Tetrabutylammonium Azide Research Articles

Transformation of Benzaldehydes to Benzonitriles via Cyanophosphates without One-Carbon Homologation

AbstractThe transformation of benzaldehydes into benzonitriles via cyanophosphates (CPs) with tetrabutylammonium azide (Bu4N·N3) was found to afford a range of benzonitriles in modest-to-high yields. As the CN-carbon of benzonitriles arises from the formyl-carbon of benzaldehydes, this is a new type of CP-reaction, distinctly different from the past one-carbon nitrile homologation. In contrast, the reaction of ketone- or aliphatic aldehyde-CPs with Bu4N·N3 resulted in mono-deethylaton forming tetrabutylammonium salts.

Synthesis and chiroptical properties of β‐1,2‐linked glycopolymers prepared by click polymerization

AbstractThis article describes the design, synthesis, and folding behaviors of β‐1,2‐linked glycopolymers as a bioconjugate‐based foldamer. The synthesis of alkyne‐containing β‐glycosyl azides has been achieved via anomeric substitution using tetrabutylammonium azide (Bu4NN3) to 1,2‐anhydro sugar and subsequent esterification with 5‐hexynoic acid. Copper‐catalyzed alkyne‐azide 1,3‐dipolar cycloaddition of the glycosyl azide leads to the formation of β‐1,2‐linked glycopolymer alternating 4‐triazolyl butanoate and tribenzylated d‐galactose (PolyGal) or d‐glucose unit (PolyGlu). The folding and chiroptical properties of the polymers are discussed through UV–vis and CD spectroscopy and anisotropic factors of CD (gCD) values. The results suggest that PolyGal would adopt a helically folded structure in ClCH2CH2Cl (DCE) or THF. Thermal stability of the folded structure of PolyGal in less polar DCE appears to increase compared with that in THF. It is found that the folded structure of PolyGal in THF denatures to a random coil above 40°C. It is indicated that PolyGlu can possibly form the helically folded structure in DCE and adopt a random coil structure at high temperature region. In polar THF, PolyGlu does not fold the conformation at all the observed temperature region. Such phenomena suggest a special role of stereochemistry at the 4 position on the folding behaviors.

Photogenerated Azido Radical Mediated Oxidation: Access to Carbonyl Functionality from Alcohols, Alkylarenes, and Olefins via Organophotoredox

AbstractAzido radical mediated photocatalytic oxidation method for the selective oxidation of various well‐known feedstocks, such as (hetero)aromatic or aliphatic alcohols, alkylarenes, and terminal alkenes, is successfully accomplished. Herein, the catalytic HAT and reversible addition/elimination strategies of azido radical have been explored to convert the commonly oxidizable functionalities into invaluable carbonyls or tertiary alcohols using an organic photocatalyst 4CzIPN with tetrabutyl ammonium azide (TBAN3) and air/O2 as an oxidant. Indeed, this mild, operationally simple, and productive method offers good to excellent product yields with a wide range of structurally diverse substrates, including pharmaceutical derivatives with good functional group tolerance. Several control experiments have been carried out to investigate the detailed reaction mechanism.magnified image

Metal-Free Fast Azidation by Using Tetrabutylammonium Azide: Effective Synthesis of Alkyl Azides and Well-Defined Azido-End Polymethacrylates.

An effective method to synthesize azido-end polymethacrylates from tetrabutylammonium azide (BNN3 ) in a nonpolar solvent (toluene) was developed. Several low-mass alkyl halides were reacted with BNN3 in toluene as model reactions and the rate constants of these reactions were determined, to confirm fast BNN3 azidation for tertiary and secondary halides. The end-group transformation of halide-end polymethacrylates was effective and nearly quantitative. Notably, the combination of organocatalyzed living (or reversible deactivation) radical polymerization and BNN3 azidation enabled the metal-free synthesis of azido-end polymethacrylates, including single-azido-end and multi-azido-end functional homopolymers and block copolymers. The rapid and quantitative reaction without the requirement for a large excess of BNN3 , metal-free and polar-solvent-free nature, and broad polymer scope are attractive features of this azidation.

PIDA/TBAB‐Promoted Oxidative Geminal Dibromofunctionalization of Alkynes: Direct Synthesis of Geminal Diazides

PIDA/TBAB‐promoted oxidative geminal diazidofunctionalization of alkynes has been described for the first time. The transformation demonstrates a mechanistically distinctive approach to access geminal diazides, in which TBAB plays a crucial role as brominating agent and for the in situ generation of tetrabutylammonium azide. Furthermore, we have demonstrated here the first cycloaminative strategy by tactically employing the two azides groups leading to quinoxalines and synthesis of bis‐triazole derivatives via copper catalysis.

An Insight into the Anionic Ring-Opening Polymerization with Tetrabutylammonium Azide for the Generation of Pure Cyclic Poly(glycidyl phenyl ether)

We evaluate the use of tetrabutylammonium azide (N3NBu4) as an anionic ring-opening polymerization initiator for synthesizing azide-terminated linear poly(glycidyl phenyl ether) and then generating monocyclic structures with high purity. In particular, we perform a detailed study on the end-group fidelity of polymers obtained by initiation with N3NBu4 in the presence and absence of trisisobutylaluminum (iBu3Al) and evaluate the purity of the cyclic structures obtained via copper-catalyzed alkyne–azide cycloaddition “click” reaction. We demonstrate that in contrast to the polymerization initiated by N3NBu4 alone, the polymerization performed in the presence of iBu3Al allows the formation of polymers with high end-group fidelity (azide groups at the α-position) for Mn < 20 kDa. The cyclic purity is evaluated by SEC with triple detection and dielectric spectroscopy. The latter technique, although not conventional for such a purpose, is shown to be very convenient to ensure cyclic purity in polymers showing a...

Tetrazol-5-ylidene Gold(III) Complexes from Sequential [2 + 3] Cycloaddition of Azide to Metal-Bound Isocyanides and N4 Alkylation

The reaction between equimolar amounts of the isocyanide complexes [AuCl3(CNR)] [R = 2,6-Me2C6H3 (Xyl), 1a; 2,4,6-Me3C6H2 (Mes), 1b; Cy, 1c; t-Bu, 1d] and tetrabutylammonium azide (2) proceeds in CH2Cl2 at room temperature for ∼10 min to furnish the gold(III) tetrazolates [n-Bu4N][AuCl3(CN4R)] (3a–d), which were obtained in 89–95% yields after purification. Subsequent reaction between equimolar amounts of 3a–d and methyl trifluoromethanesulfonate (MeOTf) proceeds in CH2Cl2 at −70 °C for ∼30 min to give the corresponding gold(III) complexes [AuCl3(CaN(Me)N2NbR)]a–b (5a–d) bearing 1,4-disubstituted tetrazol-5-ylidene ligands (69–75%). Complexes 3a–d were obtained as pale-yellow solids and characterized by elemental analyses (C, H, N), HRESI–-MS, FTIR, and 1H and 13C{1H} NMR spectroscopies. Complexes 5a–d were obtained as colorless solids and characterized by elemental analyses (C, H, N), HRESI+-MS, and 1D (1H and 13C{1H}) and 2D (1H,13C-HMBC) NMR spectroscopies. In addition, the structures of 3a, 3b, 3c, an...

Anionic polymerization of ethyl acrylate initiated by tetrabutylammonium azide: direct synthesis of end-clickable polyacrylate

Tetrabutylammonium azide, a weak nucleophile, was found to initiate the living anionic polymerization of ethyl acrylate in the presence of alkylaluminum bisphenoxides as monomer activators to afford clickable azide-end polymers.

Highly efficient three-component synthesis of 5-substituted-1H-tetrazoles from aldehydes, hydroxylamine, and tetrabutylammonium azide using doped nano-sized copper(I) oxide (Cu2O) on melamine–formaldehyde resin

A simple and facile one-pot three-component synthesis of 5-substituted 1H-tetrazole derivatives from aldehydes catalyzed by doped nano-sized Cu2O on melamine–formaldehyde resin (nano-Cu2O–MFR) is described. In this protocol, treatment of structurally diverse aldehydes, hydroxylamine hydrochloride and tetrabutylammonium azide (TBAA) as an azide source in the presence of nano-Cu2O–MFR as an efficient heterogeneous nano-catalyst affords the corresponding 5-substituted 1H-tetrazoles in good to excellent yields. The influence of different parameters on the progress of reaction was studied. The nano-Cu2O–MFR is a cheap and stable nano-catalyst that could be easily prepared, recycled and reused for many consecutive reaction runs without significant decrease in its activity.

Ultrasound promoted mild and facile one-pot, three component synthesis of 2H-indazoles by consecutive condensation, C[sbnd]N and N[sbnd]N bond formations catalysed by copper-doped silica cuprous sulphate (CDSCS) as an efficient heterogeneous nano-catalyst

An ultrasonic promoted facile and convenient one-pot three-component procedure for the synthesis of 2H-indazole derivatives using copper-doped silica cuprous sulphate (CDSCS) as a heterogeneous nano-catalyst has been described. In this approach, ultrasonic mediated reaction of different substituted 2-bromobenzaldehydes, structurally diverse primary amines, and tetrabutylammonium azide (TBAA) as an azide source in the presence of CDSCS in DMSO at room temperature furnishes 2H-indazoles in good to excellent yields. Utilizing ultrasonic irradiation techniques provided the dramatic improvements in terms of higher yields and shorter reaction times compared with conventional heating method.

Maleimide-functionalized closo-dodecaborate albumin conjugates (MID-AC): Unique ligation at cysteine and lysine residues enables efficient boron delivery to tumor for neutron capture therapy

Maleimide-conjugating closo-dodecaborate sodium form 5c (MID) synthesized by the nucleophilic ring-opening reaction of closo-dodecaborate-1,4-dioxane complex 2 with tetrabutylammonium (TBA) azide was found to conjugate to free SH of cysteine and lysine residues in BSA under physiological conditions, forming highly boronated BSA that showed high and selective accumulation in tumor and significant tumor growth inhibition in colon 26 tumor-bearing mice subjected to thermal neutron irradiation.

Nitride-bridged triiron complex and its relevance to dinitrogen activation.

Using a simple metathesis approach, the triiron(II) tribromide complex Fe3Br3L (1) reacts with tetrabutylammonium azide to afford the monoazide dibromide analogue Fe3(Br)2(N3)L (2) in high yield. The inclusion of azide was confirmed by IR spectroscopy with a ν(N3) = 2082 cm(-1) as well as combustion analysis and X-ray crystallography. Heating 2 in the solid state results in the complete loss of the azide vibration in the IR spectra and the isolation of the olive-green mononitride complex Fe3(Br)2(N)L (3). Solution magnetic susceptibility measurements support that the trimetallic core within 2 is oxidized upon generation of 3 (5.07 vs 3.09 μB). Absorption maxima in the UV-visible-near-IR (NIR) spectra of 2 and 3 support the azide-to-nitride conversion, and a broad NIR absorption centered at 1117 nm is similar to that previously reported for the intervalence charge-transfer band for a mixed-valent nitridodiiron cluster. The cyclic voltammograms recorded for 3 are comparable to those of 1 with no reductive waves observed between ∼0 and -2.5 V (vs Fc/Fc(+)), whereas a reversible one-electron redox process is observed for Fe3(NH2)3L (4). These results suggest that intercluster cooperativity is unlikely to predominate the dinitrogen reduction mechanism when 1 is treated with KC8 under N2.

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 °C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Access to Optically Active 3‐Aminopiperidines by Ring Expansion of Prolinols: Thermodynamic versus Kinetic Control

Abstract3‐Aminopiperidines are of great interest because they can possess a wide range of biological activity depending on the nitrogen substituents. Different approaches their synthesis are presented and the most efficient is a ring expansion of prolinols induced by XtalFluor‐E (diethylaminodifluorosulfinium tetrafluoroborate) in the presence of tetrabutylammonium azide, via an aziridinium intermediate, followed by the reduction of the corresponding azide. Under kinetic conditions, a 2‐(azidomethyl)pyrrolidine/3‐azidopiperidine ratio of 0:100 can be attained depending on the substituents present on the prolinol.

Kinetics and mechanism of the racemic addition of trimethylsilyl cyanide to aldehydes catalysed by Lewis bases

The mechanism by which four Lewis bases, triethylamine, tetrabutylammonium thiocyanate, tetrabutylammonium azide and tetrabutylammonium cyanide, catalyse the addition of trimethylsilyl cyanide to aldehydes is studied by a combination of kinetic and spectroscopic methods. The reactions can exhibit first or second order kinetics corresponding to three different reaction mechanisms. Spectroscopic evidence for the formation of hypervalent silicon species is obtained for reaction between all of the tetrabutylammonium salts and trimethylsilyl cyanide. The reactions are accelerated by the presence of water in the reaction mixture, an effect which is due to a change in the reaction mechanism from Lewis to Brønsted base catalysis. Tetrabutylammonium thiocyanate is shown to be an excellent catalyst for the synthesis of cyanohydrin trimethylsilyl ethers on a preparative scale.

Linear High Molar Mass Polyglycidol and its Direct α‐Azido Functionalization

AbstractSummary: Linear polyglycidols with narrow chain dispersity and controlled high molar masses were prepared in a few hours by monomer‐activated anionic polymerization of protected monomers, ethoxyethyl glycidyl ether and tert‐butyl glycidyl ether, using a system composed of tetraoctylammonium bromide as initiator and triisobutylaluminum, used in 1.5 to 5‐fold excess compared to the initiator, as co‐initiator and monomer activator. This synthetic approach was shown to give various polyglycidol‐based copolyethers in particular with propylene oxide or butene oxide. α‐Azido,ω‐hydroxy‐poly(ethoxyethyl glycidyl ether) and other polyethers were directly prepared when tetrabutylammonium azide was used as initiator. Size exclusion chromatography and matrix‐assisted laser desorption/ionization time‐of‐flight characterizations as well as “click” reactions were used to demonstrate the efficiency of the functionalization.

Access to Optically Active 3-Azido- and 3-Aminopiperidine Derivatives by Enantioselective Ring Expansion of Prolinols

The activation of N-alkyl prolinols by XtalFluor E allowed the formation of an aziridinium intermediate that can react with tetrabutylammonium azide (nBu(4)NN(3)) to produce 3-azidopiperidines and/or 2-(azidomethyl)pyrrolidines, in a ratio up to 100/0. These 3-azidopiperidines can be reduced to the corresponding 3-aminopiperidines.

Clickable Stars by Combination of AROP and Aqueous AGET ATRP

A series of star-shaped poly(ethylene oxide) (PEO) with azide groups at the end of each arm were synthesized by combination of anionic ring-opening polymerization (AROP) and aqueous activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP). First, α-azido, ω-hydroxy heterofunctional PEOs were prepared by AROP of ethylene oxide (EO) using tetrabutylammonium azide as initiator and triisobutylaluminum as catalyst. Then, a clickable PEO ATRP macroinitiator, α-azido, ω-bromoisobutyryl heterofunctional PEO, was synthesized by an esterification of the ω-hydroxy end group with 2-bromoisobutyryl bromide. Finally, an AGET ATRP of ethylene glycol diacrylate (EGDA) was carried out in water using the α-azido, ω-bromoisobutyryl heterofunctional PEOs as macroinitiator and surfactant. The absolute molecular weights of the products were characterized by static laser light scattering in water. Azide PEO stars with Mw = 6.58 × 106 and average 309 arms were obtained using azide PEO macroi...

Direct Synthesis of α-Azido,ω-hydroxypolyethers by Monomer-Activated Anionic Polymerization

α-Azido,ω-hydroxypolyethers were prepared directly by monomer-activated anionic polymerization. The introduction of the azido function in the α-position of poly(ethylene oxide), poly(propylene oxide), protected polyglycidol and polyepichlorohydrin was carried out by tetrabutylammonium azide used as initiator. A slight excess of triisobutylaluminum with respect to the ammonium salt ([i-Bu3Al]/[NBu4N3] = 1.5 to 5) was added to trigger the polymerization and get polyethers with controlled molar masses up to 30000 g/mol in a few hours. The terminal hydroxyl function was formed by deactivation of the active polymer ends. The successful and direct preparation of these N3-functionalized polyethers was proven by NMR spectroscopy, size exclusion chromatography and matrix-assisted laser desorption/ionization time-of-flight characterizations as well as “click” reactions.

Synthesis and Evaluation of Paromomycin Derivatives Modified at C(4′)

AbstractThe 2‐amino‐2‐deoxy‐α‐D‐glucopyranosyl moiety (ring I) of paromomycin was replaced by a 2,4‐diamino‐2,4‐dideoxy‐α‐D‐glucopyranosyl, 2,4‐diamino‐2,4‐dideoxy‐α‐D‐galactopyranosyl, 2‐amino‐2‐deoxy‐α‐D‐galactopyranosyl, or 3,4,5‐trideoxy‐4‐aza‐α‐D‐erythro‐heptoseptanosyl moiety to investigate the effect of the substituent at C(4′) on the interaction with ribosomal RNA. The triflate 6 was prepared from the key intermediate pentaazido 3′,6′‐dibenzyl ether 5, and the hexosulose 10 was obtained by oxidation of 5 with Dess–Martin's periodinane. Stereoselective reduction of 10 with NaBH4 gave the alcohol 11 that was transformed into the triflate 12. The epimeric hexaazides 7 and 13 were obtained by treating the triflates 6 and 12, respectively, with tetrabutylammonium azide. Periodate cleavage of glycol 2 yielded the dialdehyde 24 that was reductively aminated with aniline and benzylamine to give the 3,4,5‐trideoxy‐4‐aza‐α‐D‐erythro‐heptoseptanosides 25 and 26, respectively. Standard azide reduction and debenzylation yielded 9 (2,4‐diamino‐2,4‐dideoxy‐α‐D‐galactopyranosyl ring I), 13 (2‐amino‐2‐deoxy‐α‐D‐galactopyranosyl ring I), 17 (2,4‐diamino‐2,4‐dideoxy‐α‐D‐glucopyranosyl ring I), and 27 and 28 (3,4,5‐trideoxy‐4‐aza‐α‐D‐erythro‐heptoseptanosyl ring I). The derivatives 9 and 13 possessing a D‐galacto‐configured ring I were less active than the corresponding D‐gluco‐analogues 17 and paromomycin (1), respectively. The C(4′)‐aminodeoxy derivative 17 (D‐gluco ring I) and the known 4′‐deoxyparomomycin (23), prepared by a new route, displayed slightly lower antibacterial activities than paromomycin (1). Cell‐wall permeability is not responsible for the unexpectedly low activity for 17, as shown by cell‐free translation assays. The results evidence that the orientation of the substituent at C(4′) is more important than its nature for drug binding and activity.