Regioselective synthesis of 1,4‐disubstituted triazoles using bis[(L)prolinato‐N,O]Zn complex as an efficient catalyst in water as a sole solvent

A concise, convenient and mild route for one‐pot regioselective synthesis of N‐aryl‐ and N‐alkyltriazoles in water as a sole solvent is reported. The methodology involves a three‐component reaction comprising aryl/alkyl‐alkyne, sodium azide and aryl/alkyl/allyl halide catalyzed by zinc(II) L ‐prolinate. Prominent features of our protocol are incorporation of transition metal catalyst other than copper, water as the reaction medium, recyclability of catalyst and avoidance of hazardous aryl azide as a reactant. Copyright © 2011 John Wiley & Sons, Ltd.     

Immobilized copper(II) on nitrogen‐rich polymer‐entrapped Fe3O4 nanoparticles: a highly loaded and magnetically recoverable catalyst for aqueous click chemistry

A heterogeneous magnetic copper catalyst was prepared via anchoring of copper sulfate onto multi‐layered poly(2‐dimethylaminoethyl acrylamide)‐coated magnetic nanoparticles and was characterized using various techniques. The catalyst was found to be active, effective and selective for one‐pot three‐component reaction of alkyl halide, sodium azide and alkyne, known as copper‐catalyzed click synthesis of 1,2,3‐triazoles. As little as 0.3 mol% of catalyst was found to be effective under the optimum conditions. The catalyst could also be recycled and reused up to seven times without significant loss of activity. Thermal stability, high loading level of copper on catalyst, broad diversity of alkyl/benzyl/allyl bromide/chloride and alkyl/aryl terminal alkynes without isolation of azide intermediate, and good to excellent yields of products make this procedure highly economical. Copyright © 2015 John Wiley & Sons, Ltd.     

Copper Salt of 12‐Tungstophosphoric Acid: An Efficient and Reusable Heteropoly Acid for the Click Chemistry

Three components coupling of alkyl bromide, sodium azide and alkyne has been achieved using a catalytic amount of copper‐exchanged phosphotungstic acid (Cu‐TPA) in the presence of triethyl amine in DMF to afford substituted triazoles in good yields with high selectivity. Interestingly, the coupling of alkyl azide with alkyne proceeds readily at room temperature to furnish 1,2,3‐triazoles in excellent yields. The catalyst can be recovered and reused for three to four subsequent runs with a minimal decrease of activity. The use of copper modified heteropolyacids makes this procedure simple, convenient and environmentally friendly.     

Curtius rearrangement of aromatic carboxylic acids to access protected anilines and aromatic ureas

The reaction of a chloroformate or di-tert-butyl dicarbonate and sodium azide with an aromatic carboxylic acid produces the corresponding acyl azide, presumably through the formation of an azidoformate. The acyl azide undergoes a Curtius rearrangement to form an isocyanate derivative which is trapped either by an alkoxide or by an amine to form the aromatic carbamate or urea. The reaction conditions are compatible with a variety of functional groups and allow the synthesis of a number of aniline derivatives containing alkyl, halide, nitro, ketone, ether, and thioether substituents. [reaction: see text]     

Copper-catalyzed azide-alkyne cycloaddition reaction in water using cyclodextrin as a phase transfer catalyst

1,4-Disubstituted-1,2,3-triazoles were obtained in excellent yields from azides and terminal alkynes in H(2)O in the presence of catalytic amount of β-cyclodextrin as a phase transfer catalyst. Also, a one-pot CuAAC reaction was carried out successfully, affording 1,4-disubstituted-1,2,3-triazoles in good to high yields starting from an alkyl bromide, sodium azide, and terminal alkyne.     

Silver-catalyzed regioselective carbomagnesiation of alkynes with alkyl halides and Grignard reagents

A silver-catalyzed carbomagnesiation of alkynes with alkyl halides and Grignard reagents afforded alkenyl Grignard reagents regioselectively, where the alkyl group of the alkyl halide, but not that of the Grignard reagent, was introduced into the alkyne. Application to δ-haloalkylacetylenes yielded cyclopentanes or a tetrahydrofuran containing an exo-methylene substituent via 5-exo-dig cyclization.     

An efficient one-pot synthesis of pyrrolines and tetrahydropyridines from their chloro-precursors via in situ aza-Wittig reaction

A simple and efficient method for synthesizing pyrrolines and tetrahydropyridines via an intramolecular aza-Wittig reaction has been achieved by microwave irradiation of the corresponding chloro-alkane derivatives in the presence of tertiary phosphite and sodium azide. The in situ formation of the alkyl azides makes this a facile and safe method for aza-Wittig reactions.     

Ligand‐free,copper‐catalyzed,one‐pot,three‐component synthesis of novel 1,2,3‐triazole‐linked indoles in magnetized water

Magnetized water (MW) is used as a green and new solvent‐promoting medium for the one‐pot, three‐component synthesis of novel 1,2,3‐triazole‐linked indoles catalyzed by copper iodide. A broad range of 2‐aryl‐1‐(prop‐2‐ynyl)‐1H‐indole‐3‐carbaldehydes were reacted with alkyl halides and sodium azide via copper‐catalyzed azide–alkyne cycloaddition reactions in MW in the absence of any ligand. This method offers the advantages of short reaction times, green procedure, low cost, simple work‐up, quantitative reaction yields, and no need for any organic solvent.     

Preparation of 1H‐1,2,3‐Triazoles by Cuprous Ion Mediated Cycloaddition of Terminal Alkyne and Sodium Azide

1H‐1,2,3‐triazoles can be prepared in good yield by the reaction of terminal alkyne and sodium azide in the presence of cuprous chloride at a temperature higher than 70°C. The alkyne is unactivated and the reaction has to be carried out under inert gas. At room temperature, the reaction first gives a Cu(I)‐azide complex which is converted to a Cu‐alkyne complex when the temperature is raised to higher than 70°C. The reaction of Cu(I)‐alkyne complex and azide ion dissociated from or coordinated to Cu(I) then gives 1H‐1,2,3‐triazoles.     

Microwave-assisted synthesis of highly functionalized guanidines on soluble polymer support

An efficient method for the N,N′-di(Boc)-protected guanidines containing piperazine and homopiperazine scaffolds has been developed under multi-step microwave irradiation. Followed by alkylation of carbamate-protected guanidines with various alkyl halides is also explored. This protocol proceeds via deprotonation of the acidic N-carbamate hydrogen of the guanidine by sodium hydride on soluble polymer support. In this manner, highly functionalized guanidines were obtained after cleavage from the support. The reaction is tolerant of a wide range of functional groups on both the alkyl halide and guanidine components. In addition, the reaction is sufficiently simple workup by precipitation in each step to yield the substituted guanidines in high purity. In conjunction with microwave irradiation and soluble polymer support, this method provides an efficient route to access highly functionalized guanidines.     

An efficient reagent for 5′-azido oligonucleotide synthesis

A new bromohexyl phosphoramidite was synthesized and used for the introduction of an azide function at the 5′-end of oligonucleotides after a treatment on solid support with sodium azide and sodium iodide. The corresponding 5′-azido oligonucleotide could be further used for ‘Click’ conjugation with alkyne derivatives or by Staudinger ligation.     

New Synthesis Method of N-Alkylation of Carbazole Under Microwave Irradiation in Dry Media.

Under microwave irradiation carbazole reacts remarkably fast with a number of alkyl halides to give N-alkyl derivatives of carbazole. The reaction were carried out with high yield by simply mixing carbazole with an alkyl halide which was adsorb on potassium carbonate.     

One-pot three-component synthesis of 1,4-disubstituted 1H-1,2,3-triazoles using green and recyclable cross-linked poly(4-vinylpyridine)-supported copper sulfate/sodium ascorbate in water/t-BuOH system

Cross-linked poly(4-vinylpyridine)-supported copper sulfate, [P₄-VP]CuSO4 as a green and recyclable, heterogeneous catalyst in the presence of sodium ascorbate (NaAsc), is reported for the regioselective synthesis of 1,4-disubstituted-1,2,3-triazoles from benzyl halides, sodium azide and terminal alkyne in water/t-BuOH (1/1:V/V) at 70 °C. Various alkyl halides and benzyl halides, with electron-withdrawing groups as well as electron-donating groups, were used for synthesis of various 1,4-disubstituted-1,2,3-triazoles in high yields. The present procedure offers as short reaction time and simple reaction work up. This catalyst can be recovered by simple filtration and recycled several consecutive runs without any loss of its efficiency.     

有机磷化合物的研究 X:五价膦(磷)酸酯与卤代烷在卤化钠存在下的酯烷基交换反应

A detailed study on the ester alkyl exchange reaction of various types of quinique-valent phosphorus esters with alkyl halide in the presence of sodium bromides was reported. This ester alkyl exchange reaction was evidently influenced by the structure of phosphorus esters and alkyl halides as well as by the nature of the halides of metal ions. In contrast with the reaction without sodium hadlide, the alkyl phosphinmate is more reactive than phosphonate and phosphate by treatment with alkyl halide in the presence of sodium halide. This is consistent with the high nucleophilicity of >P(CO)O- as leaving group. The reactivity of butyl halides was decreased in the following order: n-BuBr>i-BuBr=s-BuBr>t-BuBr. Alkyl iodide was proved to be more reactive than the corresponding bromide and chloride. However, the use of iodioe is limited by the formation of alkene resulted from the elimination of HI. These structural effects show the general characteristics of a nucleophilic substitution reaction. A reaction mechanism involving the formation of sodium salt intermecutiate was proposed based on the concept of HSAB principle. This reaction may, however, be used as a convenient method for the preparation of mixed esters of quinque-valent phosphorus acids.     

Microwave-Assisted,Multicomponent, Ecofriendly Synthesis of 3-Bihetaryl-2-oxindole Derivatives Grafted with Phenothiazine Moiety

A series of 3-(3′-pyrrolyl)-2-oxindoles incorporating the phenothiazine moiety has been synthesized under both conventional and microwave heating conditions via multicomponent reaction of 3-(2-(phenothiazin-2-yl)-2-oxoethylidene)-2-oxindole derivatives, acyclic and cyclic 1,3-dicarbonyl compounds, and ammonium acetate. The resulting 2-oxindole derivatives underwent selective chloroacetylation at both the oxindole and the phenothiazine NH groups. Treatment of the dichloroacetylated compound with 2 mol of sodium azide in acetone under reflux gave the corresponding monoazide with concomitant dechloroacetylation of the N-chloroacetyl group of the oxindole ring. Huisgen 1,3-dipolar cycloaddition of the resulted alkyl azide with diethyl acetylene–dicarboxylate afforded the corresponding triazole derivative in good yield. Furthermore, the dichloroacetylated compound could be easily cyclized into 4-(3-oxo-2,3-dihydroxazolo[3,2-a]indol-9-yl)-1H-pyrrole-3-carboxylate derivative by treatment with sodium hydride in dry toluene. The yields and rate of reactions significantly improved under microwave heating conditions.     

Aqueous bile salt accelerated cascade synthesis of 1,2,3-triazoles from arylboronic acids

A facile, efficient and mild copper catalyzed strategy for cascade synthesis of various 1,4-disubstituted 1,2,3-triazoles from arylboronic acids, sodium azide and alkynes was developed by using aqueous bile salt NaDC solution as an accelerating medium. Low catalyst loading (only 1?mol% Cu source was sufficient for in situ generation of azide followed by azide–alkyne coupling), green solvent, use of bio-surfactant as additive and short reaction time make this protocol highly accessible and environment friendly.     

A convenient and efficient synthesis of C-carbamoyl-1,2,3-triazoles from alkyl bromide by a one-pot sequential addition: conversion of ester to amide using Zr(Ot-Bu)4

A convenient and efficient one-pot sequence has been developed for the synthesis of C-carbamoyl-1,2,3-triazoles from alkyl bromide using (i) sodium azide, (ii) methyl propiolate and copper iodide, and (iii) amines, zirconium tert-butoxide, and 1-hydroxybenzotriazole, under microwave irradiation. The sequential reactions in one-pot provided the desired C-carbamoyl-1,2,3-triazoles in excellent yields.     

Base-promoted reactions of bridged ketones and 1,3- and 1,4-haloalkyl azides: competitive alkylation vs azidation reactions of ketone enolates

The reactions of 1,3- and 1,4-haloalkyl azides with enolates of 2-norbornanone (and a ring-expanded analog) afford polycyclic 1,2,3-triazolines in good yields. The reaction occurs by the initial azidation of the ketone enolate, followed in order by triazoline formation and O-alkylation. An interesting element of this process is the preferential reaction of the alkyl azide with an enolate anion as opposed to the more familiar reaction of the alkyl halide (including Cl and I derivatives). Reactions of acyclic or monocyclic enolates generally lead to 1,2,3-triazoles but none of the alternative C-alkylation product.     

Synthesis and characterisation of luminescent rhenium tricarbonyl complexes with axially coordinated 1,2,3-triazole ligands

A series of 1-alkyl-4-aryl-1,2,3-triazoles (1-methyl-4-phenyl-1,2,3-triazole (1a); 1-propyl-4-phenyl-1,2,3-triazole (1b); 1-benzyl-4-phenyl-1,2,3-triazole (1c); 1-propyl-4-p-tolyl-1,2,3-triazole (1d)) have been prepared through a one-pot procedure involving in situ generation of the alkyl azide from a halide precursor followed by copper catalysed alkyne/azide cycloaddition (CuAAC) with the appropriate aryl alkyne. Cationic Re(I) complexes [Re(bpy)(CO)(3)(1a-d)]PF(6) (2a-d) were then prepared by stirring [Re(bpy)(CO)(3)Cl] with AgPF(6) in dichloromethane in the presence of ligands 1a-d. X-ray crystal structures were obtained for 2a and 2b. In the solid state, 2a adopts a highly distorted geometry, which is not seen for 2b, in which the plane of the triazole ligand tilts by 13° with respect to the Re-N bond as a result of a π-stacking interaction between the Ph substituent and one of the rings of the bpy ligand. This π-stacking interaction also results in severe twisting of the bpy ligand. Infrared spectra of 2a-d exhibit ν(CO) bands at ～2035 and ～1926 cm(-1) suggesting that these ligands are marginally better donors than pyridine (ν(CO) = 2037, 1932 cm(-1)). The complexes are luminescent in aerated dichloromethane at room temperature with emission maxima at 542 to 552 nm comparable to that of the pyridine analogue (549 nm) and blue shifted relative to the parent chloride complex. Long luminescent lifetimes are observed for the triazole complexes (475 to 513 ns) in aerated dichloromethane solutions at room temperature.