SYNTHESIS, CRYSTAL STRUCTURE AND HIRSHFELD SURFACE ANALYSIS OF A 2 – САRBOXYMETHYLTHIO-5-PHENYL-1,3,4-OXADIAZOLE

ABSTRACT

The title compound, 2 – саrboxymethylthio-5-phenyl-1,3,4-oxadiazole, was synthesized and studied by single-crystal X-ray diffraction method. The crystals of ligand are triclinic, cell parameters: а = 7.3253(6), b = 8.6265(7), с = 9.0197(7) Å, α = 73.602(7), β = 89.990(7), γ = 69.550(8) º, V = 509.24(8) ų, R1(I > 2s(I) = 3.91, Z = 2, etc. Р-1 (2). In the crystal structure molecules are linked to each other in the chains which form three-dimensional network structure by hydrogen bonds between the nitrogen atoms of the oxadiazole cycle and carboxyl-group.  It is found that the network presence of intermolecular bonds leads to the formation of a strong three-dimensional skeleton structure. On the Hirshfeld surface, the largest contributions come from the short contacts like van der Waals forces for H···H, H···O, N···H, H…C, C···O and C···C contacts are also observed.

АННОТАЦИЯ

Соединения 2 – сарбоксиметилтио-5-фенил-1,3,4-оксадиазол, синтезировано и исследовано методом монокристаллической рентгеновской дифракции. Кристаллы лиганда триклинные, клеточные параметры: а = 7.3253(6), b = 8.6265(7), с = 9.0197(7) Å, α = 73.602(7), β = 89.990(7), γ = 69.550(8) º, V = 509.24(8) Å3, R1(I> 2s(I) = 3.91, Z = 2 и т.д. Р-1(2). В кристаллической структуре молекулы связаны друг с другом в цепи, которые образуют трехмерную сетчатую структуру водородными связями между атомами азота оксадиазольного цикла и карбоксильной группы. Установлено, что сетевое наличие межмолекулярных связей приводит к формированию прочной трехмерной структуры скелета. На поверхности Хиршфельда наибольший вклад вносят короткие контакты, такие как силы Ван-дер-Ваальса для H··· H, H··· O, N··· H, H... С, С··· O и также наблюдаются C···C -контакты.

Keywords: oxadiazole, Hirschfeld surface analysis, X-ray diffraction analysis diffractometer, complexs compounds, hudrogen bonds.

Ключевые слова: оксадиазол, поверхностный анализ Хиршфельда, рентгеноструктурный анализ, дифрактометр, комплексы соединений, водородные связи.

Introduction. Interest in oxadiazole derivatives is  since they can be successfully used as selective polydentate, polyfunctional ligands in complexation reactions of some 3d metals due to the presence of competitive donor atoms [1].

One of the most widely studied representatives of five-membered heterocyclic compounds is 1,3,4-oxadiazole-2-thions containing oxygen atoms, sulfur atoms and two nitrogen atoms in their molecule, which provides great synthetic capabilities associated with the chemical nature of these compounds. Oxadiazol one derivatives, which belong to an important class of heterocyclic compounds, consist of an equilibrium mixture of its thionic and thiol forms obtained by the reaction of hydrazide-carbon desulphated ring closure. Among the various isomeric forms of oxadiazoles, derivatives of 1,3,4-oxadiazole-2-thione have shown notable contributions to heterocyclic chemistry as well as for pharmaceutical use. These compounds exhibit various biological activities, such as anti-cancer activity [2], anti-inflammatory activity [3], antimicrobial activity [4], antioxidant activity [5], antifungal activity [6], antiviral activity [7] and glucosidase inhibitors, neuraminates. Given the importance of 1,3,4-oxadiazole-2-thions, we report here, synthesis, spectral characteristics, crystalline research structures using IR spectroscopy, thermal, X-ray construction and biological analysis.

This report presents the results of X-ray diffraction analysis of the molecule 2-carboxymethylthio-5-phenyl-1,3,4-oxadiazole (L).

Materials and methods. The IR spectra are recorded on the IRT racer-100 Fourier Transform Infrared spectrophotometer complete with the MIRacle-10 attraction attachment with a diamond / ZnS prism (the spectral range on the wavenumber scale is 4000-450 sm^-1).

X-ray diffraction analysis of single crystals was carried out using an automatic diffractometer CrysAlis Red Oxford Diffraction Ltd (λCuKα, graphite monochromator).

Control over the course of the reaction and the individuality of the synthesized compounds was carried out by TLC on Silufol UV–254 (Czech Republic) and Merck silica gel 60F254 (Germany) plates in the CHCl₃ - EtOH, 24:1 system, manifestation in UV light, iodine vapor. The melting point of all synthesized substances is determined on the BOETIUS device.

Synthesis of 2-carboxymethylthio-5-phenyl-1,3,4-oxadiazole (1). 0.01 mol of 5-phenyl-1,3,4-oxadiazole-2-tion was dissolved in an aqueous solution of KOH at room temperature. 0.01 mol of monochloroacetic acid was added to the resulting transparent reaction mixture while stirring in portions, left overnight. The next day, the reaction mixture was acidified with HCl to a slightly acidic medium. The resulting thick suspension was filtered, dried, recrystallized from water and needle-shaped white crystals were obtained, i.e., 175-176ºC. 

Results and discussions. 2-carboxymethylthio-5-phenyl-1,3,4-oxadiazole, general reaction conditions and structure of preceding characteristics were synthesized in the experimental section.

The goal of the described research work was to synthesize a new biologically active molecule that could be useful in a drug development program. The structure of all synthesized compounds was elucidated spectrally (IR, PCA) data. All spectral data confirm the proposed structures assigned to the compound.

Spectral characteristics. 2-carboxymethylthio-5-phenyl-1,3,4-oxadiazole is a light yellow amorphous solid; Yield: 78%. T.pl.: 175-176ºC; Molecular Formula: C₁₀H₈N₂O₃S; Molecular Weight: 236.24; IR (KBr, sm^-1) vmax: 3335 (N-H extension), 3083 (C-H aromatic ring), 1675 (C=N oxadiazole ring), 1650 (C=O str.), 1557 (C=C aromatic), 1278 (C-O-C bond), 631 (C-S bond);

In this research paper, 2-carboxymethylthio-5-phenyl-1,3,4-oxadiazole are synthesized in a series of steps. The first ethyl benzoate (1) was prepared by re-cooling benzoic acid with ethyl alcohol in the presence of concentrated sulfuric acid for 4 hours. After maximum completion of the reaction, the end. A base solution was added to the reaction mixture to neutralize the excess organic acid and sulfuric acid to their respective salts. Using the solvent by extraction, we obtain ethyl benzoate in organic layers, both salts were washed with an aqueous layer. The next step is benzo hydrazide synthesis (2), allowing ethyl benzoate to react with 80% hydrazine hydrate to methanol at room temperature along with vigorous stirring for 3 hours. The isolated solid was filtered and washed with n-hexane. Next, the parent compound 5-phenyl-1,3,4-oxadiazole-2-thiol (3) was synthesized as a reflux compound 2 with carbon disulphide and potassium hydroxide in ethanol for 6 hours. At the completion of the reaction, ice distilled water of the reaction mixture was added, and then it was acidified to set a pH of about 2-3 to extinguish the synthesized product into the form of precipitates, which were filtered and washed by the distilled water compound names 2-carboxymethylthio-5-phenyl-1,3,4-oxadiazole (4), 0.01 mol compound 3 dissolved in an aqueous KOH solution at room temperature. Monochloroacetic acid was added to the resulting transparent reaction mixture by stirring in portions and left for 8-10 hours. The next day, the reaction mixture was acidified by HCl to a slightly acidic medium.

Ligand crystals are monoclinic, cell parameters: a = 7.3253 Å, b = 8.6265 Å, c = 9.0197 Å, α = 73.602º, β = 90.00º, γ = 90.00º, V = 509.24 ų, Z = 2, e.g. gr. P-1(2). All calculations and preliminary processing of experimental data were carried out using the Mercury software package. The structure of OLS was refined in the anisotropic approximation for non-hydrogen atoms to an R-factor of 0.04. Hydrogen atoms with nitrogen atoms and carbons of complex anions are localized in Fourier difference synthesis and refined with fixed isotropic factors B_H = 0.05 Ų. The number of independent reflexes with I>1.96δ(I) involved in the refinement is 3720 (Table 1.).

Table 1.

Experimental details 2 – саrboxymethylthio-5-phenyl-1,3,4-oxadiazole

The structure of the molecule and the relative arrangement of molecules in the crystal are shown in Fig. 1 (a, b). The coordinates of the atoms are given in Table 1. 2.

X-ray diffraction studies of single crystals

As a result of deciphering the crystal structure, it was established that the molecule has a flat structure, and the bond lengths in the oxadiazole fragment are aligned due to the delocalization of the electron density along the cycle.

Table 2.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

In the crystal structure, the molecules are linked together in chains that form a three-dimensional network structure with the help of hydrogen bonds between the nitrogen atoms of the oxadiazole cycle and the COOH group (Figure 2, Table 3).

Table 3.

Intermolecular hydrogen bonds

D = Donor A = Acceptor H = Hydrogen

Hirschfeld surface analysis. To further investigate the intermolecular interactions, present in the title compound, a Hirschfeld surface analysis was performed, and the two-dimensional fingerprint plots were generated with CrystalExplorer17. The Hirschfeld surface mapped over n_orm and corresponding colors representing various interactions are shown in Fig. 3. The large red areas on the Hirschfeld surface correspond to the O-H and N-N interactions.

Figure 3. Hirshfeld surfaces mapped over d_norm calculated for the C₁₀H₈N₂OS 

Figure 4. Contributions of the various contacts to the fingerprint plot built using the Hirshfeld surface of the title compound

The two-dimensional (2D) fingerprint plots are shown in Fig. 4. On the Hirshfeld surface, the largest contributions (24.4%, 23.9% and 13.1%) come from short contacts such as van der Waals forces, H…O, H…H and H…N contacts. H…S (9.6%), C…C (6.4%), H…C (3.3%) and C…O (3.3%) contacts are also observed. These interactions play a crucial role in the overall stabilization of the crystal packing.

Conclusion. Thus,  because of deciphering the crystal structure, the crystal and molecular structures of 2-carboxymethylthio-5-phenyl-1,3,4-oxadiazole were established. The analysis of geometric parameters showed that a significant delocalization of the electron density occurs in the molecule and a stable flat conformation of the molecule is formed. It has been established that the presence of a network of intermolecular bonds leads to the formation of a strong three-dimensional framework in the structure. Based on the analysis of the Hirschfeld surface, the large red regions corresponding to the O-H and N-N interactions on the Hirschfeld surface are considered as electrophilic centers in further syntheses, and the reaction from there proceeds.

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