Regioselective synthesis of 5-trifluoromethyl-1,2,3-triazole nucleoside analogues via TBS-directed 1,3-dipolar cycloaddition reaction

Herein described was a straightforward method for the highly regioselective synthesis of 5-trifluoromethyl-1,2,3-triazole nucleoside analogues, which featured the utilization of tert-butyldimethylsilyl (TBDMS) group as the directing group in the 1,3-dipolar cycloaddition reactions. 4-tert-Butyldimethylsilyl-5-trifluoromethyl-1,2,3-triazole nucleoside analogues were generated as the only cycloaddition products in moderate yields (15-79%) via the treatment of glycosyl azides with 3,3,3-trifluoro-1-tert-butyldimethylsilylpropyne 1 in toluene at 85 °C. Removal of TBS groups in these triazole cycloadducts with tetrabutylammonium fluoride (TBAF) smoothly afforded the various 5-trifluoromethyl-1,5-disubstituted 1,2,3-triazole nucleoside analogues in good yields (40-88%).     

Cu(II)-catalyzed acetoxylation of arenes by 1,2,3-triazole-directed C–H activation

A facile and efficient method for the regioselective acetoxylation of 1-benzyl 1,2,3-triazoles through C–H bond activation was developed. Cu(OAc)₂ and 1,2,3-triazole were applied as catalyst and elegant directing group, respectively, to convert aromatic C–H bonds directly into highly regioselective C–O bonds. The conversion can result in the synthesis of 1,2,3-triazoles bearing acetoxyl groups.     

Synthesis of potassium 2,3,4-trihydroxy-2-methylbutanoate: a leaf-closing substance of Leucaena leucocephalam

Starting from citraconic anhydride (2), a six step synthesis of leaf closing substance (±)-erythro potassium 2,3,4-trihydroxy-2-methyl-butanoate (1) has been described with 29% overall yield via diesterification, OsO₄-dihydroxylation, acetonide protection, regioselective mono hydrolysis of unhindered ester moiety, borane-dimethylsulfide induced chemoselective reduction of carboxylic group and hydrolysis pathway. Surprisingly, the sodium borohydride reduction of monoester 5 and lithium borohydride reduction of 11 furnished the undesired regioisomer 7.     

1-(4-取代苯基)-4-苯基-5-(2-羟基苄基)氨基-1,2,3-三唑类衍生物的合成及抑菌活性

将邻羟苯基引入1,2,3-三唑结构中, 设计合成了10个1-(4-取代苯基)-4-苯基-5-取代-1,2,3-三唑类衍生物. 首先, 以对位取代的芳胺为原料, 经重氮化、叠氮化、闭环和缩合反应制得1-(4-取代苯基)-4-苯基-5-水杨醛亚胺-1,2,3-三唑类衍生物(3a~3e), 再用硼氢化钠还原制得1-(4-取代苯基)-4-苯基-5-(2-羟基苄基)氨基-1,2,3-三唑类衍生物(4a~4e). 目标化合物的结构经核磁、IR及元素分析确认. 抑菌活性测试表明, 当质量浓度为0.1 mg/L时, 除化合物3e和4e外, 所有化合物对白色念球菌的抑菌率均达95%以上, 对大肠杆菌的抑菌率达85%以上, 具有强抑菌活性, 表明该类化合物在抗菌药物开发方面有重要应用价值.     

Room-temperature oxidative Suzuki coupling reaction of 1,2,3-triazole N-oxides

This study develops a new efficient pathway for synthesis of 2,4-disubstituted 1,2,3-triazoles through regioselective direct arylation between 2-aryl-1,2,3-triazole N-oxides and Ar-B(OH)₂. The reaction proceeds smoothly at room temperature and exhibits good yield and high C5 position selectivity. The possible pathway of oxidative Suzuki coupling is also discussed. This simple methodology can be used to construct 2,4-disubstituted 1,2,3-triazole moiety.     

新型多氮化合物1,1＇-偶氮-1,2,3-三唑的合成与性能研究

以1-氨基-1,2,3-三唑（1）为原料,经二氯异氰尿酸钠（SDCI）氧化偶联合成了具有稳定N8结构（8个氮原子直接相连）和光致变色特性的新型多氮化合物1,1＇-偶氮-1,2,3-三唑（2）,通过IR,Raman,1H NMR,13C NMR,MS,元素分析等手段对其进行了表征;分离出了偶合反应副产物1H-1,2,3-...     

N-Alkylation of 4-nitro-1,2,3-triazole revisited. Detection and characterization of the N3-ethylation product, 1-ethyl-5-nitro-1,2,3-triazole

The products of the alkylation of sodium 4-nitro-1,2,3-triazolate with ethyl bromide were investigated using ¹H, ¹³C, and ¹⁵N NMR spectroscopy. It was found that alkylation proceeds on the triazole nitrogen atoms giving a mixture of three isomeric N-ethyl-4-nitro-1,2,3-triazoles. The molar ratio of N1, N2, and N3-alkylation products was 4:8:1. The formation of a minor N3-isomer, namely 1-ethyl-5-nitro-1,2,3-triazole was confirmed by X-ray structural analysis of single crystals of its tetranuclear copper(II) complex obtained by reaction of copper(II) chloride dihydrate with a mixture of the N2 and N3-isomers.     

1,4-二取代-1,2,3-三唑衍生物的合成

在超声波辐射下,端基炔与叠氮基(3,3-二甲基-2,4-二氧戊环基)甲烷通过1,3-偶极环加成合成了1-(3,3-二甲基-2,4-二氧戊环基甲基)-4-芳基-1,2,3-三唑(5);5在酸性条件下脱保护得1-(2,3-二羟基丙基)-4-芳基-1,2,3-三唑,其结构经1H NMR,13C NMR,MS和元素分析表征。     

Facile solid-phase ruthenium assisted azide-alkyne cycloaddition (RuAAC) utilizing the Cp1RuCl(COD)-catalyst

The ruthenium assisted azide-alkyne cycloaddition (RuAAC) reaction is a well-established method for the generation of 1,5- and 1,4,5-substituted 1,2,3-triazoles, which we have extended to the solid-phase synthesis of 1,2,3-triazole-peptides. The 1,2,3-triazole moieties were formed upon the reaction of alkynes with a solid-phase bound secondary azide in the presence of the Cp¹RuCl(COD) catalyst at room temperature. Both terminal and internal alkynes underwent highly regioselective cycloaddition reactions under mild conditions, facilitating release of the peptide construct from the resin with intact side-chain protection. Almost quantitative conversion to the corresponding 1,2,3-triazoles was observed within 1 h.     

SYNTHESIS AND CHARACTERIZATION OF TRIAZOLE CONTAINING LIQUID CRYSTALLINE POLYMERS THROUGH 1,3-DIPOLAR CYCLOADDITION POLYMERIZATION

Liquid crystalline polymers containing 1,2,3-triazole units as linking groups have been synthesized from the monomers containing triad ester diazide and flexible dialkyne ester by 1,3-cycloaddition reaction and were characterized. Click reaction of azide and alkyne functionals catalyzed by Cu(I) yielded target polyesters with 1,2,3-triazole groups.The structure of the polymer was confirmed by spectral techniques.GPC analysis reveals that the polymers have moderate molecular weight with narrow distributio...     

Gem-dinitro compounds in organic synthesis. 3. Syntheses of 4-nitro-1,2,3-triazoles from gem-dinitro compounds

Several chemoselective syntheses have been developed for 4-nitro-1,2,3-triazoles from sodium azide and gem-dinitroethylenes prepared from readily available transformation products of dinitroacetic acid ester: N-(,-dinitroethyl)-N,N-dialkylamines, 2,2-dinitroethanol acetate, a mixture of dinitroacetic acid ester with aliphatic aldehydes, or 1,1,1-trinitroalkanes. Hitherto-unknown 4-nitro-5-amino- and 4,5-dinitro-1,2,3-triazoles have been synthesized via successive transformations of the CH₃ groups in 5-nitro-4-methyltriazole. Nitration of 4-nitro-1,2,3-triazole with nitronium fluoroborate or acetyl nitrate gave an unknown 2,4-dinitro-1,2,3-triazole.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 958–966, April, 1992.     

Total syntheses of zaragozic acids A and C by a carbonyl ylide cycloaddition strategy

A carbonyl ylide cycloaddition approach to the squalene synthase inhibitors zaragozic acids A and C is described. The carbonyl ylide precursor 8 was synthesized starting from di-tert-butyl D-tartrate (47) via an eleven-step sequence involving the regioselective reduction of the mono-MPM (MPM=4-methoxybenzyl) ether 48 with LiBH4 and the diastereoselective addition of sodium tert-butyl diazoacetate to alpha-keto ester 10. The reaction of alpha-diazo ester 8 with 3-butyn-2-one (40) in the presence of a catalytic amount of [Rh2(OAc)4] gave the desired cycloadduct 59 as a single diastereomer. The dihydroxylation of enone 59 followed by sequential transformations permitted the construction of the fully functionalized 2,8-dioxabicyclo[3.2.1]octane core 5. Alkene 79 derived from 5 serves as a common precursor to zaragozic acids A (1) and C (2), since the elongation of the C1 alkyl side chain can be attained by olefin cross-metathesis, especially under the influence of Blechert's catalyst (85).     

Efficient synthesis of N-2-aryl-1,2,3-triazole fluorophores via post-triazole arylation

Efficient post-triazole regioselective N-2 arylation was developed from C-4, C-5 disubstituted-1,2,3-NH-triazoles. Three different approaches had been investigated, including S(N)Ar, Cu(I) catalyzed aryl amidation and Cu(II) mediated boronic acid coupling. The N-2-aryl triazoles were successfully synthesized with excellent yields. The structures were characterized by X-ray crystallography and some N-2-triazole products gave strong fluorescence with various emission controlled by the C-5 groups.     

Trifluoromethyl Sulfones and Perfluoroalkanesulfonamides of the Azole Series

2-Phenyl-4-trifluoromethylsulfonylmethyl-2H-1,2,3-triazole was synthesized from 4-bromo-methyl-2-phenyl-2H-1,2,3-triazole and sodium trifluoromethanesulfinate CF₃SO₂Na. 1(2)-Ethyl-4-nitro-1(2)H-1,2,3-triazoles and 4-nitro-2-phenyl-2H-1,2,3-triazole were reduced to the corresponding amines. Intermediate 1,2-bis(1-ethyl-1H-1,2,3-triazol-4-yl)diazene 1-oxide exists as a mixture of syn and anti isomers, the former being stabilized via formation of a strong intramolecular hydrogen bond. The reduction of 2-ethyl-4-nitro-2H-1,2,3-triazole in the presence of HCl afforded the target 4-amino-2-ethyl-2H-1,2,3-triazole and also 4-amino-5-chloro-2-ethyl-2H-1,2,3-triazole. Treatment of alkyl-substituted 4-amino-1,2,3-triazoles with trifluoromethanesulfonyl chloride and pentafluoroethanesulfonyl chloride gave N-triazolyl-substituted trifluoromethane- and pentafluoroethanesulfonamides and -imides.     

Regioselective Cycloaddition of the Dimethyl Ester of Acetylenedicarboxylic Acid to 2,4,6-Triazidopyridines

2,4,6-Triazido-3,5-dichloropyridine was obtained in the reaction of pentachloropyridine with sodium azide. At room temperature, this azide reacts regioslectively with norbornene at the -azide group to give the corresponding 4-(3-azatricyclo[3.2.1.0]octanyl)-2,6-diazidopyridine in 88% yield. The cycloaddition of the dimethyl ester of acetylenedicarboxylic acid to this triazide proceeds at the azide groups at C₍₂₎ and C₍₆₎ in the pyridine ring to give 4-azido-2,6-di(4',5'-dimethoxycarbonyl)-1H-1,2,3-triazolopyridine. The analogous reaction of 2,4,6-triazido-3,5-dicyanopyridine with the dimethyl ester of acetylenedicarboxylic acid stops at the formation of 2,4-diazido-6-(4',5'-dimethoxycarbonyl)-1H-1,2,3-triazolopyridine. In contrast to reactions with electron-rich dipolarophiles, the cycloaddition of electron-deficient dipolarophiles to 2,4,6-triazidopyridines proceeds with thermodynamic control primarily a! t the azide groups bearing the highest orbital density in the HOMO.     

Sodium Borohydride–Mediated Transesterification

In the presence of sodium borohydride, esters react with alcohols with formation of the corresponding esters. The reaction is sensitive to the solvent, structure of the ester, and is often concurrent with reduction. Thioesters containing an ester group can be selectively cleaved by the reagent. Both esters and thioesters attached to solid support are resistant toward sodium borohydride. The in situ prepared sodium tetraalkoxyborate is introduced as an efficient reagent and catalyst for transesterification.     

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.     

Synthesis and Crystal Structure of 3,6-Bis（4-methyl-1,2,3-thiadiazol-5-yl）-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

The compound 3,6-bis(4-methyl-1,2,3-thiadiazol-5-yl)-1,2,4-triazolo[3,4-b][1,3,4] thiadiazole(C9H6N8S3,Mr = 322.40) has been synthesized by the reaction of 4-amino-3-(4-methyl-1,2,3-thiadiazolyl)-5-mercapto-1,2,4-triazole with 4-methyl-1,2,3-thiadiazol-5-carboxylic acid and phosphorus oxychloride,and its structure was characterized by IR,1H NMR,EI-MS,elemental analysis and single-crystal X-ray diffraction.The crystal of the title compound belongs to monoclinic,space group C2/c with a = 2.0053(4),b = 1.3081(3),c = 1.0556(2) nm,β = 112.69(3)°,Z = 4,V = 2.5548(9) nm3,Dc = 1.676 g/cm3,μ = 0.582 mm-1,F(000) = 1312,R = 0.0546 and wR = 0.1523.X-ray analysis indicates that all rings are essentially planar in this molecule,and an intermolecular hydrogen bond C(9)-H(9)…N(2) and weak intramolecular interactions between S(1)…N(7),S(3)…N(1) and S(2)…N(4) are observed.     

Synthesis of 2(5H)-Furanone Derivatives with Symmetrical and Unsymmetrical Bis-1,2,3-triazole Structure

The interesting bioactivities of 2(5H)-furanone, 1,2,3-triazole, and amino acid derivatives have promoted their combination into one multifunctional molecule. The symmetrical bis-1,2,3-triazoles and mono-1,2,3-triazoles with one free azide group are synthesized respectively by controlling the molar ratio of reactants, N-[5-alkoxy-2(5H)-furanonyl] amino acid propargyl ester and 1,4-diazidobutane. The unsymmetrical bis-1,2,3-triazoles are afforded by the subsequent reaction of mono-1,2,3-triazoles with other terminal alkynes with good to excellent yields in a short time under the same mild “click” reaction conditions. The 32 new compounds obtained in the reactions are characterized by Fourier transform infrared, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. Because of the diversity of four or five basic units in molecule, this methodology provides easy access to different chiral 2(5H)-furanone compounds with polyheterocyclic structure, especially with unsymmetrical bis-1,2,3-triazole moiety. Importantly, a simple approach is provided for the synthesis of unsymmetrical bis-1,2,3-triazoles using common diazides.     

Promotion of proton conduction in polymer electrolyte membranes by 1H-1,2,3-triazole

We report 1H-1,2,3-triazole as an active group to dramatically enhance proton conduction in a polymer electrolyte membrane (PEM). The conductivities of a poly(4-vinyl-1H-1,2,3-triazole) membrane without any acidic dopants are about 105 times greater than those of poly(4-vinylimidazole) in dry air at 50-150 degrees C. Polymers with groups promoting proton conduction attached to the backbone have great potential to offer excellent mechanical properties and long-term stability. Further, 1H-1,2,3-triazole and PEMs containing 1H-1,2,3-triazole are stable in a wide potential range, implying excellent electrochemical stability under fuel cell operating conditions.