Reusable Nano-Zirconia-Catalyzed Synthesis of Benzimidazoles and Their Antibacterial and Antifungal Activities

In this article, a zirconia-based nano-catalyst (Nano-ZrO2), with intermolecular C-N bond formation for the synthesis of various benzimidazole-fused heterocycles in a concise method is reported. The robustness of this reaction is demonstrated by the synthesis of a series of benzimidazole drugs in a one-pot method. All synthesized materials were characterized using 1HNMR, 13CNMR, and LC-MS spectroscopy as well as microanalysis data. Furthermore, the synthesis of nano-ZrO2 was processed using a standard hydrothermal technique in pure form. The crystal structure of nano-ZrO2 and phase purity were studied, and the crystallite size was calculated from XRD analysis using the Debye–Scherrer equation. Furthermore, the antimicrobial activity of the synthesized benzimidazole drugs was evaluated in terms of Gram-positive, Gram-negative, and antifungal activity, and the results were satisfactory.


Introduction
Heterocyclic compounds, particularly nitrogen-containing compounds, are extremely important because their presence in many synthetic organic compounds promotes biological activities [1]. The building of the C-N bonds of heterocyclic compounds is principally significant and has been demonstrated to be challenging to medicinal chemists [2]. The introduction of the amine functional group in a precise manner has been broadly examined by chemists and was first reported by Ullmann and Goldberg [3,4]. Given the predominance and relevance of heteroatoms in molecules of interest, C-N bond formation via direct formation of C-N bonds has attracted significant attention. In this context, numerous transition metal complexes, especially of Rh [5], Ir [6], Co [7], Ru [8], and Pd [9], have exhibited outstanding catalytic efficiency towards C-N bond formation reactions [10].
In recent decades, the application of engineered nanoparticles (NPs) has extended to various fields, such as electronics, biomedical applications, and pharmaceuticals. Zirconia  Figure 2a shows the crystalline nature and phase purity of the resulting nano-ZrO2, evaluated by measurements of room temperature XRD. The nano-ZrO2 sample diffraction peaks were indexed according to JCPDS card number 80-0965. A tetragonal phase (space group = P42/nmc) was confirmed by the XRD pattern of the investigated sample. In the synthesized powder XRD pattern, no additional peaks were found. Scherrer's formula was used to calculate the average crystallite size for the most intense diffraction peaks. =  Cos (1) where β (in radians) is the half maximum full width of XRD peaks, K = 0.94 is the shape factor, λ = 1.54178 Ǻ for Cu-Kα X-rays, θ is the diffraction angle (in degrees) corresponding to each plane. Crystallite size (D) was found to be 60 ± 5 nm for chemically

Results and Discussion
2.1. XRD, FT-IR, and TGA of Nano-ZrO 2 Figure 2a shows the crystalline nature and phase purity of the resulting nano-ZrO 2 , evaluated by measurements of room temperature XRD. The nano-ZrO 2 sample diffraction peaks were indexed according to JCPDS card number 80-0965. A tetragonal phase (space group = P42/nmc) was confirmed by the XRD pattern of the investigated sample. In the synthesized powder XRD pattern, no additional peaks were found. Scherrer's formula was used to calculate the average crystallite size for the most intense diffraction peaks.
where β (in radians) is the half maximum full width of XRD peaks, K = 0.94 is the shape factor, λ = 1.54178 Åfor Cu-Kα X-rays, θ is the diffraction angle (in degrees) corresponding to each plane. Crystallite size (D) was found to be 60 ± 5 nm for chemically synthesized nano-ZrO 2 . For (111) planes, the powder diffraction file for cubic and tetragonal ZrO 2 has the highest peak intensity and the second most intense is (220). By comparing the relative intensities of (111) at 2θ~30 • and (220) at 50 • in each sample with these data, it appears that the (111) orientation is suppressed and the (110) growth is increased at 600 • C [32,33].
Molecules 2021, 26, x FOR PEER REVIEW 4 of 14 synthesized nano-ZrO2. For (111) planes, the powder diffraction file for cubic and tetragonal ZrO2 has the highest peak intensity and the second most intense is (220). By comparing the relative intensities of (111) at 2θ~30° and (220) at 50° in each sample with these data, it appears that the (111) orientation is suppressed and the (110) growth is increased at 600 °C [32,33].

FT-IR
FT-IR of nano-ZrO2 showed bending and stretching vibrations of the O-H functional groups due to absorbed water molecules, attributed to the bands noted at 3425 cm −1 and 1638 cm −1 , respectively [29]. The band at 1386 cm −1 is ascribed to the absorption of non-bridging O-H groups. The sharp bands at 504 cm −1 and 734 cm −1 are attributed to the vibration modes of the ZrO3 2− , and ZrO2 groups, which strongly confirm the formation of nano-ZrO2, as shown in Figure 2b [34]. Figure 2c shows the TGA analysis that was performed in an inert N2 gas atmosphere to determine the thermal degradation of the sample due to the occurrence of air or oxygen atmospheric oxidation in the sample and 92.6% char residue at 800 °C [22]. It is obvious that nano-ZrO2 exhibited continuous weight loss, and the weight loss below 300 °C is attributed to the release of physically adsorbed molecules, mainly water as moisture, and the weight loss above 300 °C is due to the desorption of chemically bonded oxygenated groups and the dehydration of surface hydroxyls. Based on the result, nano-ZrO2 is highly thermally stable up to 800 °C [23]. Recently, Zhou. et al. reported the dispersion behavior of zirconia nanocrystals and their surface functionalization with vinyl group-containing ligands. Our results are similar to their TGA data [35][36][37].

TEM, Size Distribution, SEM, and EDX Analysis of Nano-ZrO2
The morphology, size, and shape of the as-synthesized nano-ZrO2 were investigated by using HR-TEM. The TEM image of nano-ZrO2 showed stretched spherical particles with diameters of ~40-60 nm. Nano-ZrO2 has been well known for several years as having a variety of sizes and shapes, however, stretched spherical nano-ZrO2, as shown in

FT-IR
FT-IR of nano-ZrO 2 showed bending and stretching vibrations of the O-H functional groups due to absorbed water molecules, attributed to the bands noted at 3425 cm −1 and 1638 cm −1 , respectively [29]. The band at 1386 cm −1 is ascribed to the absorption of non-bridging O-H groups. The sharp bands at 504 cm −1 and 734 cm −1 are attributed to the vibration modes of the ZrO3 2− , and ZrO 2 groups, which strongly confirm the formation of nano-ZrO 2 , as shown in Figure 2b [34]. Figure 2c shows the TGA analysis that was performed in an inert N 2 gas atmosphere to determine the thermal degradation of the sample due to the occurrence of air or oxygen atmospheric oxidation in the sample and 92.6% char residue at 800 • C [22]. It is obvious that nano-ZrO 2 exhibited continuous weight loss, and the weight loss below 300 • C is attributed to the release of physically adsorbed molecules, mainly water as moisture, and the weight loss above 300 • C is due to the desorption of chemically bonded oxygenated groups and the dehydration of surface hydroxyls. Based on the result, nano-ZrO 2 is highly thermally stable up to 800 • C [23]. Recently, Zhou et al. reported the dispersion behavior of zirconia nanocrystals and their surface functionalization with vinyl group-containing ligands. Our results are similar to their TGA data [35][36][37].

TEM, Size Distribution, SEM, and EDX Analysis of Nano-ZrO 2
The morphology, size, and shape of the as-synthesized nano-ZrO 2 were investigated by using HR-TEM. The TEM image of nano-ZrO 2 showed stretched spherical particles with diameters of~40-60 nm. Nano-ZrO 2 has been well known for several years as having a variety of sizes and shapes, however, stretched spherical nano-ZrO 2 , as shown in Figure 3a, is rarely found. The corresponding size distribution histogram of nano-ZrO 2 is shown in Figure 3b, and the calculated average particle size was about 60 nm, using ImageJ software. Further, the surface morphology of nano-ZrO 2 was confirmed using SEM analysis, as shown in Figure 3c. The SEM image clearly showed that nano-ZrO 2 appeared as aggregated spherical surface morphologies. The agglomeration of nano-ZrO 2 is visible in the SEM images as well. Next, the elemental composition of nano-ZrO 2 was analyzed by EDX [30]. The host material of nano-ZrO 2 exhibited three elemental peaks which correspond to zirconium and oxygen at 0.1, 1.98, and 0.56 keV, respectively. From the EDS data, the weight ratio of Zr:O was approximately 77:23 and the spectra suggested that the nano-ZrO 2 consisted of only Zr and O elements [38].  Figure 3a, is rarely found. The corresponding size distribution histogram of nano-ZrO2 is shown in Figure 3b, and the calculated average particle size was about 60 nm, using ImageJ software. Further, the surface morphology of nano-ZrO2 was confirmed using SEM analysis, as shown in Figure 3c. The SEM image clearly showed that nano-ZrO2 appeared as aggregated spherical surface morphologies. The agglomeration of nano-ZrO2 is visible in the SEM images as well. Next, the elemental composition of nano-ZrO2 was analyzed by EDX [30]. The host material of nano-ZrO2 exhibited three elemental peaks which correspond to zirconium and oxygen at 0.1, 1.98, and 0.56 keV, respectively. From the EDS data, the weight ratio of Zr:O was approximately 77:23 and the spectra suggested that the nano-ZrO2 consisted of only Zr and O elements [38].
To check the reusability of nano-ZrO 2 , when the reaction of o-PDA with various substituted aromatic aldehydes was over, the product formed was extracted with ethyl acetate and the catalyst was purified. It was washed with ethyl acetate repeatedly, dried, and reused for the reaction of o-PDA with various aryl aldehydes. The nano-ZrO 2 was found to be reusable for at least four cycles without any inactivity, and from the fifth cycle the catalytic activity was decreased (Table 3) [41]. The main advantage of nano-ZrO 2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO 2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO 2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO 2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO 2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO 2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. [a] A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4. The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  A solution of o-PDA (1 mol) and 4-MeO-benzaldehyde (1.1 mol) in dry EtOH (20 mL) was heated at 60 °C under nitrogen for 3 h in the presence of 2 mol% of nano-ZrO2, [b] determined by gas chromatography.
The main advantage of nano-ZrO2 is that besides its selectivity, it showed moderate recyclability, and it can be recovered through simple filtration, or a decantation method (Table 3). To the best of our knowledge, nano-ZrO2 is a recyclable catalyst for the synthesis of benzimidazoles by condensation of 1 and 2a to produce 3a with a good yield [10,33]. When the catalyst was recovered and reused without any treatment, the reaction rate gradually decreased (entry 1-5) due to moisture contamination. Therefore, for each successive use, we gently dried the catalyst and reused it. Nano-ZrO2 showed moderate catalytic activity after the fifth cycle, and produced 3a with an 82% yield.
With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  [12], d [13], e [14]. All the products were showed satisfactory spectroscopic (IR, 1 HNMR, & 13 CNMR) analyses data. Figure 4a shows that the cup-plate screening method is simple for measuring inhibition of microorganisms. Here, we have used this method for the antibacterial screening of the tested compounds. Nutrient agar 2%, peptone 1%, beef extract 1%, sodium chloride 0.5%, and distilled water up to 100 mL were used in culture media. All the constituents were weighed and added to the base medium water. The solution mixture was heated in a water bath for about 1.5 h until a clear solution was obtained and the nutrient medium was sterilized in an autoclave. Antibacterial activity was assessed against Gram-positive bacteria (Streptococcus pneumonia (RCMB 010010), Bacillus subtilis (RCMB 010067)) and Gram-negative bacteria (Pseudomonas aeruginosa (RCMB 010046), Escherichia coli (RCMB 010052)). Ampicillin was used as a standard in the assessment of antibacterial activity against Gram-positive bacteria and gentamicin was used as a standard in the assessment of the activity of the compounds tested against Gram-negative bacteria. The results were expressed as the mean inhibition zone in mm ± standard deviation beyond the well diameter (6 mm) produced by microorganisms using 10 mg/mL of samples tested, as shown in Table 5.   [12], d [13], e [14]. All the products were showed satisfactory spectroscopic (IR, 1 HNMR, & 13 CNMR) analyses data. Figure 4a shows that the cup-plate screening method is simple for measuring inhibition of microorganisms. Here, we have used this method for the antibacterial screening of the tested compounds. Nutrient agar 2%, peptone 1%, beef extract 1%, sodium chloride 0.5%, and distilled water up to 100 mL were used in culture media. All the constituents were weighed and added to the base medium water. The solution mixture was heated in a water bath for about 1.5 h until a clear solution was obtained and the nutrient medium was sterilized in an autoclave. Antibacterial activity was assessed against Gram-positive bacteria (Streptococcus pneumonia (RCMB 010010), Bacillus subtilis (RCMB 010067)) and Gram-negative bacteria (Pseudomonas aeruginosa (RCMB 010046), Escherichia coli (RCMB 010052)). Ampicillin was used as a standard in the assessment of antibacterial activity against Gram-positive bacteria and gentamicin was used as a standard in the assessment of the activity of the compounds tested against Gram-negative bacteria. The results were expressed as the mean inhibition zone in mm ± standard deviation beyond the well diameter (6 mm) produced by microorganisms using 10 mg/mL of samples tested, as shown in Table 5. With optimized reaction conditions, the scope of the different aryl aldehydes was examined for the synthesis of various aryl benzimidazoles. Initially, o-PDA was reacted with benzaldehyde, in the presence of 2 mol % of nano-ZrO2 and produced 2-phenylbenzimidazole, 3a, with a 95% yield. Next, the reaction of o-PDA was carried out with various aryl benzaldehydes with electron-donating groups using 2 mol % of nano-ZrO2 to produce corresponding aryl benzimidazole in good to excellent yields, 3b-3d (i.e., 93% (3b), 91% (3c), and 90% (3d)), respectively. On the other hand, the reaction of o-PDA with aryl benzaldehydes with electron-withdrawing groups at meta and ortho positions (e.g., 3-Cl and 3-Br) in the presence of 2 mol % of nano-ZrO2 produced corresponding aryl benzimidazoles with 84% (3e) and 86% (3f) yields, respectively, as shown in Table 4.  [12], d [13], e [14]. All the products were showed satisfactory spectroscopic (IR, 1 HNMR, & 13 CNMR) analyses data. Figure 4a shows that the cup-plate screening method is simple for measuring inhibition of microorganisms. Here, we have used this method for the antibacterial screening of the tested compounds. Nutrient agar 2%, peptone 1%, beef extract 1%, sodium chloride 0.5%, and distilled water up to 100 mL were used in culture media. All the constituents were weighed and added to the base medium water. The solution mixture was heated in a water bath for about 1.5 h until a clear solution was obtained and the nutrient medium was sterilized in an autoclave. Antibacterial activity was assessed against Gram-positive bacteria (Streptococcus pneumonia (RCMB 010010), Bacillus subtilis (RCMB 010067)) and Gram-negative bacteria (Pseudomonas aeruginosa (RCMB 010046), Escherichia coli (RCMB 010052)). Ampicillin was used as a standard in the assessment of antibacterial activity against Gram-positive bacteria and gentamicin was used as a standard in the assessment of the activity of the compounds tested against Gram-negative bacteria. The results were expressed as the mean inhibition zone in mm ± standard deviation beyond the well diameter (6 mm) produced by microorganisms using 10 mg/mL of samples tested, as shown in Table 5.   [12], d [13], e [14]. All the products were showed satisfactory spectroscopic (IR, 1 HNMR, & 13 CNMR) analyses data. Figure 4a shows that the cup-plate screening method is simple for measuring inhibition of microorganisms. Here, we have used this method for the antibacterial screening of the tested compounds. Nutrient agar 2%, peptone 1%, beef extract 1%, sodium chloride 0.5%, and distilled water up to 100 mL were used in culture media. All the constituents were weighed and added to the base medium water. The solution mixture was heated in a water bath for about 1.5 h until a clear solution was obtained and the nutrient medium was sterilized in an autoclave. Antibacterial activity was assessed against Gram-positive bacteria (Streptococcus pneumonia (RCMB 010010), Bacillus subtilis (RCMB 010067)) and Gram-negative bacteria (Pseudomonas aeruginosa (RCMB 010046), Escherichia coli (RCMB 010052)). Ampicillin was used as a standard in the assessment of antibacterial activity against Gram-positive bacteria and gentamicin was used as a standard in the assessment of the activity of the compounds tested against Gram-negative bacteria. The results were expressed as the mean inhibition zone in mm ± standard deviation beyond the well diameter (6 mm) produced by microorganisms using 10 mg/mL of samples tested, as shown in Table 5.  [12], d [13], e [14]. All the products were showed satisfactory spectroscopic (IR, 1 HNMR, & 13 CNMR) analyses data. Figure 4a shows that the cup-plate screening method is simple for measuring inhibition of microorganisms. Here, we have used this method for the antibacterial screening of the tested compounds. Nutrient agar 2%, peptone 1%, beef extract 1%, sodium chloride 0.5%, and distilled water up to 100 mL were used in culture media. All the constituents were weighed and added to the base medium water. The solution mixture was heated in a water bath for about 1.5 h until a clear solution was obtained and the nutrient medium was sterilized in an autoclave. Antibacterial activity was assessed against Gram-positive bacteria (Streptococcus pneumonia (RCMB 010010), Bacillus subtilis (RCMB 010067)) and Gram-negative bacteria (Pseudomonas aeruginosa (RCMB 010046), Escherichia coli (RCMB 010052)). Ampicillin was used as a standard in the assessment of antibacterial activity against Gram-positive bacteria and gentamicin was used as a standard in the assessment of the activity of the compounds tested against Gram-negative bacteria. The results were expressed as the mean inhibition zone in mm ± standard deviation beyond the well diameter (6 mm) produced by microorganisms using 10 mg/mL of samples tested, as shown in Table 5.  1 mol), in dry. ethanol (20 mL) was heated at 60 °C in nitrogen gas for 3 h in the presence of Nano ZrO2 [2 mol%], b determined by GC, c [12], d [13], e [14]. All the products were showed satisfactory spectroscopic (IR, 1 HNMR, & 13 CNMR) analyses data. Figure 4a shows that the cup-plate screening method is simple for measuring inhibition of microorganisms. Here, we have used this method for the antibacterial screening of the tested compounds. Nutrient agar 2%, peptone 1%, beef extract 1%, sodium chloride 0.5%, and distilled water up to 100 mL were used in culture media. All the constituents were weighed and added to the base medium water. The solution mixture was heated in a water bath for about 1.5 h until a clear solution was obtained and the nutrient medium was sterilized in an autoclave. Antibacterial activity was assessed against Gram-positive bacteria (Streptococcus pneumonia (RCMB 010010), Bacillus subtilis (RCMB 010067)) and Gram-negative bacteria (Pseudomonas aeruginosa (RCMB 010046), Escherichia coli (RCMB 010052)). Ampicillin was used as a standard in the assessment of antibacterial activity against Gram-positive bacteria and gentamicin was used as a standard in the assessment of the activity of the compounds tested against Gram-negative bacteria. The results were expressed as the mean inhibition zone in mm ± standard deviation beyond the well diameter (6 mm) produced by microorganisms using 10 mg/mL of samples tested, as shown in Table 5.  We investigated the microbial activity of the titled moiety, and the compounds 3b, 3c, 3i, and 3j demonstrated the highest active potency against E. coli. The compounds 3c, 3d, 3g, and 3i showed maximum active potency against P. aeruginosa. The compounds 3d and 3f showed moderate active potency against S. pneumonia. The compounds 3e and 3f showed good active potency against B. subtilis. The rest of the compounds exhibited poor to moderate active potency, as shown in Table 5.

Antibacterial Screening
We reported that tested compounds 3b, 3c, and 3i are more potent than other compounds in terms of antifungal activity. The results also showed that alkyl benzimidazoles are more active than alkyl benzotriazoles. All tested compounds in this study, except 3i, 3b, and 3c, exhibited desirable activity on Candida albicans. Some Aspergillus niger, Aspergillus flavus, and Candida albicans, which are resistant to fluconazole, were affected by the synthesized compounds 3i, 3b, and 3c, as shown in Table 6.