Benzyl Azide Research Articles

Reactions of Organic Azides with Half‐sandwich Complexes of Iridium: Preparation of Mono‐ and Bis(imine) Derivatives

Imine complexes [IrCl(η5‐C5Me5){κ1‐NH=C(H)Ar}{P(OR)3}]BPh4 (1, 2) (Ar = C6H5, 4‐CH3C6H4; R = Me, Et) were prepared by allowing chloro complexes [IrCl2(η5‐C5Me5){P(OR)3}] to react with benzyl azides ArCH2N3. Bis(imine) complexes [Ir(η5‐C5Me5){κ1‐NH=C(H)Ar}2{P(OR)3}](BPh4)2 (3, 4) were also prepared by reacting [IrCl2(η5‐C5Me5){P(OR)3}] first with AgOTf and then with benzyl azide. Depending on the experimental conditions, treatment of the dinuclear complex [IrCl2(η5‐C5Me5)]2 with benzyl azide yielded mono‐ [IrCl2(η5‐C5Me5){κ1‐NH=C(H)Ar}] (5) and bis‐[IrCl(η5‐C5Me5){κ1‐NH=C(H)Ar}2]BPh4 (6) imine derivatives. In contrast, treatment of chloro complexes [IrCl2(η5‐C5Me5){P(OR)3}] with phenyl azide C6H5N3 gave amine derivatives [IrCl(η5‐C5Me5)(C6H5NH2){P(OR)3}]BPh4 (7, 8). The complexes were characterized spectroscopically (IR, NMR) and by X‐ray crystal structure determination of [IrCl(η5‐C5Me5){κ1‐NH=C(H)C6H4‐4‐CH3}{P(OEt)3}]BPh4 (2b).

Ruthenium(II)-cored supramolecular organic framework-mediated recyclable visible light photoreduction of azides to amines and cascade formation of lactams

Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reduction of phenyl, benzyl, 2-phenylethyl and 3-phenylpropyl azides in acetonitrile to produce the corresponding amines in good to high yields. For the last two kinds of azides that bear a CO2Me group at the para-position of the benzene ring, cascade reactions take place to generate the corresponding lactams in high yields. Compared with homogeneous control [Ru(bpy)3]Cl2, SMOF-1 exhibits remarkably increased photocatalysis activity as a result of synergistic effect of the [Ru(bpy)3]2+ units that form cubic cages to host the azide molecules and related intermediates. Moreover, SMOF-1 displays high recyclability and considerable photocatalysis activity after 3 to 12 runs.

Ligand‐Based Control of Single‐Site vs. Multi‐Site Reactivity by a Trichromium Cluster

AbstractThe trichromium cluster (tbsL)Cr3(thf) ([tbsL]6−=[1,3,5‐C6H9(NC6H4‐o‐NSitBuMe2)3]6−) exhibits steric‐ and solvation‐controlled reactivity with organic azides to form three distinct products: reaction of (tbsL)Cr3(thf) with benzyl azide forms a symmetrized bridging imido complex (tbsL)Cr3(μ3‐NBn); reaction with mesityl azide in benzene affords a terminally bound imido complex (tbsL)Cr3(μ1‐NMes); whereas the reaction with mesityl azide in THF leads to terminal N‐atom excision from the azide to yield the nitride complex (tbsL)Cr3(μ3‐N). The reactivity of this complex demonstrates the ability of the cluster‐templating ligand to produce a well‐defined polynuclear transition metal cluster that can access distinct single‐site and cooperative reactivity controlled by either substrate steric demands or reaction media.

Ligand-Based Control of Single-Site vs. Multi-Site Reactivity by a Trichromium Cluster.

The trichromium cluster (tbs L)Cr3 (thf) ([tbs L]6- =[1,3,5-C6 H9 (NC6 H4 -o-NSit BuMe2 )3 ]6- ) exhibits steric- and solvation-controlled reactivity with organic azides to form three distinct products: reaction of (tbs L)Cr3 (thf) with benzyl azide forms a symmetrized bridging imido complex (tbs L)Cr3 (μ3 -NBn); reaction with mesityl azide in benzene affords a terminally bound imido complex (tbs L)Cr3 (μ1 -NMes); whereas the reaction with mesityl azide in THF leads to terminal N-atom excision from the azide to yield the nitride complex (tbs L)Cr3 (μ3 -N). The reactivity of this complex demonstrates the ability of the cluster-templating ligand to produce a well-defined polynuclear transition metal cluster that can access distinct single-site and cooperative reactivity controlled by either substrate steric demands or reaction media.

Synthesis of Isoindoles from Intramolecular Condensation of Benzyl Azides with α-Aryldiazoesters.

Rh-catalyzed intramolecular condensation of the benzyl azides with α-aryldiazoesters was explored. The reaction proceeded through the nucleophilic attack of the organic azide onto a rhodium carbenoid, while releasing nitrogen gas, affording the α-imino esters as the primary product. Tautomerization of the imino esters efficiently gave 13 desired isoindoles with good to excellent yields.

Каталитическая активность медных наночастиц на аминомодифицированном силикагеле в реакции азид-алкинового циклоприсоединения в потоке с использованием макроциклических субстратов

Using the chemical reduction method, a copper-containing catalyst on an amino-modified silica was obtained. The structure and composition of the catalyst were characterized by low-temperature nitrogen adsorption and inductively coupled plasma mass spectrometry. It was found that the modification of silica with amino groups and copper nanoparticles leads to a significant change in textural characteristics: nanoparticles and the modifier fill the pores in the size range of 5-10 nm. Obtained catalyst showed good activity in the flow cycloaddition of azides and alkynes of various nature. The comparative activity of azides and alkynes was analyzed. It has been established that among the azides studied (benzyl azide, p-nitrobenzylazide, p-methoxybenzylazide, 2-azidoethylacetate and 1-azidodecane), alkyl and aryl azides with electron-withdrawing groups were most active due to an increase in the electrophilicity of the terminal nitrogen atom of the azide group. Among the studied acetylenes (phenylacetylene, hexin-1, trimethylsilylacetylene and propargyl alcohol), propargyl alcohol was the most and trimethylsilylacetylene was the less active. Increased activity of propargyl alcohol may be due to a donor hydroxyl group capable of coordinating with copper; reduced activity of trimethylsilylacetylene can be resulted from steric hindrances. p-tert-Butyl and p-H-calix[4]arens were also used in the reaction. Full conversion of macrocycles was achieved after 3 consecutive reaction cycles. The resulting triazoles were isolated and characterized by a complex of physical methods. Thus, It has been demonstrated that carrying out the reaction in a flow by maintaining stable and fully reproducible reaction parameters makes it possible to quickly evaluate the relative reactivity of molecules.

The Cytotoxic Activity of Honokiol‐Triazole Derivatives in Ovarian Cancer Cells

Honokiol‐triazole derivatives (4–17) were synthesized via click reactions between 2‐ or 4′‐propargylated honokiol and azide compounds. Their anticancer activities were evaluated by using two ovarian cancer cells (A2780 and OVCAR3). Among the 14 compounds, compound 5 coupled with 4′‐propargylated honokiol and benzyl azide exhibited relatively potent cytotoxic activity (IC50 = 5.5 ± 0.5 μM for A2780 and IC50 = 3.97 ± 0.6 μM for OVCAR3) but was less toxic to normal cells (IC50 = 18.90 ± 0.9 μM for IOSE80PC). The cytotoxic effect of compound 5 is associated with caspase‐dependent apoptotic cell death via induction of intracellular reactive oxygen species.

Terminal Acetylenic Iminium Salts: Cycloaddition Reactions with Azides Leading to 1,2,3‐Triazoles and Bicyclic 1,2,3‐Triazolium Salts

Terminal acetylenic iminium triflate salts [HC≡C‐C(R)=N+Me2 TfO–] represent very potent dipolarophiles which undergo [3+2] cycloadditions with aryl and benzyl azides at very mild and uncatalyzed conditions, yielding 1,4‐disubstituted 1,2,3‐triazoles with complete regioselectivity. Addition of nucleophiles at the iminium group of the cycloadducts leads to diverse 1‐aryl‐(or benzyl‐)‐4‐dimethylaminomethyl‐1,2,3‐triazoles. The first formed cycloaddition adducts subsequently react with a second molecule of the acetylenic iminium salt by a consecutive Michael addition/1,5‐cyclization to form 2,4‐dihydropyrrolo[1,2‐c][1,2,3]triazol‐7‐ium triflates. Further transformations of the latter salts are described, among them the conversion into a mesoionic carbene, isolated as a monomeric silver(I) complex.

Synthesis, Antibacterial and Antifungal Activities for Novel Derivatives of 2,2'-(((1-benzylbenzoimidazol-2-yl)methyl)azanediyl)bis(ethan-1-ol)

The compound 2,2'-(((1H-benzo(d)imidazol-2-yl)methyl)azanediyl)bis(ethan-1-ol) was reacted with benzyl bromide to afford compound (1) which used as row material to prepare a series of compounds through condensation reaction, the starting compound were reacted with tosyl chloride to protect the OH group to afford compound 2, then reacted benzyl bromide to produce compound (2), then the compound (2) treated with three compounds ( 2-mercaptobenzthiazole, 2-mercaptobenimidazol and 2-chloromethyl benzimidazole) to form compounds 3a,b, 4a,b and 5a,b respectively. In the another step the click reaction of compound 2,2'-(((1H-benzo(d)imidazol-2-yl)methyl)azanediyl)bis(ethan-1-ol) with Propargyl bromide produce compound 6 which reacted with sodium azide or benzyl azide to afford the compounds 7 and 8. The synthesized compounds were characterized and measured the physical properties via the FT-IR, HNMR, besides to the CHN analysis. These newly compounds were screened their antibacterial and antifungal activity. Compounds 1, 2a and 8 showed significant antibacterial activity as well these compounds exhibited either low or moderated antifungal activity.

Straightforward synthesis of amino-3-hydroxypyridin-4-one iron chelators via BBr3-mediated tandem reduction of azides and deprotection of methyl ether

A novel and straightforward BBr3-mediated tandem reduction of organic azide and demethylation of methyl ether were described. This method provides a new approach to prepare a series of new amino-3-hydroxypyridin-4-one iron chelators, which can be used in the treatment of iron also applicable to other substrates like benzyl azides and aryl azides.

A strained alkyne-containing bipyridine reagent; synthesis, reactivity and fluorescence properties

We report the synthesis of a bipyridyl reagent containing a strained alkyne, which significantly restricts its flexibility. Upon strain-promoted alkyne-azide cycloaddition (SPAAC) with an azide, which does not require a Cu catalyst, the structure becomes significantly more flexible and an increase in fluorescence is observed. Upon addition of Zn(ii), the fluorescence is enhanced further. The reagent has the potential to act as a fluorescent labelling agent with azide-containing substrates, including biological molecules.

Rhodium(iii)-catalyzed tandem reaction: efficient synthesis of dihydrobenzo thiadiazine 1-oxide derivatives

A tandem annulation reaction triggered by rhodium(iii)-catalyzed C–H bond functionalizations has been well developed for highly efficient synthesis of dihydrobenzo thiadiazine 1-oxide derivatives from free NH-sulfoximine and two-component benzyl azides.

In Situ Generation of Copper Nanoparticles by Rongalite and Their Use as Catalyst for Click Chemistry in Water

AbstractA novel, efficient and green protocol for the copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction by using copper nanoparticles (CuNPs), generated in situ by a green reducing agent, rongalite, is reported. Terminal alkynes reacted with benzyl, aryl and alkyl azides in the presence of copper nanoparticles and β ‐cyclodextrin (β‐CD) in water. The reactions exclusively generated the corresponding regiospecific 1,4‐disubstituted 1,2,3‐triazoles in good to excellent yields. Notably, in situ generation of copper nanoparticles does not require any additional stabilizing agents or special reaction conditions. β‐cyclodextrin plays dual role as a stabilizing agent as well as phase transfer catalyst. This protocol is also applicable for gram scale reactions.

Functionalization of luminescent lanthanide-gallium metallacrowns using copper-catalyzed alkyne-azide cycloaddition and thiol-maleimide Michael addition

The synthesis and characterization of {Ln[12-MCGaIIIN(eshi)-4]}2(iph)4 and {Ln[12-MCGaIIIN(shi)-4]}2(miph)4 metallacrowns (MCs), where shi3− is salicylhydroximate, eshi3− is 4-ethynylsalicylhydroximate, iph2− is isopthalate, and miph2− is 5-maleimidoisophthalate, is reported. The ethynyl functionality allows for coupling of MCs to azides using copper(I) catalyzed alkyne-azide cycloaddition (CuAAC), while the maleimido functionality allows for coupling of the MCs to thiol-bearing compounds. We demonstrate these coupling reactions using benzyl azide for the former and cysteamine for the latter, with complete conversion shown by ESI-MS. With the Sm analogues, the MCs exhibit characteristic luminescent emission of Sm(III), which is preserved after introducing the ethynyl and maleimido groups onto the MC scaffold. Furthermore, the high stability of these compounds in solution illustrates that once functionalized, the MCs are promising for fluorescent imaging applications.

Synthesis of 1,2,3-triazolyl-5-diethylphosphonate by domino reaction

The synthesis of 1,2,3-triazolyl-5-diethylphosphonate was studied by the domino reaction of benzyl azide, phenylacetylene and diethyl phosphite. The effect of the reaction stoichiometry, the atmosphere and the amount of the catalyst were investigated.

PEG‐DIL‐based MnCl42−: A novel phase transfer catalyst for nucleophilic substitution reactions of benzyl halides

Poly(ethylene glycol) dicationic ionic liquid‐based MnCl42− was prepared by nucleophilic substitution of poly(ethylene glycol) dichloride with methylimidazole followed by reaction with MnCl2. The structural properties of the catalyst were systematically investigated using Fourier transform infrared, UV–visible and Raman spectra and thermogravimetric analysis. The application of this catalyst allows the synthesis of a variety of benzyl thiocyanates and azides in high yield under reflux conditions in water. The main advantages of this method are its easy nature, rapidity, environmental benignity and high yields.

Synthesis of 1,4-Disubstituted 1H-1,2,3-Triazoles from 4-(1-Adamantyl)benzyl Azide through a 1,3-Dipolar Cycloaddition Reaction

A series of new 1,4-disubstituted 1H-1,2,3-triazole derivatives were synthesized by an efficient copper-catalyzed 1,3-dipolar cyclo­addition reaction of 4-(1-adamantyl)benzyl azide with several terminal alkynes. The copper catalyst was used to provide 1,4-disubstituted 1,2,3-triazoles regioselectively in good yields.

Evaluation of WO2014121383 A1: a process for preparation of rufinamide and intermediates

ABSTRACTIntroduction: There is great potential in the synthetic development of rufinamide to treat childhood-onset epilepsy known as Lennox–Gastaut syndrome (LGS).Areas covered: 1,4-disubstituted triazole ring formed by 1,3-dipolar cycloaddition reaction is an important structural motif widely used to construct diverse chemotypes in chemical, biological, and material fields. 1,2,3-triazole ring containing rufinamide, an antiepileptic drug developed by Novartis, is useful in combination with other antiepileptic medicaments for the treatment of childhood-onset epilepsy known as LGS. There are numerous synthetic methods used to construct the rufinamide through 1,3-dipolar cycloaddition. The application claims processes for the preparation of rufinamide and their intermediates. The synthetic strategy covered for the synthesis of rufinamide using activated acetylenic esters. The activation is done using N-hydroxy succinimide, N-hydroxyphthalimide, 1-hydroxy benzotriazole, and 4-nitro phenol.Expert opinion: The manufacturing route appears to follow the regioselective Cu catalyzed cycloaddtion of 2,6-difluro benzyl azide with or without isolated activated acetylenic esters in three steps that provide a good lead for new synthetic strategy for the rufinamide synthesis.

Catalytic Racemization of Activated Organic Azides

The first detailed description of the catalytic racemization of activated benzylic and allylic azides under mild conditions is reported. A kinetic analysis of the observed racemization indicates a first-order dependence on azide, a first-order dependence on catalyst, and that the rate of racemization correlates to σ+. A variety of azides with varying substitution patterns undergo facile racemization, and catalyst selection can tune this process.

Preparation and Reactions of Mono- and Bis-Pivaloyloxyzinc Acetylides.

Mono-pivaloyloxyzinc acetylide and bis-pivaloyloxyzinc acetylide were selectively prepared from ethynylmagnesium bromide in quantitative yields. These zinc reagents readily underwent Negishi cross-couplings with (hetero)aryl iodides or bromides as well as subsequent Sonogashira cross-couplings. 1,3-Dipolar cycloadditions of these zinc acetylides with benzylic azides produced zincated and bis-zincated triazoles which were trapped with several electrophiles. An opposite regioselectivity compared to the Cu-catalyzed click-reactions was observed.