Reaction Of Amines Research Articles

A scalable and autoclavable oxygen nanosensor platform for metabolic monitoring of Saccharomyces cerevisiae in a bioreactor and other in situ systems.

Polymer-encapsulated dye nanoparticle sensors are a valuable approach to achieving in situ analyte measurements with luminescence; however, typical emulsion-based nanosensors are poorly suited for large-scale biological samples due to limitations of synthesis scalability and stability. Branched polyethylenimine (PEI) is a versatile polymer scaffold ideal for constructing nanoparticles with various covalently conjugated moieties due to their high density of reactive primary amines, high water solubility, and biological stability. In this work, we used branched polyethylenimine as a scaffold-based approach for making a stable and scalable ratiometric oxygen sensor. Pt (II) tetracarboxyporphine was usedas an oxygen-sensing dye and coumarin 343 as a reference dye, all covalently linked to the PEI scaffold producing a product that could withstand sterilization procedures and easily be scaled. To minimize toxicity from the PEI scaffold, we conjugated it with 2000MW PEG.Theapplicability of the sensors was demonstratedin a 200mL Saccharomyces cerevisiae yeast culture, using orthogonal luminescent and electrochemical oxygen measurements to validate sensor response and measure the metabolic activity of the yeast in our culture. This approach was able to match the sensitivity of our electrochemical measurements while improving upon drawbacks of other luminescent methods of oxygen detection, demonstrating effective monitoring for at least 20h. Our scaffold-based approach is a modular and easily translatable technology that could be useful in various biotechnological applications.

Regioselective synthesis of 5-azaindazoles based on the intramolecular amination reaction of 5-acyl-4-pyridones with hydrazines.

The labile tautomerism of N-unsubstituted 5-acyl-4-pyridones, which exist in the form of 4-pyridone or 4-hydroxypyridine depending on the solvent, has been demonstrated. This equilibrium determines the reactivity of pyridones and their ability to undergo substitution reactions of the OH group. A regioselective and convenient method for the construction of functionalized pyrazolo[4,3-c]pyridines (30-93%) based on the intramolecular amination reaction of 4-pyridones with hydrazines has been developed. The heterocyclization of N-alkyl-4-pyridones is accompanied by a dealkylation reaction. The reaction with hydroxylamine as a nucleophile can be used for the construction of the isoxazolo[4,5-c]pyridine core. Methods have been developed for further modification of the 5-azaindazole fragment via alkylation and decarboxylation. The antiproliferative properties of the prepared 5-azaindazoles were studied in relation to cancer (Hep-2, MCF) and normal cell lines (FH and Vero), and the compounds demonstrated relevant biological activity for further design of new molecules for antitumor therapy.

Enantioselective Decarboxylative Mannich Reactions of α,β-Unsaturated β'-Ketoacids and Isatin Imines: Application in the Synthesis of Spiro[indoline-3,2'-piperidine]-2,4'-diones.

Organocatalytic, enantioselective decarboxylative Mannich reactions of α,β-unsaturated β'-ketoacids and isatin N-Boc imines, to give the corresponding 3-carbamoyl-2-oxindole derivatives, were developed. Subsequent N-deprotection and diastereoselective, intramolecular, aza-Michael reaction of the free amine provides previously unreported spiro[indoline-3,2'-piperidine]-2,4'-diones.

Research on transition metals for the multicomponent synthesis of benzo-fused γ-lactams.

Benzo-fused γ-lactams are fundamental in medicinal chemistry, acting as essential elements for various therapeutic agents due to their structural adaptability and capability to enhance biological activity. In their synthesis, transition metals play a pivotal role as catalysts, offering more efficient alternatives to traditional methods by facilitating C-N bond formation through mechanisms like intramolecular coupling. Recent advances have especially spotlighted transition-metal-catalyzed C-H amination reactions for directly converting C(sp2)-H to C(sp2)-N bonds, streamlining the creation of these compounds. Furthermore, biocatalytic approaches have emerged, providing asymmetric synthesis of lactams with high yield and enantioselectivity. This review examined the transition metal-catalyzed synthesis techniques for producing benzo-fused γ-lactams, marking a significant leap in organic synthesis by proposing more effective, selective, and greener production methods. It serves as a valuable resource for researchers in the fields of transition metal catalysts and those engaged in synthesizing these lactams.

3-Amino-1-methyl-1H-pyridin-2-one as Inbuilt Directing Group for Additive-Free Late-Stage ortho-Amination under Copper Catalysis towards Biologically Relevant Molecules

AbstractArylamines are essential building blocks that are found in biologically important substances, agrochemicals, and natural products. One of the C–N bond formation methods that is conveniently step- and atom-economical is the C–H bond activated amination process. We divulge an operationally simple and general method using 3-amino-1-methyl-1H-pyridin-2-one (AMP) as inbuilt directing group (DG) for additive-free, copper(II)-catalyzed ortho amination of β-C(sp2)–H bonds of arenes and heteroarenes. Notably, this cross dehydrogenative amination reaction exhibits a broad scope regarding amine coupling partners, including heterocyclic amines, secondary aliphatic amines, and cyclic amides, with exclusive site selectivity and excellent functional group tolerance. Moreover, implementing this methodology, we could also synthesize medicinally important compounds to showcase the suitability of this inbuilt DG for late-stage functionalization.

Microwave‐assisted multicomponent synthesis of spirooxindole dihydropyridine bisphosphonates

A new, simple, catalyst‐ and solvent‐free microwave (MW)‐assisted multicomponent method was elaborated for the synthesis of spirooxindole dihydropyridine bisphosphonates as a new family of compounds by the one‐pot reaction of isatins, β‐ketophosphonates and primary amines. The synthesis was carefully optimized in respect of the molar ratio of the starting materials, the heating mode, the temperature, the reaction time and the effect of different catalysts. The substrate scope of the synthesis was also investigated, and the novel title compounds could be prepared in moderate to good yields. A proposed mechanism for the multicomponent reaction was also provided, in which the iminophosphonate compound could mean a key intermediate through the formation of the desired spiro derivatives.

Electrochemical DABCOylation enables challenging aromatic C-H amination.

The selective amination of aromatic C-H bonds is a powerful strategy to access aryl amines, functionalities found in many pharmaceuticals and agrochemicals. Despite advances in the field, a platform for the direct, selective C-H amination of electronically diverse (hetero)arenes, particularly electron-deficient (hetero)arenes, remains an unaddressed fundamental challenge.1-10 In addition, many (hetero)arenes present difficulty in common selective pre-functionalization reactions, such as halogenation11, or metal-catalyzed borylation12 and silylation13. Here, we report a general solution to these limitations that enables selective C-H amination across a comprehensive scope of (hetero)arenes. Key to this strategy's success is the oxidative generation of highly electrophilic N-radical dications from bicyclic tertiary amines (DABCO) that reacts across a wide range of arenes with high selectivity. Notably, this platform constitutes the first anodically generated N-radical cations that engage in aromatic C-H amination over well-reported hydrogen atom transfer (HAT) with weak C-H bonds.14-16 This C-H amination reaction that allows selective functionalization of both electron-rich and deficient arenes, as well as pyridines, is a rarity in the general area of non-directed aromatic C-H functionalization.1-4 This sustainable electrochemical DABCOylation reaction provides access to many complex drug-like aryl- and pyridinylpiperazines with high functionality tolerance, chemoselectivity, and site-selectivity.17.

Amination of Alkylboronic Esters

AbstractAlkylboronic esters are high value chemical building blocks which can be used to make complex, C‐sp3 rich molecules. The ability to convert the C−B bond in a range of C−C and C‐heteroatom bond‐forming reactions, in addition to their broad functional group compatibility, gives alkylboronic esters significant synthetic utility. Methods to convert boronic esters into amines have particular interest, due to the wide prevalence of nitrogen‐based functional groups in biologically active compounds, functional materials, and catalysts. In this review, we explore different methods for the amination of alkylboronic esters. These can be split into three distinct classes based on the mechanism of reaction: amination through 1,2‐metallate rearrangement, amination using nucleophilic ‘ate’ complexes, and oxidative amination reactions such as alkyl variants of the Chan‐Lam reaction.

General chemoselective hindered amide coupling enabled by TCFH-catalytic Oxyma and transient imine protection.

We report a general chemoselective strategy for amide bond formation with poorly nucleophilic amines in the presence of reactive primary alcohols or amines as the competing nucleophiles. The selectivity for less reactive amines over competing alcohols was achieved using TCFH and catalytic Oxyma as a highly reactive, inexpensive, and safe reagent combination. By temporarily masking more reactive amines as imines through the use of electron-deficient aldehydes, the hindered amines could be similarly coupled with high efficiency and selectivity.

Regioselective intermolecular carboamination of allylamines via nucleopalladation: empowering three-component synthesis of vicinal diamines.

An intermolecular carboamination reaction of allyl amines under Pd(ii)-catalysis is reported, expediting the synthesis of valuable vicinal diamines embedded in a functionally enriched linear carbon framework with high yields and exclusive Markovnikov selectivity. Central to our approach is the strategic use of a removable picolinamide auxiliary, which directs the regioselectivity during aminopalladation and stabilizes the crucial 5,5-palladacycle intermediate. This stabilization facilitates oxidative addition to carbon electrophiles, enabling the simultaneous incorporation of diverse aryl/styryl groups as well as important amine motifs, such as sulfoximines and anilines, across carbon-carbon double bonds. The protocol features broad substrate compatibility, tolerance to various functional groups, and scalability. The utility of this method is further demonstrated by the site-selective diversification of pharmaceutical agents. Additionally, these products serve as versatile intermediates for synthesizing heterocycles and function as effective ligands in catalytic transfer hydrogenation reactions. Notably, this work represents a rare instance of nucleopalladation-guided intermolecular carboamination of allylamines.

A non-derivatized high-performance liquid chromatography method for simultaneous quantification of hydroxyl acids and amino acids in ammonolysis reactions.

A non-derivatized high-performance liquid chromatographic (HPLC) method was developed for the simultaneous quantification of hydroxyl acids and their amination products in ammonolysis reaction mixtures. By optimizing the mobile phase composition and pH (0.04 M KH2PO4-5% methanol, pH = 2.7), complete separation of hydroxyl acids and their amination products was achieved, using lactic acid as a model substrate. Lactic acid exhibited excellent linearity within the range of 0.02 to 25 mM (R2 = 0.99968), with a relative standard deviation (RSD, n = 6) of 3.51% and a recovery ratio between 96.10% and 102.23%. Similarly, alanine exhibited good linearity from 0.02 to 50 mM (R2 = 0.99999) with an RSD of 4.04% and recovery ratios between 97.30% and 100.03%. Both analytes demonstrated good intra-day precision, with RSDs of 4.23% and 1.18%, respectively. The substrate universality tests confirmed the method's ability to rapidly and effectively separate other hydroxyl acids and their corresponding amino acids in ammonolysis reactions. The results of quantitative comparison with AQC, PITC, and OPA derivatization also proved the method to be a reliable approach for the individual or simultaneous quantification of hydroxyl acids and amino acids, offering essential support for monitoring the conversion ratio and selectivity in hydroxyl acid amination processes. Moreover, it provides valuable guidance for optimizing the amination reaction of hydroxyl groups, potentially extending catalytic advantages to other related reactions.

Development of a Simultaneous Analytical Method for Amines Corresponding to 10 Typical Nitrosamines.

Regulatory authorities in various countries have successively issued notices and guidance to pharmaceutical manufacturers and distributors to evaluate the risk of contamination of nitrosamines in pharmaceutical products and to take appropriate measures. Analysis of nitrosamines in pharmaceutical products is not easy due to the large number of foreign substances, and the risk of contamination is determined by first conducting a desk investigation of the manufacturing process of the APIs or pharmaceutical products. However, a desk investigation may miss the risk since this method is not based on actual measurements. Therefore, in addition to conventional desk-based investigation, a new method is required to pick up risks that cannot be covered by a desk investigation. Nitrosamines are known to be formed by the reaction of amines with nitrosating agents such as nitrite. In the case of small alkyl nitrosamines such as NDMA and NDEA, the origin of the amines is mostly residual amines in the APIs. Residual amines in the APIs are a potential nitrosamine contamination risk, although the extent of that risk has rarely been reported. In this study, we developed and validated a simultaneous analytical method for amines corresponding to 10 typical small alkyl nitrosamines. Good linearity was obtained in the range of 0.003 to 10 μg/mL for MPA, 0.003 to 2 μg/mL for DIPA and DBA, 0.003 to 1 μg/mL for MeP, DEA, EIPA, and DPA, and 0.003 to 0.2 μg/mL for DMA, MOR, and MBA. The limits of quantitation and detection were 0.003 and 0.001-0.003 μg/mL, respectively. The recovery rates ranged from 70 to 130% for 121 APIs and were more than 40% for 83 APIs. Repeatability was also good, with %RSD < 15%. Although the correlation between the amount of amines detected in the APIs and the nitrosamines in the pharmaceutical products is under investigation, we expect that this analytical method will be used to determine the residual amine contents in APIs and contribute to the risk assessment of the nitrosamine contamination.

Enhanced mechanical properties of epoxy and furfuryl amine functionalized silica nanocomposites

In this work, the effect of epoxy and furfuryl amine functionalization of silica-nanoparticles on the mechanical behaviour such as tensile and flexural properties of the anhydride epoxy nanocomposites have been investigated. The sol-gel technique has been used to synthesize silica nanoparticles, followed by grafting with Epichlorohydrin (EPR) and Furfuryl amine (FA). The effect of filler loading in the epoxy nanocomposites was also studied by changing the weight percentage to 0.5, 1, and 2%. FTIR, FESEM, and TGA analyses were performed to confirm the molecular architecture, surface morphology, and thermal degradation behaviour of the functionalized nanoparticles. Tensile and flexural tests were performed to study the mechanical behaviour of the epoxy nanocomposites. The mechanical properties of the nanocomposites were found to be significantly enhanced for all the variations of nanocomposites at a filler loading of 0.5 wt.%. The maximum tensile strength and strain were improved by ∼67% and ∼71%, respectively, in the case of the control sample at 0.5 wt.% of FA functionalized nanofiller. Flexural strength, strain, and work of fracture have been enhanced by ∼81%, ∼34%, and ∼82%, respectively with respect to control sample. These improvements are related to the better interfacial adhesion between functionalized nanofiller and epoxy matrix through the covalent reaction of furfuryl amine and anhydride functional groups of the matrix system. Thus, FA functionalized silica nanoparticles have the potential to use as an admirable, cost-effective incorporation for epoxy to counter the brittle failure of the epoxy matrix.

Synthesis of 3,5-disubstituted anilines via sequential Mo-catalyzed deoxygenative benzene formation and Pd-catalyzed amination reactions

The substituted anilines play a pivotal role as structural motifs in agrochemicals, organic polymers, and pharmaceuticals, and great efforts have been dedicated to advancing their synthesis. However, the highly efficient and selective synthesis of meta,meta-disubstituted anilines remains a challenge. Here, we report the synthesis of meta,meta-disubstituted anilines via sequential Mo-catalyzed deoxygenative benzene formation and Pd-catalyzed amination reactions. By employing this method, a wide range of meta,meta-disubstituted anilines were accessed with up to 89% yield from readily accessible ynones, allylic amines, and amines.

Iodine-Promoted C-H Bond Amination Reaction for the Synthesis of Fused Tricyclic Heteroarenes.

Fused heterocyclic scaffolds, such as benzimidazoles or larger ring systems containing a benzimidazole fragment, are frequently encountered in pharmaceutical compounds and other biologically active molecules. While there are many examples of N9- and/or C3-substituted 9H-benzo[4,5]imidazo[2,1-c][1,2,4]triazoles, current examples of the regioselective preparation of N1-substituted 1H-benzo[4,5]imidazo[2,1-c][1,2,4]triazoles are limited to N1-aryl substituted compounds, which also contain a C3-substituent. Here, we report an iodine-promoted C-H bond amination reaction that allows the selective preparation of 1H-benzo[4,5]imidazo[2,1-c][1,2,4]triazoles with a variety of aryl and alkyl N1-substituents. Not only do these cyclization reactions allow access to a new substitution pattern on the benzo[4,5]imidazo[2,1-c][1,2,4]triazole scaffold, but they are also tolerant toward a wide range of functional groups, including esters, amides, alcohols, alkynes, and alkenes. Our findings expand the synthetic toolbox for the preparation of nitrogen containing fused heteroarenes.

Controllable Synthesis of Benzo[b]furo[2,3-d]azepines or Furo[3,2-b]indoles via Intermolecular Oxidative Annulation of 2-(Furan-2-yl)anilines and Propargyl Carbonates versus Intramolecular C-H Amination Reactions.

Two novel Pd-catalyzed protocols for the controllable synthesis of benzo[b]furo[2,3-d]azepines and furo[3,2-b]indoles have been developed by intermolecular oxidative annulation of 2-(furan-2-yl)anilines and propargyl carbonates versus intramolecular C-H amination reactions. These two protocols feature great scalability, functional group tolerance, and relatively mild reaction conditions. Notably, the robust methodologies could also provide valuable opportunities for assembling azepine-fused benzothiophene, indole-fused benzothiophene, and indole-fused benzimidazole, which may have potential applications in the synthesis of related pharmaceuticals or polymeric materials.

Crystal structure and density functional theory investigations on carbon dioxide capture reactivity of primary amine and secondary amine, the case of diethylenetriamine

Crystal structure and density functional theory investigations on carbon dioxide capture reactivity of primary amine and secondary amine, the case of diethylenetriamine

Scalable Preparation of Superdurable, Self-Healing, and Biocompatible Superhydrophobic Poly(ethylene terephthalate) Fabrics.

The chemical inertness of poly(ethylene terephthalate) (PET) fabrics poses challenges in achieving superhydrophobic coatings with durable adhesion on their surfaces. Conventional surface modification methods such as alkali etching and plasma etching typically compromise the favorable mechanical properties of PET. In this study, polydopamine (PDA) was utilized to functionalize the PET fabric nondestructively by creating robust and reactive hydroxyl and amine groups on its surface, which were subsequently used as a binder of superhydrophobic modifiers such as fluorine-free octadecyltrichlorosilane (OTS). By utilizing PDA to provide reactive groups, OTS undergoes self-assembly through hydrolysis on the surface of the PET fabric without introducing any inorganic nanoparticles while simultaneously forming low surface energy, strong covalent bonds, and rough surfaces. This robust material system provides a novel strategy to design and prepare superhydrophobic PET fabrics that can withstand extreme conditions and maintain superb water repellency even after 1000 times of abrasion and 100 washing cycles. Additionally, the room-temperature self-assembly properties of OTS provide the modified PET fabrics with efficient and repeatable room-temperature self-healing capability. This entire process through an environmentally friendly two-step immersion method enables large-scale production of superhydrophobic PET fabrics with wide applications in sports shoes and clothing.

Cationic/Anionic Poly(p-Phenylene Oxide) Membranes: Preparation and Electrodialysis Performance for Nickel Recovery from Industrial Effluents.

Electrodialysis (ED) has already been applied to recover nickel in galvanizing processes, allowing nickel recovery and the production of a treated effluent with demineralized water quality. However, the growth in ED use is still limited by the production and commercialization of ion-selective membranes, currently limited to a few large companies. Therefore, this paper presents the development of homogeneous cationic and anionic membranes made from poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) for ED use. Cationic membranes were prepared by the sulfonation reaction of PPO under different experimental conditions (PPO:H2SO4 molar ratio and reaction time). Anionic membranes were prepared by the bromination reaction of PPO, followed by the amination reaction. The membranes were characterized for their chemical and electrochemical properties, including ion exchange capacity, conductivity, thermal stability, and surface morphology. The optimal conditions for cationic membrane sulfonation were achieved with a 1:4.4 PPO:H2SO4 molar ratio, and a reaction time of 0.5 h. For anionic membranes, the best results were obtained with bromination, with a PPO:NBS (N-Bromosuccinimide) molar ratio of 1:0.5, followed by 14 days of amination. Overall, 91.8% chloride, 90.9% sulfate, and 85.5% nickel ion extraction was achieved, highlighting PPO as a promising polymer for the development of anionic and cationic ion-selective membranes for ED.

AIE Active Polymeric Fluorescent Nanoaggregates from Glycogen for Sensitive Detection of Tetracycline.

Detection and monitoring of environmental contaminants such as antibiotic residues in aquatic environments is challenging. To address this, a variety of detection methods has been developed; out of which optical sensing using fluorescence is found as one of the most robust methods. However, most of the reported sensors are made from metal ions using tedious synthetic processes, on the other hand, optical sensors using biosourced polymers are rarely reported. Herein, an anionic glycogen functionalized aggregation induced emission (AIE) active system; NCMCTPN was prepared using a simple Schiff base condensation reaction of tetraphenylethene amine (TPENH2) and carboxymethyl cellulose dialdehyde (NCMCA) and its self-assembled polymeric nanoaggregates were explored for sensitive and selective turn-off fluorescence detection of a broad-spectrum tetracycline antibiotic, in an aqueous medium with a limit of detection of 127.5 ppb. The combination of factors such as inner filter effect and photoinduced electron transfer from the polymeric nanoaggregates to tetracycline through activation of a non-radiative decay process is possibly responsible for the high sensitivity of the fluorescent nanoprobe towards the antibiotic.