Reactions of 2,4-Disubstituted 5-Nitro-1,2,3-triazole 1-Oxides. 4. Dealkylation of 2-Substituted 4,5-Dinitro-1,2,3-triazole 1-Oxides

The N-dealkylation of 2-alkyl or 2-benzyl-substituted 4,5-dinitro-1,2,3-triazole 1-oxides has been studied. Conditions have been found for N-de-tert-butylation and 4-amino-5-nitro-1,2,3-triazole 1-oxide has been synthesized for the first time.     

Multistep Flow Synthesis of 5‐Amino‐2‐aryl‐2H‐[1,2,3]‐triazole‐4‐carbonitriles

1,2,3‐Triazole has become one of the most important heterocycles in contemporary medicinal chemistry. The development of the copper‐catalyzed Huisgen cycloaddition has allowed the efficient synthesis of 1‐substituted 1,2,3‐triazoles. However, only a few methods are available for the selective preparation of 2‐substituted 1,2,3‐triazole isomers. In this context, we decided to develop an efficient flow synthesis for the preparation of various 2‐aryl‐1,2,3‐triazoles. Our strategy involves a three‐step synthesis under continuous‐flow conditions that starts from the diazotization of anilines and subsequent reaction with malononitrile, followed by nucleophilic addition of amines, and finally employs a catalytic copper(II) cyclization. Potential safety hazards associated with the formation of reactive diazonium species have been addressed by inline quenching. The use of flow equipment allows reliable scale up processes with precise control of the reaction conditions. Synthesis of 2‐substituted 1,2,3‐triazoles has been achieved in good yields with excellent selectivities, thus providing a wide range of 1,2,3‐triazoles.     

CuO-promoted construction of N-2-aryl-substituted-1,2,3-triazoles via azide-chalcone oxidative cycloaddition and post-triazole arylation

An efficient one-pot three-component stepwise approach for the synthesis of N-2-aryl-substituted-1,2,3-triazoles has been developed. By using this azide-chalcone oxidative cycloaddition and post-triazole arylation, a series of N-2-aryl-substituted-1,2,3-triazoles are readily prepared under mild conditions in excellent yields and high regioselectivity. Both the catalyst and substrates are readily available.     

A new synthetic method for the 2H-[1,2,3]thiadiazolo[5,4-b]indoles

The systematic study of oxidative cyclization of 3-hydrazono-1,3-dihydroindole-2-thiones has been carried out and a series of new 2H-[1,2,3]thiadiazolo[5,4-b]indoles has been prepared. The elaborated reaction represents an efficient method for the synthesis of fused 1,2,3-thiadiazoles.     

Tandem Knoevenagel-[3+2] cycloaddition-elimination reactions: one-pot synthesis of 4,5-disubstituted 1,2,3-(NH)-triazoles

Sodium azide has been found to catalyse Knoevenagel condensation between aromatic aldehyde and cyano compound with active methylene hydrogens and this has led to a successful route for the one pot synthesis of 4,5-disubstituted 1,2,3-(NH)-triazoles from aldehydes through Knoevenagel-[3+2]cycloaddition-elimination sequence. In the formation of 5-aryl-2H-1,2,3-triazole-4-carbonitrile derivatives, the reaction has been found to occur efficiently in water.     

Conformational control in the regioselective synthesis of N-2-substituted-1,2,3-triazoles

An effective strategy for the synthesis of N-2-substituted-1,2,3-triazoles with excellent yields and regioselectivity has been developed.     

Synthesis of 1,3-dioxacyclan-2-yl-substituted 1,2,3-triazoles

A new method for preparing 4-(1,3-dioxacyclan-2-yl)-5-phenyl-1,2,3-triazoles in 30–75% yields has been developed on the basis of azide–alkyne cycloaddition to 2-phenylethinyl-1,3-dioxacyclanes. It has been shown that the best results are achieved when the reaction is carried out at 150–155°C in DMSO.     

Amine-catalyzed synthesis of N2-sulfonyl 1,2,3-triazole in water and the tunable N2-H 1,2,3-triazole synthesis in DMSO via metal-free enamine annulation

The selective synthesis of N²-sulfonyl and N²-H 1,2,3-triazoles via organocatalytic annulation of enaminone/enaminoester with sulfonyl azide has been realized. The unconventional selectivity providing N²-sulfoyl 1,2,3-triazoles takes place in pure water, wherein the hydrogen bond effect between water and the intermediate resulting from enamine-azide corporation accounts for the novel reaction selectivity. On the other hand, the reactions conducted in DMSO specifi...     

Ion chemistry of 1H-1,2,3-triazole

A combination of experimental methods, photoelectron-imaging spectroscopy, flowing afterglow-photoelectron spectroscopy and the flowing afterglow-selected ion flow tube technique, and electronic structure calculations at the B3LYP/6-311++G(d,p) level of density functional theory (DFT) have been employed to study the mechanism of the reaction of the hydroxide ion (HO-) with 1H-1,2,3-triazole. Four different product ion species have been identified experimentally, and the DFT calculations suggest that deprotonation by HO- at all sites of the triazole takes place to yield these products. Deprotonation of 1H-1,2,3-triazole at the N1-H site gives the major product ion, the 1,2,3-triazolide ion. The 335 nm photoelectron-imaging spectrum of the ion has been measured. The electron affinity (EA) of the 1,2,3-triazolyl radical has been determined to be 3.447 +/- 0.004 eV. This EA and the gas-phase acidity of 2H-1,2,3-triazole are combined in a negative ion thermochemical cycle to determine the N-H bond dissociation energy of 2H-1,2,3-triazole to be 112.2 +/- 0.6 kcal mol-1. The 363.8 nm photoelectron spectroscopic measurements have identified the other three product ions. Deprotonation of 1H-1,2,3-triazole at the C5 position initiates fragmentation of the ring structure to yield a minor product, the ketenimine anion. Another minor product, the iminodiazomethyl anion, is generated by deprotonation of 1H-1,2,3-triazole at the C4 position, followed by N1-N2 bond fission. Formation of the other minor product, the 2H-1,2,3-triazol-4-ide ion, can be rationalized by initial deprotonation of 1H-1,2,3-triazole at the N1-H site and subsequent proton exchanges within the ion-molecule complex. The EA of the 2H-1,2,3-triazol-4-yl radical is 1.865 +/- 0.004 eV.     

Spectroscopic studies of tautomeric systems—III : 2-arylhydrazones of 1,2,3-triketones

The IR and NMR spectra of a range of 2-arylhydrazones of 1,2,3-tricarbonyl compounds have been recorded. Compounds containing different end groups in the 1,2,3-tricarbonyl system can exist in two different tautomeric forms. The influence of electronic and steric factors on the structure of the preferred tautomer is discussed.     

超声辐射法在新型含双杂环芳酰基硫脲合成中的应用

以2-苯基-1,2,3-三唑-4-甲酸、氨基硫脲为原料在三氯氧磷中反应得到2-氨基-5-(2-苯基-1,2,3-三唑-4-基)-1,3,4-噻二唑,然后分别采用超声辐射法和常规加热法与芳酰基异硫氰酸酯反应合成了一系列的N-[5-(2-苯基-1,2,3-三唑-4-基) 1,3,4-噻二唑-2-基\]-N′-酰基硫脲。 通过与常规方法比较,采用超声辐射法反应时间只有原来的12.5%,反应产率提高了4%~17%,减少了副反应。 所有化合物的结构经元素分析、MS、IR、1H NMR测试技术确证。     

Synthesis and cyclization direction of 2-diazomalondiamide derivatives new rearrangement of 5-hydroxy-1,2,3-triazole-4-carboxamides

The thermal behavior of 5-hydroxy-1,2,3-triazole-4-carboxamides obtained on acidification of solutionns of triazol-5-olates has been investigated. A new rearrangement has been discovered in the 1,2,3-triazole series and the qualitative effect of the substituents in the initial triazole and of temperature have been clarified.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1208–1213, September, 1992.     

A divergent synthesis of substituted 2-aminoimidazoles from 2-aminopyrimidines

A new divergent and efficient synthesis of substituted 2-aminoimidazoles 5 and 6 has been developed starting from the readily available 2-aminopyrimidines 1 and alpha-bromocarbonyl compounds 2, using conventional heating or microwave irradiation. Thus, the cleavage of 1,2,3-substituted imidazo[1,2-a]pyrimidin-1-ium salts 4 with hydrazine or secondary amines led to 1,4,5-trisubstituted 2-aminoimidazoles 5, when the hydrazinolysis of 2-hydroxy-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-4-ium salts 3, followed by a novel Dimroth-type rearrangement, resulted in formation of 2-amino-1H-imidazoles 6. The relevant pathway of transformations was identified by characterization of the intermediates.     

CuBr2‐Promoted Multicomponent Aerobic Reaction for the Synthesis of 1,2,3‐Triaroylindolizines

An efficient synthesis of 1,2,3‐triaroylindolizines has been developed via CuBr₂‐promoted reaction of three molecules of aromatic methyl ketones and one molecule of pyridine derivative. A wide range of methyl aryl ketones and methyl heteroaryl ketones took part in the reaction and generate 1,2,3‐triaroylindolizines in good yields. This protocol also features such advantages as mild reaction conditions and high atom economy and step economy.     

A novel isomerization on interaction of antitumor-active azole-bridged dinuclear platinum(II) complexes with 9-ethylguanine. Platinum(II) atom migration from N2 to N3 on 1,2,3-triazole

The reactions of the dinuclear platinum(II) complexes, [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-pz)](NO(3))(2) (1, pz = pyrazolate), [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-1,2,3-ta-N1,N2)](NO(3))(2) (2, 1,2,3-ta = 1,2,3-triazolate), and a newly prepared [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-4-phe-1,2,3-ta-N1,N2)](NO(3))(2) (3, 4-phe-1,2,3-ta = 4-phenyl-1,2,3-triazolate), whose crystal structure was determined, with 9-ethylguanine (9EtG) have been monitored in aqueous solution at 310 K by means of (1)H NMR spectroscopy. The dinuclear platinum(II) complexes 1-3 each react with 9EtG in a bifunctional way to form 1:2 complexes, [[cis-Pt(NH(3))(2)(9EtG-N7)](2)(mu-pz)](3+) (4), [[cis-Pt(NH(3))(2)(9EtG-N7)](2)(mu-1,2,3-ta-N1,N3)](3+) (5), and [[cis-Pt(NH(3))(2)(9EtG-N7)](2)(mu-4-phe-1,2,3-ta-N1,N3)](3+) (6). The reactions of 2 and 3 involve a novel isomerization, in which the Pt atom, initially bound to N2 on the 1,2,3-ta, migrates to N3 after the first substitution by N7 of 9EtG. This isomerization reaction has been unambiguously characterized by 1D and 2D NMR spectroscopy and pH titration. The reactions of 2 and 3 with 9EtG show faster kinetics, and the second-order rate constants (k) for the reactions of 1-3are 1.57 x 10(-4), 2.53 x 10(-4), and 2.56 x 10(-4) M(-1) s(-1), respectively. The pK(a) values at the N1H site of 9EtG were determined for 4-6 from the pH titration curves. Cytotoxicity assays of 1-3 were performed in L1210 murine leukemia cell lines, respectively sensitive and resistant to cisplatin. In the parent cell line, 2 and 3 exhibit higher cytotoxicity compared to cisplatin, especially, 2 is 10 times as active as cisplatin. 1 was found to be less cytotoxic than cisplatin, but still in the active range and more active than cisplatin in a cisplatin-resistant cell line.     

Studies on Reactions of 2-Amino-5-Heterocyclyl-1,3,4- -Thia/Oxadiazole with Acylisothiocyanates

It is well known that the addition of acyl isothiocyanate with amine formed 1,3-disubstituted thiourea which possess broad spectrum biological activities, Up till now, the addition of 5-heterocyclyl-2-amino-1,3,4-thia/oxadiazole with acylisothicyanate has not been reported. We wish to describe this reaction in this paper. When the new 2-amino-5-(l-p-chlorophenyl-5-methyl-1,2,3-triazol-4-yl)-1,3,4-thiadiazole (Ⅰ) was reacted with acylisothio-cyanates (Ⅱ), not all the compounds were expected acylthiourea (Ⅲ)^[1,2], some of them were acid amide (Ⅳ). The formation of the products was determined by the substituents of the acylisothiocyanate. In order to investigate the reaction, we synthesized 2-amino-5-aryl-1,3,4-thio/oxadiazole (Ⅴa,b), and then reacted with 1-p-chlorophenyl-5-methyl-1,2,3-triazol-4-formyl-isothiocyanate (Ⅵ). As it was anticipated, the products only were N-(5-aryl-1,3,4-thia/oxadiazol-2-yl)-N'-(1-p-chlorophenyl-5-methyl-1,2,3-triazol-4-formyl) thiourea (Ⅶa,b) (Scheme).     

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.     

Amine-catalyzed [3+2] Huisgen cycloaddition strategy for the efficient assembly of highly substituted 1,2,3-triazoles

An enamine-catalyzed strategy has been utilized to fully promote the Huisgen [3+2] cycloaddition with a broad spectrum of carbonyl compounds and azides, thereby permitting the efficient assembly of a vast pool of highly substituted 1,2,3-triazoles. In particular, the employment of commonly used and commercially available carbonyl compounds has resulted in the introduction of a diverse set of functional groups, such as alkyl, aryl, nitrile, ester, and ketone groups, at the 1-, 4-, or 5-positions of the 1,2,3-triazole scaffold. This approach might be manipulated to access more useful and sophisticated heterocyclic compounds. Most significantly, the reaction process exhibits complete regioselectivity, with the formation of only one regioisomer.     

Ion chemistry of 1H-1,2,3-triazole. 2. Photoelectron spectrum of the iminodiazomethyl anion and collision induced dissociation of the 1,2,3-triazolide ion

The 363.8 nm photoelectron spectrum of the iminodiazomethyl anion has been measured. The anion is synthesized through the reaction of the hydroxide ion (HO-) with 1 H-1,2,3-triazole in helium buffer gas in a flowing afterglow ion source. The observed spectrum exhibits well-resolved vibronic structure of the iminodiazomethyl radical. Electronic structure calculations have been performed at the B3LYP/6-311++G(d,p) level of theory to study the molecular structure of the ion. Equilibrium geometries of four possible conformers of the iminodiazomethyl anion have been obtained from the calculations. Spectral simulations have been performed on the basis of the calculated geometries and normal modes of these conformationally isomeric ions and the corresponding radicals. The spectral analysis suggests that the ions of two conformations are primarily formed in the aforementioned reaction. The relative abundance of the two conformers substantially deviates from the thermal equilibrium populations, and it reflects the potential energy surfaces relevant to conformational isomerization processes. The electron affinities of the ( ZE)- and ( EE)-iminodiazomethyl radicals have been determined to be 2.484 +/- 0.007 and 2.460 +/- 0.007 eV, respectively. The energetics of the iminodiazomethyl anion is compared with that of the most stable structural isomer, the 1,2,3-triazolide ion. Collision-induced dissociation of the 1,2,3-triazolide ion has also been studied in flowing afterglow-selected ion flow tube experiments. Facile fragmentation generating a product ion of m/ z 40 has been observed. DFT calculations suggest that fragmentation of the 1,2,3-triazolide ion to the cyanomethyl anion and N2 is exothermic. The stability of the ion is discussed in comparison with other azolide ions with different numbers of N atoms in the five-membered ring.     

Synthesis and Antimicrobial Activity of 3-(1-Aryl-1H-1,2,3-triazol-4-yl)-2-(4-fluorophenyl)-1-(2-hydroxy-4-methoxyphenyl)propan-1-ones

Russian Journal of General Chemistry - A number of novel 3-(1-aryl-1H-1,2,3-triazol-4-yl)-2-(4-fluorophenyl)-1-(2-hydroxy-4-methoxyphenyl) propan-1-ones has been synthesized from...