Synthese de s-triazolo[4,3-d] et [1,5-d] triazines-1,2,4

2-substituted s-triazolo[1,5-d] and 3-substituted s-triazolo [4,3-d]-1,2-4-triazine 8-ones were obtained starting from 5-(3)-alkyl-3(5)-carboxyhydrazino-1,2,4 triazoles and ethyl orthoformate. However, the same reaction was not found to be an efficient one in the case of 5(3)-β-D-ribofuranosyl-3(5)-carboxyhydrazino-1,2,4 triazole.     

Some nucleophilic substitution reactions of s-triazolo[1,5-c]pyrimidines

Nucleophilic substitution of 5-methylthio- and 5-cyanomethylthio-7-amino-s-triazolo[1,5-c]pyrimidines has been carried out using sodium hydroxide, ammonia, hydrazine hydrate, and four amines. The cyanomethyl group is particularly reactive under these conditions and 5-cyanomethylthiotriazolopyrimidine can be used to functionalize this heterocycle.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 382–385, March, 1992.     

A simple one pot synthesis of 1-(s-triazolo[4,3-x]azinyl-3)-substituted polyols

Open-chain C-nucleosides, 1-(s-triazolo[4,3-x]azinyl-3)polyols 13–18 were prepared by one-pot synthesis from hydrazinoazines 20a,c and various D-aldoses 1–6. No protective groups were required for these transformations. 1-(s-Triazolo[4,3-b]pyridazinyl-3)-D-xylo-tetritol (15a) was isolated and characterised in the form of its 4-O-triphenylmethyl derivative 19. Reaction of hydrazinopyridazines 20a,b with methyl 2,3-di-O-acetyl-L-threuronate ( 22 ), followed by treatment with bromine, gave the corresponding (2R,3S)-2,3-diacetoxy-3-(s-triazolo[4,3-b]pyridazinyl-3)propanoic acid methyl esters 24a,b. Acetonisation of 1-(6-chloro-s-triazolo[4,3-b]pyridazinyl-3)-D-gluco-pentitol ( 17a ) gave a mixture of isomeric bis-acetonides 25 and 26 , while acetonisation of 1-(6-chloro-s-triazolo[4,3-b]pyridazinyl-3)-D-manno-pentitol ( 18a ) gave acetonide 27 as a single isomer.     

A new general synthesis of functionally substituted pyrazolo[1,5-a]pyrimidines

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A solution of structural ambiguity: s-Triazolo[1,5-a] – and s-triazolo[4.3-a] pyrimidines

The condensation of 3-amino-5-benzylthio-s-triazole ( 2 ) with acetylacetone in refluxing acetic acid has been reported to have given 3-benzylthio-5,7-dimethyl-s-triazolo[4,3-a]pyrimidine ( 3 ). However, it has now been established, with the aid of ¹³C spectra and a modification of the original synthetic work, that only 2-benzylthio-5,7-dimethyl-s-triazolo[1,5-a]pyrimidine ( 4 ) can be obtained by this method of condensation. The erroneously reported, but previously unknown 6 was synthesized and its structure and that of 4 was firmly established by ir, uv, pmr,¹³ C nmr, tlc and mixed melting point data. The correct structures of 3-mercapto-5,7-dimethyl-s-triazolo-[4,3-a]pyrimidine ( 5 ) and 2-mercapto-5,7-dimethyl-s-triazolo[1,5-a]pyrimidine ( 6 ) were also established and the facile rearrangement of 5 to 6 was demonstrated.     

Mass spectral fragmentation patterns of isomeric s-Triazolo[4,3-a]pyridines and s-triazolo[1,5-a]pyridines

The major decomposition pathway involved in the fragmentation of derivatives of the title ring systems was the loss of RCN from the five-membered ring, except when this ring had a 3-amino,3-hydroxyl or 3-mercapto substituent. In these cases, the exocyclic substituent and at least one nitrogen atom from the five-membered ring were lost.     

A new synthesis for 1,2,4-triazolo[1,5-a]-pyridines and 1,2,4-triazolo[1,5-a]isoquinolines

Summary Condensation of cyano acid hydrazide1 with cyclopentanone in refluxing ethanolic piperidine yields hydrazone2. With mixtures of aliphatic aldehydes and different active methylene reagents,2 reacts to 1,2,4-triazolo[1,5-a]pyridines (8a–f). Compound2 also reacts with arylidenes9a–g to give triazolopyridines10a–g. Reaction of2 with aromatic aldehydes affords compounds13a–c. Diazotation of2 with aryldiazonium chloride in ethanol at 0 °C leads to the azo adducts15a–d. The thieno-1,2,4-triazolopyridine16 is obtained by reaction of8a with elementary sulfur.16 undergoes cycloaddition with -nitrostyrene, maleic anhydride, N-arylmalemide, and acrylonitrile yielding the isoquinolines21–24. All new compounds have been characterized by their IR,¹H NMR, and mass spectra.

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Ein neuer Syntheseweg für 1,2,4-Triazolo[1,5-a]pyridine und 1,2,4-Triazolo[1,5-a]isochinoline

Zusammenfassung Kondensation des Cyanohydrazids1 mit Cyclopentanon in ethanolischem Piperidin bei Rückflußtemperatur ergibt das Hydrazon2. Mit Gemischen aus aliphatischen Aldehyden und verschiedenen Verbindungen mit aktiven Methylengruppen reagiert2 zu 1,2,4-Triazolo[1,5-a]pyridinen (8a–f). Verbindung2 reagiert außerdem mit den Arylidenen9a–g zu den Triazolopyridinen10a–g. Umsetzung von2 mit aromatischen Aldehyden führt zu den Verbindungen13a–c. Diazotierung von2 mit Aryldiazoniumchloriden in Ethanol bei 0°C ergibt die Azoaddukte15a–d. Das Thieno-1,2,4-triazolylpyridin16 erhält man durch Reaktion von8a mit elementarem Schwefel.16 geht it -Nitrostyrol, Maleinsäureanhydrid, N-Arylmaleimid und Acrylnitril eine Cycloaddition zu den Isochinolinen21–24 ein. Alle neuen Verbindungen wurden durch ihre IR-,¹H-NMR- und Massenspektren charakterisiert.

     

A general approach toward the synthesis of 8-acylamidopyrazolo[1,5-a]-1,3,5-triazines

An expedient synthesis of 8-acylamidopyrazolo[1,5-a]-1,3,5-triazines was developed by treating 8-amino-4-[N-(4-aminophenyl)-N-(methyl)amino]pyrazolo[1,5-a]-1,3,5-triazine with various acyl chlorides following by the displacement of the so-formed N-(methyl)-N-[4-(acylamido)phenyl]amino leaving group with various amines. Applications to high-throughput synthesis are suggested.     

A synthesis of 6-functionalized 4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidines

6-Unsubstituted 7-R-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines (R = H or Me) were synthesized via two pathways: (a) deacylation of the corresponding 5-acetyl Biginelli-like precursors in KOH/H₂O and (b) reduction of the corresponding 1,2,4-triazolo[1,5-a]pyrimidines using LiAlH₄. The products could be easily formylated at position 6, which is promising for the further synthesis of functionalized 6-substituted derivatives of 4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines. In contrast, 6-acetyl-7-(4-(N,N-dimethylaminophenyl))-5-methyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine undergoes a cascade process in KOH/H₂O, leading to the formation of a 4,5,8,9-tetrahydro[1,2,4]triazolo[5,1-b]quinazoline derivative.     

Synthesis of bridgeheaded nitrogen systems. s-triazolo[4,3-b]-as-triazine,s-triazolo[4,3-d]-as-triazine and s-triazolo[3,4-b]-1,3,4-Thiadiazole ring systems

By the reactions of hydrazino-as-triazines ( 1a-d and 5 ) with cyanogen bromide were synthesized s-triazolo-as-triazines ( 2a-d ) and ( 6 ). Likewise, similar reactions of amino-s-triazolethiols ( 7a-e ) gave s-triazolo-1,3,4-thiadiazoles ( 8a-e ). Compound 2a was brominated to 2g.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo[4,3-b]pyridazine

s-Triazolo[4,3-b]pyridazine (I) photochemically reacted with cyclooctene, cyclododecene, bicyclo[2.2.2]oct-2-ene, bicyclo[2.2.1]hept-2-ene and indene to form tri and tetracyclic triazoles (II-X). Generally, two or more products were formed. For example the reaction with cyclooctene gave 4a,5,7,8,9,10,10a,11-octahydro-11-methylene-6H-cycloocta[4,5]-pyrrole[1,2-b]-s-triazole (II) and the corresponding 11-cyanomethyl product (III). When I was reacted with open chain alkenes, various isomers of the substituted pyrrolo[1,2-b]triazoles (XI-XV) were formed. Since the reaction was not stereospecific, cycloaddition must be a two step process.     

Aminonitrile rearrangement of s-triazolo[1,5-c]pyrimidines upon reaction with aryl (alkyl) halides

Aminonitrile cleavage of the cyclic system was observed in the reaction of s-triazolo[1,5-c]pyrimidine derivatives with aryl (alkyl) halides in an alkaline medium or in dimethylfonnamide. It is shown that this transformation proceeds through the formation of intermediate quaternary salts. The effect of electron-acceptor and electron-donor substituents on their stability was ascertained. The structures of the substances were established by means of IR, UV, PMR, and mass spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 421–425, March, 1985.     

1,2,4-Triazines. Synthesis of selected members of the s-triazolo[3,4-f]- [1,2,4] triazine and tetrazolo[1,5-f] [1,2,4] triazine ring systems

A convenient synthesis of 3-amino-6-hydrazino-5(2H)[1,2,4]triazinone 4 has been developed and a study of the reactions of 4 with aliphatic acids, orthoesters and miscellaneous active carbonyl reagents has been undertaken. When 4 was refluxed in either neat acid or orthoester in dimethylformamide, a facile ring closure reaction with the N-1 nitrogen of the 1,2,4-triazine ring occurs affording a novel series of 3-aIkyl(aryl)-8(5H)-s-triazolo[3,4-f] [1,2,4]triazinones ( 6–11 ). Ring closure with carbon disulfide and cyanogen bromide is also reported affording 6-amino-3(2H)thio-8(5H)-s-triazolo[3,4-f] [1,2,4]triazinone 12 and 3,6-diamino-8(5H)-s-triazolo-[3,4-f] [1,2,4]triazinone 14 , respectively. In addition 4 has been converted into 3-amino-6-azido-5(2H)-1,2,4-triazinone 15 which was employed in a study of azide-tetrazole equilibrium affording 6-amino-8(5H)tetrazolo[1,5-f][1,2,4]triazinone 16 . Rates for interconversion at various temperatures were measured and an activation energy for the process determined.     

A novel synthesis of pyrido[2,3-b][1,5]benzodiazepines

A novel and convenient synthesis of the title compounds 4, 5, 11 , and 13 is described, involving the ring transformation of 1,5-benzodiazepine derivatives 1a and 1b with active methylene compounds.     

A new synthesis of thes-triazolo[1,5-a]pyridine ring system

Summary A novel and efficient synthesis ofs-triazolo[1,5-a]pyridines was elaborated by reacting 1,2-diaminopyridinium salts with aldehydes.Dedicated to Prof.F. Sauter on the occasion of his 65^th birthday     

A one-pot synthesis of imidazo[1,5-a]pyridines

A one-pot synthesis of imidazo[1,5-a]pyridines starting from a carboxylic acid and 2-methylaminopyridines allowing introduction of various substituents at the 1- and 3-positions is achieved using propane phosphoric acid anhydride in ethyl or n-butyl acetate at reflux.