Nitrile Functional Groups Research Articles

Metal-Free Synthesis of Benzisoxazolones Utilizing ortho-Ester and ortho-Cyano-Functionalized Diaryliodonium Salts with Protected Hydroxylamines.

Herein, we report the development of metal-free one/two-pot procedures for the synthesis of benzo[c]isoxazol-3(1H)-one (benzisoxazolone) heterocycles by designing diaryliodonium salts featuring ortho-ester or nitrile functional groups. These react smoothly with protected hydroxylamines under mild conditions to produce N-arylhydroxylamine intermediates, which readily cyclize to give benzisoxazolone derivatives under acidic conditions. This metal-free process maintains the weak N-O bond, tolerates a wide range of diaryliodonium salts and protected hydroxylamines with diverse functional/protecting groups, thereby overcoming the challenges associated with previous transformations. The protocol expands the reaction scope and broadens the chemical space of the fused isoxazolone backbones to include unprecedented five-membered heteroaryl-fused isoxazolones in high yields. This method is also applicable to gram-scale synthesis, and the resulting benzisoxazolones can be effectively derivatized at the N-position to afford valuable compounds.

Towards post-curing parameters optimization of phthalonitrile composites through the synergy of experiment and machine learning

Phthalonitrile composites are highly anticipated in fields such as aerospace, marine, and electronics due to their exceptional heat resistance, excellent high-temperature mechanical properties, and outstanding processability. The conversion of nitrile functional groups to macrocyclic structures during post-curing is essential for performance enhancement. However, the influence of post-curing conditions on the mechanical properties of phthalonitrile composites is complicated, and the underlying mechanism remains unclear. In this study, an experimental and machine learning synergic strategy was employed to optimize the post-curing parameters of the phthalonitrile composites, including temperature, time, and pressure. Through mechanical experiments conducted at both room temperature and 400 °C, scanning electron microscope, and dynamic mechanical analysis, the underlying mechanism of the influence of post-curing parameters on the composite mechanical properties was revealed. The enhancement of the polymerization degree brought about by post-curing is the decisive factor for high-temperature performance, while the room-temperature properties are a tradeoff between the polymerization degree improvement and the defect proliferation. The genetic algorithm-optimized backpropagation (GA-BP) neural network was trained for the efficient and accurate prediction of the optimal post-curing parameters. The tendency of mechanical properties with the post-curing parameters predicted by machine learning is consistent with the mechanism revealed by experiments.

Degradation of the polyacrylonitrile-based UP2W material under cementitious conditions

UP2W is a polyacrylonitrile-based filter aid material used in nuclear power plants, which is disposed in repositories for low and intermediate level radioactive waste. The degradation of UP2W was investigated in a series of batch experiments in the presence and absence of portlandite, Fe(0) and NaOH, which simulate the hyperalkaline, reducing conditions expected in repositories with cementitious engineered barriers. Degradation experiments were performed under Ar atmosphere at T = 22 or 80 (±2) °C. Aliquots of the supernatant solutions and retrieved solid phases were systematically characterized for ca. 5 years using a multi-method approach.The evolution of dissolved organic carbon shows a strong contrast between NaOH- and Ca(OH)2-buffered systems. In the absence of Ca, an early, sharp increase in the dissolved organic carbon is observed, and its magnitude correlates with the initial NaOH concentration.In Ca(OH)2-buffered systems, dissolved organic carbon remained very low (<10 ppm) up to 600 days, but steadily increased afterwards reaching ∼ 50 ppm at t ≈ 1800 days. Size-exclusion/liquid chromatography coupled with organic carbon, ultra-violet and organic nitrogen detection (LC-OCD-UVD-OND) confirmed the presence of significantly smaller fragments in solution compared to NaOH-systems, which however were found to increase with time.Overall observations underline that hydrolysis of the nitrile functional groups, chain scission of the polymer backbone and cross-linking of polymer fragments in the degradation leachates play a key role in the progress of the degradation reaction. Chain scission is hindered in the presence of Ca, possibly due to the complexation of Ca with amide and carboxylate intermediates and the consequent decrease in electron density on the β-carbon atoms. This study improves the mechanistic understanding and quantitative description of UP2W degradation in cementitious environments relevant for L/ILW disposal.

Novel Synthetic Industrial Approach for Efficient Synthesis of Baclofen through C–C Bond Formation

AbstractBaclofen is an active pharmaceutical ingredient used for the treatment of muscle spasticity. We describe our efforts to develop a novel synthetic approach through C–C bond formation and a cost-effective route to baclofen. The synthesis involved a two-step approach through C–C bond formation using the extensively and commercially available starting material 4-chlorobenzyl cyanide with chloroacetic acid as a reagent in an aprotic solvent, followed by reduction of the nitrile functional group. The synthetic route to baclofen has been demonstrated to be commercially viable, cost-effective, and environmentally friendly. Execution of the developed process led to the isolation of (+)-baclofen in an overall yield of 60% at a multikilogram scale with &gt;99.5% HPLC purity. This article also discusses the cost-effectiveness of the process, the impurity profiling, and the product quality.

Silver nanoparticles improve the fungicidal properties of Rhazya stricta decne aqueous extract against plant pathogens

One of the most promising, non-toxic, and biocompatible developments for many biological activities is the green synthesis of nanoparticles from plants. In this work, we investigated the antifungal activity of silver nanoparticles (AgNPs) biosynthesized from Rhazya stricta aqueous extract against several plant pathogenic fungi. UV–visible spectroscopy, Zeta potential analysis, Fourier-transform infrared spectroscopy (FTIR), and transmitted electron microscopy (TEM) were used to analyze the biosynthesized AgNPs. Drechslera halodes, Drechslera tetramera, Macrophomina phaseolina, Alternaria alternata, and Curvularia australiensis were tested for their potential antifungal activity. Surface Plasmon Resonance (SPR) of Aq. AgNPs and Alkaline Aq. AgNPs was observed at 405 nm and 415 nm, respectively. FTIR analysis indicated hydroxyl, nitrile, amine, and ketone functional groups. Aq. AgNPs and Alka-line Aq. AgNPs had velocities of − 27.7 mV and − 37.9 mV and sizes of 21–90 nm and 7.2–25.3 nm, respectively, according to zeta potential studies and TEM. The antifungal examination revealed that all species' mycelial development was significantly inhibited, accompanied by severe ultra-structural alterations. Among all treatments, Aq. AgNPs were the most effective fungicide. M. phaseolina was statistically the most resistant, whereas A. alternata was the most vulnerable. To the best of our knowledge, this is the first report on R. stricta's antifungal activity against these species.

Bimetallic AuNR@AgNCs for ultrasensitive surface-enhanced Raman scattering sensing of dithianon in apple juice

In this study, a bimetallic surfaced-enhanced Raman spectroscopy (SERS)-active substrate consisting of AuNR@AgNCs was proposed for the rapid detection of dithianon. Due to the significant synergistic enhancement of the core-shell nanocuboids, the obtained AuNR@AgNC substrate exhibited excellent SERS performance. The simulation findings supported the practical SERS results and demonstrated that interactions were mainly maintained by the nitrile functional group. The AuNR@AgNCs could be used to detect dithianon with an LOD value of 20 nM. Moreover, dithianon in river water and apple juice could be detected with recovery in the satisfactory ranges of 97.41%–98.35% and 97.77%–98.70%, respectively, by using this substrate under optimal conditions, indicating that the AuNR@AgNC substrate could serve as an excellent SERS detection platform for pesticide residues in fruit.

Modeling the thermochemistry of nitrogen-containing compounds via group additivity.

First-principles based kinetic modeling is essential to gain insight into the governing chemistry of nitrogen-containing compounds over a wide range of technologically important processes, e.g. pyrolysis, oxidation and combustion. It also enables the development of predictive, fundamental models key to improving understanding of the influence of nitrogen-containing compounds present as impurities or process additives, considering safety, operability and quality of the product streams. A prerequisite for the generation of detailed fundamental kinetic models is the availability of accurate thermodynamic properties. To address the scarcity of thermodynamic properties for nitrogen-containing compounds, a consistent set of 91 group additive values and three non-nearest-neighbor interactions has been determined from a dataset of CBS-QB3 calculations for 300 species, including 104 radicals. This dataset contains a wide range of nitrogen-containing functionalities, i.e. imine, nitrile, nitro, nitroso, nitrite, nitrate and azo functional groups. The group additivity model enables the approximation of the standard enthalpy of formation and standard entropy at 298 K as well as the standard heat capacities over a large temperature range, i.e. 300-1500 K. For a test set of 27 nitrogen-containing compounds, the group additivity model succeeds in approximating the ab initio calculated values for the standard enthalpy of formation with a MAD of 2.3 kJ mol-1. The MAD for the standard entropy and heat capacity is lower than 4 and 2 J mol-1 K-1, respectively. For a test set of 11 nitrogen-containing compounds, the MAD between experimental and group additivity approximated values for the standard enthalpy of formation amounts to 2.8 kJ mol-1.

Electrospray ionisation mass spectrometry (ESI-MS) adduct formation by mobile phase additives: A case study using nitrile functional groups containing selective androgen receptor modulators (SARMs).

The formation of mass adducts is common during electrospray ionization mass spectrometry (ESI-MS). However, the mechanism that leads to adduct formation is poorly understood and difficult to control. Multiplication of mass adducts at once will adversely impact the sensitivity of mass analysis and cause misinterpretation of the level of detection. Prior studies on selective androgen receptor modulators (SARMs) revealed an immense mass adduct formation in both positive and negative ESI modes. In this study, additives in the mobile phases are investigated as a potential means of controlling mass adduct formation in various SARMs. The first evidence of chloride adduct formation when SARMs are detected via ESI-MS has been reported in this research. A series of mobile phase combinations were tested in order to achieve the optimal condition for HPLC-MS. A comparison was also made between adduct formation on various grades of water used for preparing the mobile phase. A validation study using equine urine and plasma was also conducted to assess the suitability of the developed method. The results of this study will allow for a more accurate identification of SARMs, which will make it easier to investigate their illicit use in horse racing.

Voltage-Dependent FTIR and 2D Infrared Spectroscopies within the Electric Double Layer Using a Plasmonic and Conductive Electrode.

Strong electric fields exist between the electric double layer and charged surfaces. These fields impact molecular structures and chemistry at interfaces. We have developed a transparent electrode with infrared plasmonic enhancement sufficient to measure FTIR and two-dimensional infrared spectra at submonolayer coverages on the surface to which a voltage can be applied. Our device consists of an infrared transparent substrate, a 10-20 nm layer of conductive indium tin oxide (ITO), an electrically resistive layer of 3-5 nm Al2O3, and a 3 nm layer of nonconductive plasmonic gold. The materials and thicknesses are set to maximize the surface number density of the monolayer molecules, electrical conductivity, and plasmonic enhancement while minimizing background signals and avoiding Fano line shape distortions. The design was optimized by iteratively characterizing the material roughness and thickness with atomic force microscopy and electron microscopy and by monitoring the plasmon resonance enhancement with spectroscopy. The design is robust to repeated fabrication. This new electrode is tested on nitrile functional groups using a monolayer of 4-mercaptobenzonitrile as well as on CO and CC stretching modes using 4-mercaptobenzoic acid methyl ester. A voltage-dependent Stark shift is observed on both monolayers. We also observe that the transition dipole strength of the CN mode scales linearly with the applied voltage, providing a second way of measuring the surface electric field strength. We anticipate that this cell will enable many new voltage-dependent infrared experiments under applied voltages.

Thermally Activated Delayed Fluorescence and Room-Temperature Phosphorescence in Materials with Imidazo-pyrazine-5,6-dicarbonitrile Acceptors.

Three donor-acceptor compounds based on the imidazo-pyrazine-5,6-dicarbonitrile (IPDC) acceptor were synthesized. The IPDC emitters exhibit blue to near-infrared (NIR) emission with up to 54 % photoluminescent quantum yield. 9,9-Dimethyl-9,10-dihydroacridine (ACR), phenoxazine (POX), and phenothiazine (PTZ) served as electron donors. IPDC-POX displayed NIR emission in toluene solution, while showing room-temperature phosphorescence in the solid state. IPDC-ACR exhibited yellow thermally activated delayed fluorescence. Interestingly, dual-emissive behavior as well as excitation-dependent thermally activated delayed fluorescence (TADF) was found for IPDC-PTZ, arising from the two conformers of phenothiazine derivatives. Overall, this work describes a novel strong electron acceptor from the fusion of imidazole, pyrazine, and nitrile functional groups into one conjugated heterocycle for materials exhibiting NIR emission, TADF, and/or room-temperature phosphorescence (RTP).

Relationship between the intermolecular interactions of carbonyl (PC) with nitrile (HNBR) functional groups and the flash point of a gel polymer electrolyte

Flash point temperatures of HNBR–PC and HNBR–PC–LiTFSI gel polymer electrolytes with different nitrile content are reported. Molecular interactions were found to impact gel flammability.

Exploring the Vapor Phase Infiltration of Trimethylaluminum into Polyacrylonitrile Fabrics

Vapor phase infiltration (VPI) creates a hybrid organic-inorganic material by modifying the bulk of a polymer substrate with a metalorganic vapor phase precursor. In VPI, the metalorganic precursor sorbs to the polymer, then diffuses through the bulk and becomes entrapped—either by a chemical bond between the polymer and the inorganic or by a co-reaction with a second species—yielding a hybrid composed of the polymer and, often, a metal oxide. Some of the polymers that have been studied under VPI include poly(methyl methacrylate) (PMMA), polyethylene terephthalate (PET), polydimethyl siloxane (PDMS), and poly(3-hexylthiophene) (P3HT). There is a notable exception in this list: polyacrylonitrile (PAN). The high reactivity of the nitrile functional group on the backbone of the PAN polymer chain suggests PAN would perform well in VPI. PAN is used in textiles and filtration, but one of its most common applications is as a precursor to carbon fiber. Previous hybrid materials created via VPI have demonstrated new optical and thermal properties that differ from the neat polymer. If infiltrated successfully, these properties in PAN could be of use in its application spaces. In this work, we expand the VPI material space with the first study of infiltration of PAN. To explore the bounds of this system in terms of achievable inorganic loadings and hybrid material chemical structure, PAN is infiltrated with the metalorganic precursor trimethylaluminum (TMA) and co-reacted with water vapor under variable precursor exposure times, precursor desorption times, and processing temperatures. PAN is found to infiltrate with high quantities of inorganic loading (as measured by thermogravimetric analysis) that can be tuned from 1% to 17% inorganic by weight. Inorganic loading depends strongly on precursor exposure time with a sample processed at 140℃ showing a 25% increase when the exposure time is increased from 5 hours to 25 hours. Infiltration temperature also plays a significant role with hybrid materials demonstrating a 78% increase in inorganic loading when the PAN processing temperature is increased from 80℃ to 140℃. The apparent increase in inorganic loading with temperature may be related to the mass transport and reaction kinetics of the system under VPI conditions. Precursor desorption time, on the other hand, has minimal impact on inorganic loading suggesting most sorbed precursor participates in a chemical interaction with the polymer during infiltration. In exploring the resulting AlOx/PAN hybrid chemical structure with FTIR, this mechanism was supported by an observed decrease of the PAN nitrile peak at ~2240 cm-1 that scaled with inorganic loading. These structural changes in inorganic loading and chemical state are found to directly correspond to the optical (UV-Vis) and thermal (TGA) properties of the hybrid materials. The results of these characterization techniques imply that the VPI process causes a significant chemical change to the PAN fabric and suggests the process could possibly induce PAN cyclization, which may be advantageous for carbon fiber applications. Overall, this work establishes the significant and tunable inorganic loading of AlOx/PAN hybrid fabrics and expands VPI to a new polymer system.

Practical Synthesis of Polyamine Succinamides and Branched Polyamines.

Antibiotic resistance is now a growing threat to human health, further exacerbated by the lack of new antibiotics. We describe the practical synthesis of a series of substituted polyamine succinamides and branched polyamines that are potential new antibiotics against both Gram‐positive and Gram‐negative bacteria, including MRSA and Pseudomonas aeruginosa. They are prepared via 1,4‐Michael addition of acrylonitrile and then hydrogenation of the nitrile functional groups to primary amines. They are built upon the framework of the naturally occurring polyamines thermine (3.3.3, norspermine) and spermine (3.4.3), homo‐ and heterodimeric polyamine succinic amides. Linking two of the same or different polyamines together via amide bonds can be achieved by introducing a carboxylic acid group on the first polyamine, then coupling that released carboxylic acid to a free primary amine in the second polyamine. If the addition of positive charges on the amino groups along the polyamine chains are a key factor in their antimicrobial activity against Gram‐negative bacteria, then increasing them will increase the antimicrobial activity. Synthesising polyamine amide dimers will increase the total net positive charge compared to their monomers. The design and practical synthesis of such homo‐ and hetero‐dimers of linear polyamines, spermine and norspermine, are reported. Several of these compounds do not display significant antibacterial activity against Gram‐positive or Gram‐negative bacteria, including MRSA and Pseudomonas aeruginosa. However, the most charged analogue, a branched polyamine carrying eight positive charges at physiological pH, displays antibiofilm activity with a 50 % reduction in PAO1 at 16–32 μg mL−1.

Vapor-Phase Infiltration of Polymer of Intrinsic Microporosity 1 (PIM-1) with Trimethylaluminum (TMA) and Water: A Combined Computational and Experimental Study.

Vapor-phase infiltration, a postpolymerization modification process, has demonstrated the ability to create organic-inorganic hybrid membranes with excellent stability in organic solvents while maintaining critical membrane properties of high permeability and selectivity. However, the chemical reaction pathways that occur during VPI and their implications on the hybrid membrane stability are poorly understood. This paper combines in situ quartz crystal microbalance gravimetry (QCM) and ex situ chemical characterization with first-principles simulations at the atomic scale to study each processing step in the infiltration of polymer of intrinsic microporosity 1 (PIM-1) with trimethylaluminum (TMA) and its co-reaction with water vapor. Building upon results from in situ QCM experiments and SEM/EDX, which find TMA remains within PIM-1 even under long desorption times, density functional theory (DFT) simulations identify that an energetically stable coordination forms between the metal-organic precursor and PIM-1's nitrile functional group during the precursor exposure step of VPI. In the subsequent water vapor exposure step, the system undergoes a series of exothermic reactions to form the final hybrid membrane. DFT simulations indicate that these reaction pathways result in aluminum oxyhydroxide species consistent with ex situ XPS and FTIR characterization. Both NMR and DFT simulations suggest that the final aluminum structure is primarily 6-fold coordinated and that the aluminum is at least dimerized, if not further "polymerized". According to the simulations, coordination of the aluminum with at least one nitrile group from the PIM-1 appears to weaken significantly as the final inorganic structure emerges but remains present to enable the formation of the 6-fold coordination species. Water molecules are proposed to complete the coordination complex without further increasing the aluminum's oxidation state. This study provides new insights into the infiltration process and the chemical structure of the final hybrid membrane including support for the possible mechanism of solvent stability.

Utilizing Raman Spectroscopy as a Tool for Solid- and Solution-Phase Analysis of Metalloorganic Cage Host-Guest Complexes.

The host-guest chemistry of coordination cages continues to promote significant interest, not least because confinement effects can be exploited for a range of applications, such as drug delivery, sensing, and catalysis. Often a fundamental analysis of noncovalent encapsulation is required to provide the necessary insight into the design of better functional systems. In this paper, we demonstrate the use of various techniques to probe the host-guest chemistry of a novel Pd2L4 cage, which we show is preorganized to selectively bind dicyanoarene guests with high affinity through hydrogen-bonding and other weak interactions. In addition, we exemplify the use of Raman spectroscopy as a tool for analyzing coordination cages, exploiting alkyne and nitrile reporter functional groups that are contained within the host and guest, respectively.

Natural Products Containing the Nitrile Functional Group and Their Biological Activities

The importance of nitriles as a key class of chemicals with applications across the sciences is widely appreciated. The natural world is an underappreciated source of chemically diverse nitriles. With this in mind, this review describes novel nitrile-containing molecules isolated from natural sources from 1998 to 2021, as well as a discussion of the biological activity of these compounds. This study gathers 192 molecules from varied origins across the plant, animal, and microbial worlds. Their biological activity is extremely diverse, with many potential medicinal applications.

Stereoselective Palladium‐Catalyzed C(sp3)−H Mono‐Arylation of Piperidines and Tetrahydropyrans with a C(4) Directing Group

AbstractA selective Pd‐catalyzed C(3)−H cis‐functionalization of piperidine and tetrahydropyran carboxylic acids is achieved using a C(4) aminoquinoline amide auxiliary. High mono‐ and cis‐selectivity is attained by using mesityl carboxylic acid as an additive. Conditions are developed with significantly lower reaction temperatures (≤50 °C) than other reported heterocycle C(sp3)−H functionalization reactions, which is facilitated by a DoE optimization. A one‐pot C−H functionalization‐epimerization procedure provides the trans‐3,4‐disubstituted isomers directly. Divergent aminoquinoline removal is accomplished with the installation of carboxylic acid, alcohol, amide and nitrile functional groups. Overall, fragment compounds suitable for screening are generated in 3–4 steps from readily‐available heterocyclic carboxylic acids.magnified image

Enantioselective Total Synthesis of (+)-Eucophylline.

The total enantioselective synthesis of (+)-eucophylline 1 was achieved using as a key-structural motif a chiral piperidinone bearing the natural product all-carbon quaternary stereocenter. The elaboration of the latter is based on two strategies relying on the free-radical carbo-cyanation and sulfonyl-cyanation respectively of enantiopure substituted cyclopropenes and cyclobutenes. Co- or Ni-boride reduction of the nitrile functional group along with the cyclopropane and cyclobutane ring-opening then led to the formation of the chiral piperidinone ring. Further elaboration of the latter into the key 1-azabicyclo[3.3.1]nonane motif followed by its coupling with a 2-cyanoaniline allowed the formation of the tetrahydrobenzo[b][1,8]-naphthyridine skeleton of 1, which was finally accessible in 17 steps and 5.9 % overall yield from 1,1-dibromobutene.

Phosphine Ligand-Free Bimetallic Ni(0)Pd(0) Nanoparticles as a Catalyst for Facile, General, Sustainable, and Highly Selective 1,4-Reductions in Aqueous Micelles.

Phosphine ligand-free bimetallic nanoparticles (NPs) composed of Ni(0)Pd(0) catalyze highly selective 1,4-reductions of enones, enamides, enenitriles, and ketoamides under aqueous micellar conditions. A minimal amount of Pd (Ni/Pd = 25:1) is needed to prepare these NPs, which results in reductions without impacting N- and O-benzyl, aldehyde, nitrile, and nitro functional groups. A broad range of substrates has been studied, including a gram-scale reaction. The metal-micelle binding is supported by surface-enhanced Raman spectroscopy data on both the NPs and their individual components. Optical imaging, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy analyses reveal the formation of NP-containing micelles or vesicles, NP morphology, particle size distribution, and chemical composition. X-ray photoelectron spectroscopy measurements indicate the oxidation state of each metal within these bimetallic NPs.

Construction and gas uptake performance of cyano-functional hypercrosslinked polymers via knitting strategy

Fabrication of functionalized hypercrosslinked polymers (HCPs) with high specific surface area has gained significant research interest and their utilization for gas storage is still a trending research area. Considering the significance of solvent knitting strategy in construction of remarkably high surface area HCPs, we report fabrication of cyano-functional HCPs via one step Friedel-Crafts reaction. The series of HCPs were obtained by copolymerizing the rigid monomer TPB with a 2-napthonitrile in different molar ratio. The resultant co-polymerized polymers contained a plenty of nitrile functional groups and possessed high BET surface area. Among the series of such HCPs, HCP-TPB-CN-3:1 showed the highest BET surface area up to 2017 m2g−1. These HCPs have enriched nitrogen in their pore walls that enhance the facile interaction of CO2 to achieve higher capture capacity of 21.3 wt% at 273 K. Moreover, the HCP-TPB-CN was explored for CH4 storage and showed absolute adsorption capacity of 0.35 g/g at 273 K, 80 bar, which is comparable with the porous polymers reported so far. These results highlight the significance of solvent knitting strategy and broaden the scope of HCPs for versatile industrial applications.