1,2,3-三唑类含能化合物的合成研究进展

1,2,3-三唑类含能化合物具有密度高、生成焓高及热稳定性好等特点,近年来受到科研人员的广泛研究和报道.较全面地综述了单环1,2,3-三唑、多环1,2,3-三唑和稠环1,2,3-三唑类含能化合物的研究成果,对其合成方法、感度和爆轰性能进行了总结.结果表明,1,2,3-三唑含能化合物具有良好的爆轰性能和热稳定性,在含能材料领域具有重要的研究价值和应用潜力.最后,对1,2,3-三唑含能化合物的发展现状进行总结与展望,提出了各类1,2,3-三唑含能化合物未来可能的应用方向,以期为从事含能化合物研究的科研人员提供一定的参考.     

N~2-取代1,2,3-三唑的合成研究进展

N-取代1,2,3-三唑化合物在有机合成、药物化学和材料科学等领域具有广泛的应用价值.其中N~1-取代1,2,3-三唑化合物的合成方法已经非常成熟,而N~2-取代1,2,3-三唑的合成报道相对较少.在现有研究报道中,主要通过1,2,3-三唑的选择性官能化及双芳腙或偶氮苯的氧化环化两类方法得到.结合我们课题组的研究工作,综述了2000年以来N2-烷基、烯丙基、炔丙基、烯基、芳基取代1,2,3-三唑的合成方法进展.     

NH-1,2,3-三唑合成进展

NH-1,2,3-三唑是一类具有重要生理活性的含氮杂环化合物, 是用途广泛的药物中间体. 通过N-烃基化反应, NH-1,2,3-三唑还可以区域选择性的合成各种2-取代-1,2,3-三唑类化合物, 因此是有价值的有机合成中间体. 鉴于NH-1,2,3-三唑在有机合成化学和药物化学中的潜在应用价值, 结合本课题组的研究工作, 对于NH-1,2,3-三唑的主要合成方法, 尤其是近十年来的合成研究进展进行了回顾和展望. 对一些典型的反应机理研究也进行了综述.     

1-甲基-4-苯基-1H-1,2,3-三唑-5-甲酸衍生物的定向合成

1-甲基-4-苯基-1H-1,2,3-三唑-5-甲酸是一类重要的三唑类衍生物,是多种药物合成的重要中间体.以苯乙炔为原料,设计出了一条定向合成1-甲基-4-苯基-1H-1,2,3-三唑-5-甲酸的新方法.首先苯乙炔与叠氮化钠、碘甲烷在碘化亚铜催化下反应生成1-甲基-4-苯基-1H-1,2,3-三唑,再依次与正丁基锂、甲酸乙酯反应生成中间体1-甲基-4-苯基-1H-1,2,3-三唑-5-甲醛后直接氧化生成目标化合物.该合成途径原料易得、总产率较高、后处理操作简便,具有较高的应用价值.     

1,3-偶极环加成反应合成1-(取代苄基)-1,2,3-三唑类化合物

利用苄氯和取代苄氯与叠氮化钠的亲核取代反应合成了一系列苯环上带有不同取代基团的苄基叠氮化合物,亲核取代反应速率受苯环上取代基的影响:吸电子基团的存在,可以促使反应更容易进行.合成的叠氮化合物与苯乙炔经1,3-偶极环加成反应得到了相应的取代苄基1,2,3-三唑类化合物,反应条件温和.这些1,2,3-三唑类目标化合物具有对热稳定的优点.用红外、核磁、元素分析、质谱等对合成的叠氮化合物和1,2,3-三唑类化合物的结构进行了表征,重点研究了1,3-环加成反应的规律.加成反应速率取决于叠氮化合物(偶极物)的极性,即与取代基的电负性有关:苯乙炔(亲偶极物)易于与缺电子的叠氮反应,反之亦然.同时在反应过程中观察到空间位阻效应:反应可以生成两种同分异构体,其中4-苯基-1,2,3-三唑是主要产物.     

含连三唑基均三唑、噻二唑、噁二唑类衍生物的电喷雾离子化质谱法测定

许多含三唑环和1,3,4-噻二唑环的化合物具有广谱和生物活性.如抗微生物、杀真菌、驱虫、止痛和消炎等作用,同时各种1,2,4-三唑和1,3,4-噁二唑衍生物也具有杀菌、抗微生物、植物生长调节等活性,从而引起化学家们对这几类化合物的广泛兴趣,并进行深入研究.最近,研究表明,将1,2,3-三唑引入某些活性分子可明显增强其药性.因而,对于1,2,3-三唑衍生物的合成及活性研究已成为唑类化合物研究的新热点.鉴于不同活性位点在同一分子中聚集,能明显改善化合物的生物活性这一特征,将2-苯基-1,2,3-三唑基引入到上述几类杂环体系中合成了一系列新的含连三唑基的1,3,4-噻二唑、1,3,4-噁二唑类衍生物,以期实现生物活性的叠加.     

Br?nsted酸催化N1-对甲基苯磺酰基三唑与烯烃加成合成高N2选择性的烷基-1,2,3-三唑

N-取代基-1,2,3-三唑广泛应用于生物科学、材料化学和药物化学领域,近几年来引起了人们很大兴趣. N1-取代基-1,2,3-三唑既可由加热催化,也可通过金属诱导的(铜(Ⅰ)催化的1,4-双取代和钌(Ⅱ)催化的1,5-双取代)1,3偶极子环加成反应制备得到,然而有关N2-取代基-1,2,3-三唑的合成仍未获得太大进展.目前,高N2选择性的N2-芳基和N2-烯丙基-1,2,3-三唑的合成方法是利用大位阻的膦配体配位钯催化偶联反应.2008年,史晓东课题组报道了烷基卤化物与大体积的 C-4和 C-5双取代基的NH-1,2,3-三唑通过亲核反应合成N2-烷基-1,2,3-三唑,但其应用受到底物限制.我们设想N1-烷基-1,2,3-三唑可否由N1-取代1,2,3-三唑合成,由于N1-取代基-1,2,3-三唑制备的研究较多,其合成方法将可很方便地构造N2-烷基-1,2,3-三唑化合物.鉴于此,本文对单取代三唑、未取代三唑与包括乙烯基酯在内的多种烯烃的反应进行了研究.首先,我们用不同取代基的N1-1,2,3-三唑与烯烃在不同的酸催化条件下进行反应,考察了酸效应对反应收率的影响,发现 TsOH做 Br?nsted酸为催化剂时,反应产率最高;而 AuCl3做 Lewis酸为催化剂时反应几乎没有加成产物生成.然后,以 TsOH为催化剂,改变三唑与烯烃的加入比例,发现加入比例为1：6时反应产率最高.当N1取代基是 Ts-时,反应产率最高.催化剂 TsOH的加入量由1当量升至2当量时,反应产率没有明显变化.由此表明,N1-1,2,3-三唑与烯烃的最佳反应条件为：催化剂为 TsOH(1当量),N1-1,2,3-三唑的取代基为 Ts,N1-1,2,3-三唑与烯烃的加入比例为1：6.在确定了最佳反应条件后,考察了三唑类底物的适用性.结果发现, N2/N1产物的比例均很高,说明该反应具有很高的N2选择性.上述研究表明, TsOH酸催化N1-对甲苯磺酰基-1,2,3-三唑与烯烃的加成反应是一种有效合成N2-烷基-1,2,3-三唑的新方法,并通过单晶确定了最终的产物结构.单取代三唑和未取代三唑与包括乙烯基酯在内的多种烯烃反应合成N2-烷基-1,2,3-三唑都有很好的反应效果.本文提供了一种简单有效的合成N2-烷基-1,2,3-三唑的新方法.     

双-1,2,3-三唑化合物的合成与应用研究进展

双-1,2,3-三唑化合物作为重要的N-杂环化合物,近年来吸引了越来越多不同领域化学家的关注.为了合成对称的与不对称的双三唑,一些合成中的新发现、新策略、新技术不断涌现.从所用原料与合成方式等角度,可分为Click反应-氧化偶联法、原料组合法、浓度控制法、基团活性差异法、基团保护法、控制投料比法、特殊试剂法等.同时,介绍了相关双三唑化合物在药物化学、配位化学、化学传感器、分子识别、生物化学、超分子化学、表面活性剂等应用领域的新进展,并对双三唑化合物的合成与应用前景进行了展望.     

Br?nsted酸催化N~1-对甲基苯磺酰基三唑与烯烃加成合成高N~2选择性的烷基-1,2,3-三唑（英文）

N-取代基-1,2,3-三唑广泛应用于生物科学、材料化学和药物化学领域,近几年来引起了人们很大兴趣.N~1-取代基-1,2,3-三唑既可由加热催化,也可通过金属诱导的(铜(Ⅰ)催化的1,4-双取代和钌(Ⅱ)催化的1,5-双取代)1,3偶极子环加成反应制备得到,然而有关N~2-取代基-1,2,3-三唑的合成仍未获得太大进展.目前,高N~2选择性的N~2-芳基和N~2-烯丙基-1,2,3-三唑的合成方法是利用大位阻的膦配体配位钯催化偶联反应.2008年,史晓东课题组报道了烷基卤化物与大体积的C-4和C-5双取代基的NH-1,2,3-三唑通过亲核反应合成N~2-烷基-1,2,3-三唑,但其应用受到底物限制.我们设想N~1-烷基-1,2,3-三唑可否由N~1-取代1,2,3-三唑合成,由于N~1-取代基-1,2,3-三唑制备的研究较多,其合成方法将可很方便地构造N~2-烷基-1,2,3-三唑化合物.鉴于此,本文对单取代三唑、未取代三唑与包括乙烯基酯在内的多种烯烃的反应进行了研究.首先,我们用不同取代基的N~1-1,2,3-三唑与烯烃在不同的酸催化条件下进行反应,考察了酸效应对反应收率的影响,发现TsOH做Br?nsted酸为催化剂时,反应产率最高;而AuCl_3做Lewis酸为催化剂时反应几乎没有加成产物生成.然后,以TsOH为催化剂,改变三唑与烯烃的加入比例,发现加入比例为1:6时反应产率最高.当N~1取代基是Ts-时,反应产率最高.催化剂TsOH的加入量由1当量升至2当量时,反应产率没有明显变化.由此表明,N~1-1,2,3-三唑与烯烃的最佳反应条件为:催化剂为TsOH(1当量),N~1-1,2,3-三唑的取代基为Ts,N~1-1,2,3-三唑与烯烃的加入比例为1:6.在确定了最佳反应条件后,考察了三唑类底物的适用性.结果发现,N~2/N~1产物的比例均很高,说明该反应具有很高的N~2选择性.上述研究表明,TsOH酸催化N~1-对甲苯磺酰基-1,2,3-三唑与烯烃的加成反应是一种有效合成N~2-烷基-1,2,3-三唑的新方法,并通过单晶确定了最终的产物结构.单取代三唑和未取代三唑与包括乙烯基酯在内的多种烯烃反应合成N~2-烷基-1,2,3-三唑都有很好的反应效果.本文提供了一种简单有效的合成N~2-烷基-1,2,3-三唑的新方法.     

超声辐射下含1,2,3-三唑噻唑烷酮衍生物的合成

采用超声辐射法,以2-苯基-1,2,3-三唑-4-甲酰肼为原料,合成了3-(2-苯基-1,2,3-三唑-4-基)-5H-4-氧代噻唑[2,3-c].1,2,4-三唑,再与各种芳香醛进行Knoevenagel缩合反应,合成了一系列噻唑烷酮衍生物.所有目标化合物结构经元素分析,IR,1H NMR确证.     

Tandem Amine Propargylation-Huisgen Cycloaddition to Functionalized Substituted 1,2,3-Triazoles

The chemistry of 1,2,3-triazoles has received much attention because of their wide range applications.[1] They have been used as fungicides, herbicides, light stabilizers, fluorescent whiteners, optical brightening agents. Therefore, it is important to develop new and more efficient synthetic pathways to a diverse array of 1,2,3-triazoles.     

Synthesis of 5-functionalized-1,2,3-triazoles via a one-pot aerobic oxidative coupling reaction of alkynes and azicles

In this paper, an efficient synthesis of 5-alkynyl-1,2,3-triazoles through a one-pot aerobic oxidative coupling reaction of various alkynes and azides has been developed. Further derivatization of 5-alkynyl-1,2,3-triazoles readily yielded 5-carbonyl-1,2,3-triazoles, 5-carboxylic-1,2,3-triazole, 5-hydroxyalkyl-1,2,3-triazoles and 5-quinoxaline-1,2,3-triazole, which provided an entry into structurally diverse 5-functionalized-1,2,3-triazoles.     

Synthesis of 5-functionalized-1,2,3-triazoles via a one-pot aerobic oxidative coupling reaction of alkynes and azides

In this paper, an efficient synthesis of 5-alkynyl-1,2,3-triazoles through a one-pot aerobic oxidative coupling reaction of various alkynes and azides has been developed. Further derivatization of 5-alkynyl-1,2,3-triazoles readily yielded 5-carbonyl-1,2,3-triazoles, 5-carboxylic-1,2,3-triazole, 5-hydroxyalkyl-1,2,3-triazoles and 5-quinoxaline-1,2,3-triazole, which provided an entry into structurally diverse 5-functionalized-1,2,3-triazoles.     

Metal-free and azide-free synthesis of 1,2,3-triazoles derivatives

1,2,3-Triazoles, significant five-membered ring N-heterocycles, are main structural moieties in well-designed materials, pharmaceutical agents, bioactive products, and synthetic intermediates. In the research of life sciences and pharmaceuticals, by seeing the spacious applications of 1,2,3-triazoles, the progress of metal-free method is exceedingly desirable to evade the heterocyclic product metal contamination. Moreover, on a larger scale, the toxicity and explosiveness of azides makes azides discommode and hard to hold, to synthesize 1,2,3-triazoles. The need to steer the development of the synthesis of 1,2,3-triazoles toward more maintainable synthesis is a pressing issue. There are rare methods to construct 1,2,3-triazoles under azide-free and metal-free environments. These rare methods are compiled in this review. The afford of the collection and compilation of azide-free and metal-free synthesis methodologies of 1,2,3-triazole in single podium is supportive and crucial for synthetic chemist to extend the diversity of the synthesis of 1,2,3-trizoles through green protocol.     

DFT calculations of CH acidity of substituted triazoles and experimental study of their ability to undergo mercuration

The CH acidity of all possible N-methyl substituted nitrotriazoles as well as of some 4-substituted 1,2,3-triazoles and N-alkyl-4-nitro-1,2,3-triazoles in the gas phase and in THF and DMSO solution has been calculated with the density functional theory B3LYP method. Electronic effects of substituents on the CH acidity of 4-substituted 1,2,3-triazoles have been examined using linear free energy relationship (LFER) methodology. In order to investigate the relation between the CH acidity of the heterocycles and their ability to undergo electrophilic substitution involving C-H bond cleavage, we have studied the reaction of isomeric N-alkyl-4-nitro-1,2,3-triazoles (alkyl=methyl, ethyl, isopropyl and tert-butyl) with HgBr₂ in alkali solution. It was found that 1-isomers undergo mercuration readily, while mercuration of 2-substituted compounds do not occur under the same conditions, which is in agreement with the results of DFT calculations of the CH acidity of the compounds, showing that 2-isomers have considerably lower CH acidity than 1-isomers.     

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.     

Solid-phase synthesis of 1,2,3-triazoles via 1,3-dipolar cycloaddition

The solid-phase synthesis of 1,2,3-triazoles via 1,3-dipolar cycloaddition of polymer-bound azides to various alkynes is reported. Polymer-bound azides were synthesized from polymer-bound halides and sodium azide and reacted with alkynes to produce polymer-bound 1,2,3-triazoles. Cleavage of the triazoles was performed with trifluoroacetic acid. A traceless synthesis of 1,2,3-triazoles was developed using 2-methoxy-substituted resin (polymer-bound 4-hydroxy-2-methoxybenzyl alcohol). In addition, a synthesis of 4-hydroxybenzyl-substituted 1,2,3-triazoles from the bromo-Wang resin (4-(bromomethyl)phenoxymethyl polystyrene) was achieved.     

Unusual Cu(I)-catalyzed 1,3-dipolar cycloaddition of acetylenic amides: formation of bistriazoles

C-carbamoyl-1,2,3-triazoles have recently attracted much interest due to their potent biological activity. While synthesizing C-carbamoyl-1,2,3-triazoles by the copper(I)-catalyzed 1,3-dipolar cycloaddition of organic azides 1 and acetylenic amides 2, we found that the expected 1,2,3-triazole products 3 were obtained as the only products in excellent yields when CuSO₄ and sodium ascorbate were used as the Cu(I)-catalyst. Surprisingly, the unexpected bistriazole products 4 were one of the major products obtained along with the 1,2,3-triazoles 3 when using a direct Cu(I)-catalyst such as CuI or CuBr.     

Quantum-chemical investigation of certain physicochemical properties of C-nitro-1,2,3-triazole and N-alkyl-4(5)-nitro-1,2,3-triazoles

Quantum-chemical calculations have been carried out on molecular electrostatic potentials, proton affinity in the gas phase, gas phase basicity, and pK _BH+ values in aqueous solution for C-nitro- and N-alkyl-4(5)-nitro-1,2,3-triazoles, and the relative stability of the isomeric N-alkyl-4(5)-nitrotriazoles (alkyl = Me, Et, i-Pr, t-Bu) in the gas phase and in aqueous solution. For all the studied substances in the gas phase the 2H-tautomer and the N(2)-isomers were considerably more stable than the corresponding N(1) compounds, and the 3H-tautomer and N(3)-isomer were the least stable. In aqueous solution 1- and 3-isomers had close values of energies, but in the case of C-nitro-1,2,3-triazole the 1H form became even more stable than the 2H-form. It was established which ring nitrogen atoms of 1,2,3-triazoles are protonated in the gas phase and in solution. The obtained data correlate well with the results of experimental investigations on the alkylation of 1,2,3-triazoles in acidic and basic media and of the experimental investigation on the alkylation of C-nitro-1,2,3-triazoles with diethyl sulfate carried out in the present work. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1816–1828, December, 2008.