C-N Bond Research Articles

Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation

AbstractHerein, we describe a general hydrodefunctionalization protocol of alcohols and amines through a common isonitrile intermediate. To cleave the relatively inert C−NC bond, we leveraged dual hydrogen atom transfer (HAT) and photoredox catalysis to generate a nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from the isonitrile. Rapid β‐scission then accomplishes defunctionalization. This method has been applied to the hydrodefunctionalization of both amine and alcohol‐containing pharmaceuticals, natural products, and biomolecules. We extended this approach to the reduction of carbonyls and olefins to their saturated counterparts, as well as the hydrodecyanation of alkyl nitriles. Both experimental and computational studies demonstrate a facile β‐scission of the imidoyl radical, and reconcile differences in reactivity between nitriles and isonitriles within our protocol.

From Quaternary Carbon to Tertiary C(sp3)-Si and C(sp3)-Ge Bonds: Decyanative Coupling of Malononitriles with Chlorosilanes and Chlorogermanes Enabled by Ni/Ti Dual Catalysis.

Transition-metal-catalyzed C-Si/Ge cross-coupling offers promising avenues for the synthesis of organosilanes/organogermanes, yet it is fraught with long-standing challenges. A Ni/Ti-catalyzed strategy is reported here, allowing the use of disubstituted malononitriles as tertiary C(sp3) coupling partners to couple with chlorosilanes and chlorogermanes, respectively. This method enables the catalytic cleavage of the C(sp3)-CN bond of the quaternary carbon followed by the formation of C(sp3)-Si/C(sp3)-Ge bonds from ubiquitously available starting materials. The efficiency and generality are showcased by a broad scope for both of the coupling partners, therefore holding the potential to synthesize structurally diverse quaternary organosilanes and organogermanes that were difficult to access previously.

Decarboxylative stereoretentive C–N coupling by harnessing aminating reagent

In recent decades, strategies involving transition-metal catalyzed carbon-carbon or carbon-heteroatom bond coupling have emerged as potent synthetic tools for constructing intricate molecular architectures. Among these, decarboxylative carbon-nitrogen bond formation using abundant carboxylic acids or their derivatives has garnered notable attention for accessing alkyl- or arylamines, one of key pharmacophores. While several decarboxylative amination methods have been developed, the involvement of a common carboradical intermediate currently poses challenges in achieving stereospecific transformation toward chiral alkylamines. Herein, we present a base-mediated, stereoretentive decarboxylative amidation by harnessing 1,4,2-dioxazol-5-one as a reactive and robust amidating reagent under transition-metal-free ambient conditions, encompassing all types of primary, secondary and tertiary carboxylic acids, thereby providing access to the important pharmacophore, α-chiral amines. This method exhibits high functional group tolerance, convenient scalability, and ease of applicability for 15N-isotope labeling, thus accentuating its synthetic utilities. Experimental and computational mechanistic investigations reveal a sequence of elementary steps: i) nucleophilic addition of carboxylate to dioxazolone, ii) rearrangement to form a dicarbonyl N-hydroxy intermediate, iii) conversion to hydroxamate, followed by a Lossen-type rearrangement, and finally, iv) reaction of the in situ generated isocyanate with carboxylate leading to C–N bond formation in a stereoretentive manner.

Borane-Trimethylamine Complex: A Versatile Reagent in Organic Synthesis.

Borane-trimethylamine complex (Me3N·BH3; BTM) is the most stable of the amine-borane complexes that are commercially available, and it is cost-effective. It is a valuable reagent in organic chemistry with applications in the reduction of carbonyl groups and carbon-nitrogen double bond reduction, with considerable examples in the reduction of oximes, hydrazones and azines. The transfer hydrogenation of aromatic N-heterocycles and the selective N-monomethylation of primary anilines are further examples of recent applications, whereas the reduction of nitrobenzenes to anilines and the reductive deprotection of N-tritylamines are useful tools in the organic synthesis. Moreover, BTM is the main reagent in the regioselective cleavage of cyclic acetals, a reaction of great importance for carbohydrate chemistry. Recent innovative applications of BTM, such as CO2 utilization as feedstock and radical chemistry by photocatalysis, have extended their usefulness in new reactions. The present review is focused on the applications of borane-trimethylamine complex as a reagent in organic synthesis and has not been covered in previous reviews regarding amine-borane complexes.

Synthesis and anti-breast cancer evaluation of fused imidazole-imidazo[1,2-c][1,2,3]triazoles: PEG-400 mediated one-pot reaction under ultrasonic irradiation

Synthetic chemists have organized easy and effective ways for perfect synthesis in response to the requirement for scaffolds that are crucial for medical applications. To investigate the synthesis of fused 1,2,3-triazoles in the presence of ultrasound, the [3 + 2] cycloaddition followed by CN bond formation reaction between 2-chloro-N-(1-methyl-1H-imidazol-2-yl)acetamide and substituted aryl iodoalkynes was carried out ourpreviously reported condition. The cancer activity of the synthesized compounds were then tested in vitro against two breast cancer cell lines MCF-7 and MDA-MB231 and some of the compounds 5g and 5j showed more potent activity against MCF-7 compared to standard erlotinib (IC50 = 4.70 ± 0.11 μM) with IC50 values 4.02 ± 0.74 and 4.23 ± 0.65 μM. Later, in vitro EGFR results revealed that compound 5g (IC50 = 0.38 ± 0.02 μM) have shown more effective than the conventional medicine erlotinib (IC50 = 0.42 ± 0.04 μM). Compounds 5j (IC50 = 0.42 ± 0.05 μM) have shown equipotent, 5i (IC50 = 0.53 ± 0.02 μM) and 5k (IC50 = 0.58 ± 0.02 μM) were shown good activity compared to the standard erlotinib. In silico investigations of more potent compounds (5g, 5i, 5j, 5k, and 5q) and erlotinib on the EGFR protein indicated that all five compounds had comparable binding energies and inhibition constants than the erlotinib.

Properties of chromatographic columns prepared on the basis of poly(1-trimethylsilyl-1-propyne) modified with organic bases

This article describes the effect of modification with organic bases such as uracil (U) and polyethyleneimine (PEI) on the adsorption and chromatographic properties of poly(1-trimethylsilyl-1-propyne) (PTMSP) used as a stationary phase (SP) in packed and capillary columns. It was shown that the sorbents prepared on the basis of diatomite Chromosorb P NAW support and successively modified with 9 wt.% PTMSP and 1 wt.% U (or PEI) (PC-U and PC-PEI samples, respectively), have a mesoporous structure. The IR spectrum shows the presence of carbonyl groups in the sorbent modified with uracil. The impregnation of the Chromosorb P NAW + (9/1) wt.% PTMSP sorbent with a polyethyleneimine solution leads to the appearance in the spectrum of bands characterizing NH stretching and bending vibrations, as well as a band at 1310 cm−1 which can be attributed to CN bond vibrations. The chromatographic properties of the studied sorbents differ significantly from the properties of the initial PTMSP. Packed columns PC-U and PC-PEI, as well as capillary columns with a polyethyleneimine-modified PTMSP layer, allow one to selectively separate mixtures of polar and non-polar compounds and structural isomers of hydrocarbons. Methanol on these columns is eluted in the form of a symmetrical peak separately from propane, propylene and other associated hydrocarbon impurities in commercial (technical, target) n-butane.

On the role of the interface in the mechanical and electronic properties of BCN monolayers

BCN monolayers are heterostructures composed of graphene and hexagonal boron nitride (h-BN) connected in-plane by covalent bonds. Previous research revealed that altering the proportion of graphene and h-BN enables the control of the resulting material's properties. However, less attention has been devoted to the role of the bonds that constitute the interface. In this work, we employ Density Functional Theory calculations to investigate the interface. We first characterize the force response of the CC, BN, CN, and BC bond types that comprise the material. Our results reveal that the CB bond is the weakest of the four, leading us to design monolayers with and without CB bonds. Results from stress-strain calculations show that removing the CB bond increases the material's stiffness. On the other hand, the ultimate strength of the BCN monolayer with a modified interface increased or decreased depending on the elongation direction, as stress can become concentrated in the stiff CN bonds. Regarding the electronic properties, the composition changes at the interface shifted the Fermi energy, transforming the hybrid structure from a semiconductor to a metal. This work shows the importance of the bond types at the graphene/h-BN interface to the mechanical and electronic properties of the resulting BCN monolayer, revealing another tool that can be employed to manipulate the properties of two-dimensional materials.

[Fe(NCMe)6](BF4)2 is a bifunctional catalyst for styrene aziridination by nitrene transfer and heterocycle expansion by subsequent dipolar insertion

The solvated iron(II) salt [Fe(NCMe)6](BF4)2 (Me = methyl) is shown to be a bifunctional catalyst with respect to aziridination of styrene. The salt serves as an active catalyst for nitrene transfer from PhINTs to styrene to form 2-phenyl-N-tosylaziridine (Ph = phenyl; Ts = tosyl, –S{O}2–p-C6H4Me). The iron(II) salt also acts as a Lewis acid in non-coordinating CH2Cl2 solution, to catalyze heterolytic CN bond cleavage of the aziridine and insertion of dipolarophiles. The 1,3-zwitterionic intermediate is presumably supported by interaction of the metal dication with the anion, and by resonance stabilization of the carbocation. Nucleophilic dipolarophiles then insert to give a five-membered heterocyclic ring. The result is a two-step cycloaddition, formally [2 + 1 + 2], that is typically regiospecific, but not stereospecific. This reaction mechanism was confirmed by conducting a series of one-step, [3 + 2] additions of unsaturated molecules into pre-formed 2-phenyl-N-tosylaziridine, also catalyzed by [Fe(NCMe)6](BF4)2. Relevant substrates include styrenes, carbonyl compounds and alkynes. These yield five-membered heterocylic rings, including pyrrolidines, oxazolidines and dihydropyrroles, respectively. The reaction scope appears limited only by the barrier to formation of the dipolar intermediate, and by the nucleophilicity of the captured dipolarophile. The bifunctionality of an inexpensive, earth-abundant and non-toxic catalyst suggests a general strategy for one-pot construction of heterocyclic rings, as demonstrated specifically for pyrrolidine ring formation.

Copper-catalyzed C–C bond cleavage coupling with C[tbnd]N bond formation toward mild synthesis of lignin-based benzonitriles

N-participated lignin depolymerization is of great importance for the transformation of waste lignin into value-added chemicals. The vast majority of developed strategies employ organic amines as nitrogen source, and considerable methods rely on excessive use of strong base, which suffers severe environmental issues. Herein, benzonitrile derivatives are synthesized from oxidized lignin β-O-4 model compounds in the presence of solid nitrogen source (NH4)2CO3 under mild, base-free conditions over commercially available copper catalyst. Mechanism studies suggest the transformation undergoes a one-pot, highly coupled cascade reaction path involving oxidative C-C bond cleavage and in-situ formation of CN bond. Of which, Cu(OAc)2 catalyzes the transfer of hydrogen from Cβ (Cβ-H) to Cα, leading to the cleavage of Cα-Cβ bonds to offer benzaldehyde derivative, this intermediate then reacts in-situ with (NH4)2CO3 to afford the targeted aromatic nitrile product. Tetrabutylammonium iodide (TBAI), acting as a promoter, plays a key role in breaking the Cα-Cβ bonds to form the intermediate benzaldehyde derivative. With this protocol, the feasibility of the production of value-added syringonitrile from birchwood lignin has been demonstrated. This transformation provides a sustainable approach to benzonitrile chemicals from renewable source of lignin.

Ambient electrosynthesis of urea from carbon dioxide and nitrate over Mo2C nanosheet

Electrocatalytic synthesis of urea through CN bond formation, converting carbon dioxide (CO2) and nitrate (NO3–), presents a promising, less energy-intensive alternative to industrial urea production process. In this communication, we report the application of Mo2C nanosheets-decorated carbon sheets (Mo2C/C) as a highly efficient electrocatalyst for facilitating CN coupling in ambient urea electrosynthesis. In CO2-saturated 0.2 mol/L Na2SO4 solution containing 0.05 mol/L NO3–, the Mo2C/C catalyst achieves an impressive urea yield of 579.13 µg h–1 mg–1 with high Faradaic efficiency of 44.80% at –0.5 V versus the reversible hydrogen electrode. Further theoretical calculations reveal that the multiple Mo active sites enhance the formation of *CO and *NH2 intermediates and facilitate their CN coupling. This research propels the use of Mo2C-based electrodes in electrocatalysis and accentuates the capabilities of binary metal-based catalysts in CN coupling reactions.

Theoretical insights into Rh-catalyzed hydroamidation: Mechanism and chemoselectivity

Rh-catalyzed hydroamidation of unactivated alkenes were investigated by a density functional theory study. The catalytic cycle proceeds through β-H elimination, alkene addition, CO2 extrusion, nitrene migratory insertion and protodemetalation. CO2 extrusion is the rate-determining step for the overall reaction. More importantly, the hydroamidation-to-aziridination and hydroamidation-to-amidation chemoselectivities have been investigated and the origins of impossibilities of CC bond aziridination and C(sp2/sp3)H bond amidations have been elucidated. The Rh-nitrene group is more inclined to insert RhC bond rather than CC and C(sp2/sp3)H bonds to form the new CN bond of hydroamidation products. These calculation results provide valuable information for further selective synthesis of amides.

Fabrication of gelatin-polyester based biocomposite scaffold via one-step functionalization of melt electrowritten polymer blends in aqueous phase

The rapid manufacturing of biocomposite scaffold made of saturated-Poly(ε-caprolactone) (PCL) and unsaturated Polyester (PE) blends with gelatin and modified gelatin (NCO-Gel) is demonstrated. Polyester blend-based scaffold are fabricated with and without applying potential in the melt electrowriting system. Notably, the applied potential induces phase separation between PCL and PE and drives the formation of PE rich spots at the interface of electrowritten fibers. The objective of the current study is to control the phase separation between saturated and unsaturated polyesters occurring in the melt electro-writing process and utilization of this phenomenon to improve efficiency of biofunctionalization at the interface of scaffold via Aza-Michael addition reaction. Electron-deficient triple bonds of PE spots on the fibers exhibit good potential for the biofunctionalization via the aza-Michael addition reaction. PE spots are found to be pronounced in which blend compositions are PCL-PE as 90:10 and 75:25 %. The biofunctionalization of scaffold is monitored through CN bond formation appeared at 400 eV via X-ray photoelectron spectroscopy (XPS) and XPS chemical mapping. The described biofunctionalization methodology suggest avoiding use of multi-step chemical modification on additive manufacturing products and thereby rapid prototyping of functional polymer blend based scaffolds with enhanced biocompatibility and preserved mechanical properties. Additionally one-step additive manufacturing method eliminates side effects of toxic solvents and long modification steps during scaffold fabrication.

Anthraquinone-metal complex fluorescence sensing platform for monitoring PPi mediated by Al3+ and bioimaging

Anions are widely found in humans and the environment. The analysis of its content and distribution shows great potential in the fields of life science, environmental science and biochemical reactions. Herein, a new anthraquinone derivative appended fluorescent probe (HBD) was developed as a reversible fluorescent probe for the detection pyrophosphate (PPi) in methanol/urotropine buffer medium (1:1, v/v, pH 4.5). The probe displayed fluorescence “turn-on” response towards Al3+ with high specificity. Due to the cleaving of the -CN bond and subsequent creation of complex caused by coordination with Al3+, the chelation-enhanced fluorescence (CHEF) effect was activated, resulting in a significantly enhancement fluorescence response. Further, 1H NMR titration and HRMS analysis revealed that the Al3+ induced hydrolysis occurs on one side of the Schiff base and led to the formation of free primary amine compound. Moreover, the binding mechanism was also recognized density functional theory (DFT) studies. Due to the strong binding ability of PPi and Al3+, PPi could remove Al3+ from the complex, causing fluorescence quenching. The specific determination of Al3+ and PPi with the detecting limit of 31.6 nM and 56.8 nM. Due to its good biocompatibility, the sensor was successfully applied to fluorescence imaging of Al3+ and PPi in HeLa cells and zebrafish. The results show that HBD has broad application prospects in environmental and biological analysis.

Computational insights into the reaction mechanism of the synthesis of quinazoline derivatives via the cyclocondensation reaction between methyl 2-amino-4-(2-diethylaminoethoxy)-5-methoxybenzoate and formamide

In this work, the cyclocondensation reaction mechanism between methyl 2-amino-4-(2-diethylaminoethoxy)-5-methoxybenzoate (MAD, 1) and formamide (FME, 2) was theoretically explored at the DFT level using the B3LYP/6-311++G(d,p) computational method. The two paths (a and b) involved in this reaction take place through four steps. CDFT results show the most favourable electrophilic/nucleophilic interaction between the C3 electrophilic center of MAD (1) and the N4 nucleophilic center of FME (2). Activation energy analysis predicts the formation of quinazoline derivative as the main product, in reasonable agreement with experimental results. BET allowed a deeper understanding of the reaction mechanism by revealing the existence of four structural stability domains (SSD) during the processes of CN and OH bond formation. The bond process is as follows: depopulation of V(N) basin with the formation of first CN bond (appearance of V(C,N) basin), cleavage of NH bond with the creation of V(N) and V(H) monosynaptic basins, and finally the appearance of V(H,O) disynaptic basin related to the OH bond. In the case of dehydration, the transition from SSD-I to SSD-II corresponds to the cleavage of the CO bond, whose electron population is transferred to the V(O3) basin. The cleavage of N7-H9 bond with the formation of V(N) and V(H) basins is the first stage, followed by the formation of the OH bond as the second stage.

Aminative Suzuki-Miyaura coupling.

The Suzuki-Miyaura and Buchwald-Hartwig coupling reactions are widely used to form carbon-carbon (C-C) and carbon-nitrogen (C-N) bonds, respectively. We report the incorporation of a formal nitrene insertion process into the Suzuki-Miyaura reaction, altering the products from C-C-linked biaryls to C-N-C-linked diaryl amines and thereby joining the Suzuki-Miyaura and Buchwald-Hartwig coupling pathways to the same starting-material classes. A combination of a bulky ancillary phosphine ligand on palladium and a commercially available amination reagent enables efficient reactivity across aryl halides and pseudohalides, boronic acids and esters, and many functional groups and heterocycles. Mechanistic insights reveal flexibility on the order of bond-forming events, suggesting potential for expansion of the aminative cross-coupling concept to encompass diverse nucleophiles and electrophiles as well as four-component variants.

An attempted oxidative coupling approach to the scholarinine A framework

In this manuscript, an oxidative carbon–carbon bond forming reaction to construct the framework of alkaloids such as scholarinine A is explored using a constrained substrate. Instead of the desired carbon–carbon bond formation between an indole C3 position and a malonate group, a competing carbon–nitrogen bond between the malonate and indole C3 position was observed to form. This work adds to the growing body of substrates for oxidative carbon–carbon bond formation and importantly, demonstrates that these reactions are challenging for some conformationally constrained substrates.

Cationized orthogonal triad as a photosensitizer with enhanced synergistic antimicrobial activity

Single-molecule-based synergistic phototherapy holds great potential for antimicrobial treatment. Herein, we report an orthogonal molecular cationization strategy to improve the reactive oxygen species (ROS) and hyperthermia generation of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Cationic pyridine (Py) is introduced at the meso‑position of the asymmetric Cy7 with intramolecular charge transfer (ICT) to construct an atypical electron-transfer triad, which reduces ΔES1-S0, circumvents rapid charge recombination, and simultaneously enhances intersystem crossing (ISC) based on spin-orbit charge-transfer ISC (SOCT-ISC) mechanism. This unique molecular construction produces anti-Stokes luminescence (ASL) because the rotatable CN bond enriched in high vibrational-rotational energy levels improves hot-band absorption (HBA) efficiency. The obtained triad exhibits higher singlet oxygen quantum yield and photothermal conversion efficiency compared to indocyanine green (ICG) under irradiation above 800 nm. Cationization with Py enables the triad to target bacteria via intense electrostatic attractions, as well as biocidal property against a broad spectrum of bacteria in the dark. Moreover, the triad under irradiation can enhance biofilm eradication performance in vitro and statistically improve healing efficacy of MRSA-infected wound in mice. Thus, this work provides a simple but effective strategy to design small-molecule photosensitizers for synergistic phototherapy of bacterial infections. Statement of SignificanceWe developed an orthogonal molecular cationization strategy to enhance the reactive oxygen species and thermal effects of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Specifically, cationic pyridine (Py) was introduced at the meso‑position of the asymmetric Cy7 to construct an atypical electron-transfer triad, which reduced ΔES1-S0, circumvented rapid charge recombination, and simultaneously enhanced intersystem crossing (ISC). This triad, with a rotatable CN bond, produced anti-Stokes luminescence due to hot-band absorption. The triad enhanced antimicrobial performance and statistically improved the healing efficacy of MRSA-infected wounds in mice. This site-specific cationization strategy may provide insights into the design of small molecule-based photosensitizers for synergistic phototherapy of bacterial infections.

Pressure-induced bandgap engineering and polymerization of silver cyanamide

Silver cyanamide (Ag2NCN), as one of semiconductor metal cyanamides, understanding the structure-optical property links in Ag2NCN is critical for its applications. Under high pressure, Ag2NCN exhibits a redshift of the bandgap with increasing pressure up to 23.5 GPa, which is related to the bond stretching of C-N in Ag2NCN and amorphization. The XRD analysis of the Ag2NCN structure reveals that there is no structural transition and highly compressible, with a bulk modulus of 25 GPa in compression. The Raman and IR spectra indicate that the polymerization transition is associated with the cyanamides groups forming irreversible amorphous sp2 CN bonds.

Study on the degradation and metabolic mechanism of four quinolone antibiotics by mixed strains

Quinolone antibiotics are a common class of antibiotics in the environment and have received considerable attention. In this study, three groups of mixed degradation strains targeting mixed quinolone antibiotics, norfloxacin (NOR), and enrofloxacin (ENR) were selected through screening, enrichment, and microbial diversity detection experiments. The strains screened in this study are divided into two categories through degradation efficiency experiments, community composition detection and functional enrichment analysis. In groups mix and ENR, the resistant bacteria are the main microorganisms and the degrading bacteria are the secondary ones, while in group NOR, the strains with degradation effects are the main ones, and the strains with resistance effects are the secondary ones. What’s more, that carbon sources have little effect on the community composition of the quinolone antibiotic degrading and tolerant bacteria, the difference between groups is mainly controlled by the type of antibiotics. On this basis, we found the key to NOR degradation is the cleavage of carbon nitrogen bonds on the piperazine ring, followed by oxygenation and deethylation. Preliminary studies have confirmed that the optimal degradation conditions for NOR degrading strains, and also found that environmental factors did not significantly affect the degradation efficiency of the Mix and NOR degrading strains, which indicating that the mixed bacteria can degrade NOR in different real environments effectively such as tap water, seawater, river water, and lake water. This manuscript is the first report on a mixed strain of quinolone antibiotic microbial degradation, and it is also the study with the highest NOR degradation efficiency among known reports. It has great research value for the co-metabolism and biodegradation of quinolone antibiotics in the environment.

Gold(III)-Catalyzed Propargylic Substitution Reaction Followed by Cycloisomerization for Synthesis of Poly-Substituted Furans from N-Tosylpropargyl Amines with 1,3-Dicarbonyl Compounds.

The treatment of N-tosylpropargyl amines 1 with 1,3-dicarbonyl compounds 2 in the presence of AuBr3 (5 mol%) and AgOTf (15 mol%) afforded poly-substituted furans 3 in good-to-high yields via the gold-catalyzed cleavage of the sp3 carbon-nitrogen bond.