give intermediate and then furnished the intermediate product, which upon intra‐ molecular cyclization and rearrangement gave rise to 4H‐ naphthopyrans 4a and 4b (Scheme 2). Structure of compound 4a and 4b was established on the basis of spectral data. The IR spectrum of compound 4a showed the presence of a NH bands at ν 3417, 3327, 3207 cm‐1 and a CN band at ν 2196 cm‐1, while for compound 4b showed the appearance of a NH2 bands ν 3417, 3380, 3126 and a CO band at ν 1675 cm‐1. The UV spectra revealed a weak shoulder characteristic for 4H‐pyran [41] at λmax (CH3COCH3) 268.80‐ 267.58 nm (log ε 4.82‐4.81). By applying DFT, we shed light on the geometries and electronic properties. The compound which we have studied compound 4b have two possibilities, two tautomer amino form and imino form; it was esteemed that imino form would be good as biologically active molecule. Then, we have compared the properties with compound 4b. Moreover, the effect of NH2 and NH at position 2 in compound 4b and 4b‐ imine (Scheme 3) has been studied. 360 Mohamed et al. / European Journal of Chemistry 8 (4) (2017) 358‐366 Scheme 2 O N COOEt N N Cl H H 4b 4b-imine 1 2 3 4 5 67 8 9 10 4a 6a O NH COOEt N N Cl 1 2 3 4 5 67 8 9 10 4a 6a Scheme 3 The mass spectra of compounds 4a and 4b showed, the corresponding molecular ion peaks at m/z 436 (M+, 20.4) and 483 (M+, 9.22). The 1H NMR and 13C NMR spectra of compound 4a showed signals at δ 4.84 ppm for NH2 proton exchangeable by D2O, at δ 4.95 ppm for CH‐pyran proton and at δ 40.74 ppm for CH‐pyran (C‐4) carbon. In compound 4b, the amino group gave 1H signals at δ 6.54 ppm for NH2 proton exchangeable by D2O, at δ 5.14 ppm for CH‐pyran proton and ester group at δ 4.11 ppm for CH2, at δ 1.21 ppm for CH3, with the corres‐ ponding signals in the 13C NMR at δ 169.15 ppm for carbonyl, at δ 59.73 ppm for CH2, at δ 40.37 ppm for CH‐pyran (C‐4) and at δ 14.37 ppm CH3 carbon (Figure 1). 3.2. Molecular geometry Molecular geometrical data for compound 4a and 4b were computed using quantum density functional theory DFT, at B3LYP/6‐31G(d). Selected geometrical parameters are displayed in Figure 2. Both compounds 4a and 4b could be present in two tautomeric forms, amine and imine as shown in Figure 3. Each imine form could also be present in two confor‐ mations as shown in Figure 3. All these possible structures were studied and optimized at B3LYP/6‐31G(d). Relative total energies are displayed in Figure 3. For compound 4a, the amine tautomer is more stable than the imine one by about 6.866 kcal/mol while compound 4b amine tautomer is more stable than the imine one by about 8.507 kcal/mol. The difference in relative energies between compound 4a and 4b is due to extra stabilization in compound 4b via intramole‐ cular hydrogen bonding as shown in Figure 3. Hydrogen bond distance N‐H···O is 1.977 Å in compound 4b which is elongated to 2.077 Å in compound 4b‐imine‐1. For compound 4a, the order of stability goes 4a > 4a‐imine‐2 > 4a‐imine‐1. Imine conformers are inter‐convertible at room temperature (difference is only 0.584 kcal/mol). For compound 4b, the order of stability goes 4b > 4b‐imine‐2 > 4b‐imine‐1. Imine conformers are also inter‐convertible at room temperature (difference is only 0.438 kcal/mol). The geometry of compound 4a and 4b were optimized at B3LYP/6‐31+G(d). Based on tautomerization and conforma‐ tional preferences three minimum energy structures were found as displayed in Figure 3. The computed geometrical parameters (Figure 2) show that the naphthalene ring and the two phenyl rings are perfect planar structures as shown from the dihedral angles (~0.0°). The pyran ring is not that perfect planar where ring dihedral angles are between 0.0 and 20.0°. The p‐chlorophenyl ring tends to perpendicular to the pyran ring with a torsion angle ~60.0° in all structures. The amine structure in compound 4b is stabilized by a weak intramolecular hydrogen bond NH…O of length 1.977 Å and angle N15‐H43‐O17 126.7°. Aromatic rings show typical values for C‐Car (~1.4 Å) bond length and C‐C‐C bond angles (120°). The azo N=N distance is 1.260 Å in both structures. 3.3. Chemical reactivity Chemical reactivity descriptors were computed to explore the reactivity of compound 4a and 4b. The density of electrons on an atom is an important property that contains all the information about the molecular systems. Descriptors of chemical reactivity are good tools for predicting and understanding reactivity of compounds. These descriptors initially developed within the density functional theory framework. Mohamed et al. / European Journal of Chemistry 8 (4) (2017) 358‐366 361 Figure 1. 1H NMR and 13C NMR spectral of compound 4a and 4b. (4a) (4b) Figure 2. Optimized geometry of compound 4a and 4b at B3LYP/6‐31+G(d) level. Global quantities as chemical potential (µ), electro‐ negativity (χ), chemical hardness (ƞ), chemical softness (S), and electrophilicity (ω) of compounds 4a and 4b were calculated according to the equations presented elsewhere [42] and presented in Table 1. Softness of a molecule is a measure of its polarizability and hence, its reactivity. From the results in Table 1, it may be observed that the global softness of compound 4b is larger than that of compound 4a. Compound 4b has the higher global electrophilicity (6.152) and higher softness (0.310). Chemical hardness (ƞ), reflects the resistance of the molecule to polarizability and hence susceptibility for chemical reaction. Chemical hardness (ƞ) for compound 4b (1.614) is smaller than that of compound 4a (1.622). Fukui [43] introduced a qualitative approach of chemical reactivity in the form of what we call Frontier Orbital Theory. Later, this theory was demonstrated [44,45] in the framework of DFT. In a molecular system, the atomic site, which possesses highest condensed Fukui function, favors the higher reactivity. Table 2 and 3 show the condensed Fukui functions as calculated based on Mulliken and Hirshfeld charges for compound 4a and 4b. Isosurface maps for Fukui functions of electrophilic, nucleophilic and radical attack for compound 4b are given in Figure 4. 362 Mohamed et al. / European Journal of Chemistry 8 (4) (2017) 358‐366 Table 1. Calculated global quantities: chemical potential (µ), electronegativity (χ), hardness (ƞ), softness (S), and electrophilicity (ω) and energy of HOMO and LUMO and their difference. Compound µ χ ƞ S ω EHOMO ELUMO ∆EL‐H 4a ‐4.467 4.467 1.622 0.308 6.152 ‐6.089 ‐2.845 3.244 4b ‐4.289 4.289 1.614 0.310 5.700 ‐5.903 ‐2.675 3.227 4a 4b 4a‐imine‐1 4b‐imine‐1 4a‐imine‐2 4b‐imine‐2 Figure 3. Optimized structures of compound 4a and 4b and their tautomers and conformers showing their relative energies and H‐bonding. Isosurface maps show that compound 4b acts better as nucleophile/electrophile than being involved in free radical attack. Naphthalene ring system, azo group, O‐pyran and amino group in compound 4b have the electrophilic/ nuclophilic centers. On the other hand, free radical attack is shown on the azo group. From the results of Table 2 for compound 4a, according to Hirshfeld charges the reactivity for the radical attack was found on N(18) > C(7) > N(49) > N(17) > C (23) > C9 > C6 > C1 > C2. For electrophilic attack, the most reactive sites are N18 (0.099) and N17 (0.092). The order of reactivity toward electrophilic attack could be ranked as N18 > N17 > C23 > C7 > C9 > N49 > C20 > C21. On the other hand, for nucleophilic attack, the most reactive site is N49 (0.061). The reactivity order toward nucleophilic attack could be ranked as N49 > C10 > C23 = C7 > C1=C2=C6 > C5=N18. From Table 3, it is clear that compound 4b is more reactive than compound 4a when comparing values (Mulliken and Hirshfeld) of condensed Fukui functions for electrophilic attack as shown, also, from Figure 4. Mohamed et al. / European Journal of Chemistry 8 (4) (2017) 358‐366 363 Table 2. Condensed Fukui functions (fk0) (fk+) and (fk–) indices of compound 4a. Atom Radical attack Electrophilic attack Nucleophilic attack Mulliken Hirshfeld Mulliken Hirshfeld Mulliken Hirshfeld C (1) 0.017 0.035 0.014 0.031 0.021 0.039 C (2) 0.025 0.033 0.020 0.026 0.030 0.039 C (3) 0.002 0.010 ‐0.002 0.012 0.005 0.009 C (4) 0.009 0.008 0.017 0.010 0.001 0.007 C (5) 0.016 0.024 0.003 0.009 0.030 0.038 C (6) 0.019 0.036 0.018 0.033 0.020 0.039 C (7) 0.060 0.049 0.071 0.053 0.049 0.045 C (8) 0.008 0.024 ‐0.005 0.017 0.022 0.031 C (9) 0.042 0.042 0.059 0.050 0.026 0.034 C (10) 0.027 0.032 0.001 0.015 0.052 0.050 O (11) 0.021 0.026 0.008 0.015 0.033 0.037 C (12) ‐0.002 0.007 ‐0.004 0.004 0.000 0.010 C (13) 0.028 0.019 0.015 0.007 0.042 0.031 C (14) ‐0.009 0.004 ‐0.004 0.002 ‐0.014 0.006 N (15) 0.014 0.016 0.012 0.014 0.016 0.018 C (16) 0.004 0.009 ‐0.001 0.005 0.008 0.013 N (17) 0.050 0.052 0.090 0.092 0.011 0.013 N (18) 0.066 0.069 0.098 0.099 0.033 0.038 C (19) ‐0.003 0.012 ‐0.010 0.011 0.005 0.014 C (20) 0.024 0.031 0.027 0.035 0.021 0.026 C (21) 0.027 0.027 0.037 0.034 0.017 0.020 C (22) 0.005 0.026 0.003 0.030 0.006 0.022 C (23) 0.037 0.052 0.044 0.059 0.030 0.045 C (24) 0.007 0.027 0.008 0.032 0.006 0.023 C (25) ‐0.012 ‐0.009 ‐0.013 ‐0.010 ‐0.011 ‐0.008 C (26) ‐0.002 0.002 ‐0.003 0.000 ‐0.001 0.003 C (27) ‐0.006 ‐0.004 ‐0.007 ‐0.004 ‐0.006 ‐0.004 C (28) 0.005 0.008 0.004 0.007 0.005 0.009 C (29) 0.001 0.010 0.000 0.009 0.001 0.012 C (30) 0.003 0.009 0.002 0.007 0.005 0.011 Cl (31) 0.037 0.030 0.034 0.027 0.041 0.033 H (32) 0.041 0.022 0.039 0.020 0.044 0.024 H (33) 0.033 0.018 0.032 0.017 0.034 0.019 H (34) 0.021 0.012 0.012 0.007 0.030 0.017 H (35) 0.040 0.021 0.036 0.020 0.043 0.023 H (36) 0.032 0.019 0.031 0.021 0.033 0.017 H (37) 0.021 0.011 0.012 0.006 0.029 0.016 H (38) 0.012 0.009 0.01 0.008 0.014 0.011 H (39) 0.015 0.011 0.014 0.01 0.017 0.012 H (40) 0.031 0.016 0.037 0.019 0.024 0.013 H (41) 0.022 0.013 0.028 0.017 0.015 0.009 H (42) 0.038 0.019 0.044 0.022 0.032 0.016 H (43) 0.044 0.026 0.050 0.030 0.039 0.022 H (44) 0.039 0.020 0.045 0.023 0.033 0.017 H (45) 0.008 0.003 0.006 0.002 0.010 0.004 H (46) ‐0.005 ‐0.002 ‐0.004 ‐0.002 ‐0.006 ‐0.002 H (47) 0.016 0.008 0.014 0.007 0.017 0.008 H (48) 0.018 0.009 0.016 0.007 0.020 0.010 N (49) 0.055 0.049 0.044 0.037 0.067 0.061 ƒ(‐) ƒ(+) ƒ(0) Figure 4. Isosurface maps for Fukui functions of electrophilic, nucleophilic and radical attack for compound 4b. For neuclophilic attack, the highest Fukui function value is accommodated on the azo nitrogen N22 (0.098) and N21 (0.092). The order of the neuclophilic attack is N22 > N21 > C27 > C7 > C9 > C24. For electrophilic attack, the most nucleophilic site is C10 (Fukui function value is 0.054) and the tendency for electrophilic attack decreases as C10 > C7 > C27 > C2 > C1=C5=C6 >N22. Compound 4b has larger tendency for nucleophilic attack (0.098 on N22) than compound 4a (0.061 on N49). Compound 4a has larger tendency for electrophilic attack (0.099 on azo nitrogen) than compound 4b (0.054 on C10). 364 Mohamed et al. / European Journal of Chemistry 8 (4) (2017) 358‐366 Table 3. Condensed Fukui functions (fk0) (fk+) and (fk–) indices of compound 4b. Atom Radical attack Electrophilic attack Nucleophilic attack Mulliken Hirshfeld Mulliken Hirshfeld Mulliken Hirshfeld C (1) 0.017 0.036 0.021 0.041 0.013 0.030 C (2) 0.026 0.034 0.033 0.043 0.020 0.026 C (3) 0.001 0.011 0.004 0.009 ‐0.002 0.012 C (4) 0.009 0.008 0.001 0.007 0.017 0.010 C (5) 0.017 0.025 0.032 0.041 0.002 0.009 C (6) 0.019 0.037 0.021 0.041 0.018 0.033 C (7) 0.063 0.051 0.055 0.049 0.072 0.053 C (8) 0.009 0.025 0.023 0.034 ‐0.006 0.017 C (9) 0.043 0.043 0.026 0.034 0.060 0.051 C (10) 0.027 0.034 0.055 0.054 0.000 0.014 O (11) 0.020 0.025 0.032 0.034 0.009 0.015 C (12) 0.004 0.004 0.004 0.005 ‐0.004 0.003 C (13) 0.024 0.015 0.035 0.025 0.013 0.006 C (14) 0.009 0.003 0.014 0.006 ‐0.005 0.001 N (15) 0.013 0.015 0.014 0.016 0.012 0.014 C (16) 0.011 0.009 0.012 0.010 0.01 0.007 O (17) 0.002 0.006 0.003 0.007 0.001 0.004 C (18) 0.009 0.004 0.011 0.004 ‐0.008 0.003 C (19) 0.004 0.003 0.005 0.004 ‐0.004 0.003 O (20) 0.021 0.019 0.027 0.024 0.015 0.014 N (21) 0.049 0.051 0.007 0.009 0.090 0.092 N (22) 0.065 0.068 0.033 0.039 0.097 0.098 C (23) 0.002 0.013 0.005 0.014 ‐0.009 0.011 C (24) 0.024 0.031 0.022 0.027 0.027 0.035 C (25) 0.027 0.028 0.018 0.021 0.037 0.034 C (26) 0.005 0.026 0.006 0.022 0.003 0.029 C (27) 0.038 0.052 0.031 0.046 0.044 0.059 C (28) 0.007 0.028 0.006 0.023 0.008 0.032 C (29) 0.010 0.009 0.009 0.008 ‐0.011 ‐0.01 C (30) 0.001 0.002 0.000 0.003 ‐0.003 0.001 C (31) 0.006 0.005 0.005 0.005 ‐0.006 ‐0.005 C (32) 0.004 0.007 0.005 0.008 0.004 0.006 C (33) 0.001 0.010 0.001 0.011 0.000 0.009 C (34) 0.004 0.010 0.005 0.011 0.003 0.008 Cl (35) 0.036 0.029 0.040 0.032 0.033 0.026 H (36) 0.042 0.022 0.046 0.024 0.039 0.020 H (37) 0.035 0.019 0.037 0.020 0.032 0.017 H (38) 0.021 0.012 0.032 0.017 0.011 0.007 H (39) 0.040 0.022 0.045 0.024 0.036 0.020 H (40) 0.033 0.02 0.035 0.018 0.032 0.021 H (41) 0.017 0.009 0.025 0.013 0.01 0.004 H (42) 0.010 0.008 0.011 0.009 0.009 0.007 H (43) 0.014 0.010 0.016 0.010 0.013 0.009 H (44) 0.010 0.005 0.011 0.005 0.008 0.004 H (45) 0.009 0.004 0.011 0.005 0.007 0.003 H (46) 0.015 0.008 0.017 0.009 0.013 0.007 H (47) 0.004 0.002 0.004 0.003 0.003 0.002 H (48) 0.005 0.003 0.005 0.003 0.004 0.002 H (49) 0.031 0.016 0.025 0.013 0.037 0.019 H (50) 0.021 0.013 0.015 0.009 0.028 0.017 H (51) 0.038 0.019 0.033 0.017 0.044 0.022 H (52) 0.044 0.026 0.039 0.022 0.050 0.030 H (53) 0.039 0.02 0.034 0.017 0.045 0.023 H (54) 0.008 0.003 0.010 0.004 0.007 0.002 H (55) 0.009 0.003 0.010 0.003 ‐0.008 ‐0.003 H (56) 0.015 0.007 0.016 0.008 0.014 0.006 H (57) 0.018 0.009 0.020 0.010 0.016 0.008 3.4. Frontier orbital analysis Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) for compound 4a and 4b are calculated and presented in Figure 5. HOMO and LUMO, as frontier molecular orbitals, are considered as very important molecular parameters for the stability and chemical reactivity of the species [46,47]. HOMO and LUMO energies, and LUMO‐HOMO energy gap (∆EL‐H), in eV, are displayed in Table 1. The lower HOMO energy, the easier of that orbital to participate in chemical reaction by donating electrons. LUMO energy, on the other hand, determine the ability to accept an electron in a chemical change. LUMO‐HOMO energy gap reflects the chemical hardness–softness and polarizability of the molecule and hence its biological activity [48,49]. The energy values of HOMO are computed as ‐6.089, ‐5.903 eV and LUMO are ‐2.845, ‐2.675 eV, and the energy gap values are 3.244 and 3.227 eV for compound 4a and 4b, respectively. Computed values of ∆EL‐H shows that compound 4b is more reactive than compound 4a. This is also, in accord with the calculated chemical softness 0.308 and 0.310 for compound 4a, and 4b, respectively. HOMO and LUMO plots of compound 4a and 4b are pre‐ sented in Figure 5. As can be seen in Figure 5, the HOMO of compound 4a is delocalized mainly on the azo nitrogen, carbons that are ortho and para to the azo group, naphthalene ring (except for C3‐C4) and O‐pyran. C1‐C6, C3‐C4 and C8‐C9 bonds show anti‐bonding nature where no electron projection at these regions. LUMO of compound 4a is being participated mainly from C7 and C9 as well as bonds of C4‐C5, C10‐N17 and C19‐N18. It is clear from Figure 5 that, the LUMO of compound 4a shows antibonding character over the C‐H bonds, p‐ chlorophenyl ring. The HOMO of compound 4b is delocalized on bonds of C1‐ C2, C5‐C6, C7‐C8, C9‐C10, N21‐N22, C23‐C24 and C23‐C25. LUMO of compound 4b is being participated mainly from C7, C9, C1, C2, and C6 as well as bonds of C4‐C5, C10‐N17 and C19‐ N18. Mohamed et al. / European Journal of Chemistry 8 (4) (2017) 358‐366 365 HOMO of compound 4a LUMO of compound 4a HOMO of compound 4b LUMO of compound 4b Figure 5. HOMO and LUMO plots of compound 4a and 4b. 4. Conclusion Efficient one‐pot three‐component method for the synthesis of various 4H‐naphthopyran derivatives by reaction of aldehydes, malononitrile or ethyl cyanoacetate cyano ester and 4‐phenyldiazenyl‐1‐naphthol catalyzed by piperidine is reported. The density functional theory was employed to compute molecular geometry of compound 4a and 4b at B3LYP/6‐31+G(d) level. Amine tautomers are about 7.158 and 8.726 kcal/mole lower energy than imine tautomers for compound 4a and 4b, respectively. This difference allows separation at room temperature. 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