Isocyanide-based four-component synthesis of 1,3-indandionylamidinium betaines

An efficient approach for the synthesis of novel 1,3-indandionylamidinium betaines via four-component reaction of 1,3-indandione, aldehydes, amines, and isocyanides, without assistance of any catalyst and under mild reaction conditions has been reported. The structures of these compounds were confirmed by IR, mass spectroscopic, ¹H NMR, ¹³C NMR, and single-crystal X-ray diffraction studies.     

A novel synthesis of 1,5-disubstituted fluorinated tetrazoles from 1,1-difluoroazides

A new one-step reaction between 1,1-difluoroazides and primary amines is reported as an efficient synthetic approach for tetrazole formation. Examples include the syntheses of fluorine-containing 1,5-substituted tetrazoles from three fluorinated azide precursors and various amines. Greater substituent diversity in comparison with conventional methods is achieved.     

A two-step synthesis of 1,5-disubstituted tetrazoles containing a siloxy or sulfonamide group

A simple two-step route to the synthesis of 1,5-disubstituted tetrazoles containing a β-siloxy or β-sulfonamide group is presented. The synthesis takes place via an isocyanide-based multicomponent reaction and allows incorporation of a wide variety of substitution patterns starting from commercially available reagents. This is followed by cyclization of the ketenimines with trimethylsilyl azide without using any catalyst or activation.     

A simple four-component synthesis of ferrocenyl amidodiesters and ferrocenyl triamides

Ferrocenyl amidodiesters and ferrocenyl triamides were synthesized in good yields by a four-component reaction of ferrocenecarboxaldehyde, isocyanides, Meldrom’s acid and alcohols or amines in CH₂Cl₂ at room temperature.     

Preparation of highly functionalized 1,5-disubstituted tetrazoles via palladium-catalyzed Suzuki coupling

The preparation of a range of 1,5-disubstituted tetrazoles has been achieved through palladium-catalyzed Suzuki coupling. Using appropriately substituted 5-p-toluenesulfonyltetrazoles as substrates (obtained by cycloaddition of a substituted azide with p-toluenesulfonyl cyanide), this methodology provides access to a variety of highly substituted tetrazoles that would be difficult to access otherwise. The procedure is compatible with functional groups commonly found in drug-like molecules, and has been used to generate a number of compounds of potential biological interest.     

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.     

Improved conditions for converting sterically hindered amides to 1,5-disubstituted tetrazoles

Improved conditions for converting amides into 1,5-disubstituted tetrazoles are described. The optimum reaction conditions [diisopropyl azodicarboxylate (DIAD), diphenylphosphoryl azide (DPPA), and diphenyl-2-pyridyl phosphine in THF at 45 °C] converted sterically hindered amides to their corresponding tetrazoles in good yield.     

Mass spectral fragmentation of 1,5-disubstituted tetrazoles and rearrangement of the resulting nitrenes

In agreement with the thermolysis characteristics of 1,5-disubstituted tetrazoles, the fragmentation pattern of 1-(o-, m-, and p-tolyl)-5-phenyltetrazoles has been shown to consist of a sequence of reactions, namely, initial tautomeric conversion to an azide structure, followed by elimination of a molecule of nitrogen, and rearrangement of the resulting nitrene intermediate to a cation-radical derivative of a methyl-substituted 2-phenylbenzimidazole compound. In the case of 1-(o-tolyl)-5-phenyltetrazole an alternative pathway is observed, involving cyclization of the nitrene intermediate at the methyl group (an insertion reaction into a C-H bond) to form dihydroquinazoline derivatives. An analogous cyclization process has been noted for the thermolysis process as well.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 925–930, July, 1988.     

Synthesis of 1,5-disubstituted tetrazoles via Suzuki-Miyaura cross-coupling of 5-chloro-1-phenyltetrazole

Suzuki-Miyaura coupling reactions of 5-chloro-1-phenyl-tetrazole with various functionalized arylboronic acids were investigated. In the presence of catalytic amounts of SPhos/Pd(OAc)₂ or RuPhos/Pd(OAc)₂, the reaction proceeded smoothly to afford 1,5-diaryltetrazoles in good to excellent yields.     

Mechanism of the monomolecular thermal decomposition of 1,5- and 2,5-disubstituted tetrazoles

The kinetic parameters of the thermal decomposition of several pairs of 1(2)-R-5-R-disubstituted tetrazoles have been determined using the manometric method. The isomers differ only by the position of the substituents linked with the heterocyclic nitrogen atom. The activation entropies are equal to ca. +8 cal mol^–1 K^–1, the activation energies range from 39 to 48 kcal mol^–1. A linear correlation between the logarithms of the rate constants of decomposition of the isomers has been established. The limiting stages of the stepwise mechanism of the monomolecular decomposition, which determines the experimental rates of nitrogen evolution, include the reversible formation followed by decomposition of intermediate azidoazomethines in the case of 1,5-disubstituted tetrazoles and azodiazo compounds for isomeric 2,5-disubstituted tetrazoles. The enthalpies of formation of R(N₃)C=NR (R = Me, Ph), C₂H₃(N₃)C=NMe and increments _f H°[C_d–(C)(N₃)], _f H°[C_d-(C_b)(N₃)], and _f H°[C_d–(C_d)(N₃)] have been estimated.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2209–2215, September, 1996.     

A simple synthesis of ferrocenyl bis-amides by a Ugi four-component reaction

An efficient and simple synthesis of ferrocenyl bis-amides by the Ugi four-component reaction of ferrocenecarboxaldehyde, carboxylic acids, isocyanides and amines in methanol at room temperature is reported.     

Regioselective synthesis of 2,8-disubstituted 1,5-diphenylglycolurils

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Solid-phase synthesis of 1,5-disubstituted 2-aryliminoimidazolidines

The solid-phase synthesis of 1,5-disubstituted 2-aryliminoimidazolidines, starting from resin-bound N-acylated amino acid amides, is described. Exhaustive reduction of resin-bound acylated amino acid amides with borane-THF afforded the corresponding disecondary amines. Further reaction with arylisothiocyanates in the presence of mercuric chloride (HgCl(2)) yielded the corresponding resin-bound 1,5-disubstituted 2-aryliminoimidazolidines. Cleavage of the product from the resin using HF/anisole (95/5) for 1.5 h at 0 degrees C gave the desired products in good yield and purity. The preparation of a large combinatorial library of such compounds is also discussed.     

Metal triflate catalyzed reactions of alkenes, NBS, nitriles, and TMSN3: synthesis of 1,5-disubstituted tetrazoles

A versatile and highly efficient protocol for the synthesis of 1,5-disubstituted tetrazoles has been developed by metal triflate catalyzed one-pot reaction of alkenes, NBS, nitriles, and TMSN3. Among the metal triflates, Zn(OTf)2 was found to be the best catalyst. Use of different combinations of alkenes and nitriles generate a variety of 1,5-disubstituted tetrazoles containing an additional alpha-bromo functionality of the N1-alkyl substituent.     

Synthesis of bis(1,5-disubstituted tetrazoles) via double four component Azido-Ugi reaction

A double four component Azido-Ugi reaction of isocyanide, TMSN₃, aldehyde, and 4,4′-sulfonyldianiline with two amine functional groups in MeOH at 65°C has been described. The synthesis of pharmacologically and structurally interesting compounds with two 1,5-disubstituted tetrazole rings via a reaction from available and inexpensive reagents under a convenient process and mild reaction conditions has been reported. Modifications in the structure of the reaction product could be followed by varying the aldehyde or isocyanide component. The products are new and were well described by Mass, ¹H NMR, and ¹³C NMR spectral studies.     

Practical synthesis of functionalized 1,5-disubstituted 1,2,4-triazole derivatives

A general approach for the synthesis of 1,5-disubstituted-1,2,4-triazole compounds is described. A series of new oxamide-derived amidine reagents can be accessed in excellent yield with minimal purification necessary. Typically, these amidine reagents are stable crystalline solids and in certain cases were found to exist in a cyclic form as determined by NMR spectroscopy. Under optimized conditions, the direct reaction of these prepared reagents with various hydrazine hydrochloride salts efficiently generates the target triazoles. Both aromatic and aliphatic hydrazines react readily with the amidine reagents under very mild reaction conditions, delivering desired 1,5-disubstituted-1,2,4-triazole derivatives in good yields.     

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.