Azide Precursor Research Articles

Polymerization of Potassium Azide in Liquid Nitrogen Using Nanosecond-Pulsed Spark Plasma

In this manuscript, we report on the synthesis of a polynitrogen material from a potassium azide precursor using nanosecond-pulsed spark discharge plasma in liquid nitrogen. The polynitrogen material was characterized using Raman and Fourier transform infrared (FTIR) spectroscopy and identified as K2N6, with planar N6 rings and K- ions that have P6/mmm symmetry. An analysis of the mechanism behind such a transformation shows the importance of direct plasma–chemical effects in polymerization, while the crystal structure changes are believed to be due to plasma-emitted radiation in the ultraviolet range.

Ultrafast photogeneration of a metal-organic nitrene from 1,1'-diazidoferrocene.

Ferrocene and its derivatives have fascinated chemists for more than 70 years, not least due to the analogies with the properties of benzene. Despite these similarities, the obvious difference between benzene and ferrocene is the presence of an iron ion and hence the availability of d-orbitals for properties and reactivity. Phenylnitrene with its rich photochemistry can be considered an analogue of nitrenoferrocene. As with most organic and inorganic nitrenes, nitrenoferrocene can be obtained by irradiating the azide precursor. We study the photophysical and photochemical processes of dinitrogen release from 1,1'-diazidoferrocene to form 1-azido-1'-nitrenoferrocene with UV-pump-mid-IR-probe transient absorption spectroscopy and time-dependent density functional theory calculations including spin-orbit coupling. An intermediate with a bent azide moiety is identified that is pre-organised for dinitrogen release via a low-lying transition state. The photochemical decay paths on the singlet and triplet surfaces including the importance of spin-orbit coupling are discussed. We compare our findings with the processes discussed for photochemical dinitrogen activation and highlight implications for the photochemistry of azides more generally.

Azide Thermolysis Frameworks: Self‐inflating, Porous, and Lightweight Materials

AbstractPorous organic materials have received increasing attention due to their potential applications, such as gas storage, gas separation, and catalysis. In this work, we present a series of aromatic, polyazide‐containing building blocks that enable the formation of a new class of amorphous porous organic materials. The azide precursors are obtained in moderate to good yields following an easy synthesis procedure. By thermal decomposition, self‐inflating porous structures named Azide Thermolysis Frameworks (ATFs) can be obtained. Modified thermogravimetric analysis is used to determine the onset temperature at which the azides decompose and the frameworks are formed. The frameworks are further investigated via infrared (IR) spectroscopy, elemental analysis, scanning electron microscopy (SEM), and gas adsorption measurements. Specific surface areas and pore sizes are determined by nitrogen adsorption measurements at 77 K using the Brunauer–Emmett–Teller method (BET) to give surface areas of up to 677 m2/g for the ATF resulting from the thermolysis of TPB‐Azide at 450 °C, which can compete with early Covalent Organic Frameworks (COFs). The specific surface area can be tuned by varying the thermolysis temperature.

Photoinduced Metallonitrene Formation by N2 Elimination from Azide Diradical Ligands.

Transition-metal nitrides/nitrenes are highly promising reagents for catalytic nitrogen-atom-transfer reactivity. They are typically prepared in situ upon optically induced N2 elimination from azido precursors. A full exploitation of their catalytic potential, however, requires in-depth knowledge of the primary photo-induced processes and the structural/electronic factors mediating the N2 loss with birth of the terminal metal-nitrogen core. Using femtosecond infrared spectroscopy, we elucidate here the primary molecular-level mechanisms responsible for the formation of a unique platinum(II) nitrene with a triplet ground state from a closed-shell platinum(II) azide precursor. The spectroscopic data in combination with quantum-chemical calculations provide compelling evidence that product formation requires the initial occupation of a singlet excited state with an anionic azide diradical ligand that is bound to a low-spin d8 -configured PtII ion. Subsequent intersystem crossing generates the Pt-bound triplet azide diradical, which smoothly evolves into the triplet nitrene via N2 loss in a near barrierless adiabatic dissociation. Our data highlight the importance of the productive, N2 -releasing state possessing azide ππ* character as a design principle for accessing efficient N-atom-transfer catalysts.

Photoinduzierte Metallonitrenbildung durch N2 Abspaltung aus Azid‐Diradikal‐Liganden

AbstractÜbergangsmetallnitride/nitrene sind vielversprechende Reagenzien für katalytischen Stickstoffatomtransfer, die in situ durch optisch induzierte N2‐Eliminierung aus Azidkomplexen zugänglich sind. Um ihr synthetisches Potenzial für die Katalyse voll ausschöpfen zu können, ist ein grundlegendes Verständnis der primären photoinduzierten Prozesse und der stereoelektronischen Faktoren, welche die N2‐Dissoziation kontrollieren, unerlässlich. Mit Hilfe von Femtosekunden‐Infrarotspektroskopie klären wir hier die primären molekularen Mechanismen auf, die für die Bildung eines einzigartigen Platin(II)nitrens mit Triplett‐Grundzustand aus einem geschlossenschaligen Platin(II)azidkomplex verantwortlich sind. Die spektroskopischen Daten in Kombination mit quantenchemischen Rechnungen ergeben einen konsistenten Mechanismus: Produktbildung erfordert die anfängliche Besetzung eines angeregten Singulett‐Zustands mit anionischen Azid‐Diradikal‐Liganden, der an ein low‐spin d8‐konfiguriertes PtII‐Ion gebunden ist. Anschließende Interkombination erzeugt das an Platin gebundene Triplett‐Aziddiradikal, welches sich durch N2‐Verlust in einer nahezu barrierelosen, adiabatischen Dissoziation nahtlos in das Triplett‐Nitren umwandelt. Unsere Daten unterstreichen die Bedeutung des produktiven, N2‐freisetzenden Zustands mit Azid ππ* Charakter als Konstruktionsprinzip für den Zugang zu effizienten Stickstoffatomtransfer‐Katalysatoren.

Immunostimulation with chemotherapy of a ruthenium-arene complex via blockading CD47 signal in chronic myelogenous leukemia cells

Combination of novel immunomodulation and traditional chemotherapy has become a new tendency in cancer treatment. Increasing evidence suggests that blocking the “don't eat me” signal transmitted by the CD47 can promote the phagocytic ability of macrophages to cancer cells, which might be promising for improved cancer chemoimmunotherapy. In this work, we conjugated CPI-alkyne modified by Devimistat (CPI-613) with ruthenium-arene azide precursor Ru-N3 by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to construct Ru complex CPI-Ru. CPI-Ru exhibited satisfactory cytotoxicity towards the K562 cells while nearly non-toxic towards the normal HLF cells. CPI-Ru has been demonstrated to cause severe damage to mitochondria and DNA, ultimately inducing cancer cell death through the autophagic pathway. Moreover, CPI-Ru could significantly downregulate the expression of CD47 on the surface of K562 accompanied by the enhanced immune response by targeting the blockade of CD47. This work provides a new strategy for utilizing metal-based anticancer agents to block CD47 signal to achieve chemoimmunotherapy in chronic myeloid leukemia treatment.

Iron Catalysis of C(sp3)-H Azidation Using a Heteroarene Radical Cation Strategy.

The FeIII(phen)3 catalysis of the benzylic C(sp3)-H azidation of indoles has been investigated. The Fe(III) complex can selectively oxidize indoles to form arene radical cations, which are transformed into benzylic C(sp3) radical intermediates. This strategy exhibits a difference in reactivity between N-heteroarenes and benzene, which is difficult to achieve via direct hydrogen abstraction approaches. Various biorelevant azide precursors were constructed, highlighting the utility of this mild first-row transition-metal catalyst system.

Decarboxylative Triazolation Enables Direct Construction of Triazoles from Carboxylic Acids.

Triazoles have major roles in chemistry, medicine, and materials science, as centrally important heterocyclic motifs and bioisosteric replacements for amides, carboxylic acids, and other carbonyl groups, as well as some of the most widely used linkers in click chemistry. Yet, the chemical space and molecular diversity of triazoles remains limited by the accessibility of synthetically challenging organoazides, thereby requiring preinstallation of the azide precursors and restricting triazole applications. We report herein a photocatalytic, tricomponent decarboxylative triazolation reaction that for the first time enables direct conversion of carboxylic acids to triazoles in a single-step, triple catalytic coupling with alkynes and a simple azide reagent. Data-guided inquiry of the accessible chemical space of decarboxylative triazolation indicates that the transformation can improve access to the structural diversity and molecular complexity of triazoles. Experimental studies demonstrate a broad scope of the synthetic method that includes a variety of carboxylic acid, polymer, and peptide substrates. When performed in the absence of alkynes, the reaction can also be used to access organoazides, thereby obviating preactivation and specialized azide reagents and providing a two-pronged approach to C-N bond-forming decarboxylative functional group interconversions.

Efficient Synthesis of Nanoscale Cadmium Azide from Intercalated Cadmium Hydroxide for Nanoexplosive Applications

Due to its good sensitivity, detonation ability, and high-temperature resistance, cadmium azide is expected to be applied to microinitiating systems. Here we demonstrate an effective synthetic methodology (GAF-IH) to prepare nanoscale cadmium azide. A nanoscale mesoporous configuration is designed to construct azide precursor utilizing controlled self-assembly of inorganic and organic molecules followed by in situ carbonization crystallization. The nanoscale porous precursors can react with HN3 gas to form nanoscale cadmium azide composites (CdA/SA and CdA/C) in just 3 h, which takes much less time than traditional preparation methods of cadmium azide. The organic molecules and their carbonized skeletons can act as the carriers of nanoscale cadmium compounds to avoid agglomeration, as supporting materials for building HN3 azide gas channels, and as functional components in the nanoscale cadmium azide composites to influence their performance. CdA/C prepared by this route has favorable comprehensive properties, which not only has a high content of CdA (93.8%), indicating excellent detonation performance (tID < 10 μs), but also has good high-temperature resistance (Tp = 365 °C) and low electrostatic sensitivity (E50 = 1.76 J). Thanks to its nanoscale characteristics and outstanding performance, CdA/C has the potential to replace CA and modified CA in the application of microinitiating devices.

Differential Tunneling-Driven and Vibrationally-Induced Reactivity in Isomeric Benzazirines.

Quantum mechanical tunneling of heavy-atoms and vibrational excitation chemistry are unconventional and scarcely explored types of reactivity. Once fully understood, they might bring new avenues to conduct chemical transformations, providing access to a new world of molecules or ways of exquisite reaction control. In this context, we present here the discovery of two isomeric benzazirines exhibiting differential tunneling-driven and vibrationally-induced reactivity, which constitute exceptional results for probing into the nature of these phenomena. The isomeric 6-fluoro- and 2-fluoro-4-hydroxy-2H-benzazirines (3-a and 3'-s) were generated in cryogenic krypton matrices by visible-light irradiation of the corresponding triplet nitrene 3 2-a, which was produced by UV-light irradiation of its azide precursor. The 3'-s was found to be stable under matrix dark conditions, whereas 3-a spontaneously rearranges (τ1/2 ∼64 h at 10 and 20 K) by heavy-atom tunneling to 3 2-a. Near-IR-light irradiation at the first OH stretching overtone frequencies (remote vibrational antenna) of the benzazirines induces the 3'-s ring-expansion reaction to a seven-member cyclic ketenimine, but the 3-a undergoes 2H-azirine ring-opening reaction to triplet nitrene 3 2-a. Computations demonstrate that 3-a and 3'-s have distinct reaction energy profiles, which explain the different experimental results. The spectroscopic direct measurement of the tunneling of 3-a to 3 2-a constitutes a unique example of an observation of a species reacting only by nitrogen tunneling. Moreover, the vibrationally-induced sole activation of the most favorable bond-breaking/bond-forming pathway available for 3-a and 3'-s provides pioneer results regarding the selective nature of such processes.

Reactivity of Multimetallic Thorium Nitrides Generated by Reduction of Thorium Azides.

Thorium nitrides are likely intermediates in the reported cleavage and functionalization of dinitrogen by molecular thorium complexes and are attractive compounds for the study of multiple bond formation in f-element chemistry, but only one example of thorium nitride isolable from solution was reported. Here, we show that stable multimetallic azide/nitride thorium complexes can be generated by reduction of thorium azide precursors─a route that has failed so far to produce Th nitrides. Once isolated, the thorium azide/nitride clusters, M3Th═N═Th (M = K or Cs), are stable in solutions probably due to the presence of alkali ions capping the nitride, but their synthesis requires a careful control of the reaction conditions (solvent, temperature, nature of precursor, and alkali ion). The nature of the cation plays an important role in generating a nitride product and results in large structural differences with a bent Th═N═Th moiety found in the K-bound nitride as a result of a strong K-nitride interaction and a linear arrangement in the Cs-bound nitride. Reactivity studies demonstrated the ability of Th nitrides to cleave CO in ambient conditions yielding CN-.

Cyclisations and Strategies for Stereoselective Synthesis of Piperidine Iminosugars.

This personal account focuses on synthesis of polyhydroxylated piperidines, a subset of compounds within the iminosugar family. Cyclisations to form the piperidine ring include reductive amination, substitution via amines, iminium ions and cyclic nitrones, transamidification (N-acyl transfer), addition to alkenes, ring contraction and expansion, photoinduced electron transfer, multicomponent Ugi reaction and ring closing metathesis. Enantiomerically pure piperidines are obtained from chiral pool precursors (e. g. sugars, amino acids, Garner's aldehyde) or asymmetric reactions (e. g. epoxidation, dihydroxylation, aminohydroxylation, aldol, biotransformation). Our laboratory have contributed cascades based on reductive amination from glycosyl azide precursors as well as Huisgen azide-alkene cycloaddition. The latter's combination with allylic azide rearrangement has given substituted piperidines, including those with quaternary centres adjacent to nitrogen.

Synthesis, anticancer activity and molecular docking of new triazolo[4,5-d]pyrimidines based thienopyrimidine system and their derived N-glycosides and thioglycosides

A series of new substituted triazolo[4,5-d]pyrimidine derivatives linked to thienopyrimidine ring system were prepared as a hybrid heterocyclic systems, as possible nucleobases analogs, starting from the key carboxamide derivative 2 and its azide precursor via heterocyclization reactions and their structures were characterized. Glycosylation of the prepared triazolopyrimidine derivatives was performed and afforded, regioselctively, the corresponding thienopyrimidine-triazolopyrimidine hybrid N 1-glycosides and their thioglycoside analogues in good yields. The synthesized glycosyl heterocycles were studied for their cytotoxic activity against HepG-2 and MCF-7 human cancer cells and significant results were obtained. Compounds 7a, 8 b, 9 b, 9a and 7 b demonstrated promising activities comparable to the activity of the doxorubicin for (HepG-2) cell line. Furthermore, a number of the afforded triazolopyrimidine glycosides were found potent against cancer cells (MCF-7). Furthermore, docking simulation the promising thienopyrimidine analogues 7-13 was done against EGFR kinase to provide a binding model that could serve in discovery of further anticancer agents.

Switching on H-Tunneling through Conformational Control.

H-tunneling is a ubiquitous phenomenon, relevant to fields from biochemistry to materials science, but harnessing it for mastering the manipulation of chemical structures still remains nearly illusory. Here, we demonstrate how to switch on H-tunneling by conformational control using external radiation. This is outlined with a triplet 2-hydroxyphenylnitrene generated in an N2 matrix at 10 K by UV-irradiation of an azide precursor. The anti-orientation of the nitrene's OH moiety was converted to syn by selective vibrational excitation at the 2ν(OH) frequency, thereby moving the H atom closer to the vicinal nitrene center. This triggers spontaneous H-tunneling to a singlet 6-imino-2,4-cyclohexadienone. Computations reveal that such fast H-tunneling occurs through crossing the triplet-to-singlet potential energy surfaces. Our experimental realization provides an exciting novel strategy to attain control over tunneling, opening new avenues for directing chemical transformations.

Application of 1,4-Oxazinone Precursors to the Construction of Pyridine Derivatives by Tandem Intermolecular Cycloaddition/Cycloreversion.

This study reveals a new method for the preparation of 1,4-oxazinone derivatives by Staudinger reductive cyclization of functionalized vinyl azide precursors. The resulting oxazinone derivatives prepared in this manner were intercepted with terminal alkyne substrates through an intermolecular cycloaddition/cycloreversion sequence to afford polysubstituted pyridine products. Alkyne substrates bearing propargyl oxygen substitution showed good regioselectivity in the cycloaddition operation selectively affording 2,4,6-substituted pyridines. Application of this chemistry to the synthesis of an ErbB4 receptor inhibitor is also described.

Photochemical Synthesis of a Stable Terminal Uranium(VI) Nitride.

Terminal uranium nitrides have so far proven impossible to isolate by photolysis of azides. Here we report the second ever example of an isolated terminal uranium(VI) nitride. We show that the terminal nitride [NBu4][U(OSi(OtBu)3)4(N)], 3, can be prepared upon photolysis with UV light of the U(IV) azide analogue. This is achieved by careful tailoring of the azide precursor and of the reaction conditions. Complex 3 is stable under ambient conditions but reacts readily with electrophiles (H+ and CO).

Synthesis and characterization of S,N-heterotetracenes.

The synthesis and optoelectronic properties of novel S,N-heterotetracenes consisting of fused heterocyclic thiophene and pyrrole rings are presented. Tetracyclic and benzannulated derivatives with a varying number and sequence of sulfur and nitrogen heteroatoms were synthesized in multistep synthetic routes. A Buchwald–Hartwig amination of brominated precursors, thermolysis of azide precursors, and a Cadogan reaction of nitro-substituted precursors were successfully applied to eventually build-up pyrrole rings to stable and soluble fused systems. The various obtained heteroatom sequences ‘SSNS’ (SN4), ‘SNNS’ (SN4’’), and ‘NSSN’ (SN4’) allowed for evaluation of structure–property relationships relative to the sulfur analogue tetrathienoacene (‘SSSS’). In line with the results for the whole series of S,N-heteroacenes, we find that replacement of sulfur by nitrogen atoms in the tetra- and hexacyclic systems leads to a red-shift in absorption, a decrease in oxidation potential and energy gap. On the other hand, the replacement of a thiophene ring by benzene leads to the opposite effects.

Heavy-Atom Tunneling Through Crossing Potential Energy Surfaces: Cyclization of a Triplet 2-Formylarylnitrene to a Singlet 2,1-Benzisoxazole.

Not long ago, the occurrence of quantum mechanical tunneling (QMT) chemistry involving atoms heavier than hydrogen was considered unreasonable. Contributing to the shift of this paradigm, we present here the discovery of a new and distinct heavy-atom QMT reaction. Triplet syn-2-formyl-3-fluorophenylnitrene, generated in argon matrices by UV-irradiation of an azide precursor, was found to spontaneously cyclize to singlet 4-fluoro-2,1-benzisoxazole. Monitoring the transformation by IR spectroscopy, temperature-independent rate constants (k≈1.4×10-3 s-1 ; half-life of ≈8 min) were measured from 10 to 20 K. Computational estimated rate constants are in fair agreement with experimental values, providing evidence for a mechanism involving heavy-atom QMT through crossing triplet to singlet potential energy surfaces. Moreover, the heavy-atom QMT takes place with considerable displacement of the oxygen atom, which establishes a new limit for the heavier atom involved in a QMT reaction in cryogenic matrices.

Heavy‐Atom Tunneling Through Crossing Potential Energy Surfaces: Cyclization of a Triplet 2‐Formylarylnitrene to a Singlet 2,1‐Benzisoxazole

AbstractNot long ago, the occurrence of quantum mechanical tunneling (QMT) chemistry involving atoms heavier than hydrogen was considered unreasonable. Contributing to the shift of this paradigm, we present here the discovery of a new and distinct heavy‐atom QMT reaction. Triplet syn‐2‐formyl‐3‐fluorophenylnitrene, generated in argon matrices by UV‐irradiation of an azide precursor, was found to spontaneously cyclize to singlet 4‐fluoro‐2,1‐benzisoxazole. Monitoring the transformation by IR spectroscopy, temperature‐independent rate constants (k≈1.4×10−3 s−1; half‐life of ≈8 min) were measured from 10 to 20 K. Computational estimated rate constants are in fair agreement with experimental values, providing evidence for a mechanism involving heavy‐atom QMT through crossing triplet to singlet potential energy surfaces. Moreover, the heavy‐atom QMT takes place with considerable displacement of the oxygen atom, which establishes a new limit for the heavier atom involved in a QMT reaction in cryogenic matrices.

Acryloylnitrenes: Spectroscopic Characterization, Spin Multiplicities, and Rearrangement to Vinyl Isocyanates.

The simplest acryloylnitrene, CH2═CHC(O)N (1b), and two halogenated derivatives, CH2═CFC(O)N (2b) and CH2═CBrC(O)N (3b), were generated through the 266 nm laser photolysis of the corresponding azide precursors in solid N2-matrices at 15 K. The IR spectroscopic characterization of these new acylnitrenes is supported by 15N-labeling and quantum chemical calculations at the B3LYP/6-311++G(3df,3pd) level of theory. For the three nitrenes 1b, 2b, and 3b, two conformers exhibiting syn and anti configurations between the C═C and C═O bonds with respect to the C-C bonds have been identified. Consistent with the CBS-QB3 calculated singlet-triplet energy gaps (ΔEST < 0 kcal mol-1), the IR spectral analysis suggests that all these acryloylnitrenes adopt oxazirine-like structures with closed-shell singlet spin multiplicity. Upon subsequent green light (532 nm) irradiation, these acryloylnitrenes rearrange to form vinyl isocyanates CH2═CXNCO (X = H, F, Br), for which the IR spectra have also been obtained. According to the calculations on the α,β-fluorinated acryloylnitrenes at the CBS-QB3 level, their spin multiplicities can be switched from singlet CH2═CFC(O)N (ΔEST = -0.86 kcal mol-1) to triplet CF2═CFC(O)N (ΔEST = +0.61 kcal mol-1), whereas CFH═CFC(O)N is magnetically bistable due to a rather small ΔEST (+0.09 kcal mol-1).