Green synthesis of benzimidazole derivatives by using zinc boron nitride catalyst and their application from DFT (B3LYP) study

A new zinc-based boron nitride (Zn-BNT) material was synthesized from boron nitride and zinc acetate in 95% yield. The morphological and spectroscopic properties of Zn-BNT were elucidated by SEM, XRD, BET, DSC-TGA, and FT-IR. Zn-BNT catalyzed the synthesis of benzimidazoles (3a–3h) through a reaction between o-phenylenediamine and different aromatic aldehydes under microwave conditions for 15 min. The compounds were purified by silica-gel chromatography. The synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. Zn-BNT was reused eight times with only a 5% loss of catalytic activity. Furthermore, 2-(4-fluorophenyl)-1H-benzo[d]imidazole (3f) was selected for a computational study of the IR and NMR spectrum, which matched the experimentally generated spectra. The HOMO-LUMO gap was 4.48, and the Fukui function analysis showed high activity in the reactive sites.


Introduction
Heterogeneous catalysis plays a significant role in synthesizing organic compounds for agrochemicals, pharmaceuticals, and fine chemicals for a sustainable future. These catalysts have contributed to developing technology to produce green chemicals from biomass-derived platform chemicals under environmentally benign processes and avoid using toxic or hazardous materials [1]. However, the design and development of novel eco-friendly solid catalysts require appropriate techniques and strategies for improved recoverability, recyclability, and eco-friendliness [2]. In addition, there is an urgent need to acquire new organic compounds which might find possible applications in diverse areas of study.
Hence more environmentally and eco-friendly heterogeneous catalysts are being sought to expedite the synthesis of nitrogen-based heterocycles because of their enhanced biological activities [3].
Porous hexagonal boron nitride (h-BN) is a material that demonstrates unique physical and chemical properties, including low density, high specific surface area, high thermal conductivity, oxidation resistance, and chemical durability [4,5]. These features make h-BN a promising catalyst for their application in various research areas, especially those related to adsorption, like gaseous uptake and pollutant adsorption. Furthermore, h-BN is excellent catalyst support [6] since they possess a hexagonally shaped crystal structure composed of continuous boron-nitrogen bonds, wherein lone pair of electrons on the nitrogen atoms can coordinate with certain metals. The hBN/metal substrates functions as supports for metal clusters with Cr(110), Molybdenum(110), Rhenium(0001), Iron(110), Iridium(111), Copper(111), Gold(111), Silver(111), Nickel(111), and Platinum(111), metal-organic complexes, and organic molecules [7]. Water-soluble and porous boron nitride is usually biocompatible and can effectively employ as a nanocarrier for loading anti-cancer drug doxorubicin [8]. Moreover, several studies supported the use of interactions of h-BN through calcium coordination bonding towards reduced graphene oxide yielded nanocomposites to enhance the mechanical, electrical and thermal properties substantially [9,10,11]. Therefore, we aimed to investigate a metal and concoct a novel h-BN metal-based material that could be used as a catalyst to synthesize new nitrogen heterocycles. Hence, we investigated the suitability of a novel zinc boron nitride (Zn-BNT) material to synthesize new benzimidazoles through a simple condensation reaction.
Benzimidazole scaffold is widely used in the organic synthesis of drugs and drug intermediates [24]. Principally, two protocols are adopted for synthesizing 2-substituted benzimidazoles and their analogs. The first protocol involves a coupling of 1,2-phenylene-diamines with carboxylic acids, whereas the second protocol involves condensation of 1,2-phenylenediamine with aldehydes followed by oxidative cyclodehydrogenation [25,26]. Benzimidazole moiety can be constructed through reactions involving the use of several types of catalysts such as ammonium chloride [27], alumina [28], sodium metabisulphite [29], lanthanum chloride [30], indium triflate [31], sodium hexafluroaluminate [32], nickel acetate [33], iodine [34], and sodium dodecyl sulfate [35]. At the same time, some biologically active quinoline molecules are synthesized using boron modified sulphonic acid catalyst [36,37,38]. However, the methods have several drawbacks, such as the use of hazardous organic solvents, strongly acidic conditions, high moisture-sensitivity or tedious workup conditions, low yields, and difficulty isolating the products from the reaction mixture, and strong oxidizing nature of the reagents employed. Hence our research thrust was to prepare a new catalyst and evaluate its potential to synthesize benzimidazole derivatives. Furthermore, the theoretical calculations are studied for FT-IR and NMR spectra, HOMO-LUMO gap, Mulliken charge analysis, molecular electrostatic potential map, and Fukui function analysis.

Materials and methods
All the reagents were purchased from commercial sources and used as received. The reactions' progress and the compounds' purity were monitored by thin-layer chromatography (TLC) on pre-coated silica gel plates procured from E. Merck and Co. (Darmstadt, Germany). TLC spots were visualized by UV light and using an iodine-vapor chamber. The melting points of the synthesized compounds were determined using a Stuart SMP 10 melting point apparatus and are uncorrected. The IR spectra were recorded on Varian Scimitar 1000 FT-IR using KBr pellets, and the absorption frequencies are expressed in reciprocal centimeters (cm À1 ). In addition, 1 H and 13 C NMR were recorded on either a Bruker 400 or 600 MHz spectrometer: DMSO-d 6 was the solvent while TMS was an internal reference. The chemical shift values are recorded on δ scale, and the coupling constants (J) are in hertz. The elemental analyses (C, H, N) were obtained from a PerkinElmer precisely 2400 analyzer. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were conducted using TA Instruments. A Carl Zeiss Ultra Plus scanning electron microscope with EDX detector was used. The X-ray diffraction analysis was conducted with a Philips PW 1050 diffractometer set at 1 / min with a scanning step size of 0.02 from 40 to 100 2Ѳ using monochromated Cuk α radiation. Data were captured with a sietonics 122D automated microprocessor linked to the diffractometer [39].

Synthesis and characterization of Zn-BNT
To a solution of Zn(OAc) 2 (24.9 mg), in acetonitrile (50 ml), was added boron nitride (2.50 mg, 0.1 mmol), and the suspension was stirred at room temperature for seven days under an inert atmosphere. The resulting suspension was filtered, and the solid was washed with aqueous methanol and dried under reduced pressure to give Zn-BNT as a white powder in 95% yield.

Synthesis and characterization of 2-aryl benzimidazole derivatives (3a-h)
Equimolar quantities (1 mmol) of o-phenylenediamine (1) and aromatic aldehydes (2a-h) in acetonitrile (6 ml) were transferred to a 50 ml round bottom flask, and Zn-BNT (10 mol%) was added. The mixture was heated under reflux for12 h, and TLC was used to monitor the progress of the reaction mixture. Upon completion of the reaction, the mixture was filtered to recover the catalyst. The solid was washed with chloroform followed by methanol and dried at 120 C while the filtrate was purified by silica-gel column chromatography using ethyl acetate and petroleum ether 10:90 (v, v 10%) as an eluent to yield the 2-arylbenzimidazoles 3a-h, quantitatively.
The spectra data is presented below:

Synthesis and characterization of Zn-BNT
The new catalyst Zn-BNT ( Figure 2) was synthesized through a simple reaction between boron nitride, zinc acetate in acetonitrile under an inert   atmosphere by stirring at room temperature for seven days. The novel catalyst was characterized using FT-IR, XRD, SEM, SEM-EDX, SEMmapping, BET, and DSC-TGA.

FT-IR spectrum of Zn-BNT
The FT-IR spectrum of Zn-BNT is presented in Figure S1 (Supporting Information). The FT-IR revealed the presence of functional bond stretching frequencies N-B-N at 1738 cm À1 , B-N at 1365 cm À1 , and B-N-B at 920 cm À1 , with other additional bands for Zn-N at 1365 cm À1 and 1217 cm À1 assigned as asymmetric and symmetric stretching frequencies, respectively.

Powder XRD pattern of Zn-BNT
The powder XRD diffraction analysis [5] showed the crystal-like

Scanning electron microscope image of Zn-BNT
Zn-BNT was analyzed by scanning electron microscopy (SEM) for morphological characteristics. The particles appeared to be randomly  distributed, spherical and elongated needle-shaped for 1% Zn-BNT ( Figure 4a). An agglomeration of particles was observed, which probably led to the formation of the larger particles for 2% Zn-BNT ( Figure 4b). Consistent morphology and clusters of metal particles on the support surface of 4% Zn-BNT was observed in Figure 4c. The size of the rod-like particles of Zn was observed as 50-150 nm (length) and 16 nm (width) on the BN surface for 4% Zn-BNT (Figure 4d). The particles observed in 1% Zn-BNT were small and have a high surface area with a smaller number of active sites compared to 2% Zn-BNT. Similarly, the particles appeared larger and therefore had a smaller surface area in 4% Zn-BNT compared with 2% Zn-BNT.

SEM-mapping of Zn-BNT
The particles were observed as small and had a high surface area with a smaller number of active sites. Furthermore, the SEM mapping indicated the elements of Zn-BNT (Figure 5a, b, c, and d) Zn-BNT, boron, nitrogen, and zinc. The morphology of Zn-BNT material was further confirmed by SEM-EDX analysis.

SEM-EDX spectrum of Zn-BNT
The SEM-EDX spectrum of Zn-BNT ( Figure 6) displayed elements B, N, O, and Zn of weight (%) 20.11, 9.13, 70.72, and 0.04, respectively. Au peaks were due to the sample being coated with Au in the sampling process.

BET analysis of Zn-BNT
Brunauer-Emmett-Teller (BET) specific surface was determined from the nitrogen adsorption data at the relative pressure using a multipoint method. Figure 7(a) and (b) shows the isotherms of a 2 and 4% Zn-BNT in N 2 adsorption-desorption. The sample exhibited type-III isotherms. The type-III isotherm is closely related to the mesoporous structure of the catalyst and therefore no identifiable monolayer formation; the adsorbent-adsorbate interactions are now relatively weak and the adsorbed molecules are clustered around the most favorable sites on the surface of the solid. 2% Zn-BNT material showed a surface area of 25.42 m 2 g À1 with a pore volume of 0.119 cm 3 g -1 and 4% Zn-BNT material showed a surface area of 23.58 m 2 g À1 with a pore volume of 0.114 cm 3 g -1 and a pore size 188.74 Aº thereby indicating a mesoporous structure and effective as a catalyst for organic reactions.

Thermal analysis of Zn-BNT
Zn-BNT was analysed for its thermal properties from room temperature to 800 C. Figure 8 presents the DSC-TGA profile of the Zn-BNT material. The DSC curve of the sample indicated a broad exothermic peak. The weight loss occurred in stages; about 1.2% loss up to 200 C due to moisture and other volatile materials, whereas a loss of about 1.8% occurred until 800 C. These results demonstrated that Zn-BNT has good thermal stability; hence, it can be used effectively as suitable for the catalyst for several organic reactions.

Synthesis and characterization of 2-aryl benzimidazole derivatives (3a-h)
Briefly, equimolar quantities of o-phenylenediamine (1) and differently substituted aromatic aldehydes (2a-h) were added in acetonitrile. Zn-BNT was added, and the mixture was subjected to microwave irradiation for 15 min. The crude product was purified by silica-gel column chromatography using ethyl acetate and petroleum ether (10:90) to yield the pure 2-arylbenzimidazoles (3a-h) quantitatively. The recovered catalyst was reused for other reactions. The facile, one-step synthetic route is shown in Scheme 1. Notably, various aromatic aldehydes containing both electron-withdrawing and electron-donating groups underwent condensation to afford the target compounds. The results show that aromatic aldehydes bearing electron-donating groups such as hydroxyl and methyl afforded corresponding 2-arylbenzimidazole derivatives in better yields than the aldehydes having electron-withdrawing groups.

Solvent optimization methodology
The effect of different solvents, such as protic and aprotic, with different polarities were investigated (Table 1) on the model reaction to synthesize 3a. An initial reaction of ortho-phenylenediamine with benzaldehyde, in acetonitrile under reflux for 12 h produced a 75% yield of 3a. Protic solvents such as methanol and ethanol and aprotic solvents such as toluene, dichloromethane, tetrahydrofuran, and dioxane were investigated. The yield of 3a varied with the nature of the solvents used in the reaction. Since dioxane and acetonitrile gave the highest yield of 3a, we selected these two solvents and used microwave irradiation to decrease the reaction time and increase the yield of 3a. For a reaction time of 15 min, the yield of 3a was 55% and 97% for dioxane and acetonitrile, respectively ( Table 1, entry [8][9]. Published data on benzimidazole synthesis was analyzed and presented in Table 2. It was obvious that Zn-BNT outclassed published data; however, further work should be undertaken with named catalysts and under similar reaction conditions. Although the synthesis of the Zn-BNT material was recorded as seven days, the catalyst showed excellent catalytic activity, is environmentally friendly, non-toxic, and produces a high product yield ( Table 2).
After optimizing the reaction, 3a-h were synthesized using acetonitrile and Zn-BNT under MW conditions at 140 C for 15 min. Appropriate ortho-phenylenediamine 1 and different aldehyde (2a-h) were used. The yield of the products (Table 3) ranged from 82 to 97%. The products 3a-h were characterized by spectroscopic techniques FT-IR, 1 H-NMR, 13 C-NMR, and elemental analysis. The spectral confirmation of 3a is discussed as a template analysis. The FT-IR spectrum displayed the characteristic vibrational band as a single sharp peak at 3321 cm À1 , which indicated the formation of new aromatic secondary amino -N-H stretch, while there was no shoulder peak in the region of 3500-3400 cm À1, which would strongly indicate the NH 2 . A strong peak at 1625 cm À1 demonstrated the C¼N stretch. Also, there was no signal for the C¼O stretch in the region of 1680-1715 cm À1 , indicating the absence of the aromatic aldehyde, one of the starting materials. Thus, the new C¼N bond and N-H bond confirmed the main functional groups of 3a. Moreover, the characteristic peaks at 1551 cm À1 , 1467 cm À1 and 1422 cm À1 indicated the Ar-C¼C stretch and a sharp peak at 3177 cm À1 represented the ¼ CH stretch.
The 1 H-NMR spectrum of 3a showed a distinctive N-H proton broad singlet at δ 12.91, and no broad singlets were observed in the region of δ 5-7 ppm corresponding to the starting compound. The 13 C-NMR displayed the N¼C-N signal at δ 151. 18 (Table 3) ranged from 82 to 97%. The products 3a-h were characterized by spectroscopic techniques FT-IR, 1 H-NMR, 13 C-NMR, and elemental analysis.

Reusability of the Zn-BNT catalyst
The condensation reaction was conducted using acetonitrile as the solvent at 140 C and different amounts of 2% Zn-BNT catalyst in the range of 0.05-1 g. The best yield of product 3a was obtained with 0.07 g of the catalyst. Higher amounts of the catalyst did not improve the yield. The catalyst could be quickly recovered by simple filtration of the reaction mixture, followed by washing with chloroform and then methanol: the solid was dried at 105 C and then used for subsequent reactions. The reusability potential of Zn-BNT was also investigated in the model reaction to synthesize 3a. Recovery of the catalytic activity of Zn-BNT was better than other catalysts. Zn-BNT could be reused up to 8 times with only 5% loss of catalytic activity (Table 4), indicating good potential if undertaken on an industrial scale for synthesizing any benzimidazole derivatives.

Computational details
The ground state (DFT) optimization energy calculations were performed using the hybrid exchange-correlation functional B3LYP [40] with the basis set for the 6-311þþG(d,p) [41]. The various possible conformers for compound 3f were optimized in the gas phase. The conformer with the lowest energy with the fundamental frequencies in the ground state was considered and shown in Table S1 and Figure S13 (Supplementary Information). The total energy and Cartesian coordinates for the optimized minimum energy structure are given in Table S2. The infra-red (IR) spectrum and frequency values of 3f from DFT calculations are shown in Figure S15 and Table S3. Further, the NMR shielding tensors computed 3f with the gauge-independent atomic orbital (GIAO) method is shown in Figure S16 and Table S4. All the calculations were carried out with the Gaussian09 program package [42].

Molecular orbitals, Mulliken charge analysis, and electrostatic potential map
The energy level of the highest-occupied molecular orbital (E HOMO ) and lowest-unoccupied molecular orbital (E LUMO ) energies, along with the E HOMO-LUMO gap is an important parameter [43] to evaluate the reactivity of 3f. The HOMO-LUMO plot is given in Figure 9. The energy gap value of 3f was E H-L ¼ 4.48 eV. The large E H-L energy gap denotes the compound's high stability and lower reactivity.
The atomic charge distribution of 3f is obtained using Mulliken charge analysis [44] in Figure S14. The nitrogen and fluorine atoms show negative charge distribution due to electronegative properties. Consistently, the hydrogen zones represent a positive charge distribution in compound 3f.
The electrostatic potential surface (ESP) [45] ranges an isosurface from À0.02 a.u. to 0.02 a.u., as shown in Figure 10. The ESP map showed the high electron density for the blue region, which is due to higher electronegativity (nitrogen zones). In contrast, the red region denoted low electron density (hydrogen zones). The results mentioned above indicated that the C-N bond is an active site.

Fukui function
Fukui function predicts the most probable sites of the nucleophilic, electrophilic, and radical attack selectivity and chemical reactivity using DFT calculation shown in Figure S17 [46]. The Fukui function indices on The f þ i , f À i and f 0 i is represent the nucleophilic, electrophilic, and free radical attack on the reference compound 3f. From Eqs. (1), (2), and (3), q i denotes the atomic charge at the ith atomic sites of the chemical species are anionic (N þ 1), cationic (N À 1), and neutral (N), respectively. Here, the Fukui function for f þ i , f À i and f 0 i attack is calculated using Mulliken charge analysis.

Conclusion
In this work, we developed a facile, one-pot synthesis of 2substituted benzimidazole derivatives through a reaction between ophenylenediamine and different aromatic aldehydes in the presence of a novel zinc-boron nitride catalyst. The advantages of the developed method include the environmental-friendly reaction conditions, simple operation, broad substrate scope, satisfying yields, easy isolation of the product, and reusability of the catalyst. Furthermore, 2-(4-fluorophenyl)-1H-benzo[d]imidazole (3f) was selected for a computational study of the IR and NMR spectrum, which matched the experimentally generated spectra. The HOMO-LUMO gap was calculated as 4.48 eV. Moreover, the novel catalyst could be employed to synthesize other heterocyclic compounds, and their biological activity can be evaluated.

Data availability statement
The data that has been used is confidential.

Declaration of interests statement
The authors declare no conflict of interest.

Additional information
Supplementary content related to this article has been published online at https://doi.org/10.1016/j.heliyon.2022.e11480.