Acyl and Sulfonyl Derivatives of 3,5-Diamino-1-R-1,2,4-triazoles

3-Acylamino-5-amino-1-R-1,2,4-triazoles are formed regioselectively on acylating 3,5-diamino-1-R-1,2,4-triazoles with an equimolar amount of anhydrides, carboxylic acid chlorides, and sulfonyl chlorides. With an excess of anhydride and carboxylic acid chloride 3,5-diacylamino-1-R-1,2,4-triazoles are formed. 3-Acylamino-5-amino-1-R-1,2,4-triazoles do not interact with sulfonyl chlorides. The higher reactivity of the 3-amino group towards acylating agents is determined by electronic and not steric factors. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1342–1350, September, 2005.     

Efficient in Situ Synthesis of 3,5-Disubstituted-1,2,4-triazoles Under Microwave-Assisted Conditions

Based on an efficient in situ metal/ligand reaction, a serial of 3,5-disubstituted-1,2,4-triazoles were synthesized via cycloaddition of organonitriles and ammonia under microwave conditions. This synthetic protocol provides a concise and high-yield access to 3,5-disubstituted-1,2,4-triazoles in organic synthesis. Moreover, the tautomerism of the product was also investigated.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resources: Full experimental and spectral details.]     

Facile synthesis of 3,5-diaryl-1,2,4-triazoles via copper-catalyzed domino nucleophilic substitution/oxidative cyclization using amidines or imidates as substrates

Two methods for the synthesis of 3,5-diaryl-1,2,4-triazoles, both domino reactions, are reported. The first procedure, the Cu(OTf)₂-catalyzed reaction between two amidines using NaHCO₃ as a base, 1,10-phenanthroline as an additive and K₃[Fe(CN)₆]/atmospheric oxygen as the oxidant, delivers 3,5-diaryl-1,2,4-triazoles with yields up to 68%. The second procedure for the synthesis of 3,5-diaryl-1,2,4-triazoles with yields up to 64% rests on the Cu(OTf)₂-catalyzed reaction between two imidates and ammonium carbonate. This method features the formation of three bonds in a single synthetic step.     

Synthesis of 1,3,5-trisubstituted 1,2,4-triazolio-4-nitroimides

A method for the synthesis of 1,3,5-trisubstituted 1,2,4-triazolio-4-nitroimides was developed. The method is based on the alkylation of the corresponding salts of 3,5-disubstituted 4-nitramino-1,2,4-triazoles.     

A novel method for the synthesis of 3,5-disubstituted-(NH)-1,2,4-triazoles from 3,6-diaryl-1,2,4,5-tetrazines

The reaction of 3,6-diaryl-1,2,4,5-tetrazines and 2-aryl substituted acetonitriles, under basic conditions, leads unexpectedly to 3,5-diaryl-(NH)-1,2,4-triazoles in moderate yields. A mechanism is proposed.     

Reaction of thiosemicarbazide with n-cyanoguanidine: synthesis of 3,5-diamino-1-thiocarbamoyl-and 3,5-diamino-1-thiazol-2-yl-1,2,4-triazoles

The reaction of thiosemicarbazide with N-cyanoguanidine in an acidic medium afforded 3,5-diamino-1-thiocarbamoyl-1,2,4-triazole, whose condensation with α-halo ketones gave 3,5-diamino-1-thiazol-2-yl-1,2,4-triazoles 7a–d. The latter were also prepared by the independent synthesis from 2-hydrazinothiazoles and N-cyanoguanidine. Acylation of compounds 7a,d under mild conditions and their condensation with aldehydes occur at the C(3′)NH₂group. The structure of aroyl derivative 11c was established by X-ray diffraction. Acylation of diaminothiazolyltriazole 7a in boiling Ac₂O afforded 3,5-diacetylamino-1-(4-phenylthiazol-2-yl)-1,2,4-triazole. Hydrogenation of arylidene derivatives 14b,c and aroyl derivative 11c gave the corresponding benzylaminotriazoles 15a,b. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 329–334, February, 2006.     

Reaktionen vonN-Sulfinylverbindungen mit dem 1,2,4-Trithia-3,5-diborolan-Ringsystem und Substitutionsreaktionen am 1,2,4-Trithia-3,5-diborolan und 1,2-Dithia-4-aza-3,5-diborolidin

The reaction of trimethylsilyl- and pentafluorophenyl-N-sulfinylamine respectively with 3,5-dihalogeno-1,2,4-trithia-3,5-diborolanes yields the 1,2-dithia-4-aza-3,5-diborolidines1-3.Tert-butyl-N-sulfinylamine and 3,5-dimethyl-1,2,4-trithia-3,5-diborolane react analogous. OtherN-sulfinylamines however split the disulfane bridge in 3,5-dimethyl-1,2,4-trithia-3,5-diborolane and the 1,4-dithia-2-aza-3,5-diborolidines5A-7(A) are formed. Besides of boroxines, cyclo-2,4,6-trimethyl-1,3-dioxa-5-aza-2,4,6-triboranes and cyclo-2,4,6-trimethyl-1-oxa-3,5-diaza-2,4,6-triboranes are formed as byproducts,8–10 have been isolated. In 1,2,4-trithia-3,5-diborolanes and 1,2-dithia-4-aza-3,5-diborolidines the bromo-atoms can be substituted by alkyl (13, 14), by amino (15–20) and by isothiocyanato groups. The compounds were characterised analytically and spectroscopically (MS; NMR:¹H,¹¹B,¹⁹F,²⁹Si; IR).

     

A novel traceless route to synthesize 3,5-disubstituted-1,2,4-triazoles on PEG6000

A novel traceless route to 3,5-disubstituted-1,2,4-triazoles has been described, which allows the incorporation of two elements of diversity. This method provided a library of 3,5-disubstituted-1,2,4-triazoles with high yields and purity.     

Reactions of 4-Aryl-1,2,4-triazolidine-3,5-dithione with Some Electrophilic Reagents

Reaction of 4-aryl-1,2,4-triazolidine-3,5-dithiones in an alkaline medium with chloroacetic acid and its derivatives, as well as with -bromo ketones, results in their conversion to 4-aryl-1,2,4-triazole-3,5-bis(sulfides). The aminomethylation in a neutral medium leads to the formation of 1-(aminomethyl)-4-aryl-1,2,4-triazolidine-3,5-dithiones.     

Alkylation of acyl and sulfonyl derivatives of 3,5-diamino-1-phenyl-1,2,4-triazole

Alkylation of 3-acylamino-, 5-amino-1-phenyl-3-tosylamino-1,2,4-triazoles and 3,5-diacetylamino-1-phenyl-1,2,4-triazole in the presence of an equimolar amount of sodium methylate in DMSO occurs regioselectively at the amide (sulfamide) group nitrogen atom. The benzylation of 3-acetylamino-5-amino-1-phenyl-1,2,4-triazole with excess base and benzyl chloride also alkylates the amino group at position 5. Alkylamino-1-R-1,2,4-triazoles can be conveniently prepared by alkylation of the corresponding acetylamino-1,2,4-triazoles in the presence of base and subsequent acid hydrolysis of the N-acetyl-N-alkyl derivatives. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 557–567, April, 2009.     

Heterocyclic Synthesis Using Nitrilimines,Part 12: Synthesis and Bioactivity of 5-Carboxymethylthio-1,2,4-triazoles

The reaction of 4-amino-5-phenyl-3,5-thiaaza-4-pentenoic acid 3 with various nitrilimines 2 led to the formation of substituted carboxymethylthio derivatives of 1,2,4-triazoles (4a–l) rather than the amino derivatives 5 or imidazole derivatives 6. The spectral data of the synthesized compounds are in full agreement with its molecular structure.     

A base-catalyzed, direct synthesis of 3,5-disubstituted 1,2,4-triazoles from nitriles and hydrazides

A convenient and efficient one step, base-catalyzed synthesis of 3,5-disubstituted 1,2,4-triazoles by the condensation of a nitrile and a hydrazide is presented. A diverse range of functionality and heterocycles are tolerated under the reaction conditions developed, and the reactivity of the nitrile partner is relatively insensitive to electronic effects.     

‘One-flask’ synthesis to 3,5-disubstituted 1,2,4-triazoles from aldehydes with hydrazonoyl hydrochlorides via 1,3-dipolar cycloaddition

A new ‘one-flask’ synthesis of 3,5-disubstituted 1,2,4-triazoles has successfully been developed to synthesize a series of 3,5-disubstituted 1,2,4-triazoles. The transformation involves the 1,3-dipolar cycloaddition reaction of hydrazonoyl hydrochlorides with oxime intermediates prepared from aldehydes with hydroxylamine hydrochloride in the presence of excess amount of triethylamine. In this ‘one-flask’ 1,3-dipolar reaction, hydrazonoyl hydrochlorides was concerned as the masked 1,3-dipole nitrilimine under basic condition. Furthermore, this newly developed methodology can be applied to various aldehyde substrates including aliphatic, cyclic aliphatic, aromatic, and heterocyclic aldehydes.     

A convenient synthesis of 4-amino-3,5-dialkyl-4H-1,2,4-triazoles

Ester tert-butoxycarbonylhydrazones 2 were reacted with some carboxylic acid hydrazides to give 4 -terrtutoxycarbonylamino-3,5-dialkyl-4H-1,2,4-triazoles 3–6 . Treatment of 3–5 with 6 N hydrochloric acid under mild conditions resulted in the formation of 4-ammo-3,5-dialkyl-4H-1,2,4-triazole hydrochlorides 7–9 in good yields. Compound 7a was converted to the free 4 -amino compound 10a upon treatment with ethanolic sodium ethoxide solution.     

A simple one step synthesis of new 3,5-disubstituted-4-amino-1,2,4-triazoles

A number of symmetrically 3,5-disubstituted 4-amino-1,2,4-triazoles have been prepared by the reaction of aromatic nitriles with hydrazine dihydrochloride or sulfate with an excess of hydrazine hydrate in ethyl ene or diethylene glycol under a nitrogen atmosphere. The structures of the new triazoles derivatives were confirmed by analytical and spectral data.     

Synthesis of 3,5-disubstituted 1,2,4-triazoles containing an amino group

3,5-Disubstituted 1,2,4-triazoles containing linear and cyclic amine fragments have been synthesized by thermal cyclization of N′-(1-iminoalkyl) hydrazides prepared by condensation of imido esters with carboxylic acid hydrazides. The initial imido esters have been synthesized by the Pinner reaction, as well as by reaction of nitriles with methanol in the presence of a catalytic amount of sodium methoxide. A procedure has been developed for the synthesis of 5-substituted 3-(3-nitrophenyl)-1,2,4-triazoles which have been converted to 3-aminophenyl derivatives by reduction with hydrazine hydrate over Raney nickel.     

Polymer-supported 1,3-oxazolium-5-olates: synthesis of 1,2,4-triazoles

A traceless synthesis of 3,5-disubstituted 1,2,4-triazoles has been developed on polymeric supports. The synthetic process utilizes immobilized mesoionic 1,3-oxazolium-5-olates (munchnones) as key intermediates in the 1,3-dipolar cycloaddition reaction. The initial step in the synthesis involves reductive alkylation of phenylglycine methyl esters with Ameba resin. The resulting immobilized amino acid esters were subsequently acylated with a variety of carboxylic acid chlorides and subjected to hydrolysis with 15% KOH to yield the polymer-bound carboxylic acids. Finally, the cycloaddition between diethyl diazocarboxylate or 4-phenyl-4H-1,2,4-triazoline-3,5-dione and the polymer-bound munchnones generated from the corresponding carboxylic acids afforded the polymer-bound 3,5-disubstituted 1,2,4-triazoles. Cleavage from the polymeric support using trifluoroacetic acid gave the desired 3,5-disubstituted 1,2,4-triazoles with excellent yield and high purity.     

A convenient synthesis of 3,5-disubstituted-1,2,4-triazoles

The condensation of an acyl hydrazide and an amidine to afford an acylamidrazone, followed by thermal cyclization, provides a convenient method for preparing 3,5-disubstituted-1,2,4-triazoles in high yields.     

The reaction of aroylhydrazines with N-phenylsulfonylarenehydrazonoyl chlorides. A route to substituted 4-amino-(4H)-1,2,4-triazoles and 1,3,4-oxadiazoles

Treatment of N-phenylsulfonylarenehydrazonoyl chlorides (II) with equivalent amounts of aroylhydrazines (III) in ethanol gave 3,5-diaryl-4-phenylsulfonylamino-1,2,4-triazoles (IV). Reaction of II with two equivalents of III in tetrahydrofuran gave 2,5-diaryl-1,3,4-oxadiazoles (V), in addition to IV. Addition of triethylamine to II or its mixture with III yielded only the tetrazenes (VIII). The possible pathways leading to IV-V and VIII are discussed. J. Chem. Soc., 14, 1089 (1977)     

Heterocyclic nitro compounds. 26. Reaction of 1-substituted 3,5-dinitro-1,2,4-triazoles with anions of heterocyclic NH acids

1-Substituted 3-nitro-5-(N-azolyl)-1,2,4-triazoles mixed with 1-substituted 3-nitro-1,2,4-triazol-5-ones are obtained in the reaction of 1-substituted 3,5-dinitro-1,2,4-triazoles with anions of heterocyclic NH acids (1,2,4-triazole, 1,2,3-triazole, pyrazole, benzotriazole, benzimidazole, and indazole derivatives). 1-Methyl-3-nitro-5-amino-1,2,4-triazole is formed instead of the expected 5-tetrazolyl derivative in the reaction of 1-methyl-3,5-dinitro-1,2,4-triazole with tetrazole in alkaline media. See [1] for communication 25. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 257–261, February, 1980.