Reduction Of Azides Research Articles

Characterization of Iminobismuthanes and Catalytic Reduction of Organic Azides via Bi(I)/Bi(III) Redox Cycling

Characterization of Iminobismuthanes and Catalytic Reduction of Organic Azides via Bi(I)/Bi(III) Redox Cycling

Characterization of Iminobismuthanes and Catalytic Reduction of Organic Azides via Bi(I)/Bi(III) Redox Cycling.

We report the stoichiometric and catalytic reactivity of organobismuth(I) complexes with organic azides. Treatment of N,C,N-pincer bismuthinidenes with organic azides (acyl, sulfonyl, and bulky aryl) results in isolable monomeric iminobismuthanes which can be structurally characterized-including the formal Bi=N double bond-by multinuclear NMR spectroscopy and single-crystal X-ray diffraction. Building upon the stoichiometric reactivity of the monomeric iminobismuthanes, catalytic reduction of a broad range of organic azides is developed. DFT calculations of the catalytic reaction pathway support the redox nature of the overall process.

Determination of lethal dose and growth reduction of EMS and sodium azide treated dragon fruit (Hylocereus spp.) cultivars

Determination of lethal dose and growth reduction of EMS and sodium azide treated dragon fruit (Hylocereus spp.) cultivars

Catalysed Aryl Amine Syntheses via Azides: From Azidation of Aryl Halides to Azide Reduction and Direct Amination

AbstractThis review summarises and discusses aryl amine and azide syntheses from aryl halides employing azides. The majority of the reported reactions proceed with copper catalysis or mediation. Often, an aryl azide is formed in the first step, which is then reduced in situ to an aryl amine in a second step. The occurrence of the second step, the reduction, depends on the chosen reaction conditions and the substrates. The formation of only aryl azides through Cu‐mediated C−N bond formations is discussed, followed by mediated and catalytic aryl azide reduction employing different catalytic systems, and azidation with in situ azide reduction to amines, viz. azidation‐amination strategies. The azidation‐amination allows for the synthesis of complex heterocycles in multi‐step one‐pot procedures, of which several are summarised here. Examples of the application of azidation‐amination for synthesising important aryl amines employed in or as biologically active compounds, catalysis and materials science are also summarised. Finally, conducted control reactions have been collected and discussed in combination with mechanistic proposals. This literature survey allows us to pinpoint design criteria for the azide reduction to valuable amines, which includes the choice of reaction conditions such as solvent system and additives, involved metal and promising substrates.

Regioselective quinazoline C2 modifications through the azide-tetrazole tautomeric equilibrium.

2-Chloro-4-sulfonylquinazolines undergo functional group swap when treated with an azide nucleophile: 1) the azide replaces the sulfonyl group at the C4 position; 2) the intrinsic azide-tetrazole tautomeric equilibrium directs the nucleofugal sulfinate from the first step to replace chloride at the C2 position. This transformation is effective with quinazolines bearing electron-rich substituents. Therefore, the title transformations are demonstrated on the 6,7-dimethoxyquinazoline core, which is present in pharmaceutically active substances. The methodology application is showcased by transforming the obtained 4-azido-6,7-dimethoxy-2-sulfonylquinazolines into the α1-adrenoceptor blockers terazosin and prazosin by further C2-selective SNAr reaction and azide reduction.

Practical Synthesis from Streptomycin and Regioselective Partial Deprotections of (-)-(1R,2S,3R,4R,5S,6S)-1,3-Di(deamino)-1,3-diazido-2,5,6-tri-O-benzylstreptamine.

We describe the gram-scale synthesis of (-)-(1R,2S,3R,4R,5S,6S)-1,3-di(diamino)-1,3-diazido-2,5,6-tri-O-benzylstreptamine from streptomycin by (i) hydrolysis of the two streptomycin guanidine residues, (ii) reprotection of the amines as azides, (iii) protection of all alcohols as benzyl ethers, and (iv) glycosidic bond cleavage with HCl in methanol. Protocols for regioselective monodebenzylation and regioselective reduction of a single azide in the product are also described, providing four optically pure building blocks for exploitation in novel aminoglycoside synthesis.

Myoglobin-Catalyzed Azide Reduction Proceeds via an Anionic Metal Amide Intermediate.

Nitrene transfer reactions catalyzed by heme proteins have broad potential for the stereoselective formation of carbon-nitrogen bonds. However, competition between productive nitrene transfer and the undesirable reduction of nitrene precursors limits the broad implementation of such biocatalytic methods. Here, we investigated the reduction of azides by the model heme protein myoglobin to gain mechanistic insights into the factors that control the fate of key reaction intermediates. In this system, the reaction proceeds via a proposed nitrene intermediate that is rapidly reduced and protonated to give a reactive ferrous amide species, which we characterized by UV/vis and Mössbauer spectroscopies, quantum mechanical calculations, and X-ray crystallography. Rate-limiting protonation of the ferrous amide to produce the corresponding amine is the final step in the catalytic cycle. These findings contribute to our understanding of the heme protein-catalyzed reduction of azides and provide a guide for future enzyme engineering campaigns to create more efficient nitrene transferases. Moreover, harnessing the reduction reaction in a chemoenzymatic cascade provided a potentially practical route to substituted pyrroles.

Self-detachable protecting group function of CO2 in the electrochemical reduction of aryl azides

A unique self-detachable protecting group function of CO2 and its application in the electrochemical reduction of aryl azides are demonstrated.

Intramolecular C-H bond amination catalyzed by myoglobin reconstituted with iron porphycene

C−H bond amination is an effective way to obtain nitrogen-containing products. In this work, we demonstrate that myoglobin reconstituted with iron porphycene (rMb(FePc)) catalyzes intramolecular C(sp3)−H bond amination of arylsulfonyl azides to yield corresponding sultam analogs. The total turnover number of rMb(FePc) is up to 5.7 × 104 for the C−H bond amination of 2,4,6-triisopropylbenzenesulfonyl azide. Moreover, rMb(FePc) exhibits higher selectivity for the desired C-H bond amination than the competing azide reduction compared to native myoglobin. Kinetic studies reveal that the kcat value of rMb(FePc) is 4-fold higher than that of native myoglobin. Furthermore, H64A, H64V and H64I mutants of rMb(FePc) enhance the turnover number (TON) and enantioselectivity for the C−H bond amination of 2,4,6-triethylbenzenesulfonyl azide. The present findings indicate that iron porphycene is an attractive artificial cofactor for myoglobin toward the C−H bond amination reaction.

Ring Transformation of α‐Amino‐β‐oxoesters to δ‐Butyrolactams

Abstractδ‐Butyrolactams with an exocyclic ester moiety in the δ‐position were accessed by reduction of 1‐azido‐2‐cyclopentanone carboxylates with PBu3 or Zn−AcOH. The ring transformation proceeded readily under the conditions of this reduction which is an unprecedented process. Primary amines formed by catalytic hydrogenation of α‐azido‐β‐oxoesters with larger ring sizes or with benzannulation do not show this rearrangement under the conditions of the azide reduction. In these cases, the ring transformation to respective lactams was achieved by treatment of the α‐amino‐β‐oxoesters with a stoichiometric amount of lithium diisopropylamide.

Iron-Catalyzed Synthesis of α-Azido α-Amino Esters via the Alkylazidation of Alkenes.

An iron-catalyzed alkylazidation of dehydroamino acids using peroxides as alkyl radical precursors is described. Non-natural azidated amino esters bearing an α-alkyl chain could be obtained in 18-94% yields using TMSN3 as an azide source. The obtained α-alkyl-α-azide α-amino esters could be further functionalized through cycloaddition or azide reduction with amide couplings to afford aminal-type peptides, α-triazolo amino acids, and tetrahydro-triazolopyridine, showing the great versatility of this now easily accessible class of amino acids.

Flow chemistry based catalytic hydrogenation for improving the synthesis of 1-deoxynojirimycin (DNJ) from an l-sorbose derived precursor

1-Deoxynojirimycin (1-DNJ) is a glycoprocessing inhibitor, and it serves as a synthetic precursor to two of three currently marketed iminosugar drugs, miglustat (N-butyl DNJ/Zavesca®) and miglitol (Glyset®). Herein a continuous flow procedure is presented that shortens a synthesis of 1-DNJ from an intermediate prepared from l-sorbose. Batch reactions involving an azide reduction, subsequent reductive amination-based cyclisation, and O-benzyl deprotection in a previous report required two steps and the use of an acid. Here, this sequence is achieved in one step using the H-Cube® MiniPlus continuous flow reactor. Subsequent reductive amination of 1-DNJ with butanal using the H-Cube® gave NB-DNJ.

An Insight into the Asymmetric Resolution of 1‐Aminoindane Derivatives

AbstractCompounds with 1‐aminoindane motif exhibit vital biological activities in the central nervous system. Therefore, it is very important to synthesize new compounds with this moiety and to obtain them in high enantiopurity. In this study, novel substituted 1‐aminoindane derivatives were synthesized, and their asymmetric resolutions were carried out. Accordingly, the reduction of 1‐indanones with NaBH4, conversion of alcohols to azides via an alternative Mitsunobu reaction followed by reduction of azides afforded (±)‐1‐aminoindane hydrochloride or hydrobromide salts. Amine salts were converted into their free amines by using excess amount of Et3N and then in situ occurred free (±)‐amines were reacted with (R)‐O‐acetylmandeloyl chloride to give diastereomeric mixtures. The crystallization of the diastereomeric mixtures followed by hydrolysis yielded the corresponding asymmetric amines with high enantio‐purity.

A bio-friendly biotin-coupled and azide-functionalized naphthalimide for real-time endogenous hydrogen sulfide analysis in living cells

Hydrogen sulfide (H2S) is involved in various biological processes. Thereby, abnormal levels of H2S are reported to be related to various human diseases including cancer. Currently, many fluorescent probes are pioneered to detect H2S by taking advantages of naphthalimides’ unique internal charge transfer (ICT) property. However, most probes often require a high content of organic solvents or surfactants, and are limited to the analysis of exogenous H2S treated externally in live cell studies, and have difficulties in analyzing endogenous H2S, thus limiting their practical use. In this study, we developed a bio-friendly biotin-coupled and azide-functionalized naphthalimide (1) as a fluorescent probe enabling real-time analysis of H2S in living system. Probe was able to provide a fluorescence at 545 nm via H2S-mediated azide reduction selectively without interference by biologically abundant constituents and pH effects. In a biological study using A549 cells, probe readily penetrated living cells without cytotoxicity, and unreacted probes showed almost no fluorescence, enabling real-time detection of H2S in living cells without requiring separate washing process. More importantly, under stimulation with various H2S inducers and inhibitors, probe was able to provide an effective fluorescence response against fluctuations in endogenous H2S, a key requirement for H2S studies. Probe 1 can be applied as a useful chemical tool and enables the analysis of H2S and the study of H2S-related cell functions in a variety of environments.

Kinetic and mechanistic studies of the Staudinger reduction: On the chemistry of aryl phosphazides

AbstractThe Staudinger reduction of heteroaryl azides containing an N‐oxide moiety with triphenylphosphine in mixed aqueous/THF solutions yields a mixture of amine and iminophosphorane products. A product analysis study using a combination of 1H and 31P NMR spectroscopic techniques indicates that in these systems, even under mild conditions, the amine product is generated, not from the hydrolysis of the iminophosphorane as expected from the standard reaction mechanism, but via hydrolysis of the phosphazide intermediate. The amount of amine generated is dependent on the structure of the starting azides, the composition of solvent, and the reaction conditions. The possible mechanisms of amine formation under acidic, neutral, and basic conditions are discussed.

Ortho-Phosphinoarenesulfonamide-Mediated Staudinger Reduction of Aryl and Alkyl Azides.

Conventional Staudinger reductions of organic azides are sluggish with aryl or bulky aliphatic azides. In addition, Staudinger reduction usually requires a large excess of water to promote the decomposition of the aza-ylide intermediate into phosphine oxide and amine products. To overcome the challenges above, we designed a novel triaryl phosphine reagent 2c with an ortho-SO2NH2 substituent. Herein, we report that such phosphine reagents are able to mediate the Staudinger reduction of both aryl and alkyl azides in either anhydrous or wet solvents. Good to excellent yields were obtained in all cases (even at a diluted concentration of 0.01 M). The formation of B-TAP, a cyclic aza-ylide, instead of phosphine oxide, eliminates the requirement of water in the Staudinger reduction. In addition, computational studies disclose that the intramolecular protonation of the aza-ylide by the ortho-SO2NH2 group is kinetically favorable and responsible for the acceleration of Staudinger reduction of the aryl azides.

Front Cover Picture: Cu(I) Mediated Azidation of Halobenzenes, and Cu Catalysed Selective Azide Reduction to Corresponding Amines (Adv. Synth. Catal. 17/2022)

The front cover image illustrates the complex mixture of a selective copper-mediated reaction of a bromobenzene bearing a bromoalkanoyl chain to an amine-azide. It proceeds stepwise via a bis-azide intermediate and produces copper nanostructures simultaneously, which grow on the PTFE stirring bar. The copper in the reaction mixture is responsible for the aryl azide reduction, and the mild protocol is broadly applicable for bromobenzenes with electron withdrawing groups. Furthermore, the copper nanostructures can mediate azide-alkyne click reactions. Details can be found in the Research Article by Max Roemer and co-workers (M. Roemer, I. Luck, N. Proschogo, Adv. Synth. Catal. 2022, 364, XXXX–XXXX; DOI: 10.1002/adsc.202200594)

Continuous-Flow Direct Azidation of Alcohols and Peroxides for the Synthesis of Quinoxalinone, Benzooxazinone, and Triazole Derivatives.

Continuous-flow reactors provide an ideal tool for the synthesis of potentially explosive but synthetically useful organic substances like organic azides due to their intrinsically small volume leading to very effective collision and highly controlled reaction conditions. Herein, we report the continuous-flow direct azidation of various alcohols by using TMSN3 as an azide transfer reagent in the presence of Amberlyst-15 as a recyclable catalyst. Numerous 3-hydroxy-2-oxindoles effectively undergo azide transfer to afford azide-functionalized quaternary stereocenters in a continuous-flow module. Interestingly, peroxyoxindole undergoes sequential skeletal rearrangement to generate a carbocation followed by nucleophilic azidation to afford a library of substituted 2-azido-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives under continuous flow. Furthermore, a continuous-flow Cu-catalyzed click reaction afforded triazole-functionalized deivatives. Next, reduction of azide in the presence of PPh3 affords the amine derivatives in good yields. The continuous-flow application was extended further for the thermolytic skeletal rearrangement of 3-azide-2-oxindole for the synthesis of biologically important quinoxalin-2(1H)-ones without any reagents. Furthermore, this continuous-flow direct azidation reaction is scaled up to 6.144 g of azides with a turnover number of 9.24 under safer conditions.

Cu(I) Mediated Azidation of Halobenzenes, and Cu Catalysed Selective Azide Reduction to Corresponding Amines

AbstractAryl amines are synthesized from halobenzenes via copper mediated reactions employing sodium azide under mild conditions in ethanol/water. The reaction proceeds stepwise via the aryl azide, which is reduced to the corresponding amine in‐situ. The methodology allows syntheses of amines from corresponding para‐, meta‐ and ortho‐bromobenzenes bearing electron withdrawing groups. Bifunctional halobenzenes bearing alkanoyl chains with terminal bromides are selectively transformed, generating an aniline and an aliphatic azide, as this azide position is stable to reduction. A one‐pot multistep sequence for preparation of the target amines was designed. The azide formation is mediated by CuI while elemental Cu is generated simultaneously, which is deposited onto the employed PTFE stirring bar used in the reaction. The Cu films were quantified and analysed by SEM/EDS. The Cu, either deposited or in solution, is responsible for the azide reduction, possibly involving nitrene intermediates. An application of the modified stirring bars as a heterogeneous catalyst for a click reaction is demonstrated.magnified image

Site-selective reactions mediated by molecular containers.

In this review, we summarize various site-selective reactions mediated by molecular containers. The emphasis is on those reactions that give different product distributions on the potential reactive sites inside the containers than they do outside, free in solution. Specific cases include site-selective cycloaddition and addition of arenes, reduction of epoxides, α,β-unsaturated aldehydes, azides, halides and alkenes, oxidation of remote C–H bonds and alkenes, and substitution reactions involving ring-opening cyclization of epoxides, nucleophilic substitution of allylic chlorides, and hydrolysis reactions. The product selectivity is interpreted as the consequence of the space shape and environment inside the container. The containers include supramolecular structures self-assembled through metal/ligand interactions or hydrogen bonding and open-ended covalent structures such as cyclodextrins and cavitands. Challenges and prospects for the future are also provided.