Azolyl-substituted 1,2,3-triazoles

Huisgen reaction of (E)-1,5-diarylpent-2-en-4-yn-1-ones and (E)-1,5-diarylpent-1-en-4-yn-3-ones afforded 1-aryl-3-(5-aryl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones and 3-aryl-1-(5-aryl-1H-1,2,3-triazol-4-yl)-prop-2-en-1-ones, respectively. (E)-1-Aryl-3-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones reacted with hydrazine hydrate and phenylhydrazine to give 72–93% of 4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles which underwent dehydrogenation on heating in boiling acetic acid with formation of the corresponding pyrazole derivatives. The molecular structures of (E)-3-phenyl-1-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-one and 4-[3-(4-methylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-yl]-5-phenyl-1H-1,2,3-triazole were studied by X-ray analysis. 4-(3-Aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles showed toxicity against Daphnia magna.     

Three-component assembly of 5-halo-1,2,3-triazoles via aerobic oxidative halogenation

An effective synthetic protocol for 5-halo-1,2,3-triazoles was developed by novel TBDMSCl (tert-butyldimethylsilyl chloride)-activated aerobic oxidative halogenations in this Letter. TBDMSCl, for the first time, was found to activate aerobic oxidation of CuX to produce X₂ with Cu⁺ which then could effectively promote one-pot syntheses of 5-halo-1,2,3-triazole from alkyne, azide, and CuX (X = I, Br) under O₂ atmosphere at room temperature. The advantages in this method include inexpensive and green O₂ as oxidant, use of mild and non-oxidative additive, and wide scope of substrates.     

Direction of glycosylation of 5-substituted 4-chloro-1,2,3-triazoles

The structures of previously obtained nucleosides of 5-substituted 4-chloro-1, 2,3-triazoles were refined by means of high-resolution mass spectrometry and ¹³C NMR spectroscopy. It is shown that fusion of 5-substituted 4-chloro,1,2,3-triazoles with tetra-0-acylribofuranoses in the presence of di(p-nitrophenyl) phosphate leads to the formation of 2-nucleosides of the corresponding triazoles. The signals of the carbon atoms in the ¹³C NMR spectra of the 4,5-di-substituted triazoles and their nucleosides were assigned.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 937–940, July, 1987.     

4-Aryl(benzyl)sulfonyl-2-chloro-5-polyfluoroalkyl-1,2,3-triazoles. The first monocyclic N-chloro-1,2,3-triazoles

Treatment of 4-aryl(benzyl)sulfonyl-5-polyfluoroalkyl-v-triazoles with NaOCl gave the 4-aryl(benzyl)-sulfonyl-2-chloro-5-polyfluoroalkyl-v-triazole derivatives which contain a chlorine atom only on the N₍₂₎ atom of the heterocycle. The structure of 2-chloro-5-(1,1,2,2,3,3-hexafluoropropyl)-4-(p-tolyl-sulfonyl)-2H-[1,2,3]triazole has been established by X-ray structural investigation. The presence of a highly polarized N—Cl bond with a positive halogen atom causes the N-chlorotriazoles to react with KCN and KF as strong acids to form the potassium salts of the triazoles and to form 4-arylsulfonyl-2-(2-chloro-1-ethoxyethyl)-5-polyfluoroalkyl-2H-[1,2,3]triazoles with vinyl ethyl ether. It was found that chlorination of 4-arylsulfonyl-5-polyfluoroalkyl-v-triazoles in the presence of KF gives 4-chloro-5-polyfluoroalkyl-2H-[1,2,3]triazoles. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1342–1352, September, 2007.     

Syntheses and properties of H-1,2,3-triazoles

About twenty new H-1,2,3-triazoles (T) were readily synthesized by nucleophilic attack of sodium azide on activated acetylenes in dimethylformamide. Typical activating groups were COR, COOR, O₂NC₆H₄ PO(OC₂H₅, COT, and (C₆H₅)₃P⁺. Propynyl 4-triazolyl ketone or phenylethynyl 4-triazolyl ketone may be converted to acylic adducts (triazolylketoenamines), biheteroaromatic systems (isoxazolytriazoles, pyrazolytriazoles), as well as to ditriazolyl ketones. Certain T properties were examined in detail. The apparent pK′s for our group of ca 30 triazoles were in the range 4·95?9·45 in ethanol-water (v/v 1/1) at 25°. The Hammett correlation for five 4-aryl-T was log K_a = 0·89σ^? ?9·21 and for seven 4-aryl-5-carbethoxy-T was log K_a = 1·45σ?6·95. The UV spectra of T are similar to those of other heteroaromatic and phenyl compounds: interesting analogies between triazolyl and phenyl, e.g., ”ortho“ crowding effects, appear to be indicated in the spectra of compounds related to biphenyl, stilhene and benzophenone. With regard to structure assignment on the basis of spectra, characteristic features of UV and IR spectra of the H-1,2,3-triazoles are discussed.     

DABCO-mediated aza-Michael addition of 4-aryl-1H-1,2,3-triazoles to cycloalkenones. Regioselective synthesis of disubstituted 1,2,3-triazoles

Aza-Michael addition of 4-aryl-1H-1,2,3-triazoles to 2-cycloalken-1-ones has been studied in the presence of DABCO as organic base. The reactions were carried out in acetonitrile at room temperature to provide 2,4-disubstituted 2H-1,2,3-triazoles as major adducts and 1,4-disubstituted 1H-1,2,3-triazoles as minor adducts. Though the reaction times are longer (4–8 days), the two regioisomers were separated by using column chromatography and the adducts were obtained in very good to excellent combined chemical yields. The electron-rich and electron-poor substituents on aryl moiety of 4-aryl-triazoles could tolerate the reaction conditions to afford the title adducts.     

Mass-spectrometric study of isomeric 5-amino-1,2,3-thiadiazoles and 5-mercapto-1,2,3-triazoles

The behavior of the isomeric 5-amino-1,2,3-thiadiazoles and 5-mercapto-1,2,3-triazoles under electron impact was studied. It was shown that mass spectrometry can serve as a rapid and reliable method for the identification of these compounds. Key factors in the assignment of a compound to one or the other class are the peaks of the [M-N₂]⁺ ions, which are more intense in the case of the thiadiazoles, and the ions determined by the decomposition of the prototropic forms of the triazoles. The compositions of the ions were determined by the high-resolution mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 681–689, May, 1987.     

Molecular rearrangements of 5-azido substituted 1,2,3-triazoles

5-Azido-4-methoxycarbonyl-1-phenyl-1,2,3-triazole ($\text{8a}$) and its phenyl substituted derivatives $\text{8b}$,$\text{c}$ rearrange at 60–80°C to give tetrazolyldiazoacetates $\text{9}$, which have been isolated. When the reactions are allowed to go to completion, products derived from the diazo compounds are obtained; i.e. norcaradienes ($\text{10}$) from benzene solutions and imidazotetrazoles ($\text{12}$) from nitrite solutions. The latter decompose photochemically into diazacyclopentadienonimines ($\text{13}$). A kinetic study of the rearrangement $\text{8}$ → $\text{9}$ has been carried out and the mechanism (Scheme VI) is discussed in comparison with the Dimroth rearrangement.     

Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles via coupling reaction of diaminomaleonitrile with aromatic diazonium salts

A mild procedure for the preparation of 2-(5-amino-1-aryl-1H-1,2,3-triazol-4-yl)-2-iminoacetonitriles and 2-(5-amino-1-aryl-1H-1,2,3-triazol-4-yl)-2-oxoacetonitriles was achieved by the reaction of diaminomaleonitrile and phenyl/substituted phenyl diazonium chlorides. 4-Nitrophenyl diazonium chloride afforded 2-amino-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)maleonitrile. Triazole iminoacetonitrile and maleonitrile derivatives were reacted further with excess acetone and benzaldehyde with a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene to yield 5-(5-imino-2,2-dimethyl-2,5-dihydrooxazol-4-yl)-3-aryl-3H-1,2,3-triazol-4-amine and (E)-N-benzylidene-5-(5-imino-2-aryl-2,5-dihydrooxazol-4-yl)-3-aryl-3H-1,2,3-triazol-4-amine, respectively. Two competitive reactions, i.e., nucleophilic substitution and nucleophilic addition, were observed when triazole oxoacetonitrile and maleonitrile derivatives were reacted with hydroxylamine hydrochloride in the presence of sodium acetate.     

Synthesis of 1,2,3,4-tetrazine 1,3-dioxides annulated with 1,2,3-triazoles and 1,2,3-triazole 1-oxides

1,2,3,4-Tetrazine 1,3-dioxides annulated with 1,2,3-triazoles and 1,2,3-triazole 1-oxides have been synthesized by the reaction of 4-amino-5-(tert-butyl-NNO-azoxy)-2-R-2H-1,2,3-triazoles (R=Me, i-Pr, t-Bu) and their 1-oxides (R=H, Me, Et, i-Pr) with the HNO₃/H₂SO₄/Ac₂O system. Their thermal stability, spectroscopic, and X-ray properties have been studied.     

5-卤代1,2,3,-三唑互变异构的密度泛函理论研究

用密度泛函B3LYP/6-311 G**方法,对气相和水相中的1,2,3三,-唑及5-卤(-F、C l和-B r)代1,2,3,-三唑互变异构体进行了几何构型全自由度优化,获得了它们在气相和水相中的几何结构和电子结构。计算结果显示,在气相和水相中1,2,3三-唑和5-卤代1,2,3三-唑的N2-H型要比对应的N1-H型和N3-H型稳定。讨论了不同的取代基团和溶剂化效应对互变异构体的几何结构、能量和电荷分布以及互变异构反应活化能的影响带。并进一步研究了N1-H、N2-H和N3-H型三唑之间的互变异构机理:(a)分子内质子转移;(b)水助质子转移。计算结果表明,途径(b)所需要的活化能较小,为120.06KJ/mol,途径(a)为204.12KJ/mol。     

Selenium-catalyzed oxidative carbonylation of 1,2,3-thiadiazol-5-amine with amines to 1,2,3-thiadiazol-5-ylureas

With cheap and easily available 1,2,3-thiadiazol-5-amine and amines as raw materials, cheap and reusable selenium as the catalyst, CO as the carbonylation reagent and O₂ as the oxidizing agent, the selenium-catalyzed oxidative carbonylation reaction of 1,2,3-thiadiazol-5-amine can proceed smoothly with a series of amines in one-pot manner in the presence of triethylamine, affording 1,2,3-thiadiazol-5-ylureas mostly in moderate to good yields.     

Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles by copper-catalyzed cycloaddition-coupling of azides and terminal alkynes

Primary, secondary, and aromatic azides undergo 1,3 dipolar cycloaddition-coupling with an excess of alkyne in the presence of Cu(CH₃CN)₄PF₆ as catalyst, N,N,N′-trimethylethylenediamine as ligand, molecular oxygen, and 4-methoxymorpholine N-oxide (NMO) as co-oxidant to afford 1,4,5-trisubstituted-1,2,3-triazoles.     

1-Nucleosides of 5-substituted 4-chloro-1,2,3-triazoles

1-Nucleosides of 5-substituted 4-chloro-1,2,3-triazoles were produced by glycosylation of the corresponding triazoles by the method of fusion with tetra-0-acyl-D-ribofuranose in the presence of bis-p-nitrophenyl phosphate. The structure of the compounds obtained and their conformational peculiarities were studied by the methods of mass spectrometry and NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1556–1564, November, 1984.     

Novel rearrangement of N-enoyl oxazolidinethiones to N-substituted 1,3-thiazine-2,4-diones promoted by NbCl5

NbCl₅ has been employed as promoter of a novel rearrangement to afford chiral N-substituted 1,3-thiazine-2,4-diones with one or two new stereogenic centers from di- and trisubstituted N-enoyl oxazolidinethiones. The trisubstituted E-isomers provide the anti-diastereomers mainly.     

Synthesis and mass spectra of some 1-aroylamino-5-arylaminomethyl-1,2,3-triazoles

The title compounds 2 are prepared from the reaction of 1-(N, N-diaroyl)amino-5-bromomethyl-1,2,3-triazoles with aromatic amines. The fragmentation pattern upon electron impact at 70 eV of compounds 2 is studied. The molecular ion peak is present in all the spectra examined. Besides the [M-28]⁺⁺, there is also a more abundant [M-29]⁺ peak, corresponding to a N₂H loss of the molecular ion. The ion Ar²NH = CH₂ is the base or the most prominent peak.     

Orthogonal synthesis of pyrroles and 1,2,3-triazoles from vinyl azides and 1,3-dicarbonyl compounds

Tri- and tetrasubstituted N-H pyrroles were prepared by the simple treatment of vinyl azides with 1,3-dicarbonyl compounds in toluene at 100 °C via 2H-azirine intermediates generated in situ. When the reactions of vinyl azides and 1,3-dicarbonyl compounds were performed in DMF in the presence of a catalytic amount of K₂CO₃, 1-vinyl-1,2,3-triazoles were obtained via 1,3-dipolar cycloaddition. These methodologies exploited orthogonal modes of chemical reactivity of vinyl azides, which could be achieved by slight modification of the reaction conditions.     

Metal-free,highly regioselective sulfonylation of NH-1,2,3-triazoles with sodium sulfinates and thiosulfonates

A convenient and metal-free protocol for the highly regioselective sulfonylation of NH-1,2,3-triazoles is described. A range of readily accessible NH-1,2,3-triazoles were sulfonylated with various aryl sulfinates in the presence of molecular iodine. The scope was extended to thiosulfonates as an efficient sulfonylating agent and nitrochromene derived triazoles were also explored for selective N-sulfonylation. A variety of synthetically viable N²-sulfonyl triazoles were obtained in moderate to high yields with excellent regioselectivities via N–S bond construction under mild reaction conditions.     

Synthesis of D-mannitol substituted ether-linked bis-1,2,3-triazoles as models of gemini surfactants

Readily available and low cost D-mannitol was converted into 1,2,5,6-di-O-isopropylidene-D-mannitol (1) in the presence of acetone and zinc chloride. Williamson etherfication of 1 with propargyl bromide afforded the bisalkyne 2 in a very good yield. 1,3-Dipolar cycloaddition of 2 with four different alkyl azides using click conditions gave four novel bistriazoles 3a-d. Removal of the acetal groups of 3a-d afforded the deprotected bistriazoles 4a-d in excellent yields. Products 3 and 4 represent models of gemini surfactants.     

Functional desymmetrization of 1,3-dioximes for the obtention of 1,2,3-hetero trisubstituted carbocycles

Carbocylic 1,3-dioximes react with acyl chlorides giving systems that may, upon heating, suffer [3,3]-sigmatropic rearrangements in high yields in only one of the oximes esters, yielding 1,3-dinitrogen-2-oxygen trisubstituted carbocycles. Use of more reactive electrophiles, such as p-toluenesulfonyl chloride and diethyl chlorophosphate, introduces the halogen at position 2, while cleaving the N-O bond of just one of the oxime functions.