Triazolopyridines. Part 24: New polynitrogenated potential helicating ligands

The synthesis of novel 7-{[1,2,3]triazolo[1,5-a]pyridin-3-yl}-[1,2,3]triazolo[1,5-a]pyridines 7, 2-pyridyl-[1,2,3]triazolo[1,5-a]pyrid-7-ylmethanols 11, 3-(6-substituted-2-pyridyl)-[1,2,3]triazolo[1,5-a]pyridines 12, and 7,7′-disubstituted-3,3′-[1,2,3]triazolo[1,5-a]pyridine 20, interesting polynitrogenated ligands as potential helicating compounds or luminescent sensors, from [1,2,3]triazolo[1,5-a]pyridines is described.     

Novel Selected Tandem Transformations of the Amino and Carbonyl/Nitrile Groups in the Gewald Thiophenes

Novel transformations of the amino and carbonyl/nitrile groups in the Gewald thiophenes were studied for thienopyrimidine synthesis. It was found that 2-amino-thiophene-3-carboxamides and ethyl 2-(acetylamino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carbo- xylate did not yield tetrazole derivatives, neither in the reaction with triethyl orthoformate and sodium azide, nor in the reaction with phosphorus oxychloride and sodium azide, correspondingly. On the contrary, derivatives of thieno[2,3-d]pyrimidin-4(3H)-one and thieno[2,3-d][1,3]oxazin-4-one were isolated. New 2-azidothiophenes [2-azido-4,5,6,7-tetra hydro-1-benzothiophene-3-carbonitrile and 2-azido-4,5,6,7-tetrahydro-1-benzothiophen-3-yl(phenyl)methanone] were synthesized and used in anionic domino reactions with activated acetonitriles to yield thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidines and/or 2-(5-amino-1H-1,2,3-triazol-1-yl)thiophenes. Finally, a new ring system of thieno[3,2-e]pyrazolo[1,5-a]pyrimidine was synthesized via a domino reaction of ethyl 2-[(2Z)-2-(1-chloro-2-ethoxy-2-oxoethylidene)hydrazino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate with activated acetonitriles.     

Triazolopyridines. Part 28. The ring–chain isomerization strategy: triazolopyridine- and triazoloquinoline–pyridine based fluorescence ligands

The ring–chain isomerization of [1,2,3]triazolo[1,5-a]pyridines or [1,2,3]triazolo[1,5-a] quinolines has been efficiently employed as a tool to provide tridentate fluorescent structures. Based on these scaffolds, a new family of highly fluorescent compounds has been synthesized and evaluated for the recognition of zinc or copper cations. In addition, the 1:1 Zn⁺²-L complex of a naphthalene triazolopyridine–pyridine derivative revealed high efficiency as sensor for anions providing large binding constants for nitrite and cyanide.     

Synthesis of [1,2,3]Triazolo[1,5-a]quinoline-3-carboxamides Promoted by Organocatalyst and Base

We described here a simple and metal-free protocol to synthesize [1,2,3]triazolo[1,5-a]quinoline 3-carboxamides through a two-step synthetic strategy, in which the first step uses organocatalysis (10 mol % of diethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene, while the second step involves the use of inorganic base (1.2 or 0.1 equiv. of potassium hydroxide). These reactions were performed between β-keto amides and o-carbonyl phenylazides in dimethylsulfoxide as solvent at 70 °C for 2 h. The synthetic protocol is ample, which thirteen examples of secondary [1,2,3]triazolo[1,5-a]quinoline 3-carboxamides were synthesized ranging from good to excellent yields (63-96 %), and six different tertiary [1,2,3]triazolo[1,5-a]quinolines 3-carboxamides were obtained ranging from moderate to good yields (48–76 %).     

Cyclocondensation of 6-acetyl-4,7-dihydro-5-methyl-7-phenyl[1,2,4]triazolo[1,5-a]pyrimidine with hydroxylamine and hydrazine

The cyclocondensation of 6-acetyl-4,7-dihydro-5-methyl-7-phenyl[1,2,4]triazolo[1,5-a]pyrimidine (3) with hydroxylamine or hydrazine leads to 3a,4,9,9a-tetrahydro-3,9a-dimethyl-4-phenylisoxazolo-[5,4-d][1,2,4]triazolo[1,5-a]pyrimidine ( 4a ) and 3a,4,9,9a-tetrahydro-3,9a-dimethyl-4-phenyl-1H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidine ( 4b ), respectively. In the presence of methanolic hydrogen chloride, 4b undergoes a cleavage of the pyrimidine ring to yield (5-amino-1,2,4-triazol-1-yl)(3,5-dimethylpyrazol-4-yl)phenylmethane ( 5 ). The structure determination of the compounds obtained is based on ¹H and ¹³C nmr spectra including NOE measurements.     

On triazoles XXIV . Synthesis of cycloalka[1,2,4]triazolo[1,5-a]pyrimidinones

The uv and nmr spectral data of some 6,7,8,9,10,11-hexahydrocyclohepta[d][1,2,4]triazolo[1,5-a]pyrimidin-5-one, 5,6,7,8,9,11-hexahydrocyclohepta[e][1,2,4]triazolo[1,5-a]pyrimidin-10-one, 6,7,8,9,10,11-hexahydrocycloocta[d][1,2,4]triazolo[1,5-a]pyrimidin-5(12H)-one, 5,6,7,8,9,10-hexahydrocycloocta[e][1,2,4]triazolo[1,5-a]-pyrimidin-11(12H)-one, 6,7,8,9,10,11,12,13,14,15-decahydrocyclododeca[d][1,2,4]triazolo[1,5-a]pyrimidin-5(16H)-one and 5,6,7,8,9,10,11,12,13,14-decahydrocyclododeca[e][1,2,4]triazolo[1,5-a]pyrimidin-15(16H)-one as well as their N-benzylated derivatives representing six novel ring systems were compared to prove their structure. The N-benzylation of the highly insoluble cyclic amides to yield the isomeric N-benzyl derivatives 3/1, 3/2 and 3/3 distinguished by INAPT was performed through their readily soluble tetrabutylammonium salts.     

Synthesis of some fused triazoloquinolines

The reaction of 3 -amino-1,2,4-triazolo[4,3-a]quinoline ( II ) with diethyl ethoxymethylenemalonate and ethyl acetoacetate/ethyl trifluoroacetoacetate afforded 10-carboethoxy-9-oxo-9H-pyrimido[1′,2′:1,5][1,2,4]triazolo-[4,3-a]quinoline ( III ) and 11-methyl/trifluoromethyl-9-oxo-9H-pyrimido[1′,2′:1,5][1,2,4]triazolo[4,3-a]quinoline ( IV/V ) respectively. 2-Chloropyridine-3-carboxylic acid chloride reacted with II to yield 5-oxo-5H-pyrido-[3″,2″:5′,6′]pyrimido[1′,2′:1,5][1,2,4]triazolo[4,3-a]quinoline ( VII ), a new ring system.     

The reaction of β-lactam carbenes with 3,6-di(2-pyrimidinyl)tetrazine: regulating products by reaction conditions

The reaction of β-lactam carbenes with 3,6-di(2-pyrimidinyl)tetrazine was studied, which produced good yields of novel 5-(3-[1,2,3]triazolo[1,5-a]pyrimidinyl)pyrrol-2-ones or pyrrolo[3′,2′:3,4]pyrrolo[1,2-a]pyrimidin-2-ones under heating at 100 °C or 140 °C, respectively. This work provided a highly efficient strategy for the construction of both [1,2,3]triazolo[1,5-a]pyrimidine and pyrrolo[3′,2′:3,4]pyrrolo[1,2-a]pyrimidine ring systems from the same reactants, and extended the application of β-lactam carbenes in the syntheses of complex heterocycles.     

Reaction of 3-oxo-N-phenylbutanethioamide with 5-amino-1H-1,2,4-triazoles

Reactions of 3-oxo-N-phenylbutanethioamide with 3-substituted 5-amino-1H-1,2,4-triazoles in acetic acid led to the formation of 5-methyl-7,8-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-thiones, 7-methyl-5,8-dihydrol[1,2,4]triazolo[1,5-a]pyrimidine-5-thiones and 7-methyl-5-phenylamino[1,2,4]triazolo[1,5-a]pyrimidines. The structure of the products was proved by the ¹H and ¹³C NMR spectra, X-ray diffraction data, and chemical transformations.     

New routes to the v-triazolo[1,5-a]pyridine and pyrazolo[1,5-a]pyridine ring systems

New routes to the v-triazolo[1,5-a]pyridine and pyrazolo[1,5-a]pyridine ring systems are described. Treatment of the N-amine salts of 2-picolinealdehyde oxime or 2-pyridyl ketone oximes with polyphosphoric acid gave v-triazolo[1,5-a]pyridines in fair yields. Treatment of 2-picolyl ketones or their oximes with O-mesitylenesulfonylhydroxylamine produced directly pyrazolo-[1,5-a]pyridines. These reactions were extended to the quinoline cases.     

Fluorescence studies of some 1,2,3-triazolo[1,5-a]pyridine and imidazo[1,2-a]pyridine esters and their vinylogues

The relative fluorescence intensity of a number of 1,2,3-triazolo[1,5-a]pyridine esters 6 and 7 and imidazo-[1,2-a]pyridine esters 10 and 11 were determined and compared with methyl imidazo[1,2-a]pyridine-5-carboxylate 2 and 4 -methylumbelliferone 3 .     

Dimroth rearrangement in the row of new pyrano[3,4-c][1,2,4]triazolo[4,3-a][1,5-a]pyridines and synthesis of new heterocyclic systems: Pyranopyrazolo[4,3-e][1,2,4]triazolopyridines

New and effective methods for the synthesis of derivatives of pyrano[3,4-c][1,2,4]triazolo[4,3-a][1,5-a]pyridines were developed. Synthesized new tetracyclic heterocyclic systems containing pyrano[3,4-c]pyridine ring unknown in the literature were obtained for the first time. The rearrangement of Dimroth in the triazolo[4,3-a]pyridine systems for the first time was studied. The possibility of rearrangement of Dimroth in the new heterocyclic system has been investigated.     

Reduction of Imidazo[4,5-c]pyridine and [1,2,3]Triazolo[4,5-c]pyridine Derivatives to Spinaceamines and 2-Azaspinaceamines

Reduction of 1-substituted [1,2,3]triazolo[4,5-c]pyridines with nickel-aluminum alloy in aqueous alkali gave 2-azaspinaceamines. Reduction of imidazo[4,5-c]pyridine and [1,2,3]triazolo[4,5-c]pyridine derivatives with formic acid in the presence of triethylamine resulted in formation of 5-formylspinaceamines and 2-azaspinaceamines. The 5-formyl group in the latter can be removed by acid hydrolysis. Unsubstituted 2-azaspinaceamine, an aza analog of natural spinaceamine, was synthesized for the first time.     

Reactions of 4-oxobenz[1,3-e]oxazinium perchlorates with α-aminoazoles

Reactions of 4-oxo benz[1,3-e]oxazinium perchlorates with 1-R¹-3-R²-5-aminopyrazoles lead to the formation of derivatives of pyrazolo[3,4-d]pyrimidine and pyrazolo[1,5-a]1,3,5]triazine series, and with 3-amino-1,2,4-triazole, to [1,2,4]triazolo[1,5-a][1,3,5]triazines.     

Reactions of pyridinium or isoquinolinium ketene dithioacetals with aromatic N-imines and S-imines

Reactions of ketene dithioacetals, 1-[1-substituted 2,2-bis(methylthio)ethenyl]pyridinium 1a-i or -isoquinolinium 2a,b iodides with aromatic N-imines, 1-aminopyridinium 3a-1,1 -aminoquinolinium ( 4 ), and 2-amino-isoquinolinium ( 5 ) mesitylene sulfonates gave the corresponding 2-methylthioimidazo[1,2-a]pyridines 9a-k , 2-methylthiopyrazolo[1,5-a]pyridines 11a-q , 2-methylthioimidazo[2,1-a]isoquinoline derivatives 10a,b and 2-methylthiopyrazolo[1,5-a]quinoline ( 12 ). The benzoyl compounds, 1-[1-benzoyl-2,2-bis(methylthio)ethenyl]-pyridinium iodides 1g,h,i reacted with N-imine 3a to give the 3-benzoyl-2-methylthioimidazo[1,2-a]pyridines 9h-k . The reaction of pyridinium ketene dithioacetals 1a,f,g (R¹ = COOE_t, COPh, and CN) with substituted pyridinium N-imines having an electron-withdrawing group on the pyridine ring afforded only the corresponding pyrazolo[1,5-a]pyridine derivatives 11j-r in good yields. Reactions of ketene dithioacetals with various S-imines are also described. Possible mechanisms for the formation of 9 and 11 are described.     

Cyclization of substituted 3,4-diaminopyridines into 1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxide derivatives during the nitration process

The nitration of pyridine-3,4-diamine, its N,N′-diacetyl derivative, and N ⁴-alkylpyridine-3,4-diamines with excess nitric acid in concentrated sulfuric acid at 60°C was accompanied by cyclization with formation of the corresponding 1-substituted 4-nitro-1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxides. 4-Chloro-1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxide derivatives were obtained under analogous conditions from 2-chloropyridine-3,4-diamine, its N,N′-diacetyl derivative, and 2-chloro-N ⁴-methylpyridine-3,4-diamine. The nitration of these compounds at 80–90°C gave 4-chloro-7-nitro-1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxides.     

Synthesis of novel triazolopyridylboronic acids and esters. Study of potential application to Suzuki-type reactions

This paper describes a general method for the synthesis of novel [1,2,3]triazolo[1,5-a]pyridylboronic acids and esters, and the first results on Suzuki cross-coupling reactions with these new compounds and [1,2,3]triazolo[5,1-a]isoquinolylboronic acid, reacting with a variety of aryl halides as a route to 7-aryltriazolopyridines and 5-aryltriazoloisoquinolines.     

Synthèse et étude physicochimique des 1,2,4-triazolo[4,3-a]-pyridines et des 1,2,4-triazolo[2,3-a]pyridines

The synthesis of 1,2,4-triazolo[4,3-a] and [2,3-a]pyridines 7, 8 was achieved by cyclization of 2-hydrazino-8-nitropyridine 3a with formic acid. The 4,5,6,7-tetrahydro-1,2,4-triazolo[2,3-a]pyridine 13 and 8-amino-1,2,4-triazolo[2,3-a]pyridine 9 were obtained by catalytic hydrogenation. The reduction of triazolo pyridine 8 using stannous chloride led to the intermediate compound 10 which with acetic anhydride afforded 8-acetylamino-5-chloro-1,2,4-triazolo[2,3-a]pyridine 10a . The structure of the derivatives was determined by ¹H-nmr (DMSO-d₆).     

Efficient multicomponent synthesis of highly substituted [1,2,3]triazolo[1,5-a]pyrimidines

Abstract  

An efficient and facile multicomponent procedure for the synthesis of highly substituted [1,2,3]triazolo[1,5-a]pyrimidines by reaction of equimolar amounts of aromatic aldehyde, CH-acid, and 5-amino-1,2,3-triazole in refluxing dimethylformamide is described.     

Chemical reactivity of [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts

The chemical reactivity of the [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts towards morpholine, water and sodium methoxide have been studied. Among others, new 1-aza and 2-azabutadienes substituted by a [1,2,3]-triazole ring were obtained in the course of the opening of the positively charged pyrimidine ring.