Synthesis of Nitrogen Heterocycles from Methyl α‐ and β‐d‐Glucopyranosides

Eight nitrogen heterocycles, mono and disubstituted tetrazoles and oxadiazoles, were synthesized from methyl d‐glucopyranoside anomers. The monosubstituted tetrazoles resulted from the reaction of 6‐cyanoglucopyranoside derivatives with sodium azide. By alkylation of the monosubstituted tetrazoles, the 1,5 and 2,5 disubstituted tetrazoles were obtained. The monosubstituted tetrazoles were reacted with acetic anhydride to give the oxadiazoles.     

Azo coupling of benzenesulfonylhydrazones of heterocyclic aldehydes

The reaction of aldehyde phenylsulfonylhydrazones (VII-XI) with diazotized aromatic and heterocyclic primary amines gave the tetrazoles (XIV-XIX). The yield of the tetrazoles was found to depend to some extent on the nature of the substituent present in the aldehyde moiety. The structures of the tetrazoles obtained was established on the basis of their analytical and spectral data. A tentative explanation for their formation is proposed. The acid dissociation constants of the tetrazoles (XIV) were also determined.     

Synthesis and properties of tetrazole-containing oligomers

Linear, star-shaped, and hyperbranched oligomeric compounds containing tetrazole cycles in the main chains are synthesized via the polycondensation (polyalkylation) of N-H unsubstituted bis(tetrazoles), tris(tetrazoles), and tetrakis(tetrazoles) with compounds containing mobile halogen atoms. Some properties of the oligomers are studied. Some of the oligomers are characterized by high density and a large content of nitrogen.     

Efficient synthesis of 2,5-disubstituted tetrazoles via the Cu2O-catalyzed aerobic oxidative direct cross-coupling of N-H free tetrazoles with boronic acids

We present a new protocol that allows for the synthesis of 2,5-disubstituted tetrazoles via the direct coupling of N-H free tetrazoles and low toxic boronic acids in the presence of only a catalytic amount of Cu(2)O (5 mol%) as catalyst and 1 atm of environmentally benign O(2) as oxidant, without the need for other additives. This method represents a simple, green, and atom-efficient synthesis of 2,5-disubstituted tetrazoles.     

Quantum-Chemical Study of the Relative Stability of N-Substituted Tetrazole Isomers

The enthalpies of formation and total energies of a series of 1- and 2-substituted tetrazoles in the gas phase and in solution were calculated by MNDO and AM1 semiempirical methods and by a set of nonempirical procedures. The effect of solvent on the relative stability of N-substituted tetrazoles was estimated in terms of the PCM, SM5, and SCRF models. The possibility for isomerization of N-substituted tetrazoles, depending on the substituent in position 1 or 2, was studied at the MP2/6-31G*//HF/6-31G* level. According to the results of nonempirical calculations, 2-substituted tetrazoles are more stable in the gas phase, in keeping with the experimental data for the corresponding isomers. The solvent nature is an important factor affecting isomerization of N-substituted tetrazoles: Rise in the solvent polarity leads to displacement of the equilibrium toward 1-substituted isomers.     

Synthesis of (difluoroamino)tetrazoles and [(difluoroamino)alkyl]tetrazoles

(Difluoroamino)tetrazoles were obtained by direct fluorination of 5-aminotetrazoles with gaseous fluorine. Reactions of 2-(oxoalkyl)- and 2-(hydroxyalkyl)tetrazoles with difluoroamine yielded [(difluoroamino)alkyl]tetrazoles. Deceased Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 950–952, May, 2000.     

Tetrazoles as carboxylic acid isosteres: chemistry and biology

Tetrazoles are often used as metabolism-resistant isosteric replacements for carboxylic acids in SAR-driven medicinal chemistry analogue syntheses. Tetrazoles have not been found in nature; with rare exceptions, these compounds do not exhibit appreciable biological activity, but they are at the same time resistant to biological degradation. This property makes it possible to use tetrazoles as isosteric substituents of various functional groups in the development of biologically active substances. The tetrazole motif has been used in various drug pharmacophores as a suitable replacement of carboxylic acid moiety and different methods have been used for the synthesis of tetrazoles using different reaction conditions. This review tries to give a vivid look on the different synthetic methods, using catalysts or different reagents for the synthesis of tetrazoles. The biological importance of tetrazoles has also been highlighted.     

Advances in the chemistry of tetrazoles (review)

The review is devoted to the newest advances in the chemistry of tetrazoles. New data on the electronic structures, crystal structures, and dipole moments are presented successively. The electronic, vibrational, NMR, and mass spectra are discussed. Data on the acid-base properties and tautomerism of tetrazoles are presented. Numerous methods for the preparation of tetrazole and mono- and disubstituted tetrazoles are reported. The chemical properties of tetrazoles, viz., electrophilic substitution at the ring carbon atom, nucleophilic substitution, alkylation, electrophilic and nucleophilic substitution in the side chain, and the effect of oxidizing and reducing agents, are discussed. Reactions that lead to cleavage of the tetrazole ring, viz., acylation and thermolysis, are examined separately. New data on the use of tetrazoles in medicine, biology, agriculture, the manufacture of polymeric materials, etc. are presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1299–1326, October, 1981.     

1-Isocyanomethylbenzotriazole and 2,2,4,4-tetramethylbutylisocyanide—cleavable isocyanides useful for the preparation of α-aminomethyl tetrazoles

1-Isocyanomethylbenzotriazole and 2,2,4,4-tetramethylbutylisocyanide smoothly undergo Ugi type reaction toward 1,5-disubstituted aminomethyl tetrazoles and can be subsequently cleaved under acidic conditions yielding substituted α-aminomethyl tetrazoles.     

Tautomerism and acid-base properties of tetrazoles (review)

The prototropic tautomerism and acid-base properties of tetrazoles are discussed in this review. Major attention is directed to the factors that determine the state of the tautomeric equilibria, the acidities and basicities of tetrazoles, and the reactivities of tetrazoles. The available data are interpreted from the point of view of quantum-chemical calculations and modern concepts regarding the behavior of weak organic bases in solutions of acids.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 867–879, July, 1980.     

Mass spectrometry of methyltetrazoles

The mass spectra of tetrazole, all isomers of monomethyl- and dimethyltetrazole, several trifluoromethyl substituted tetrazoles, as well as deuterated analogs, were recorded. Loss of N₂ was the important fragmentation of the molecular ions of tetrazole and 2-methyl substituted tetrazoles; however, HN₂ loss was more important for 1-methyl substituted tetrazoles. The 1-methyl-tetrazoles showed molecular ion peaks while the 2-methyltetrazoles exhibited an unprecedented [M + 1] peak with no molecular ion.     

Stereospecific synthesis of 1,5-disubstituted tetrazoles from ketoximes via a Beckmann rearrangement facilitated by diphenyl phosphorazidate

A novel method for the stereospecific synthesis of 1,5-disubstituted tetrazoles from ketoximes via the Beckmann rearrangement was developed using diphenyl phosphorazidate (DPPA) as both the oxime activator and azide source. Various ketoximes were transformed into the corresponding 1,5-disubstituted tetrazoles with exclusive trans-group migration and no E-Z isomerization of the ketoxime. This method enables the preparation of 1,5-disubstituted tetrazoles without using toxic or explosive azidation reagents.     

Equilibria of the 5-substituted-1,2-acylated tetrazoles and imidoyl azides

Equilibrium of acylated-5-alkyloxy (aryloxy) tetrazoles and acylated-imidoyl azides was measured by (1)H NMR and/or IR spectroscopy. In nonpolar solvents the relatively weakly electron-withdrawing acyl group (CO(2)CH(3)) favored acylation at the 2-position of the 5-substituted tetrazoles. Moderately electron-withdrawing groups (CO(2)CH(2)CCl(3), CO(2)CCl(3)) move the equilibrium to the side of 1-acyl-5-substituted tetrazole. Strong electron-withdrawing groups (CN, SO(2)CH(3), SO(2)CF(3)) favored the formation of the azide. The rate of isomerization of tetrazoles and the azide increases at higher concentrations and polarity of the solvent. In solid phase or in the nonpolar solvent (diethyl ether), only one of the three isomers is present, its structure depending on the nature of the substituents at the 1 or 2 positions of tetrazoles.     

Selective synthesis of binuclear N-substituted tetrazoles and tetrazolium salts

The selective alkylation of mononuclear tetrazoles by 2,5-dimethyl-2,5-hexanediol and of N-unsubstituted binuclear tetrazoles by tert-butyl alcohol was realized in perchloric and sulfuric acids. A series of previously unknown N-substituted binuclear tetrazoles and tetrazolium salts were synthesized. Data from X-ray crystallographic analysis of 2,5-dimethyl-2,5-di(5-phenyl-2-tetrazolyl)hexane are presented.Scientific-Research Institute of Physicochemical Problems, Belorus State University, Minsk; e-mail: fhp@fhp.bsu.unibel.by. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 387–395, March, 2000.     

Prototropic tautomerism of 5‐aryloxy‐1(2)H‐tetrazoles

The structure of 5‐(2,6‐dimethylphenoxy)‐1H‐ and 2H‐tetrazoles together with those of 5‐(2,6‐diisopropyl‐phenoxy)‐1H and 2H‐tetrazoles have been theoretically studied including absolute shieldings and energies. The conclusion of these studies is that a slow tautomerism between 1H‐ and 2H‐tetrazoles cannot explain the experimental observations reported recently in the literature. Copyright © 2012 John Wiley & Sons, Ltd.     

Catalytic Synthesis of 5‐Substituted Tetrazoles: Unexpected Reactions and Products

Tetrazoles are incredibly useful organic molecules with a wide range of applications from medicinal chemistry as carboxylic acid isosteres to high energy density materials in space research. In an effort to develop an easy protocol for the synthesis of tetrazoles from nitriles, we used nano‐Ag‐TiO₂ as an efficient heterogeneous catalyst for the reaction of various nitriles and sodium azide to afford 5‐substituted tetrazoles in excellent yields. By this method, a wide variety of aryl nitriles underwent [3 + 2] cycloaddition to afford tetrazoles in excellent yields. Further reaction of tetrazoles with ethylchloroacetate resulted in the formation of expected products, except for a bis‐tetrazole, which underwent ring opening and subsequent reaction to afford an unusual product. The bis‐tetrazole also formed an unusual polymeric sodium complex in aq. NaOH solution. X‐ray crystallography revealed a distorted octahedral geometry for the complex, which forms a three‐dimensional network of chains interlinked by bis‐tetrazole moieties through a network of H‐bonds.     

Facile,efficient and diastereoselective synthesis of α-hydrazine tetrazoles through a novel one-pot four-component reaction

A novel and efficient method for the diastereoselective synthesis of α-hydrazine tetrazoles via an isocyanide-based multicomponent reaction is reported in good yields. The α-hydrazine tetrazoles were obtained by a facile azide Ugi four-component reaction (U-4CR) using cyclic ketones, trimethylsilyl azide, hydrazides, and corresponding isocyanide without any catalyst and with high bond forming efficiency at room temperature.     

Solid-phase synthesis of 5-biphenyl-2-yl-1H-tetrazoles

The combinatorial synthesis of novel biphenyl tetrazoles is described. Key steps include the simultaneous biphenyl formation and phenol deallylation under Suzuki cross-coupling conditions as well as the tetrazole ring formation on solid support. A representative library of 20 biphenyl tetrazoles was synthesized.     

Synthesis of 1-substituted tetrazoles via the acid-catalyzed [3+2] cycloaddition between isocyanides and trimethylsilyl azide

1-Substituted tetrazoles were synthesized via the [3+2] cycloaddition between isocyanides and trimethylsilyl azide in the presence of an acid catalyst and MeOH. Various 1-substituted tetrazoles were obtained in good to high yields. The reaction probably proceeds through the in situ formation of hydrazoic acid, followed by a successive [3+2] cycloaddition with the isocyanide activated by an acid.