ALI Rmzni FATEMEH Zinli Nsrbi, b YOUNES Hnihpour SANG WOO Joo MASOOME Shikhi KATARZYNA ?lpokur TADEUSZ Lis FARIDEH Gournlou

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Synthesis, Crystal Structure and Theoretical Calculations of N-Benzyl-1-(5-(3-chlorophenyl)-1,3,4- oxadiazol-2-yl)cyclopentanamine①

ALI Ramazania②FATEMEH Zeinali Nasrabadia, bYOUNES Hanifehpourc②SANG WOO Jooc②MASOOME SheikhidKATARZYNA ?lepokuraeTADEUSZ LiseFARIDEH Gouranlouf

a(45195-313,)b()c(712-749,)d()e(50-383)f()

-benzyl-1-(5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl)cyclopentanamine was syn- thesized via one-pot reaction of appropriate benzylamine, cyclopentanone, (-isocyanimino)tri- phenylphosphorane and-chlorobenzoic acid. The quantum theoretical calculations for crystal structure were performed by density functional theory (DFT/B3LYP/6-311+G*). From the optimized structure, geometric parameters were obtained and experimental measurements were compared with the calculated data. Frontier molecular orbitals (FMOs), total density of states (DOS), molecular electrostatic potential (MEP), molecular properties, natural charges, NMR parameters and NBO analysis for the product were investigated by theoretical calculations.

-isocyaniminotriphenylphosphorane, cyclopentanone,-chlorobenzoic acid, 1,3,4-oxadiazole, aza-Wittig reaction, DFT, NBO analysis;

1 INTRODUCTION

Multicomponent reactions (MCR) have appeared as an efficient and powerful tool in modern syn- thetic organic chemistry due to their valued features such as atom economy, straightforward reaction design, and the opportunity to construct target com- pounds by the introduction of several diversity elements in a single chemical event[1]. MCR, leading to interesting heterocyclic scaffolds, are especially useful for the construction of diverse chemical libraries of ‘druglike’ molecules. The iso- cyanide-based MCR are very important in this area[2-4]. Isocyanide-based multicomponent reactions (abbreviated to IMCRs by Ugi and D?mling) by virtue of their synthetic potential, their inherent atom efficiency, convergent nature, ease implemen- tation, and the generation of molecular diversity,have attracted considerable attention because of the advantages that they offer to the field of combina- torial chemistry[5-7].

In recent years, there has been considerable inves- tigation on different classes of oxadiazoles. Particu- larly, compounds containing 1,3,4-oxadiazole nuc- leus have been shown to possess a wide range of pharmacological and therapeutic activities. Some 1,3,4-oxadiazoles have shown analgesic, anti- inflammatory, anticonvulsant, tranquilizing, myore- laxant, antidepressant, vasodilatatory, diuretic, antiulcer, antiarythmic, antiserotoninic, spasmolytic, hypotensive, antibronchocontrictive, anticholinergic, and antiemetic activities. Additionally, many 1,3,4- oxadiazole derivatives have been reported as active inhibitors of several enzymes[8-11].

Recently, the intramolecular version of the- Wittig-type reaction has attracted much attention because it has exhibited high potential for the synthesis of a wide variety of nitrogen heterocycles, which can be attributed, in good measure, to the rapid progress in the preparation of functionalized iminophosphoranes. Existence of the nucleophilicity at the nitrogen is a factor of essential mechanistic importance in the use of these iminophosphoranes as-Wittig reagents. Iminophosphoranes are important reagents in synthetic organic chemistry, especially in the synthesis of naturally occurring products, compounds with biological and pharmaco- logical activity[12, 13]. However, the organic chemi- stry of (-isocyanimino) triphenylphosphorane 4 remains almost unexplored. (-isocyanimino)tri- phenylphosphorane 4 is expected to have synthetic potential because it provides a reaction system in which the iminophosphorane group can react with a reagent having a carbonyl functionality[12, 13]. In recent years, we have established a one-pot method for the synthesis of organophosphorus com- pounds[14-16]. In this paper, we report an interesting four-component reaction of (-isocyanimino)tri- phenylphosphorane 4 (Scheme 1).

In recent years, computational chemistry has become an important tool for chemists and a well- accepted partner for experimental chemistry[17-19]. Density functional theory (DFT) method has become a major tool in the methodological arsenal of computational organic chemists. Wang et al. investigated intramolecular charge-transfer in symmetric bi-1,3,4-oxadiazole derivatives with TD-CAM-B3LYP method (CAM-B3LYP/6- 311+G**)[20]. Ge et al. studied frontier molecular orbitals of the novel 5-(3-aryl-1H-pyrazol-5-yl)-2-(3-butyl-1-chloroimidazo[1,5-a]-pyridin-7-yl)-1,3,4-oxadiazole derivatives with existence different substitutions using the DFT calculations[21]. Srinivas et al. reported DFT and TD-DFT studies of 1,3,4-oxadiazole derivatives. In fact, they investigated the effect of various substituents on electronic, optical and geometric properties of compounds[22]. Behzad et al. studied four possible tautomers of 5-amino- 1,3,4-oxadiazole-2(3H)-one by calculations at the DFT-B3LYP/6-311++G* level of theory in the gas phase and in solution and in a micro hydrated environment[23]. In the present work, we investigate the energetic and structural properties of the crystal structures of-benzyl-1-(5-(3-chlorophenyl)-1,3,4- oxadiazol-2-yl)cyclopentanamine using the DFT calculations. The optimized geometry, frontier mole- cular orbitals (FMO), detail of quantum molecular descriptors, molecular electrostatic potential (MEP), chemical tensors, natural charge and NBO analysis were calculated.

2 EXPERIMENTAL

2. 1 Materials and methods

(-Isocyanimino)triphenylphosphorane 4 was prepared based on reported procedures[13]. Other starting materials and solvents were obtained from Merck (Germany) and Fluka (Switzerland) and were used without further purification. The methods used to follow the reactions are TLC and NMR which indicated that there is no side product. Melting point was measured on an Electrothermal 9100 apparatus and uncorrected. IR spectrum was measured on a Jasco 6300 FTIR spectrometer.1H and13C NMR spectra (CDCl3) were recorded on a BRUKER DRX-250 AVANCE spectrometer at 250.1 and 62.9 MHz, and a BRUKER AVANCE III spectrometer at 400.2 and 100.6 MHz, respectively. Elemental analyses were performed using a Heraeus CHN- O-Rapid analyzer. Preparative layer chromato- graphy (PLC) plates were prepared from Merck silica gel (F254) powder.

2. 2 General procedure for the preparation of compound 5

To a magnetically stirred solution of benzyl amine 2 (1 mmol), cyclopentanone 1 (1 mmol) and (-isocyanimino)triphenylphosphorane 4 (1 mmol) in CH2Cl2(5 mL) was added dropwise a solution of-chlorobenzoic acid 3 (1 mmol) in CH2Cl2(5 mL) at room temperature over 15 min. The mixture was stirred for 12 h. The solvent was removed under reduced pressure, and the viscous residue was purified by preparative layer chromatography (PLC) (silica gel (F254) powder; petroleum ether-ethyl acetate 4:1). The characterization data of the compound are given below.

2. 2. 1-benzyl-1-(5-(3-chlorophenyl)- 1,3,4-oxadiazol-2-yl)cyclopentanamine (5)

White powder, m.p. 81～83; yield: 90%. IR (KBr): 3289, 2971, 1694, 1547,1440, 884, 791, 693 cm?1.1H NMR (250.0 MHzCDCl3):= 1.42～2.33 (9H, m, CH2of cyclopentan and NHamine), 3.67 (2H, s, CH2), 7.27～8.00 (9H,m, CHarom).13C NMR (62.5 MHzCDCl3):= 32.88, 37.56 (CH2of cyclopentan), 48.99 (CH2), 64.38 (C of cyclopentan), 124.97, 126.83, 127.04, 128.10, 128.41, 130.39, 131.64 (9CH), 125.65, 135.12, 140.10 (3C), 163.82, 171.00 (2C=N). Anal. Calcd. (%) for C20H20ClN3O (353.85): C, 67.89; H, 5.70; N, 11.88. Found (%): C, 67.81; H, 5.76; N, 11.80.

2. 3 Preparation of single crystals of N-benzyl-1-(5-(3-chlorophenyl)-1,3,4-oxadiazol-2 yl)cyclopentanamine (5)

Colorless single crystals of-benzyl-1-(5-(3- chlorophenyl)-1,3,4-oxadiazol-2-yl)cyclopentanamine (5) were obtained from slow evaporation of its dichloromethane/light petroleum ether (1:3) solution (20～25 ℃). The colorless single crystals were filtered off, washed with a cold mixture of dichloro- methane/light petroleum ether (1:3) and dried at room temperature.

2. 4 X-ray crystallography of compound 5

The crystallographic measurement of 5 was performed on a Kuma KM4-CCD κ-geometry auto- mated four-circle diffractometer with graphite-monochromatizedMoradiation (= 0.71073 ?) (Fig. 1). The data were collected at 110(2) K by using the Oxford-Cryosystems cooler. Data were corrected for Lorentz and polarization effects. Data collection, cell refinement, data reduction, and analysis were carried out with CrysAlisCCD and CrysAlisRED, respectively[24]. The structure was solved by direct methods with the SHELXS97 program[25], and refined by full-matrix least-squares technique with SHELXL2013[25]and anisotropic thermal parameters for non-H atoms. All H atoms were found in difference Fourier maps and refined isotropically. In the final refinement cycles, the C-bonded H atoms were repositioned in their cal- culated positions and refined using a riding model, with C–H = 0.95～0.99 ? andiso(H) = 1.2eq(C). N-bonded H atom was refined isotropically withiso(H) = 1.2eq(N). Figures were made with the Diamond program[26].

C20H20ClN3O,M= 353.84, colorless block, crystal size 0.27 × 0.17 × 0.10 mm3,monoclinic, space group21/,= 5.420(2),= 36.782(8),= 8.814(3) ?,= 93.67(3)°,= 1753.5(10) ?3,= 110(2) K,= 4,= 0.23 mm-1(for Mo,= 0.71073 ?),absorption correction: multi-scan,min= 0.968,max= 1.000, 28708 reflections measured, 7811 unique (int= 0.029), 5561 observed (2()), (sin/)max= 0.844 ??1, parameters = 229, restraints = 0,=0.043 (observed refl.),= 0.112 (all refl.),= 1.01, (Δmax) = 0.52 and (Δmin) = –0.20 e·??3.

3 COMPUTATIONAL DETAILS

In this work, we have carried out quantum theoretical calculations and optimized its structure (starting from the solid-state structure) using B3LYP/6-311+G* level (DFT)[27]by the Gaussian 09W program package[28]and calculate its pro-perties. The electronic properties such as EHOMO, ELUMO, HOMO-LUMO energy gap (?),HOMO-1,LUMO+1, natural charges, molecular properties, dipole moment (μ) and point group were detec- ted[17]. The optimized molecular structure, HOMO and LUMO surfaces were visualized using GaussView 05 program[29]. Also we calculated NMR parameters such as chemical shift isotropic (CSI) and chemical shift anisotropic (CSA) for the title structures using B3LYP/6-311+G* level[30, 31]. The electronic structure of the title compound was studied by using Natural Bond Orbital (NBO) analysis at the same level in order to understand various second-order interactions between the filled orbitals of one subsystem and vacant orbitals of another subsystem, which is a measure of the inter-molecular delocalization or hyper conjugation[32].

4 RESULTS AND DISCUSSION

The 1:1 imine intermediate generated by the condensation reaction of cyclopentanone 1 with benzyl amine 2 is trapped by 4 in the presence of-chlorobenzoic acid 3 and leads to the formation of 1,3,4-oxadiazole derivatives 5 and triphenylphos- phine oxide 6 (Scheme 2). The reaction proceeds smoothly and cleanly under mild and neutral conditions and no side reactions were observed.

Scheme 1. Four-component synthesis of 1,3,4-oxadiazole 5

We also used 3-chlorobenzoperoxoic acid instead of 3-chlorobenzoic acid in this reaction, but the same product of 1,3,4-oxadiazole was observed.

A mechanistic pathway for the reaction is provided in Scheme 2. On the basis of the chemistry of isocyanides, it is reasonable to assume that the first step may involve the formation of imine 7 by the condensation reaction of cyclopentanone 1 with the benzyl amine 2. The next step may involve nucleophilic addition of the (-isocyanimino)tri- phenylphosphorane 4 to the imine intermediate 7, which is facilitated by its protonation with the-chlorobenzoic acid 3, leading to nitrilium intermediate 8. This intermediate may be attacked by the conjugate base of the carboxylic acid to form the 1:1:1 adduct 9. The intermediate 9 then under- goes intramolecular-Wittig reaction[33-36]of iminophosphorane moiety with the ester carbonyl group to afford the isolated sterically congested 1,3,4-oxadiazole 5 by the removal of triphenyl- phosphine oxide 6 from intermediate 10.

Scheme 2. Proposed mechanism for the formation of sterically congested 1,3,4-oxadiazole 5

4. 1 Crystal structure and optimized geometry

The optimized structure of compound 5 has been calculated by DFT (B3LYP/6-311+G*) (see Fig. 1b) and the selected bond lengths and bond angles of the crystal structure and the theoretical parameters (for the molecule of the opposite configuration,with the opposite values of torsion angles) are listed in Table 1.

The crystal of 5 is built up from molecules shown in Fig. 1a. The values of bond lengths and valence angles correspond well with those typical for the respective types of chemical connections[37]. In the crystal structure of 5 the angle between 1,3,4-oxa- diazole and phenyl rings is about 63°. The chloro- phenyl ring is only slightly twisted relative to the oxadiazole, which is reflected in the value of O(1)– C(14)–C(15)–C(20) torsion angle close to 10° (see Table 1 for details). Cyclopentyl ring adopts enve- lope conformation with the C(8) atom puckered (Cremer--Pople puckering parameters2 and2[38]= 0.429(1) ? and 352.1(2)°, respectively; pseudoro- tation parametersandm[39]= 154.0(1)° and 44.1(1)°, respectively; calculated with Platon[40]).

In the crystal lattice, molecules of 5 are joined to each other via N–H×××N hydrogen bonds giving rise to chains running down the-axis as shown in Fig. 2a (for geometrical details see Table 2). The adjacent chains are further linked by C–H×××and C–Cl×××interactions to form double layers parallel to the (010) plane (Fig. 2b).

As can be seen in Table 1, the calculated para- meters reveal good approximation and can be used as a foundation to calculate the other parameters for the title compound. We found that most of the calcu- lated bond lengths are slightly longer than X-ray values due to the fact that experimental result corresponds to interacting molecules in the crystal lattice, whereas computational method deals with an isolated molecule in gaseous phase[41]. The average differences of the theoretical parameters from the experimental for bond lengths of compound 5 were found to be about 0.001 ? (O1–C14), 0.003 ? (O1–C13), 0.009 ? (N1–C1), 0.003 ? (N1–C8), 0.001 ? (N2–C13), 0.02 ? (N2–N3) and 0.004 ? (N3–C14). According to Table 1, the bond lengths of N1–C1in X-ray and optimized structure of compound 5 are 1.4602(13) and 1.4689 ? respectively, whereas experimental and theoretical values for the bond lengths of N1–C8are 1.4707(12) and 1.4686 ?, respectively. It is shown the N1–C1is shorter than N1–C8.

Fig. 1. (a) X-ray crystal structure of compound 5 at 50% probability displacement ellipsoids(b) Theoretical geometric structure of compound 5 (optimized using the B3LYP/6-311+G* level)

Table 1. Selected Experimental and Calculated Interatomic Distances (?), Dihedral Angles (°) and Torsion Angles (°) for 5

Fig. 2. Arrangement of molecule 5 within the () molecular chain running down the-axis, and () the layer parallel to (010) plane. N–H···N, C–H···and C–Cl···interactions are shown as dashed and dotted lines, respectively. H atoms not involved in these contacts are omitted for clarity. Symmetry codes are as in Table 1

Table 2. Geometry of N–H···N, C–H···π and C–Cl···π Interactions (?, o) in 5

Symmetry codes: (i)+1,,; (ii)–1,,; (iii),,+1; (iv), –+0.5,-0.5;1 isthe centroid of C2～C7 ring;2 is the centroid of the oxadiazole ring

4. 2 Electronic properties

Quantum chemical methods are important for obtaining information about molecular structure and electrochemical behavior. A frontier molecular orbitals (FMO) analysis[42]was done for the compound using at the B3LYP/6-311+G* level. FMO results such asHOMO,HOMO-1,LUMO,LUMO+1and the HOMO-LUMO energy gap (?) of the title compound, are summarized in Table 3. The values of energy of the highest occupied molecular orbital (HOMO) can act as an electron donor and the lowest unoccupied molecular orbital (LUMO) can act as the electron acceptor[43]. As shown in Fig. 3 and Table 3,HOMO,HOMO-1,LUMOandLUMO+1of the title compound are –6.65, 7.02, –2.0 and –1.11 eV, respectively. As seen in Fig. 4, charge transfer is taking place within molecule. The graphic pictures of orbitals show the HOMO-1 orbital of molecule is localized mainly on oxadiazole ring and CH2–NH group, whereas the HOMO orbital of molecule is localized mainly on chlorinated ring and the Cl atom. The LUMO orbital of molecule is localized mainly on the oxadiazoleand chlorinated rings, whereas the LUMO+1 orbital of molecule is localized mainly on the phenyl ring. As seen in Fig. 3, the HOMO-LUMO energy gap (?) of the compound is 4.65 eV that reflects the chemical activity of the molecule. Also the calculated energy gap clearly is shown in DOS plot (see Fig. 4)[42].

A detail of quantum molecular descriptors of the title compound such as ionization potential (), electron affinity (), chemical hardness (), electronic chemical potential () and electrophilicity () were calculated and are listed in Table 2. Dipole moment (μ) is a good measure for the asymmetric nature of a structure[17]. The size of the dipole moment depends on the composition and dimen- sionality of the 3structures. As shown in Table 3, dipole moment of the title structure is 4.143 Debye that the high value of dipole moment is due to its asymmetric character that the atoms are irregularly arranged which gives rise to the increased dipole moment. Also the point group of structure is1 (see Table 3).

Table 3. Molecular Properties of Compound 5 Calculated Using the DFT (B3LYP/6-311+G*)

Fig. 3. Calculated Frontier molecular orbitals of compound 5 (?E: energy gap between LUMO and HOMO)

Fig. 4. Calculated DOS plots of compound (using the B3LYP/6-311+G* method)

4. 3 Molecular electrostatic potential (MEP)

The molecular electrostatic potential (MEP) was checked out by theoretical calculations using B3LYP/6-311+G* level of theory. Molecular elec- trostatic potential shows the electronic density and is useful in recognition sites for electrophilic attack and nucleophilic reactions as well as hydrogen bonding interactions[44]. The electrostatic potential at the surface is different values and different colors. The negative areas (red, orange and yellow color) of MEP were related to electrophilic reactivity, the positive areas (blue color) to the nucleophilic reactivity and green color is neutral regions. According to the MEP map in Fig. 5, negative region of the compound is mainly focused on N17and N18atoms and phenyl ring with more red color intensity. Therefore, there are three positions on the compound for electrophilic attack. Also the lowest electron density with the highest intensity blue color is observed for hydrogen atom in N8–H33. Therefore, it is the suitable site for nucleophilic activity.

Fig. 5. Molecular electrostatic potential (MEP) maps of compound 5 calculated using the B3LYP/6-311+G* level

4. 4 Atomic charge and NMR parameters

We calculated the charge distributions for equilibrium geometry of molecule by NBO method (natural charge)[17]using the B3LYP/6-311+G* level (Atoms labeling is according to Fig. 2). The total charge of the investigated molecules is equal to zero. According to Table 4, the results of NBO analysis reveal the highest positive charge is observed for C10and C16atoms in the oxadiazole ring (0.519 and 0.488 e, respectively), while the highest value of negative charge is observed for the N8atom (–0.664 e). Also the O15atom has great negative charge (–0.494 e). All carbon atoms of the chlorinated ring and phenyl ring have negative charges. The carbon atoms of cyclopentan ring bear negative charges except the C9atom that has positive charge (0.073 e). All hydrogen atoms have positive charges and the H33atom in N–H group has the highest positive charge (0.354 e).

The NMR parameters such as isotropic chemical shift (CSI) and anisotropic chemical shift (CSA) for the title compound are summarized in Table 3. Of carbon atoms, the C10and C16atoms have the lowest CSIvalue, so they are deshielded more (CSIvalue = 6.172 ppm and CSIvalue = 11.487 ppm, respec- tively) than the other carbons atoms due to their direct connect to O15atom. While the C12and C13atoms are shielded more (CSIvalue = 157.160 ppm and CSAvalue = 156.795 ppm) than the other carbon atoms. The Cl25atom has the highest CSI(677.527 ppm) and CSA(507.547 ppm) values. Therefore, it is shielded more than the other atoms.

Table 4. Natural Charge (NBO Charges, e) and NMR Parameters (ppm) Such as Chemical Shift Isotropic (CSI) and Chemical Shift Anisotropic (CSA) for Compound 5 Using the B3LYP/6-311+G* Method (Atom Numbering is According to Fig. 2)

4. 5 NBO analysis

Natural bond orbital (NBO) analysis is an important method for studying intra- and intermo- lecular bonding and interaction between bonds[45]. The results of NBO analysis such as the occupation numbers with their energies for the interacting NBOs (interaction between natural bond orbital A and natural bond orbital B (A-B)) and the polariza- tion coefficient amounts of atoms for structure 5 are presented using the B3LYP/6-311+G* level is summarized in Table 5 (Atoms labeling is according to Fig. 2). The size of polarization coefficients shows the importance of two hybrids in the formation of bond. In structure 5, the calculated bonding orbital for O15–C16is BD(1) = 0.83062.28+ 0.55693.080.01with high occupancy 1.98862 a.u. and low energy –0.93176 a.u.. The polarization coefficients of O15= 0.8306 and C16= 0.5569 show importance of O15in forming the O15–C16bond rather than the C6atom. Also the high polarization coefficient of O15atom instead of C16suggests the O15atom is more electron-rich (–0.494 e) than the C16atom (0.488 e). The calculated bonding orbital for the C9–C10bond is the BD(1) = 0.69903.09+ 0.71521.42with high occupancy 1.96814 a.u. and energy –0.67046 a.u.. The polarization coefficients of C9= 0.6990 and C10= 0.7152 show importance of C10in forming the C9–C10bond instead of the C9atom. According to the calculated bonding orbital for the C7–N8, C10–N18, C16–N17and N8–C9bonds, the polarization coefficient of Na toms is greater than the C atoms, which shows the importance of N atoms in forming C7–N8, C10–N18, C16–N17and N8–C9bonds rather than C atoms. The bonding orbitals of C10–N18and C16–N17bonds have high occupancy (1.99169 and 1.99135 a.u., respectively) and the low energy (–0.91008 and –0.90137 a.u., respectively), while the occupancy of bonding orbital of C7–N8and N8–C9bonds is 1.98344 and 1.97717 a.u. with energies of –0.71288 and –0.73149 a.u., respectively. In the other hand, the C–N bonds in oxadiazole ring have high occupancy and low energy than C–N bonds in the amine group.

Table 5. Calculated Natural Bond Orbitals (NBO) and the Polarization Coefficient for Each Hybrid in Selected Bonds of Compound 5 Using the B3LYP/6-311+G* Level (Atoms Numbering is According to Fig. 1)

aA–B is the bond between atoms A and B (A: natural bond orbital and the polarization coefficient of atom; A–B: natural bond orbital and the polarization coefficient of atom B)

Electron donor orbital, acceptor orbital and the interacting stabilization energy resulting from the second-order micro disturbance theory[45]are repor- ted in Table 6. The electron delocalization from filled NBOs (donors) to the empty NBOs (acceptors) describes a conjugative electron transfer process between them[46]. For each donor () and acceptor (), the stabilization energy(2)associated with the delocalization→is estimated. The resonance energy ((2)) detected the quantity of participation of electrons in the resonance between atoms[46]. According to Table 9, the BD(2)C10–N18orbital par- ticipates as donor and the anti-bonding BD*(1)N8– C9, BD*(2)C9–C11and BD*(2)C16–N17orbitals as acceptor, and their resonance energies (E(2)) are 3.05, 1.95 and 10.47 kcal/mol, respectively. These values indicate large charge transfer from the BD(2)C10– N18to the anti-bonding orbital of BD*(2)C16–N17(BD(2)C10–N18→BD*(2)C16–N17). Also the reso- nance energies ((2)) for BD(2)C16–N17→ BD*(2)C10–N18and BD(2)C16–N17→BD*(2)C19– C20are 10.30 and 8.73 kcal/mol, respectively, showing large charge transfer from the BD(2)C16– N17to the anti-bonding orbital of BD*(2)C10–N18. From the NBO analysis results, the LP(1)N8orbital participates as donor and the anti-bonding BD*(1)C2–C7, BD*(1)C9–C10, BD*(1)C9–C11and BD*(1)C9–C15orbitals as acceptor and their resonance energies ((2)) are 0.73, 8.97, 0.64 and 1.15 kcal/mol, respectively. These values indicate large charge transfer from the LP(1)N8to anti- bonding orbital of BD*(1)C9–C10(LP(1)N8→ BD*(1)C9–C10). The LP(1)Cl25and LP(2)Cl25orbital participates as donor and the anti-bonding BD*(1)C23-C24orbital as acceptor and their resona- nce energies ((2)) are 1.57 and 4.15 kcal/mol, respectively. Therefore, charge transfer from the LP(2)Cl25to the anti-bonding orbital of BD*(1)C23– C24(LP(1)Cl15→BD*(1)C23–C24) is more than the LP(1)Cl15→BD*(1)C23–C24. While charge transfer in LP(3)Cl15→BD*(2)C23–C24has more resonance energy ((2)= 12.50 kcal/mol) than LP(1)Cl15→ BD*(1)C23–C24and LP(2)Cl15→BD*(1)C23–C24.

Table 6. Significant Donor–acceptor Interactions and the Second Order Perturbation Energies of Compound 5 Calculated Using the B3LYP/6-311+G* Level (Atoms Numbering is According to Fig. 2)

a(2)means energy of hyperconjucative interactions.bEnergy difference between donor and acceptorandNBO orbitals.c(,) is the Fock matrix element betweenandNBO orbitals.

5 CONCLUSION

In summary, we believe that the reported method offers a mild, simple, and efficient route for the preparation of fully substituted 1,3,4-oxadiazol of type 5. Ease work-up, high yield and fairly mild reaction conditions make it a useful addition to modern synthetic methodologies. Other aspects of this synthetic process are under investigation. In the present study, also the electronic properties and geometric parameters of compound 5 have been analyzed using the DFT calculations (B3LYP/6- 311+G*). The theoretical results and the experi- mental data have been found to support each other. The FMO analysis suggests that charge transfer is taking place within molecule 5 and the HOMO orbital is localized mainly on chlorinated ring and the Cl atom,whereas the LUMO orbital resides on the oxadiazole ring and chlorinated ring. According to the MEP map, negative region of compound is mainly focused on both N atoms of 1,3,4-oxadiazole ring and phenyl ring, whereas the lowest electron density is observed for amine hydrogen atom, so it is a suitable site for nucleophilic activity.

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12 May 2017;

26 February 2018 (CCDC 1422045)

① This project was supported by the University of Zanjan, the grant NRF-2015-002423 of the National Research Foundation of Korea

E-mails: aliramazani@gmail.com, aliramazani@znu.ac.ir, y_hanifehpour@yu.ac.kr, swjoo1@gmail.com and swjoo@yu.ac.kr

10.14102/j.cnki.0254-5861.2011-1720