Synthesis and selected transformations of 1-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)ethanones and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl]ethanones

By cycloaddition of arylazides to acetylacetone are obtained derivatives of 1,2,3-triazole. In the reaction of 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] ethanones (VIIa-VIIe) with isatin are obtained 2-[1-(R-phenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-4-quinolinecarboxylic acids (IIIa–IIIe) and 2-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] -4-quinolinecarboxylic acids (IXa, IXb), respectively. We found that 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) readily transform into [5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] acetic acids (IVa–IVc) by the method of Wilgerodt-Kindler. The (5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)acetic acid reacts with 5-phenyl-4-amino-4H-1,2,4-triazol-3-thiol affording 6-[(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl) methyl]-3-phenyl[1,2,4] triazolo[3,4-b] [1,3,4] thiadiazole (VI). Original Russian Text ? N.T. Pokhodylo, R.D. Savka, V.S. Matiichuk, N.D. Obushak, 2009, published in Zhurnal Obshchei Khimii, 2009, vol. 79, no. 2, pp. 320–325.     

7-(2-fluorobenzyl)-4-(substituted)-7-H-imidazo[4,5-d −1,2,3-triazines and −7H-pyrazolo[3,4-d]-1,2,3-triazines. Synthesis and anticonvulsant activity

The imidazo[4,5-d]-1,2,3-triazine and pyrazolo[3,4-d]-1,2,3-triazine analogues of the potent anticonvul-sant purine, BW 78U79 (9-(2-fluorobenzyl)-6-methylamino-9H-purine, 1 ), were synthesized and tested for anticonvulsant activity. The imidazo[4,5-d]-1,2,3-triazines 11–13 were prepared in four steps from 5-aminoimidazole-4-carboxamide (2) and the pyrazolo[3,4-d]-1,2,3-triazines 18–21 were synthesized starting with 5-amino-1-(2-fluorobenzyl)pyrazole-4-carbonitrile (14) . The intermediate 1,2,3-triazin-4-ones 6 and 16 were converted to the 4-substituted targets via the 4-(4-dimethylaminopyridinium) salts 10 and 17 . Imidazotriazine 11 had potent anticonvulsant activity against maximal electroshock-induced seizures, but its propensity to cause emesis precluded further development.     

A tandem of the Cornforth rearrangements of 4-(1,2,3-triazol-1-yl)iminomethyl-1,2,3-thiadiazole

The method for the synthesis of 5-(2,6-dimethylmorpholino)-1,2,3-thiadiazole-4-carbaldehyde was proposed. Its reaction with sodium 1-amino-4-(N-methyl)carbamoyl-1,2,3-triazol-5-olate proceeds through a tandem of the Cornforth rearrangements. The initially formed azomethine isomerizes into sodium 4"-(2,6-dimethylmorpholino)thiocarbonyl-4-(N-methyl)carbamoyl-1,1"-bis[1,2,3]triazolyl-5-olate, which then rearranges to give sodium 4-{N-[4-(2,6-dimethylmorpholinothiocarbonyl)-1,2,3-triazol-1-yl]carbamoyl}-1-methyl-1,2,3-triazol-5-olate.     

Synthesis of [5-(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)-1,3,4-oxadiazol-2-yl]pyridines

2-, 3-, and 4-[5-(1-Aryl-5-R-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazol-2-yl]pyridines were synthesized from the corresponding 1-aryl-5-R-1H-1,2,3-triazole-4-carbonyl chlorides and 2-, 3-, and 4-(1H-tetrazol-5-yl)-pyridines.     

Synthesis and spectroscopic characterization of 1-[1,2,3-triazol-1-yl]-4-aroylazetidin-2-ones

1-(N-Phenacylidene)amino-1,2,3-triazoles 3 react with propionylchloride and phenoxyacetylchloride in the presence of triethylamine to give trans- ( 5 ) and cis- ( 6 ) 1-(1,2,3-triazol-1-yl)-4-aroylaztidin-2-ones in a 1:1 ratio, on the contrary to the 1-(N-arylidene)amino-1,2,3-triazoles, which do not give any reaction product with the same acid chlorides. The spectroscopic characteristics of these new N-triazolyl-β-lactams are also discussed.     

Functionalisation of 1,2,3-triazole via lithiation of 1-[2-(trimethylsilyl)ethoxy]methyl-1H-1,2,3-triazole

The preparation of a number of 5-substituted 1-[2-(trimethylsilyl)ethoxy]methyl-1H-1,2,3-triazoles via reaction of 1-[2-(trimethylsilyl)ethoxy]methyl-1H-1,2,3-triazole with n-butyllithium followed by addition of various electrophiles is reported. Removal of the protecting group by action of diluted aqueous hydrochloric acid or by tetrabutylammonium fluoride in tetrahydrofuran leads to the appropriate 4-substituted 1H-1,2,3-triazoles.     

Synthesis of 6-amino-1,2,3-triazolo[4,5-c] pyridin-4(5H)one (8-aza-3-deazaguanine) and 6-amino-1-(β-D-ribofuranosyl)-1,2,3-triazolo[4,5-c] pyridin-4(5H)one (8-Aza-3-deazaguanosine) via novel ring closure procedures

The total synthesis of 6-amino-1,2,3-triazolo[4,5-c]pyridin-4(5H)one (8-aza-3-deazaguanine, 3 ) and 6-amino-1-(β-D-ribofuranosyl)-1,2,3-triazolo[4,5-c]pyridin-4(5H)one (8-aza-3-deazaguano-sine, 22 ) has been described for the first time by a novel base-catalyzed ring closure of 4(5)-cyanomethyl-1,2,3-triazole-5(4)carboxamide (14) and methyl 5-cyanomethyl-1-(2,3,5-tri-O-ben-zoyl-β-D-ribofuranosyl)-1,2,3-triazole-4-carboxylate (17) , respectively. Under the catalysis of DBU, 2,4-dinitrophenylhydrazone of dimethyl 1,3-acetonedicarboxylate (7) was converted to methyl 5-methoxycarbonylmethyl-1-(2,4-dinitroanilino)-1,2,3-triazole-4-carboxylate (12) via dimethyl 2-diazo-3-iminoglutarate (8) . Catalytic reduction of 12 gave methyl 4(5)methoxycar-bonylmethyl-1,2,3-triazole-5(4)carboxylate (11) from which methyl 4(5)carbamoylmethyl-1,2,3-triazole-5(4)carboxylate (10) was obtained by ammonolysis. Dehydration of 10 provided methyl 4(5)cyanomethyl-1,2,3-triazole-5(4)carboxylate (13) which on amination gave 14 . The 1,2,3-triazole nucleosides 17, 18 and 19 were obtained from the stannic chloride-catalyzed condensation of the trimethylsilyl 13 and a fully acylated β-D-ribofuranose. The yield and ratio of the ribofuranosyl derivatives of 13 markedly depends on the ratio of stannic chloride used. The structures of the nucleosides 22 and 23 were established by a combination of NOE, ¹H-nmr and ¹³C-nmr spectroscopy.     

1,2,3-Selenadiazolyl-1,3,4-oxadiazole, 1,2,3-Thiadiazolyl-1,3,4-oxadiazole and 5-(1,2,3-Thiadiazolyl)-s-triazolo[3,4-b]-1,3,4-thiadiazoles

A series of 5-substituted-2-(4-alkyl or phenyl-1,2,3-thia(or selena)diazol-5-yl)-1,3,4-oxadiazoles were prepared. 5-Substituted-2-(4-phenyl-1,2,3-selenadiazol-5-yl)-1,3,4-oxadiazoles upon pyrolysis afforded the corresponding alkynes. Also, a series of 5-substituted-4-amino-3-(1,2,3-thiadiazol-5-yl)-s-triazoles and 5-(1,2,3-thiadiazolyl)-s-triazolo[3,4-b]-1,3,4-thiadiazoles were prepared.     

Synthesis of 1-(4-methylsulfone-phenyl)-5-(4-fluoro-phenyl)-5-[14C]-1,2,3-triazole and 1-(4-sulfonamide-phenyl)-5-(4-fluoro-phenyl)-5-[14C]-1,2,3-triazole as novel carbon-14 anticonvulsant

Summary Two 1,2,3-triazole anticonvulsants, 1-(4-methylsulfone-phenyl)-5-(4-fluoro-phenyl)-5-[¹⁴C]-1,2,3-triazole and 1-(4-sulfonamide-phenyl)-5-(4-fluoro-phenyl)-5-[¹⁴C]-1,2,3-triazole, both labeled with carbon-14 in the 5-position were prepared from para-fluoro-benzonitrile-[cyano-¹⁴C].     

Synthesis and Some Properties of 2-(5-Methyl-2-Phenyl-2H-1,2,3-Diazaphosphol-4-yl)-4H-Benzo[d]-1,3,2-Dioxaphosphorin-4-One

Abstract

2-(5-Methyl-2-phenyl-2Н-1,2,3-diazaphosphol-4-yl)-4H-benzo[d]-1,3,2-dioxaphosphorin-4-one 1 readily reacts with hexafluoroacetone, mesoxalic acid diethyl ester, trifluoropyruvic acid ethyl ester and chloral to give 2-(5-methyl-2-phenyl-2H-1,2,3-dizaphosphole-4-yl)-derivatives of 1,3,2- and 1,4,2-dioxaphosphepines.     

Identification of 4,5-unsymmetrically substituted l-amino- and 1-(N-arylacetylamino)-1,2,3-triazoles by 13C-NMR

¹³C nmr chemical shifts are used for the structural assignment of isomeric 1-amino-1,2,3-triazoles and 1-(N-arylacetylamino)-1,2,3-triazoles unsymmetrically substituted with phenyl, methyl or hydrogen in the 4,5-positions of the triazole ring. A signal at 11 ± 0.6 ppm indicates a 4-methyl triazole derivative, whereas a signal at 7.9 ± 1 ppm indicates a 5-methyl triazole. A signal at 120 ± 0.5 ppm (C-5) indicates a hydrogen in the 5-position (unsubstituted triazole).     

Studies on Condensed Heterocyclic Compounds XVII. Synthesis of 6-(1-Aryl-5-methyl-1,2,3-triazol-4-yl)-3-phenyl-s-triazolo[3,4-b]-1,3,4-thiadiazoles

Treatment of 4-amino-5-mercapto-3-phenyl-1,2,4-triazole 2 with 1-aryl-4-carboxy-5-methyl-1,2,3-triazoles 1a-1j in a one-step reaction yielded several 6-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-3-phenyl-s-triazolo[3,4-b]-1,3,4-thiadiazoles 3a-3j . The structures of all the products were established on the basis of elemental analyses and spectral data. The fragmentation of the mass spectra of 3a-3j under electron impact was discussed.     

3-Oxy-5-phenyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-4-carboxylic Acid. Synthesis,Structure, and Properties

The structure of 3-oxy-5-phenyl-1H-1,2,3-triazole-4-carboxylic acid was determined both experimentally (by the X-ray diffraction method) and by quantum-chemical calculations. Alkylation of 3-oxy-5-phenyl-1H-1,2,3-triazole-4-carboxylic acid (as crystal hydrate) with methyl iodide, depending on the reactant ratio, gives 1-methoxy-4-phenyl-1H-1,2,3-triazole-5-carboxylic acid and methyl 1-methoxy-4-phenyl-1H-1,2,3-triazole-5-carboxylate. Nitration of the title compound under mild conditions occurs at the 5-phenyl group with formation of meta-nitro derivative, while under more severe conditions 3,5-dinitrobenzoic acid is obtained. 3-Oxy-5-phenyl-1H-1,2,3-triazole-4-carboxylic acid was also converted into the corresponding acid chloride and substituted amide.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 4, 2005, pp. 601–608.Original Russian Text Copyright © 2005 by Shtabova, Shaposhnikov, Mel’nikova, Tselinskii, Nather, Traulsen, Friedrichsen.     

Ring Transformation of 7-Nitro-1-(4-nitrophenyl)-4,5-dihydro-1H-imidazo- and -[1,2,3]triazolo[4,5-c]pyridin-4-ones

Nitration of 1-phenyl-4,5-dihydroimidazo- and -1,2,3-triazolo[4,5-c]pyridin-4-ones initially occurs at the para position of the phenyl ring, and the subsequent nitration yields the corresponding 7-nitro-1-(4-nitrophenyl) derivatives. Treatment of the latter with hydrazine hydrate leads to formation of 1-(4-aminophenyl)-7-methyl-4,5-dihydroimidazo- and -1,2,3-triazolo[4,5-d]pyridazin-4-ones.     

Vinylphosphonium Salt Mediated Facile Synthesis of Trialkyl 4-(2-Quinolyl)-1-cyclobutene-1,2,3-tricarboxylates and Dialkyl 3-Ethoxy-4-oxo-5-(2-(1H)-quinolinylidene)-2-cyclopentene-1,2-dicarboxylates

Summary.  The reactive 1:1 intermediate produced in the reaction between dialkyl acetylenedicarboxylates and triphenylphosphine was trapped by ethyl 3-(1,2-dihydroquinoline-2-ylidene)-pyruvate to yield the isomeric dialkyl 3-ethoxy-4-oxo-5-(2-(1H)-quinolinylidene)-2-cyclopentene-1,2-dicarboxylates and trialkyl 4-(2-quinolyl)-1-cyclobutene-1,2,3-tricarboxylates in nearly 4:1 ratio. Received April 3, 2001. Accepted (revised) May 22, 2001     

Synthesis of 1,2,4- and 1,3,4-oxadiazoles from 1-aryl-5-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-4-carbonyl chlorides

5-Substituted 2-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazoles were synthesized by reaction of 1-aryl-5-methyl-1H-1,2,3-triazole-4-carbonyl chlorides with the corresponding 5-substituted 1H-tetrazoles. 5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl chloride reacted with N′-hydroxybenzimidamides to give 3-aryl-5-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazoles. Reactions of 4-(5-methyl-1H-1,2,3-triazol-1-yl)benzoic acid with N′-hydroxybenzimidamides resulted in the formation of 3-aryl-5-[4-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl]-1,2,4-oxadiazoles.     

The interaction of 2-(5-methyl-2-phenyl-2h-1,2,3-diazaphosphol-4-yl)-4h-benzo[e]-1,3,2-dioxaphosphinin-4-one with activated carbonyl compounds. Synthesis of bis-heterocyclic systems containing di- and tetracoordinated phosphorus

The interaction of 2-(5-methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-4H-benzo[e]-1,3,2-dioxaphosphinin-4-one with mesoxalic and trifluoropyruvic acids ethyl and diethyl esters, hexafluoroacetone and chloral proceeds with an exclusive participation of P(III) atom and allows to obtain 2-(5-methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-derivatives of 1,4,2- and 1,3,2-dioxaphosphepines as well as dichlorovinylphosphonate, being the product of Perkow reaction in the case of chloral.     

One-potCuAAC synthesis of (1H-1,2,3-triazol-1-yl)methyl-1,3,4/1,2,4-oxadiazoles starting from available chloromethyl-1,3,4/1,2,4-oxadiazoles

The one-pot CuAAC synthesis of (1H-1,2,3-triazol-1-yl)methyl-1,3,4-oxadiazole and (1H-1,2,3-triazol-1-yl)methyl-1,2,4-oxadiazole derivatives via three-component reaction of consequent nucleophilic substitution of chlorine, with azide, and its further “click” reaction, with alkynes, in the presence of CuI was studied. The utility of newly synthesized 2-(azidomethyl)-1,3,4/1,2,4-oxadiazoles and chloromethyl-1,3,4/1,2,4-oxadiazole derivatives was explored, and their limitations were determined. Novel 5-([4-aryl-1H-1,2,3-triazol-1-yl]methyl)-3-(aryl)-1,2,4-oxadiazoles, 2-([4-aryl-1H-1,2,3-triazol-1-yl]methyl)-5-(aryl)-1,3,4-oxadiazoles were obtained in good yields.     

Synthesis of a 1,2,3-triazolo[1,5-a]-1,3,5-triazine. A new heterocyclic system

The synthesis of 3-methyl-7-oxo-5-thioxo-4H,6H-1,2,3-triazolo[1,5-a]-1,3,5- triazine (a new bicyclic system) is described. The key step involves reaction of 4-amino-5-methyl-1,2,3-triazole with carbethoxyisothiocyanate followed by cyclization with alkali.     

Heterocyclic studies. 2. 5-Chloro-1H-1,2,3-triazole-4-carboxaldehydes,preparation and rearrangement reactions

A general procedure for synthesis of 5-chloro-1H-1,2,3-triazole-4-carboxaldehydes 4 and the rearrangement reaction of 4-(N-substituted)iminomethylene-1H-1,2,3-triazol-5-ols 6 into N-substituted-1H-1,2,3-triazole-4-carboxamides 7 are described.