Multicomponent reactions (MCRs) can be regarded as an effective and robust means in today’s synthetic organic chemistry; this is owing to the good qualities like atom economy and good reaction design, as well as the possibility of constructing target compounds by introducing a number of components in one single chemical incident . Also, products purification resulted from MCR is usually not complicated as the whole organic reagents are applied and can be inserted into the targeted compound [2-4]. MCRs, resulting in notable heterocyclic scaffolds, are especially suitable for constructing varied “druglike” molecules chemical libraries. Isocyanide-based MCRs are particularly significant in such an area [5,6]. Of MCRs to date, the ones based on isocyanides are the most effective reactions. Isocyanide-based multicomponent reactions (IMCRs) have been of much recent research interest due to their interesting synthetic potential, implementation ease, and the possibility of molecular variety in the combinatorial chemistry field [7,8].
Camphor and its derivatives are considered as one of the most widely used enantiopure building blocks, agents shift reagents in the NMR spectroscopy, and ligands in a wide range of asymmetric reagents as well as catalysts [9-11]. Camphorquinone, 6- oxocamphor, also known as 2,3-bornanedione is a photo initiator applied in curing dental composites . (1R)-(–)-Campherchinon (Figure 1) is one of the camphor derivatives, which can be used as a chiral starting material for the preparation of diverse and different chiral organic compound [13,14]. Likewise, various camphor derivatives have been used in asymmetric hydrogenation reactions [15,16]. Moreover, some of the camphor derivatives demonstrate fascinating biological and pharmaceutical activities. By the way, camphorsulphonylbenzimidazoles contain an anti-bacterial , and anti-spasmodic effect has been applied in the pharmaceutical field .
Over past years, the substantial research has been carried out on various types of oxadiazoles. Especially, organic compounds including 1,3,4-oxadiazole base have been demonstrated to have a vast array of pharmacological and therapeutic activities. A group of 1,3,4-oxadiazoles have revealed myorelaxant, painkiller, hypotensive, and antiemetic activities [19-21]. A suitable procedure has been previously reported for the synthesis of 1,3,4-oxadiazoles [22,23].
Theoretical chemistry is a part of chemistry with the simulation of molecules and atoms which can help researchers to find better chemical structures. It assists the experimental chemists to predict molecular structure , identify the correlation between the chemical structures and molecular properties , to find the chemical approaches for synthesis of organic and inorganic compounds , drug design , etc. Hartree-Fock calculation (abbreviated as HF) is a common kind of ab initio method. In HF methods, the central field approximation is the early approximation. By definition, the coulombic electron-electron excretion is inverted by integrating the repulsion period. A strong method leading to the quantum chemistry for the prediction of the electron structure of molecules is Density functional theory (DFT). The DFT methods are being more and more useful. The results deduced by DFT methods are comparable to the results presented by ab initio methods. The most popular of DFT model is B3LYP . Due to our interest in the synthesis of heterocycle compounds [28,29], single crystal X-ray structure [30-32] and computational chemistry as DFT studies [33-39], in the current study, we reported a theoretical investigation, and compared it with the experimental analysis such as FT-IR spectra, the frontier orbitals of HOMO, LUMO, HOMO-1, and LUMO+1 analysis, heat capacity, entropy, charge distribution and molecular electrostatic plots in association with the compound mentioned earlier.
The 3-hydroxyl-1,7,7-trimethyl-3-[5–(4-methylphenyl)–1,3,4-oxadiazol–2–yl]bicyclo[2.2.1]heptan-2-one (1A) was obtained using the procedure described in a previous study . The molecular structure of 1A was displayed in Figure 2. Colorless single crystals were grown by gradual vaporization of its petroleum ether/methanol (1:1) solution. The colorless single crystals were filtered, washed with a cold mixture of petroleum ether/methanol (1:1) and dried at room temperature.
Single crystal X-ray diffraction of 1A
We measured the crystallographic measurement on an Xcalibur R κ-geometry automated four-circle diffractometer accompanied by a CCD camera Ruby and graphite-monochromatized MoKα radiation (λ = 0.71073 Å). The data collection was conducted at 80(2) K using the Oxford-Cryosystems cooler. Data were corrected for Lorentz and polarization impacts. Xcalibur R software, CrysAlisPro was applied to gather the data, refine cell, reduce, and analyze the data . Using direct methods with the SHELXS97 program, we solved the structure , refined it by a full-matrix least-squares technique with SHELXL2013 , and considered anisotropic thermal parameters for non-H atoms. The whole H atoms were detected in various Fourier maps and refined isotropically. As for the final refinement stages, the C-bonded H atoms experienced repositioning in their computed positions and were refined applying a riding model, with C–H = 0.95–1.00 Å, and Uiso(H) = 1.2Ueq(C) for CH and CH2, as well as 1.5Ueq(C) for CH3. Hydroxyl H atom was refined without restriction. DIAMOND program was utilized to make figures . Details of the conditions for the data collection and structures refinements are given in the crystallographic information file (CIF) deposited with The Cambridge Crystallographic Data Centre (www.ccdc.cam.ac.uk/; deposition number CCDC-2089303) and provided as ancillary data.
C19H22N2O3, Mr = 326.38, colorless block, crystal size 0.44 × 0.43 × 0.41 mm, trigonal, space group P32, a = 11.050(3), c = 12.319(3) Å, V = 1302.7(8) Å3,T = 80(2) K, Z = 3, μ = 0.09 mm−1 (for Mo Kα, λ = 0.71073 Å), the empirical absorption correction (multi-can), Tmin = 0.990, Tmax = 1.000, 10018 reflections measured, 5223 unique (Rint = 0.020), 5025 observed (I > 2σ(I)), (sin θ/λ)max = 0.746 Å−1, 225 parameters, 1 restraint, R = 0.035 (observed refl.), wR = 0.091 (all refl.), GOOF = S = 1.03, (Δρmax) = 0.35, and (Δρmin) = −0.25 e Å−3. Absolute configuration was known.
The theoretical study was calculated using the Gaussian 09W software package . The DFT method get the Becke3 exchange functional completed with Lee, Yang, Parr (LYP) correlation functional [45,46]. The geometry optimizations were achieved by HF and DFT/B3LYP methods as well as 6-31G, 6-311G* basis sets, respectively, to take the closest structure. The wavenumbers were calculated at B3LYP/6-311G*. It was indicated by specializing part of Gauss View 6.0 software which reveals the FT-IR spectrum of the vibration models . The molecular geometries were fully optimized and shown at B3LYP/6-311G*.
Results and discussion
To develop powerful methods for providing heterocyclic compounds included in our ongoing program, the synthesis of 1,3,4-oxadiazoles by a three-component condensation of (N-isocyanimino)triphenylphosphorane, 4-methylbenzoic acid, and (1R)-(-)-campherchinon was tested. The FT-IR, 1H NMR, and 13C NMR spectroscopy was used to confirm the product’s structure .
The molecular structure of 1A was optimized using B3LYP/6-311G* (Figure 3). The energy of optimization, frontier orbitals of HOMO, LUMO, HOMO-1, LUMO+1, and energy gap were obtained within B3LYP/6-311G* as displayed in Table 1.
The FT-IR spectrum of the molecule 1A was obtained by B3LYP/6-311G* method and basis set. The FT-IR diagrams of compound 1A were designed by animation option of Gauss view 6.0 software, as illustrated in Figure 4. The comparison between the experimental  and theoretical FT-IR spectra results demonstrate that these two results are in good agreement.
Frontier high occupied molecular orbital (HOMO) and low unoccupied molecular orbital (LUMO) of 1A plotted in 3D by B3LYP/6-311G* method and basis sets are displayed in Figure 5. Optimization energy, heat capacity, entropy, HOMO, LUMO, HOMO-1, LUMO+1, and the energy gap for compound 1A are depicted in Table 1. With a vector in three dimensions, the dipole moment can be revealed by molecular charge distribution. Thus, it can be suitable as an explanator to determine the movement of electric charges throughout the molecules . The nucleophilicity and electrophilicity properties, dipole moments, and the molecules interactions with each other can be predicted by charge distribution in the molecules. The molecular electrostatic potential (MEP), electron density surface plots (ESP), and the molecular charge distributions on the surface of the compound 1A calculated at B3LYP/6-311G* method and basis set are depicted in Figure 5. According to Figure 6, the oxadiazole ring, carbonyl, and hydroxyl groups are negative (-) regions (red area), and methyl group and phenyl ring are positive (+) regions (green area). The Mullikan charge distribution plots of compound 1A calculated by B3LYP/ 6-311G* are shown in Figure 7, confirming the obtained results by MEP and ESP contour plots.
X-ray crystal structure
The molecular structure of 1A was determined with the use of X-ray crystallography (Figure 8). The compound crystallizes in the chiral trigonal P32 space group. As indicated in Table 2, (4-methylphenyl)–1,3,4-oxadiazole fragment of the molecule is almost planar, with the p-tolyl being only slightly twisted relative to the oxadiazole ring (C14—C13—C12—O1 torsion angle of 18.8(2)°). To this planar part, bicyclic camphor moiety is linked via the chiral atom C3 (absolute configuration S). The C3-bound OH group is an acceptor of weak intramolecular C–H···O contact (Figure 8), and a donor of intermolecular N–H···O hydrogen bond (Table 3). As a result of the latter interactions between molecules resulting from the action of threefold screw axis 32, helical chains (running down the c-axis) are shaped in the crystal of 1A (Figure 9).
In this study, DFT calculation analysis and comparison between theoretical and experimental for 1A were obtained. The frontier orbitals of HOMO and LUMO, thermodynamic properties, charge distribution, spectroscopic FT-IR, ESP, and MEP studies were carried out using B3LYP methods and 6-311G(d,p) basis set. According to the ESP and MEP plots illustrated that oxadiazole ring and carbonyl/hydroxyl group are negative (-) region (red area) and methyl group and phenyl ring are positive (+) region (green area). Based on the results, the molecular geometry parameter represents a good agreement with the experimental results.
This research was supported by “Zanjan University”.
Ali Ramazani: https://www.orcid.org/0000-0003-3072-7924
Hamideh Ahankar: https://www.orcid.org/0000-0002-2717-8920
How to cite this article: Ghasem Moghadam, Ali Ramazani*, Fatemeh Zeinali Nasrabadi*, Hamideh Ahankar, Katarzyna Ślepokura, Tadeusz Lis, Ali Kazami Babaheydari. Single crystal X-ray structure analysis and DFT studies of 3-hydroxyl-1,7,7-trimethyl-3-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]bicycle [2.2.1]heptan-2-one. Eurasian Chemical Communications, 2022, 4(8), 759-767. Link: http://www.echemcom.com/article_147983.html
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