5-substituted 1H-tetrazole Derivatives Research Articles

One-pot synthesis, computational chemical study, molecular docking, biological study, and in silico prediction ADME/pharmacokinetics properties of 5-substituted 1H-tetrazole derivatives

An efficient synthesis of 5-substituted 1H-tetrazoles was successfully achieved through one-pot multi-component condensation reactions of some aromatic aldehydes or indolin-2,3-dione with malononitrile and sodium azide using diverse reaction conditions to obtain considerable product yields. Furthermore, it has been achieved for the first time to construct desired products under neat condition. Molecular docking studies with CSNK2A1 receptor disclosed the lowest binding energy displayed by the dimethoxyphenyl derivative 4c with − 6.8687 kcal/mol. The synthesized tetrazoles were screened for their in-vitro cytotoxic activity against epidermoid cancer cell line (A431) and colon cancer line (HCT116) with respect to normal skin fibroblast cell line (BJ-1) using MTT assay, and antimicrobial activity against the bacteria: K. pneumonia, S. aureus, and the fungi: Candida albicans, as well as their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay. In addition, the toxicity of tetrazole derivative was assessed by determination of their approximate lethal dose fifty (LD50), calculated via an oral administration to rats, through measurement of ALT and bilirubin levels in serum. The antitumor results can suggest that the potent tetrazole derivative namely, 3-(3,4-dimethoxyphenyl)-2-(1H-tetrazol-5-yl)acrylonitrile (4c) could be a potential drug against epidermoid carcinoma. The antioxidant results indicated to tetrazoles exhibited great antioxidant properties even at very low doses. A molecular dynamics simulation was performed for the synthesized compounds (ligands) to investigate their tendency for binding with the active sites of protein.

New ecofriendly heterogeneous nano-catalyst for the synthesis of 1-substituted and 5-substituted 1H-tetrazole derivatives

A novel ecofriendly heterogeneous catalyst containing Schiff base coordinated Cu(II) covalently attached to Fe3O4@SiO2 nanoparticles through imidazolium linker [Fe3O4@SiO2-Im(Br)-SB-Cu (II)] was synthesized and characterized by using various techniques. The catalytic efficiency of this nano-catalyst was tested in water in the synthesis of tetrazole derivatives using two one-pot multicomponent reaction (MCR) models: The synthesis of 1-aryl 1H-tetrazole derivatives from the reaction of aniline, triethyl orthoformate, and sodium azide and the synthesis of 5-aryl 1H-tetrazole derivatives from the reaction of benzaldehyde, hydroxy amine hydrochloride, and sodium azide. The investigation showed that (i) The catalyst is highly efficient in the synthesis of tetrazole derivatives with high yield (97%) in aqueous medium and mild temperatures; (ii) The catalytic effectiveness is due to the synergy between the metallic center and the imidazolium ion and (iii) The reuse advantage of the catalyst without contamination or significant loss (12% of loss range) in the catalytic activity.

A Schiff base complex of lanthanum on modified MCM-41 as a reusable nanocatalyst in the homoselective synthesis of 5-substituted 1H-tetrazoles.

In this work, mesoporous MCM-41 was modified by a new Schiff-base formed from the condensation of triethylenetatramine and 5-bromosalicylaldehyde. Then, it was used for the stabilization of lanthanum metal (La-Schiff base@MCM-41) as a homoselective, reusable, efficient and biocompatible catalyst in the synthesis of 5-substituted 1H-tetrazole derivatives. The synthesized tetrazoles were characterized using 1H NMR and FT-IR spectroscopy and methods to measure their physical properties. La-Schiff base@MCM-41 was characterized by using various techniques such as ICP, CHN, XRD, TGA, BET, FT-IR spectroscopy, SEM, EDS and WDX. This catalyst has good stability and a heterogeneous nature, enabling it to be easily recovered and reused several times without significant loss in catalytic activity. This present strategy has important advantages such as utilizing PEG as a green solvent, short reaction times, excellent yields, easy recycling of the catalyst and pure separation of the products. The recovered La-Schiff base@MCM-41 catalyst was characterized by using FT-IR spectroscopy, SEM and AAS.

Investigation of Fe3O4@boehmite NPs as efficient and magnetically recoverable nanocatalyst in the homoselective synthesis of tetrazoles.

Magnetic boehmite nanoparticles (Fe3O4@boehmite NPs) were synthesized from a hybrid of boehmite and Fe3O4 nanoparticles. At first, boehmite nanoparticles (aluminum oxide hydroxide) were prepared via a simple procedure in water using commercially available materials such as sodium hydroxide and aluminum nitrate. Then, these nanoparticles were magnetized using Fe3O4 NPs in a basic solution of FeCl2·4H2O and FeCl3·6H2O. Fe3O4@boehmite NPs have advantages of both boehmite nanoparticles and Fe3O4 magnetic materials. Magnetic boehmite nanoparticles have been characterized by various techniques such as TEM, SEM, EDS, WDX, ICP, FT-IR, Raman, XRD and VSM. SEM and TEM images confirmed that particles size are less than 50 nm in diameter with a cubic orthorhombic structure. Then, Fe3O4@boehmite NPs were applied as a homoselective, highly efficient, cheap, biocompatibility, heterogeneous and magnetically recoverable nanocatalyst in the synthesis of 5-substituted 1H-tetrazole derivatives. Fe3O4@boehmite NPs can be recycled for several runs in the synthesis of tetrazoles. Also, all tetrazoles were isolated in high yields, which reveals high activity of Fe3O4@boehmite NPs in the synthesis of tetrazole derivatives. Fe3O4@boehmite NPs shows a good homoselectivity in synthesis of 5-substituted 1H-tetrazole derivatives.

1-Disulfo-[2,2-bipyridine]-1,1-diium chloride ionic liquid as an efficient catalyst for the green synthesis of 5-substituted 1H-tetrazoles

A simple, green and efficient method has been developed for the synthesis of 5-substituted 1H-tetrazole derivatives through [2+3] cycloaddition reaction in good to excellent yields between various benzonitriles and sodium azide. For this purpose, 1-disulfo-[2,2-bipyridine]-1,1-diium chloride ([BiPy](HSO3)2Cl2) system as an ionic liquid catalyst have been extended for the construction of these valuable products. This procedure has significant advantages, including using ethylene glycol as a green solvent. The other advantages of this method are inexpensive and ease the preparation of the catalyst, mild reaction conditions, green reaction medium, easy workup, short reaction time, and simple experimental process.

Retraction: Monodisperse Pt NPs@rGO as highly efficient and reusable heterogeneous catalysts for the synthesis of 5-substituted 1H-tetrazole derivatives

Retraction of ‘Monodisperse Pt NPs@rGO as highly efficient and reusable heterogeneous catalysts for the synthesis of 5-substituted 1H-tetrazole derivatives’ by İbrahim Esirden et al., Catal. Sci. Technol., 2015, 5, 4452–4457, DOI: 10.1039/C5CY00864F.

Highly Active and Reusable Cu/C Catalyst for Synthesis of 5-Substituted 1H-Tetrazoles Starting from Aromatic Aldehydes

A new, efficient and convenient method for the synthesis of 5-substituted 1H-tetrazole derivatives with a wide range of substituents in good to excellent yields has been developed. The synthesis was performed by the one-pot three-component [3+2]cycloaddition reaction between aldehyde, hydroxylamine and sodium azide in the presence of Cu/C. The reaction probably proceeds by the in situ formation of nitriles followed by successive [3+2]cycloaddition with sodium azide. A variety of aldehydes were used to obtain the corresponding tetrazoles. The catalyst was recovered by simple filtration and reused at least five times without significant loss of catalytic activity. The use of this method offers additional advantages for the synthesis of 5-substituted 1H-tetrazole derivatives, including the easy availability of starting materials, mild conditions, experimental simplicity and good yields.

Catalytic conversion of 2,4,5-trisubstituted imidazole and 5-substituted 1H-tetrazole derivatives using a new series of half-sandwich (η6-p-cymene)Ruthenium(II) complexes with thiophene-2-carboxylic acid hydrazone ligands

A new series of half-sandwich (η6-p-cymene) ruthenium(II) complexes with thiophene-2-carboxylic acid hydrazide derivatives [Ru(η6-p-cymene)(Cl)(L)] [L = N'-(naphthalen-1-ylmethylene)thiophene-2-carbohydrazide (L1), N'-(anthracen-9-ylmethylene)thiophene-2-carbohydrazide (L2) and N'-(pyren-1-ylmethylene)thiophene-2-carbohydrazide (L3)] were synthesized. The ligand precursors and their Ru(II) complexes (1–3) were structurally characterized by spectral (IR, UV–Vis, NMR and mass spectrometry) and elemental analysis. The molecular structures of the ruthenium(II) complexes 1–3 were determined by single-crystal X-ray diffraction. All complexes were used as catalysts for the one-pot three-component syntheses of 2,4,5-trisubstitued imidazole and 5-substituted 1H-tetrazole derivatives. The catalytic studies optimized parameters as solvent, temperature and catalyst. The catalysts revealed very active for a broad range of aromatic aldehydes presenting either electron attractor or electron donor substituents and, although less active, moderate to high activities were observed for alkyl aldehydes.

L-cysteine complex of palladium onto mesoporous channels of MCM-41 as reusable, homoselective and organic–inorganic hybrid nanocatalyst for the synthesis of tetrazoles

In this study, ordered structure with a hexagonal arrangement MCM-41 was synthesized and functionalized with L-cysteine group and further palladium particles has been supported on its surface (L-cysteine-Pd@MCM-41). The prepared catalyst is well characterized by various techniques such as low-angle X-ray diffraction (XRD), thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), N2 adsorption–desorption measurement isotherms, energy-dispersive X-ray spectroscopy (EDS), X-ray Mapping (WDX), scanning electron microscopy (SEM) and inductively coupled plasma (ICP) techniques. The collected data from all techniques provided evidence that palladium complex was immobilized onto MCM-41 pores. The obtained nanocatalyst demonstrated excellent activity as a new heterogeneous catalyst for the homoselective synthesis of 5-substituted 1H-tetrazole derivatives. This method has the advantages of simple methodology, eco-friendly and simplicity in the separation of catalyst, shorter reaction times, and high yields of the product. Finally, easy catalyst recovery was achieved and the catalyst could be recycled for six times without a significant decrease in activity and selectivity.

A Facile Approach to Catalyst-Free Cyanation and Azidation of ­Organic Compounds and a One-Pot Preparation of 5-Substituted 1H-Tetrazoles by Using a Dimethyl Sulfoxide–Nitric Acid Combination

In this study, cyanations or azidations of imines were performed by using hydroxy(dimethyl)-λ4-sulfanecarbonitrile or azido(dimethyl)-λ4-sulfanol, respectively, prepared in situ by treatment of potassium cyanide or sodium azide with a dimethyl sulfoxide–nitric acid combination. Furthermore, a one-pot preparation of 5-substituted 1H-tetrazole derivatives was carried out by using this reagent combination in the presence of an aldehyde, hydroxylamine hydrochloride, and sodium azide under mild conditions.

Anchoring of triethanolamine–Cu(II) complex on magnetic carbon nanotube as a promising recyclable catalyst for the synthesis of 5-substituted 1H-tetrazoles from aldehydes

The development of heterogenization of copper nanoparticles on conductive supports is very challenging and has received much attention. Here, we synthesize a practical, efficient, and inexpensive heterogeneous catalyst to grow stable metallic copper(II) nanoparticles on the surface of magnetic carbon nanotube (Fe3O4-CNT) catalyst support physically functionalized with triethanolamine (TEA) that acts as a low-cost and non-toxic ligand to capture the copper nanoparticles [Fe3O4-CNT-TEA-Cu(II)]. The as-prepared heterogeneous catalyst was characterized by different techniques, such as Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, vibrating sample magnetometer, X-ray diffraction patterns, field-emission scanning electron microscopy, and atomic absorption spectroscopy analysis. The catalytic behavior of Fe3O4-CNT-TEA-Cu(II) was investigated in the preparation of 5-substituted 1H-tetrazole derivatives via one-pot, three-component reaction between aromatic aldehydes, hydroxylamine, and sodium azide. The low catalyst loading, wide substrate scope, use of inexpensive materials, simple separation of the catalyst from the reaction mixture by an external magnet, short reaction times, easy workup, affordability, and superb yield are some advantages of this protocol.

MCM-41-SO3H: as an efficient reusable Nano-ordered heterogeneous catalyst for the synthesis of divers 1- & 5-substituted 1H-tetrazoles

An improved and efficient method for the synthesis of 1- & 5-substituted 1H-tetrazole derivatives has been described in the presence of nano-ordered MCM-41-SO3H as an effective heterogeneous catalyst. This metal-free protocol, [2+3] cycloaddition of sodium azide to various nitriles or ethyl N-phenyl formimidate intermediate under mild reaction conditions, afford a wide range of 1H-tetrazoles in good to excellent yields. The catalyst was reused for five times without significant loss of catalytic activity.

One pot three-component synthesis of 5-substituted 1H-tetrazole from aldehyde

A versatile, robust and efficient strategy for the synthesis of vast range of highly functionalized 5-substituted 1H-tetrazole derivatives by using one pot three-component synthesis from various aldehydes, hydroxylamine hydrochloride and sodium azide in presence of a catalytic amount of ceric ammonium sulphate, a non toxic, easily available, inexpensive, unexplored and reusable catalyst is reported. This one-pot synthesis has several advantages such as mild reaction conditions, shorter reaction time, low catalyst loading, good to moderate yields and functional group tolerance making this methodology practically feasible. The synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS.

Undergraduate Organic Experiment: Tetrazole Formation by Microwave Heated (3 + 2) Cycloaddition in Aqueous Solution

An undergraduate experiment for the organic laboratory is described that utilizes microwave heating to prepare 5-substituted 1H-tetrazole derivatives through a (3 + 2) cycloaddition between aryl nitriles and sodium azide. The reaction mixture is analyzed by thin layer chromatography. The products are purified through an acid–base extraction and recrystallization. Characterization is accomplished using melting point, infrared, 1H NMR, and 13C NMR spectroscopy. Students are tasked with determining and confirming the structure of their product based on their assigned nitrile and characterization data.

Diisopropylethylammonium acetate (DIPEAc): An efficient and recyclable catalyst for the rapid synthesis of 5-substituted-1H-tetrazoles

ABSTRACTA simple and efficient protocol developed for the synthesis of 5-substituted 1H-tetrazole derivatives through [2+3] cycloaddition reaction between benzonitriles and sodium azide using diisopropylethylammonium acetate as a recyclable reaction medium is described. The reactions proceed well at 80 °C and provide the corresponding tetrazoles in good to excellent yields (up to 94% yield). Developed method has notable advantages, such as simple and mild conditions, easy workup, reusability with consistent catalytic activity, and safer alternative to hazardous, corrosive conventional Lewis acid catalysts.

Antimicrobial Evaluation of 5-Substituted Aryl 1H-Tetrazoles

Tetrazole derivatives such as 1-substituted dinitrobenzyl tetrazoles and their oxa and selanyl analogs have previously been studied against drug-susceptible and multidrug-resistant mycobacteria. In addition, other tetrazole derivatives have been shown to inhibit CTX-M class A b-lactamases. To study the antibacterial activity of 5-substituted aryl 1H-tetrazole derivatives. The antibacterial activity of several known 5-substituted aryl 1H-tetrazole derivatives was evaluated against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The activity was assessed by determining the minimum inhibitory concentration of these tetrazole derivatives and comparing them to the known antibiotics amoxicillin, trimethoprim and sulfamethoxazole. Some derivatives showed significant antibacterial activity with the most active derivatives exhibiting a minimum inhibitory concentration (MIC) of 125-250 mg/mL against Staphylococcus aureus and Escherichia coli. Using some of these tetrazole compounds in combination with trimethoprim led to a synergistic effect that gave MIC values ranging from 0.24-1.95 mg/mL against Escherichia coli and 3.91-31.3 mg/mL against Staphylococcus aureus. The tetrazole derivatives were prepared in an isopropanol/water mixture using microwave heating at 160 oC for 1 h. The cycloaddition between organonitriles and sodium azide was catalyzed by indium chloride. This study shows a significant synergistic effect between the tetrazole compounds tested and trimethoprim which could be used to potentially develop new antibacterial agents.

ChemInform Abstract: Indium(III) Chloride Catalyzed Synthesis of 5‐Substituted 1H‐Tetrazoles from Oximes and Sodium Azide.

A simple and efficient protocol has been developed for the synthesis of 5-substituted 1H-tetrazole derivatives in good to excellent yields from various oximes and sodium azide by using indium(III) chloride as a Lewis acid catalyst. The present method has significant advantages, such as an inexpensive catalyst, low catalyst loading, mild reaction conditions, and simple experimental procedures.

Highly efficient three-component synthesis of 5-substituted-1H-tetrazoles from aldehydes, hydroxylamine, and tetrabutylammonium azide using doped nano-sized copper(I) oxide (Cu2O) on melamine–formaldehyde resin

A simple and facile one-pot three-component synthesis of 5-substituted 1H-tetrazole derivatives from aldehydes catalyzed by doped nano-sized Cu2O on melamine–formaldehyde resin (nano-Cu2O–MFR) is described. In this protocol, treatment of structurally diverse aldehydes, hydroxylamine hydrochloride and tetrabutylammonium azide (TBAA) as an azide source in the presence of nano-Cu2O–MFR as an efficient heterogeneous nano-catalyst affords the corresponding 5-substituted 1H-tetrazoles in good to excellent yields. The influence of different parameters on the progress of reaction was studied. The nano-Cu2O–MFR is a cheap and stable nano-catalyst that could be easily prepared, recycled and reused for many consecutive reaction runs without significant decrease in its activity.

Ni–S-methylisothiourea complexes supported on boehmite nanoparticles and their application in the synthesis of 5-substituted tetrazoles

Boehmite nanoparticles were immobilized with a new type of nickel complex and applied for the synthesis of 5-substituted 1H-tetrazole derivatives in PEG-400.

ChemInform Abstract: Multi‐Component One‐Pot Reaction of Aldehyde, Hydroxylamine and Sodium Azide Catalyzed by Cu‐MCM‐41 Nanoparticles: A Novel Method for the Synthesis of 5‐Substituted 1H‐Tetrazole Derivatives.

A simple and efficient procedure for the synthesis of 5-substituted 1H-tetrazole derivatives has been developed using a one-pot, three-component reaction of various aldehydes, hydroxylamine and sodium azide in the presence of a catalytic amount of Cu-MCM-41, as a nanostructured, heterogeneous and reusable catalyst. In this research, Cu-MCM-41 nanoparticles with three Cu/Si molar ratios were prepared and characterized using various techniques. The characterization and optimization results show that the catalyst with a Cu/Si molar ratio of 0.050 has the best catalytic activity.