5-substituted Tetrazoles Research Articles

A new Schiff-base-N-propylhydrazine-1-carbothioamide complex of copper on boehmite nanoparticles as a recoverable catalyst in the homoselective synthesis of 5-substituted tetrazoles

In this work, 2-(2-hydroxybenzylidene)hydrazine-1-carbothioamide (Schiff-base-HBHCT) was synthesized, and it was identified by FT-IR, 1H NMR, and 13C NMR spectroscopies. Besides, 3-iodopropyltrimethoxysilane (3-IPTMS) was synthesized by a simple SN2 reaction of 3-chloropropyltrimethoxysilane and potassium iodide in dry acetone. Also, boehmite nanoparticles are synthesized by a simple route and available commercial materials. Then, the surface of boehmite nanoparticles was modified by 3-IPTMS, and then it was further functionalized by Schiff-base-HBHCT. Finally, the copper ion became complex with functionalized Schiff-base-HBHCT (Cu-Schiff-base-HBHCT@boehmite). The particle size and morphology of Cu-Schiff-base-HBHCT@boehmite were studied by SEM images. Organic moieties and elemental composition of Cu-Schiff-base-HBHCT@boehmite were investigated by TGA, AAS, EDS, and WDX analysis. The surface area of Cu-Schiff-base-HBHCT@boehmite was calculated by nitrogen adsorption/desorption analysis, including BJH and BET methods. In the final step, the catalytic application of Cu-Schiff-base-HBHCT@boehmite was studied in the homoselective synthesis of tetrazoles. This catalyst has shown good reusability in the synthesis of tetrazoles.

Sequential, Electrochemical-Photochemical Synthesis of 1,2,4-Triazolo-[4,3-a]pyrazines.

1,2,4-triazolo-[4,3-a]pyrazine was prepared via a two-step electrochemical, photochemical process. First, a 5-substituted tetrazole is electrochemically coupled to 2,6-dimethoxypyrazine to yield 1,5- and 2,5- disubstituted tetrazoles. Subsequent photochemical excitation of the 2,5-disubstituted tetrazole species using an ultraviolet lamp releases nitrogen gas and produces a short-lived nitrilimine intermediate. Subsequent cyclization of the nitrilimine intermediate yields a 1,2,4-triazolo-[4,3-a]pyrazine backbone. The scope of this reaction was explored using various tetrazoles and pyrazines. Materials produced were identified using chemical analytical techniques and computationally studied for potential application as an insensitive energetic material.

A new Schiff base 2-benzoylpyridine-based copper complex on boehmite nanoparticles as a recoverable nanocatalyst for the homoselective synthesis of 5-substituted tetrazoles.

In this study, boehmite nanoparticles (B-NPs) were prepared by a simple process and then their surface was modified by (3-aminopropyl)triethoxysilane (3-APTES). The modified B-NPs (3-APTES@B-NPs) were functionalized by 2-benzoylpyridine Schiff-base ligand toward the immobilization of the Schiff-base 2-benzoylpyridine ligand on the 3-APTES@B-NPs's surface (2BP-Schiff-base@B-NPs). Finally, copper ions were coordinated with the supported Schiff-base ligand on B-NPs toward the formation of the final catalyst (Cu-2BP-Schiff-base@B-NPs). The prepared Cu-2BP-Schiff-base@B-NPs were characterized using FT-IR spectroscopy, BET analysis, XRD, SEM, AAS, TGA, EDX and elemental mapping. Further, Cu-2BP-Schiff-base@B-NPs were applied as a homoselective and recyclable catalyst for the synthesis of a diverse range of 5-substituted tetrazoles in PEG-400 as a green solvent. The main benefits of this protocol are high homoselectivity attributes, short reaction times, high product yields and TOF values, and further addition to the catalyst ability to be recycled at least four times without significantly losing catalytic efficiency.

5-Aminotetrazoles – An Overview of Synthetic Methodologies through the Desulfurization of Thioureas

Abstract: Tetrazoles are important heterocycles in diverse branches of chemistry. Among the 5-substituted tetrazoles, the 5-amino derivatives are the most important by far as they show high chemical versatility and relevant applications in material chemistry, catalysis, agrochemistry, etc. Particularly in medicinal chemistry, they present a wide range of pharmacological properties. In the present review, we focus on the synthesis of 5- aminotetrazol from the desulfurization processes of thioureas using metal salts, hypervalent iodine compounds and halogenated reagents.

Design, synthesis and biological evaluation of novel lipophilic 2, 5-disubstituted tetrazole analogues of muramyl dipeptide as NOD2 agonists

A focused library of six new 2, 5-disubstituted tetrazole (2, 5-DST) analogues of N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) as potential immunomodulators were synthesized by the bioisosteric replacement of α-amide of d-isoglutamine with 5-substituted tetrazole (5-ST). Another parameter ‘lipophilicity’ was also considered to improve the pharmacological properties of MDP through the alkylation of 5-substituted tetrazole during synthesis. In total, six 2, 5-DST analogues of MDP were synthesized and bio-evaluated for the study of human NOD2 stimulation activity in the innate immune response. Interestingly, among the varied lengths of the alkyl chain in 2, 5-disubstituted tetrazole derivatives, the tetrazole analogues 12b bearing the -Butyl (C4) and 12c having -Octyl (C8) chain showed the best NOD2 stimulation potency equivalent with reference compound MDP. These analogues were evaluated for their adjuvanticity against dengue antigen and analogues 12b and 12c have elicited a potent humoral and cell mediated response.

Efficient synthesis, molecular docking and ADMET studies of new 5-substituted tetrazole derivatives

In the present study, novel 5-substituted tetrazole derivatives bearing the sulfonamide group were synthesized using an azide-nitrile cycloaddition reaction. The easy availability of the inexpensive starting materials, avoiding isolation and handling of hazardous organic azide, and mild reaction conditions make this synthetic protocol a valuable tool for the synthesis of functionalized tetrazole derivatives. All reactions proceeded smoothly to achieve the corresponding 5-substituted tetrazole derivatives 5a-f in moderate to good yields (32-85%) using ZnBr2 as a catalyst and green solvent system H2O/2-propanol. The structure of all products was confirmed by FT-IR, 1HNMR, and 13CNMR analysis. Furthermore, we used molecular docking and ADMET studies to investigate the possible drug-likeness of the synthesized molecules 5a-f, revealing that some molecules are the most promising drug-like molecules out of the seven synthesized molecules. Antifungal activity of the compound 5c against standard strains of pathogenic fungi was also investigated in the final section of study.

L-proline catalyzed ring transformation of 5-substituted tetrazole to 1,3,4-oxadiazoles as anti-tubercular agents

An innovative class of novel 2-aryl-5-(1-aryl-1H-pyrazol-3-yl)-1,3,4-oxadiazoles 5i–w have been synthesized from ring transformation using L-proline as an organocatalyst. This novel method using organocatalyst is a splendid example of the green reaction with improved yields. The molecular docking analysis of compounds 5i–w were investigated with enoyl-acyl carrier protein reductase (InhA) enzyme (PDB ID: 4TZK) as anti-tubercular target molecules. The docking study implied that the synthesized compounds exhibited favorable binding modes and affinity. Further, the anti-tubercular activity was investigated against Mycobacterium tuberculosis (MTB) H37Rv strain which demonstrated that the compounds 5i, 5j, 5k, and 5l exhibited excellent activity at the 6.25 µg/ml concentrations, whereas the compounds 5m, 5n, 5o, 5s, and 5w have shown the activity at 12.50 µg/ml concentration, respectively.

Ultrasound and microwave irradiated sustainable synthesis of 5- and 1-substituted tetrazoles in TAIm[I] ionic liquid

Ultrasound and microwave irradiated sustainable synthesis of 5- and 1-substituted tetrazoles in TAIm[I] ionic liquid

Synthesis of 5-Substituted Tetrazoles: Reaction of Azide Salts with Organonitriles Catalyzed by Trialkylammonium Salts in Non-polar Media

Synthesis of 5-Substituted Tetrazoles: Reaction of Azide Salts with Organonitriles Catalyzed by Trialkylammonium Salts in Non-polar Media

Practical synthesis of tetrazoles from amides and phosphorazidates in the presence of aromatic bases

Tetrazoles were effectively synthesized from amides using diphenyl phosphorazidate or bis(p-nitrophenyl) phosphorazidate in the presence of aromatic bases. Various amides underwent the proposed cycloaddition reaction to provide the corresponding tetrazoles. Studies on the racemization of chiral substrates were also performed. Overall, the proposed synthesis method enables the preparation of 1,5-disubstituted and 1-substituted tetrazoles, and 5-substituted 1H-tetrazoles without using toxic or explosive reagents.

Synthesis of some new organotellurium compounds based on 1-substituted tetrazole

New organotellurium compounds are derived from 1-butyl-5H-tetrazole (1). 1-butyl tetrazole-5-yl mercury (II) chloride (2) was synthesized from the reaction of compound 1 with mercury acetate and sodium chloride. The 1:1 and 1:2 ratio reactions of tellurium tetrabromide with compound 2 gave 1-butyl tetrazole-5-yl tellurium tribromide (3) and di (1-butyl tetrazole-5-yl) tellurium dibromide (4), respectively. The reduction of compounds 3 and 4 by the alcoholic solution of aqueous hydrazine gave di (1-butyl tetrazole-5-yl) ditelluride (5) and di (1-butyl tetrazole-5-yl) telluride (6), respectively. The reaction of compound 5 with iodine and thionyl chloride gave 1-butyl tetrazole-5-yl tellurium triiodide (7) and 1-butyl tetrazole-5-yl tellurium trichloride (8), respectively. The reaction of compound 6 with iodine and thionyl chloride gave di (1-butyl tetrazole-5-yl) tellurium diiodide (9) and di (1-butyl tetrazole-5-yl) tellurium dichloride (10), respectively. The prepared compounds were characterized and the molar conductivities proved that the compounds 2–3 and 7–10 behaved as electrolytes (1:1).

UV-Induced 1,3,4-Oxadiazole Formation from 5-Substituted Tetrazoles and Carboxylic Acids in Flow.

A range of 1,3,4‐oxadiazoles have been synthesized using a UV‐B activated flow approach starting from carboxylic acids and 5‐substituted tetrazoles. The application of UV light represents an attractive alternative to the traditional thermolytic approach and has demonstrated comparable efficiency and versatility, with a diverse substrate scope, including the incorporation of highly substituted amino acids.

Alkylation of 5-Substituted Tetrazoles with Various Alcohols in 1,2-Dichloroethane in the Presence of BF3·Et2O

The alkylation of 1H-tetrazole, 5-methyl-1H-tetrazole, and 5-phenyl-1H-tetrazole with primary, secondary, and tertiary alcohols, including benzylic and allylic ones, have been studied in 1,2-dichloroethane in the presence of boron trifluoride–diethyl ether complex. Neither primary nor secondary saturated alcohols alkylated tetrazoles in the given system. Tertiary alcohols such tert-butyl alcohol and adamantan-1-ol reacted with unsubstituted and 5-substituted tetrazoles to give 70–85% of the corresponding 2-alkyl-5-R-tetrazoles with high regioselectivity. The alkylation of 1H-tetrazole with benzyl alcohol afforded 55% of 2-benzyl-2H-tetrazole as the only product. The alkylation of 1H-tetrazole with various allylic alcohols led to the formation of mixtures of 2-alkyl-2H-tetrazoles with isomeric alkyl substituents.

Cobalt-Catalyzed Hydroamination of Alkenes with 5-Substituted Tetrazoles: Facile Access to 2,5-Disubstituted Tetrazoles and Asymmetric Intermolecular Hydroaminations.

Herein, we describe a novel synthetic method for 2,5-disubstituted tetrazoles from 5-substituted tetrazoles using cobalt-catalyzed intermolecular hydroamination reaction of nonactivated olefins. Owing to its mild conditions, the method enabled the use of substrates having acid-labile functional groups, such as silyloxy and methoxymethyloxy groups. By using optically active cobalt complexes, asymmetric intermolecular hydroamination of nonactivated olefins, a longstanding challenge in synthetic organic chemistry, was developed to produce optically active disubstituted tetrazoles.

5-Aryltetrazoles from Direct C-H Arylation with Aryl Bromides.

A mild, direct C-H arylation of 1-substituted tetrazoles to 5-aryltetrazoles is developed using a Pd/Cu cocatalytic system with readily available aryl bromides. The methodology avoids late-stage usage of azides and tolerates a wide range of functionalities.

Diphenyl phosphate creatine immobilized on magnetite nanoparticles: an efficient and recyclable catalyst for Aza-Michael reaction

In this paper, diphenyl phosphate creatine was successfully immobilized on Fe3O4 nanoparticles and used as the highly efficient catalyst for the aza-Michael reaction of 5-substituted tetrazole and α,β-unsaturated carbonyl. The prepared nanocatalyst was fully analyzed by various techniques such as Fourier-transform Infrared Spectroscopy (FT-IR), Field Emission Scanning electron microscope (FE-SEM), Vibrating Sample Magnetometer (VSM), Thermal Gravimetric Analysis (TGA) and X-ray Diffraction (XRD). This procedure possesses numerous advantages such as simple work-up, high yield and short reaction times. This paper discusses a method for the synthesis of substituted tetrazoles via aza-Michael reaction using Fe3O4@Diphenyl phosphate creatine nanoparticles as a new catalyst.

Synthesis of 5-substituted tetrazoles via DNA-conjugated nitrile.

A zinc bromide-catalyzed synthesis of 5-substituted tetrazoles via DNA-conjugated nitriles using sodium azide has been developed. The protocol offered moderate to excellent yields of tetrazoles with a broad range of substrates, including a variety of functionalized aromatic, heterocyclic, and aliphatic nitriles. In addition, the electronic effect within the substrate scope was evaluated. DNA fidelity was assessed by ligation efficiency and amplifiability analysis. The ability to generate tetrazoles expands the diversity of heterocycles in the preparation of DNA-encoded chemical libraries.

Survey reactivity of 5-substituted tetrazoles toward pentafluoropyridine

Reactivity of some 5-substituted tetrazoles with pentafluoropyridine under basic conditions in acetonitrile was investigated. The reaction of pentafluoropyridine with tetrazoles regioselectively occurs at the 4-position of pyridine ring by N2 in the tetrazole ring. Tetrazoles with substituents at the position 5 such as Ph, 4-NO2C6H4, 4-CF3CONHC6H4, 4-ClC6H4CH2, EtOOCCH2, and 5-tetrazolyl−CH2 gave products containing unchanged tetrazole moiety. In contrast, tetrazole with substituents at the position 5 such as 3-(5-tetrazolyl)C6H4, 4-MeOC6H4, and 3-CF3CONHC6H4, gave hydrazide products via degradation of tetrazole ring.

Synthesis of 1-Substituted 1H-1,2,3,4-Tetrazoles Using Biosynthesized Ag/Sodium Borosilicate Nanocomposite.

An expedient solvent-free methodology has been developed to produce 1-substituted 1H-1,2,3,4-tetrazoles using sodium borosilicate glass-supported silver nanoparticles (Ag NPs) as a novel heterogeneous catalyst. A cost-efficient, facile, and greener method was deployed for the creation of Ag/sodium borosilicate nanocomposite (ASBN) catalyst by using Aleurites moluccana leaf extract as a stabilizing and reducing agent. The ASBN catalyst was identified using the latest microscopic and spectroscopic techniques such as FT-IR, TEM, FESEM, XRD, EDS, and elemental mapping. The deployment of this new catalyst enables the preparation of assorted 1-substituted tetrazoles in good to high yields via an easy work-up procedure in a relatively short reaction time under environmentally friendly conditions without using harmful and toxic reducing agents. The ASBN catalyst can be recycled and reused multiple times without meaningful loss of activity. To extend the application of the ASBN, the performance of the quantitative structure–activity relationships model was investigated for protein binding and toxicity hazard considerations.

Regioselective Alkylation of 5-Substituted Tetrazoles with 3-Chlorobut-2-en-1-ol in Acid Medium

The alkylation of 5-R-tetrazoles (R = H, Me, Ph) with 3-chlorobut-2-en-1-ol was studied in 1,2-dichloroethane, chlorofom, and methylene chloride in the presence of boron trifluoride—diethyl ether complex, as well as in trifluoroacetic acid and in ethyl acetate in the presence of sulfuric acid. The reaction in 1,2-dichloroethane catalyzed by BF3 · Et2O gave 70–80% of the alkylation products containing no less than 99% of the 2-substituted isomer.