Novel Synthesis of 1,2,3-Triazoles via 1,3-Dipolar Cycloadditions of Alkynes to Azides in Ionic Liquid^＋

2-Azido-3,5-dichloropyridine and 2-azido-5-chloro-3-fluoropyridine were given by reaction of sodium azide with 2,3,5-trichloropyridine, 3,5-dichloro-2-fluoropyridine or 5-chloro-2,3-difluoropyridine in ionic liquids. 1,3-Dipolar cycloaddition of 2-azido-3,5-dichloropyridine or 2-azido-5-chloro-3-fluoropyridine to alkynes in ionic liquids afforded the corresponding 1,4,5-trisubstituted [1,2,3]-triazoles in good yields and regioselectivities.     

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.     

Novel sydnone derivatives carrying azidomethyl-1,2, 4-oxadiazole unit and their 1,3-dipolar cycloadditions

A series of 1,2,4-oxadiazolymethyl sydnones carrying azido group were synthesized and subjected to react with a variety of alkenic and acetylenic dipolarophilic reagents; N-phenyl maleimide, phenyl vinyl sulfone, and phenyl propiolic acid. All the new products are identified by spectral/physical data including high-resolution mass measurements and X-ray diffraction data.     

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。     

Regioselective Synthesis of 5-Trifluoromethyl 1,2,4-Triazoles via [3 + 2]-Cycloaddition of Nitrile Imines with CF3CN

We herein describe a general approach to 5-trifluoromethyl 1,2,4-triazoles via the [3 + 2]-cycloaddition of nitrile imines generated in situ from hydrazonyl chloride with CF₃CN, utilizing 2,2,2-trifluoroacetaldehyde O-(aryl)oxime as the precursor of trifluoroacetonitrile. Various functional groups, including alkyl-substituted hydrazonyl chloride, were tolerated during cycloaddition. Furthermore, the gram-scale synthesis and common downstream transformations proved the potential synthetic relevance of this developed methodology.     

One-Pot Synthesis of 1,2,3-Triazoles using Polymer-Supported Propyne in Aqueous Solution

A practical and efficient liquid-phase synthesis of 1,2,3-triazoles using poly（ethylene glycol） as support in aqueous solution was described. The title compounds, 1,2,3-triazoles 5 were obtained by a one-pot three-component 1,3-dipolar cycloaddition reaction in middle yields. In addition, a series of unexpected products 7 of Sonogashira reaction were also formed under the same condition.     

One-Pot Synthesis of Novel Spiro Pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine Derivatives

In a one-pot synthesis, 1′-methyl-2,3″-dioxo-5″-aryl-1,2,5a″,7″,8″,9a″-hexahydro-5″H,6″H-dispiro[indole-3,2′-pyrrolidine-3′,2″-pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine]-4′-carboxylic acid methyl ester was prepared via the sequential reaction of 4-aryl-octahydro-pyrano[2,3-d]pyrimidine-2-thione, dimethyl acetylenedicarboxylate (DMAD), and a mixture of isatin and sarcosine. All the novel spiro compounds, in moderate yields, were characterized thoroughly by infrared, NMR, mass spectromentry, and elemental analysis together with x-ray crystallographic analysis.     

Synthesis of Naphtho[2,1-b]pyrano Pyrrolothiazole Derivatives through 1,3-Cycloaddition Reaction

Facile synthesis of a series of naphtho[2,1,b]pyrano pyrrolo thiazoles was accomplished in good yields in a one-pot reaction through intramolecular 1,3-dipolar cycloaddition of cyclic azomethine ylides with Baylis–Hillman adducts as dipolarophiles. The protocol is applicable to a wide variety of photochromic and biologically active napthopyrano products. The regio- and stereochemical outcome of the cycloaddition reaction was ascertained by x-ray crystallographic study of one of the cycloadducts.     

Facile One-Pot Synthesis of 1,2,3-Triazoles Featuring Oxygen,Nitrogen, and Sulfur Functionalized Pendant Arms

A practical and efficient one-pot synthesis of novel 1,2,3-triazoles featuring nitrogen, oxygen, and sulfur functionalized pendant arms has been developed. The click reaction of mono-propargyl derivatives supported by aniline, thiophenol, and benzyl alcohol, with sodium azide and p-substituted benzyl halogenides, renders a series of N-substituted-1,2,3-triazoles in good yields under mild reaction conditions. The catalyst system was based in Cu(OAc)₂ · H₂O, sodium L-ascorbate, and 1,10-phenanthroline monohydrate, and all reactions were performed in a mixture H₂O–ethanol (4:1 v/v). Additionally, the preparation of bis-1,2,3-triazoles supported by di-propargylated aniline was carried out, demonstrating the versatility of the present methodology.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Stereoselective Synthesis of Novel Dispiro Oxindole-pyrrolothiazole-androsterone Hybrids

A facile synthesis of novel dispiro oxindole-pyrrolothiazole-androsterone hybrid heterocycles has been achieved through 1,3-dipolar cycloaddition. The reaction proceeds stereo- and regioselectively, affording a single isomer of the product in excellent yields with the formation of two C–C and one C–N bonds and creation of four new contiguous stereocenters in one step.     

Reaction of 2-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carbaldehyde oximes with electron-deficient olefins and acetylenes

A facile oxime-nitrone isomerization through the 1,2-hydrogen shift in 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carbaldehyde oximes is discussed. The resultant NH-nitrones are trapped by maleimides to afford intermolecular cycloadducts. The reaction of the oximes with electron-deficient acetylenes undergoes via another path initiated by a nucleophilic attack of the oxime to acetylene moiety.     

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.     

噁二唑并[5,4-d][1,5]苯并硫氮杂衍生物的合成、表征及晶体结构

以1,5-苯并硫氮杂(1a～1o)为原料, 在三乙胺作用下与α-氯代喹喔啉-2-甲醛肟(2)发生1,3-偶极环加成反应得到一系列噁二唑并[5,4-d][1,5]苯并硫氮杂衍生物3a～3o. 产物的结构经元素分析、IR和1H NMR确认. 并用X射线衍射法测定了化合物3a的晶体结构. 化合物3a属三斜晶系, 空间群P-1, 晶胞参数: a＝0.97376(19) nm, b＝1.0017(2) nm, c＝1.3526(3) nm, α＝78.50(3)°, β＝84.30(3)°, γ＝68.26(3)°, Mr＝486.58, V＝1.2005(4) nm3, Dc＝1.346 Mg/m3, Z＝2, F(000)＝508.     

Synthesis and cytotoxicity of oxindoles dispiro derivatives with thiohydantoin and adamantane fragments

Abstract

An effective and highly regio- and diastereoselective one-pot synthesis of two types of dispiro heterocyclic systems (2-thioxodispiro[imidazolidine-4,3′-pyrrolidine-2′,3″-indoline]-2″,5-diones and 2-thioxodispiro[imidazolidine-4,3′-pyrrolidine-4′,3″-indoline]-2″,5-diones) comprising pyrrolidinyl-oxindole, thiohydantoin and adamantane moieties has been developed based on a 1,3-dipolar cycloaddition of azomethine ylides, generated from isatin and sarcosine or formaldehyde and sarcosine, to adamantane-containing electron-deficient alkenes. Several molecules have demonstrated a considerable cytotoxicity against A549, HEK293T, MCF7 and VA13 cancer cell lines. The possible mechanism of anticancer activity of the synthesized compounds based on literature data may be the inhibition of p53/MDM2 interaction; however, we did not observe significant p53 activation using a reporter construction in A549 cell line in the relevant concentration range.     

3-(4-β-D-吡喃阿洛糖苷苯基)-4-胺羰基-5-甲氧羰基异噁唑衍生物的 合成及其镇静活性的研究

4-(β-D-吡喃阿洛糖苷)-α-氯代苯甲醛肟与N-芳基马来酰亚胺在三乙胺作用下, 以甲醇为溶剂, 通过1,3-偶极环加成, 合成了一系列未见文献报道的3-(4-β-D-吡喃阿洛糖苷苯基)-4-胺羰基-5-甲氧羰基异噁唑衍生物; 其结构经1H NMR, IR, MS (HRMS)加以确证. 并对4a～4h和5a进行了药理活性筛选, 结果表明, 部分化合物具有良好的镇静活性. 其中, 化合物4b (200 mg•kg－1), 4c (200 mg•kg－1), 4h (200 mg•kg－1), 与豆腐果苷相比较具有更强的活性.     

Efficient One-Pot,Four-Component Synthesis of 1,2,3-Triazole-Linked Tetrahydrobenzo[b]pyrans

A one-pot procedure has been developed for the synthesis of (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4H-chromene derivatives by concurrent reaction of aryloxy propargylated aldehydes, various azides, active methylene compounds, and 1,3-cyclohexanediones using catalytic amounts of Cu(OAc)₂ / sodium ascorbate and diammonium hydrogen phosphate in aqueous ethanol media. Excellent conversion of starting materials was achieved to the desired (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4H-chromene products.     

Asymmetric Synthesis of Tetrahydroisoquinoline Derivatives through 1,3-Dipolar Cycloaddition of C,N-Cyclic Azomethine Imines with Allyl Alkyl Ketones

A [3 + 2] 1,3-Dipolar cycloaddition of C,N-cyclic azomethine imines with allyl alkyl ketones has been achieved. The reaction proceeds under mild conditions and tolerates a wide range of functional groups. An array of tetrahydroisoquinoline derivatives is generally constructed with good diastereoselectivities and enantioselectivities (up to >25:1 dr, >95% ee). Moreover, the absolute configuration of the product was previously determined by using the quantum electronic circular dichroism calculation and ECD spectrum method.