Reaction Of Azide Research Articles

Capsules for Automated Azide-Alkyne Click Reactions.

The development of an automated and reproducible process for copper-mediated click reactions of alkynes and azides into 1,4-disubstituted 1,2,3-triazole products is described. This method utilizes prepacked capsules that contain all necessary reagents and materials for the reaction and purification processes. The reaction and product isolation steps are fully automated with no further user involvement, resulting in the triazole products in high purity. The effectiveness of capsule-based automated organic synthesis was further demonstrated by sequencing the automated synthesis of organic azides, followed by a second capsule for CuAAC with no intermediate purification.

Combination energetic materials consisting of strained rings combined with high heat of formation tetrazoles.

The reaction of cyanogen azide with strained-ring containing primary and secondary amines led to the isolation of energetic molecules deriving their energy content from both strained rings as well as aminotetrazoles. Azo-coupling of these materials afforded novel high-nitrogen energetic materials of very high sensitivity. All compounds were chemically characterized by IR, NMR, single-crystal X-ray crystallography, and high-resolution mass spectrometry. Their impact and friction sensitivities were experimentally determined, and their energetic performances were calculated.

Direct Utilization of Calcium Carbide with Transition Metal‐Free Condition to Synthesize of 1‐Monosubstituted‐1,2,3‐triazoles from Azides

AbstractThe utilization of calcium carbide as an acetylide specie was an increasing concern in chemical society. Under transition metal‐ and base free conditions, calcium carbide was successfully proved as the acetylide resource to synthesize 1‐monosubstituted‐1,2,3‐triazoles from nucleophilic addition with azides. In this reaction, aryl azides achieved corresponding 1,2,3‐triazoles in good to excellent yields, and a gram‐scale reaction of phenyl azide with calcium carbide was conducted with an excellent yield. Alkyl azides could also participate in the reaction to prepare corresponding 1,2,3‐triazoles with moderate yield. Calcium acetylide hydroxide Ca(OH)C≡CH might be the critical intermediate. The process provided a green and sustainable prospect to utilize calcium carbide resource.

4-(1H-Tetrazol-5-yl)-2-(p-tolyl)quinoline

The synthesis of 4-(1H-tetrazol-5-yl)-2-(p-tolyl)quinoline 4 as a possible modification of the biphenyltetrazole substructure of losartan 1 is described. The transformation of 2-(p-tolyl)quinoline-4-carbonitrile 3 to the corresponding tetrazole 4 was carried out by the reaction of trimethysilyl azide and dibutyltin oxide as a catalyst in refluxing toluene. The title compound (4) was characterized by IR, 1H NMR, 13C NMR, and HRMS.

Synthesis of 5-substituted-1H-tetrazoles by lemon juice as a homogeneous and natural catalyst under green reaction conditions

Tetrazole, as a heterocyclic compound, exhibits a wide spectrum of applications in various industries. This research focuses on utilizing a natural catalyst in the synthesis of tetrazole derivatives. Leveraging the acidic nature of lemon juice (LJ), we employed it as a potential catalyst in the synthesis of 5-substituted-1H-tetrazole. LJ would act as the reaction medium as well. This synthesis involves the cycloaddition reaction (3 + 2) of sodium azide to benzonitrile under solvent-free conditions. Optimization of the reaction conditions including temperature, reaction time, and solvent type was tuned towards the highest yield considering the mild reaction time. The best product yield (97 %) was obtained at 90 °C, 40 min, in the absence of additional solvent. Various benzonitrile derivatives were examined at the optimized reaction condition.

A Review of the Use of the Nickel Catalyst in Azide‐Alkyne Cycloaddition Reactions

ABSTRACTTrying to find beneficial and effective catalysis for synthesizing biologically active and valuable 1,2,3‐triazoles is continually being studied to make the procedure more efficient, green, and eco‐friendly. The click reaction is famous in green chemistry for its high selectivity and efficiency in generating 1,2,3‐triazoles with important pharmaceutical and biological activities. 1,3‐Dipolar cycloaddition reaction of organic azides and alkynes by copper‐mediated have a great deal of attention paid to and developed to provide 1,2,3‐triazoles. However, utilizing Cu(II) species frequently requires a reducing reagent, making this approach less atom‐economic. Recently, notable progress has been made in designing and developing metal‐catalyzed click reactions to prepare 1,2,3‐triazoles. As appropriate alternatives to copper catalysts, nickel catalysts can be a good choice in click reactions. This review thoroughly studies the excellent potential of nickel catalysts in azide‐alkyne cycloaddition reactions and recommends using them as proper alternatives to traditional copper catalysts. This review can pave the path for further application of nickel catalysts in click reactions.

Iron Corrole-Catalyzed Intramolecular Amination Reactions of Alkyl Azides. Spectroscopic Characterization and Reactivity of [FeV(Cor)(NAd)

As nitrogen analogues of iron-oxo species, high-valent iron-imido species have attracted great interest in the past decades. FeV-alkylimido species are generally considered to be key reaction intermediates in Fe(III)-catalyzed C(sp3)─H bond aminations of alkyl azides but remain underexplored. Here, it is reported that iron-corrole (Cor) complexes can catalyze a wide range of intramolecular C─H amination reactions of alkyl azides to afford a variety of 5-, 6- and 7-membered N-heterocycles, including alkaloids and natural product derivatives, with up to 3880 turnover numbers (TONs) and excellent diastereoselectivity (>99:1d.r.). Mechanistic studies including density functional theory (DFT) calculations and intermolecular hydrogen atom abstraction (HAA) reactions reveal key reactive FeV-alkylimido intermediates. The [FeV(Cor)(NAd)] (Ad = adamantyl) complex is independently prepared and characterized through electron paramagnetic resonance (EPR), resonance Raman (rR) measurement, and X-ray photoelectron spectroscopy (XPS). This complex is reactive toward HAA reactions with kinetic isotope effects (KIEs) similar to [Fe(Cor)]-catalyzed intramolecular C─H amination of alkyl azides.

A new route for the synthesis of multi-substituted pyrrole derivatives containing a sulfonyl scaffold via the chemistry of N-sulfonylketenimine

A rapid practical new synthesis of multi-substituted pyrrole derivatives with high yields through a novel four-component reaction of sulfonyl azides, terminal alkynes, nitro compounds, and trichloroacetonitril is a remarkable achievement in organic chemistry. This strategy offers a direct and efficient route to access complex molecular structures from readily available starting materials. To expand the work, the reaction of the final product with sulfinate salt under simple conditions and room temperature, poly-substituted pyrroles with sulfone functional group are formed. The combination of available starting materials, catalytic systems, mild reaction conditions, and ease of purification procedures contributes to the attractiveness of this method for the synthesis of diverse multi-substituted pyrrole derivatives.

Copper(I)-Catalyzed Formal [4 + 2] Cyclocondensation of ortho-Hydroxybenzyl Alcohol, Aromatic Terminal Alkynes, and Sulfonyl Azides: An Alternative Approach to 2-Sulfonyliminocoumarins.

In this paper, an alternative and efficient copper(I)-catalyzed synthesis of 2-sulfonyliminocoumarins is developed through a three-component reaction of ortho-hydroxybenzyl alcohol, alkynes, and p-toluenesulfonyl azide. The proposed route for access to the 2-iminocoumarin ring involves a [4 + 2] hetero-Diels-Alder reaction between ortho-quinone methide and ketenimine intermediates generated in situ.

Synthesis and reactivity of an N-heterocyclic carbene-stabilized diazoborane.

Diazo compounds and organic azides are widely used as reagents for accessing valuable molecules in multiple areas of fundamental and applied chemistry. Their capacity to undergo versatile chemical transformations arises from the reactive nature of an incipient dinitrogen molecule at the terminal position. In this work, we report the synthesis and characterization of an N-heterocyclic carbene (NHC)-stabilized diazoborane-a boron-centered analog of organic azides and diazoalkanes. The diazoborane displays a strong tendency to release dinitrogen, thus serving as a borylene source, in analogy to organic azides and diazoalkanes serving as nitrene and carbene sources, respectively. Also reminiscent of diazoalkane and organic azide reactivity, the diazoborane serves as a 1,3-dipole that undergoes uncatalyzed [3+2] cycloaddition with an unactivated terminal alkyne, affording a five-membered heterocycle after a two-step rearrangement.

First site-specific conjugation method for native goat IgG antibodies via glycan remodeling at the conserved Fc region.

Despite their triumph in treating human diseases, antibody therapies for animals have gained momentum more slowly. However, the first approvals of animal antibodies for osteoarthritic pain in cats and dogs may herald the dawn of a new era. For example, goats are vital to economies around the world for their milk, meat, and hide products. It is therefore imperative to develop therapies to safeguard goats-with antibodies at the forefront. Goat antibodies will be crucial in the development of therapeutic antibodies, for example, as tracers to study antibody distribution in vivo, reagents to develop other therapeutic antibodies, and therapeutic agents themselves (e.g., antibody-drug conjugates). Hamstringing this effort is a still-burgeoning understanding of goat antibodies and their derivatization. Historically, goat antibody conjugates were generated through stochastic chemical modifications, producing numerous attachment sites and modification ratios, thereby deleteriously impacting antigen binding. Site-specific methods exist but often require substantial engineering and have not been demonstrated with goat antibodies. Nevertheless, we present herein a novel method to site-specifically conjugate native goat antibodies: chemo-enzymatic remodeling of the native Fc N-glycan introduces a reactive azide handle, after which click chemistry with strained alkyne partners affords homogeneous conjugates labeled only on the Fc domain. This process is robust, and resulting conjugates retain their antigen binding and specificity. To our knowledge, our report is the first for site-specific conjugation of native goat antibodies. Furthermore, our approach should be applicable to other animal antibodies-even with limited structural information-with similar success.

Synthesis of 1,3-Dicarbonyl Azepines via Photoinitiated Reactions of Aryl Azides with Carbon-Based Nucleophiles.

A photoinduced one-pot method for the synthesis of azepines by the reaction of aryl azides with 1,3-dicarbonyl compounds under weakly basic conditions is described. This method offers a simple route for the synthesis of 1,3-dicarbonyl-substituted azepines in good to excellent yields and high regioselectivity and was tested on 1,3-dicarbonyl compounds with different acidity levels. The resulting azepines have electrophilic and nucleophilic centers of varying degrees of activity, which facilitate reactions leading to further structural transformations.

Continuous preparation and reaction of nonaflyl azide (NfN3) for the synthesis of organic azides and 1,2,3-triazoles

Organic azides are widely used in organic synthesis. Continuous flow processing can be used to bypass their isolation, and can therefore be useful in mitigating the hazards associated with these potentially toxic and explosive reagents. Nonaflyl azide has been reported as an effective, bench-stable, and relatively safe diazo transfer reagent that can be useful in the preparation of azides from amines and so avoid the use of alkyl halides. Here we demonstrate the synthesis and purification of nonaflyl azide in continuous flow with isolation of the neat, pure reagent by membrane filtration. The neat reagent was used in the preparation of organic azides from primary amines, and then applied to the synthesis of triazoles. A variety of triazoles, including the antiseizure drug Rufinamide, were prepared from primary amines and alkynes via the CuAAC click reaction in a semi-batch parallel array without isolation of alkyl azide intermediates. A telescoped two-stage continuous flow process was also designed and demonstrated to form triazoles via the same CuAAC reaction, which avoids the handling of the intermediate reactive azides.

Enantioselective copper-catalyzed azidation/click cascade reaction for access to chiral 1,2,3-triazoles

Chiral 1,2,3-triazoles are highly attractive motifs in various fields. However, achieving catalytic asymmetric click reactions of azides and alkynes for chiral triazole synthesis remains a significant challenge, mainly due to the limited catalytic systems and substrate scope. Herein, we report an enantioselective azidation/click cascade reaction of N-propargyl-β-ketoamides with a readily available and potent azido transfer reagent via copper catalysis, which affords a variety of chiral 1,2,3-triazoles with up to 99% yield and 95% ee under mild conditions. Notably, chiral 1,5-disubstituted triazoles that have not been accessed by previous asymmetric click reactions are also prepared with good functional group tolerance.

Synthesis and estrogenic activity of BODIPY-labeled estradiol conjugates

Novel BODIPY–estradiol conjugates have been synthesized by selecting position C-3-O for labeling. The conjugation strategy was based on Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) or etherification. Estradiol derivatives used as azide partners bearing an ω-azidoalkyl function through C4–C8-long linkers have been prepared. CuAAC reactions of estradiol azides with BODIPY alkyne furnished fluorescent 3-O-labeled conjugates bearing the triazole ring as a coupling moiety. Williamson etherifications of 3-O-(ω-bromoalkyl)-17β-estradiol derivatives with BODIPY-OH resulted in labeled conjugates connected with an ether moiety. Interactions of the conjugates with estrogen receptor (ER) were investigated using molecular docking calculations in comparison with estradiol. The conjugates occupied both the classical and alternative binding sites on human ERα, with slightly lower binding affinity to references estradiol and diethystilbestrol. All compounds have displayed reasonable estrogenic activity. They increased the proliferation of ER-positive breast cancer cell line MCF7 contrary to ER-negative SKBR-3 cell line. The most potent compound 13a induced the transcriptional activity of ER in dose-dependent manner in dual luciferase recombinant reporter model and increased progesterone receptor's expression, proving the retained estrogenic activity. The fluorescence of candidate compound 13a co-localised with the ERα. The newly synthesized labeled compounds might serve as good starting point for further development of fluorescent probes for modern biological applications. In addition to studying steroid uptake and transport in cells, e.g. in the processes of biodegradation of estrogen-hormones micropollutants, they could also be utilized in examination of estrogen-binding proteins.

Sustainable, recyclable and biodegradable castor oil-derived elastomers enabled by dynamic acetoacetyl formed amides

Developing sustainable, recyclable, and biodegradable elastomers with the mechanical properties comparable to commercial polymers presents a formidable challenge. To this end, we synthesize a kind of mechanically robust elastomers cross-linked by acetoacetyl formed amides (AFAs) through reacting biomass-based derivatives castor oil acetoacetates (ACO) and terephthaloyl diazides (TPD). Inspired by the transformation of acyl azides into isocyanates via Curtius rearrangement upon thermal treatment, we show for the first time that the reaction of acetoacetates and acyl azides could afford AFAs as well. The AFAs, which have been demonstrated dynamic in our previous works, impart excellent thermal recyclability and healability to the obtained elastomers. Upon controlling the content of AFAs, the mechanical properties and dielectric properties of the elastomers could be flexibly adjusted. Moreover, the elastomers exhibit notable biodegradability, degrading in soil within 24 weeks. We anticipate that this recyclable and biodegradable elastomer represents a promising alternative to its conventional, nonrecyclable polymer counterparts.

Improved determination of nitrate isotopes in irrigated agricultural areas and Bayesian mixing model quantification of nitrate sources and fate

Technological advancements in isotope techniques have been widely utilized in environmental pollution research, particularly for the monitoring of nitrate pollution in water. The utilization of pretreatment with an aqueous nitric acid solution offers numerous advantages in analyzing isotopic composition; however, there is still room for improvement regarding conversion efficiency, reduced reaction time, and cost control. In light of this, this study proposes an enhanced chemical conversion method that involves mitigating the interference caused by the nitrogen azide reaction during the pretreatment process, optimizing the purge gas to remove interfering factors, and improving the inlet device for measuring nitrous oxide. The improved method was applied to determine nitrate isotopes in the Ulansuhai Basin, Inner Mongolia and its reliability was verified through analytical results obtained from bacterial denitrification methods. The mean δ15N-NO3- and δ18O-NO3- values determined using the chemical transformation method were 4.85‰ and 23.44‰, respectively. Compared with the previous method, the improved method enhanced the maneuverability of precise control, the pretreatment time was reduced from 2 to 3 hours to 1.5 hours, and the experimental cost was scaled down to half of the original one. In addition, the contribution of each source was calculated by combining nitrate isotopes with a Bayesian stable isotope mixing model. It was found that manure sewage accounted for (50.1±22.6) % while soil nitrogen sources contributed (25.1±20.4) % to nitrate levels in Ulansuhai Lake's water. The chemical conversion methods successfully improved within this study can also be applied to other watersheds or regions. These research findings provide a valuable theoretical foundation for managing nitrogen sources within watersheds.

Study on the Effect of Nanoporous Copper Particle Size on Copper-Based Azide.

Preparing copper-based azide by in situ reaction is well-suited for MEMS processing technology and holds promising prospects in the field of MEMS micro-initiators. This study involved the preparation of porous copper with particle sizes of approximately 30 nm, 60 nm and 100 nm through powder sintering. These were used as precursors for a gas-solid in situ azide reaction to produce copper-based azide with varying morphologies and compositions. Copper-based azide micro-initiators were designed, and their output performance was evaluated using CL-20 and HNS-IV explosives. Analytical results revealed that the product from the reaction of the 100 nm precursor exhibited a lumpy and uneven structure with a conversion rate of 90.36%. The product from the 60 nm precursor reaction had a dense surface with a conversion rate of 94.56%, while the 30 nm precursor resulted in a needle-like form with a conversion rate of 92.82%. Detonation experiments demonstrated that the copper-based azide micro-initiators prepared with 100 nm of a porous copper precursor exhibited unstable output performance, requiring a 1.6 mg charge to successfully detonate CL-20 explosives. On the other hand, copper-based azide micro-initiators prepared from 60 nm and 30 nm of porous copper precursors exhibited stable output performance. A charge of 0.8 mg was adequate for reliably and consistently detonating CL-20 and HNS-IV explosives. The reduced particle size of the precursor enhanced the output performance of the copper-based azide micro-initiators, providing increased energy redundancy during detonation and improving overall usage reliability.

Synthesis of Multisubstituted 1,2,3-Triazoles: Regioselective Formation and Reaction Mechanism.

A synthetically useful approach to functionalized triazoles is described via the reaction of β-carbonyl phosphonates and azides. 1,4- and 1,5-disubstituted and 1,4,5-trisubstituted triazoles can be regio- and chemoselectively accessed under mild conditions in good to excellent yields (31 examples, up to 99%). A mechanism is proposed that rationalizes the avoidance of the 4-phosphonate byproducts, which is aligned with crystallographic and experimental evidence.

Copper-Catalyzed Synthesis of 4-CF3-1,2,3-Triazoles: An Efficient and Facile Approach via Click Reaction.

Incorporation of a trifluoromethyl group with 1,2,3-triazoles motifs was described. We explored a click reaction approach for regioselective synthesis of 1-susbstituted-4-trifluoromethyl-1,2,3-triazoles in which 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) reacts with commercial 2-bromo-3,3,3-trifluoropropene (BTP) to form 3,3,3-trifloropropyne (TFP) in situ. Arising from merits associated with the availability and stability of BTP, and the high efficiencies of CuI/1,10-Phenanthroline (Phen)-catalyzed cycloaddition reactions of azides with alkynes, this readily performed click process takes place to form the target 1,2,3-triazoles in high yields, and with a wide azide substrate scope. The potential value of this protocol was demonstrated by its application to a gram-scale reaction.