Reaction Of Amines Research Articles

SYNTHESIS OF N-ALKENYL(ALKYNYL)-5,6-DIMETHYL-2-(THIOPHEN-2-YL)THIENO[2,3-d]PYRIMIDIN-4-AMINES AND THEIR IN SILICO STUDY ON GROUP II CHITINASE (ChtII) INHIBITION

Research in the chemistry of heterocyclic compounds, particularly condensed pyrimidine frameworks, aimed at developing drugs with diverse therapeutic properties. Among these compounds, special attention is given to thieno[2,3-d]pyrimidine derivatives due to their potential as drug candidates. This study presents the synthesis of a series of N-alkenyl(alkynyl)-5,6-dimethyl-2-(thiophen-2-yl)-thieno[2,3-d]pyrimidin-4-amines via the amination reaction of 5,6-dimethyl-2-(thiophen-2-yl)-4-chlorothieno[2,3-d]pyrimidine with unsaturated amines (allyl-, diallyl-, and propargylamine), enabling potential application in electrophilic intramolecular heterocyclization reactions. Using molecular docking, the inhibitory potential of 5,6-dimethyl-2-(thiophen-2-yl)-thieno[2,3-d]pyrimidin-4-amines against ChtII chitinase, specific to the pest Asian corn borer (Ostrinia furnacalis), was assessed. The leading compound, N-propargyl-5,6-dimethyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidin-4-amine, showed the highest binding affinity to the target protein (binding energy of -9.09 kcal/mol), indicating its promise for further research.

Synthesis and Antioxidant Activity (4-(Benzo[d][1,3]-dioxol-6-yl)-tetrahydro-2H-pyran-4-yl)methylsubstituted Aryloxypropanolamines, Aminoamides and Sulfanilamides

Alkylation of 3,4-methylenedioxyphenylacetоnitrile with 2,2-dichlorodiethyl ether gave the corresponding nitrile the reduction of which with lithium aluminum hydride isolated (4-(benzo[d][1,3]dioxol-6-yl)-tetrahydro-2H-pyran-4-yl)methylamine. The interaction of the latter with aryloxymethyloxiranes gave the corresponding 1-((4-(benzo[d][1,3]dioxol-6-yl)-tetrahydro-2H-pyran-4-yl)methylamino)-3-aryloxypropan-2-ols. By the reaction of the same amine with chloroacetyl chloride isolated chloroacetamide, the interaction of which with a variety of secondary amines and heterylthiols synthesized the corresponding substituted amino- and sulfanylacetamides - derivatives of (4-(benzo[d][1,3]dioxol-6-yl)-tetrahydro-2H-pyran-4-yl)methylamine. The antioxidant activity of the obtained compounds was studied.

Copper‐Mediated C−H Functionalization of Amines, Imines, and Amides: Recent Developments and Synthetic Applications

AbstractCopper‐mediated C−H functionalization has emerged as a powerful strategy for the selective modification of nitrogen‐containing molecules, offering significant advancements in organic synthesis. This review provides a comprehensive overview of recent developments in copper‐catalyzed C−H functionalization reactions of amines, imines, and amides, from 2013 to present, emphasizing their synthetic applications and mechanistic insights. It also discusses the impact of these methodologies on the construction of complex molecular architectures, including pharmaceuticals and natural products. This review aims to provide valuable guidance for researchers seeking to leverage copper‐mediated strategies in their synthetic endeavors by creating current knowledge and identifying future directions. We have highlighted the new bonds formed through C−H functionalizations for the convenience of readers.

Structural and Reactivity Implications of Homo- and Heterobimetallic Co(II) Amides Prepared via Trans(amination) Reactions

Structural and Reactivity Implications of Homo- and Heterobimetallic Co(II) Amides Prepared via Trans(amination) Reactions

Synthesis and Antitumor Activity of Some New N1-(8-fluoro-4-oxoquinolin-5-yl)amidrazones.

Hydrazonoyl chloride, accessible from the respective 5-amino-8-fluoro- 4-oxoquinoline-3-carboxylate, undergoes a reaction with sec-cyclic amines to generate N1-(1- ethyl-8-fluoro-4-oxoquinolin-5-yl)amidrazone carboxylates. A novel set of N1-(1-ethyl-8-fluoro-4-oxoquinolin-5-yl)amidrazone carboxylates (7a-h) incorporating N-piperazines or related congeners was synthesized via interaction of the hydrazonoyl chloride (6), accessible from the respective 5-amino-8-fluoro-4-oxoquinoline-3-carboxylate, with the appropriate sec-cyclic amine. These new compounds were characterized by 1HNMR, 13C-NMR, and HRMS spectral data and screened for their anticancer activities. This study aimed at the synthesis of novel N1-( 4-oxoquinolin-5-yl)amidrazone carboxylate derivatives and investigated their potential as anticancer agents. The reaction of hydrazonoyl chloride with the appropriate sec-cyclic amine was applied to synthesize a novel set of N1-(1-ethyl-8-fluoro-4-oxoquinolin-5- yl)amidrazone carboxylates that incorporate N piperazines. A direct reaction of piperazines and related sec-cyclic amines with N-(4-oxoquinolin-5- yl)nitrile imine (1,3-dipole) was carried out for 8-10 h. The 1,3-dipole, generated in situ from its hydrazonoyl chloride precursor in the presence of trimethylamine, is suitable for the facile synthesis of N1-(1-ethyl-8-fluoro-4-oxoquinolin-5- yl)amidrazone carboxylates. This study led to the successful synthesis of novel N1-(8-fluoro-4-oxoquinolin-5- yl)amidrazones. All the examined compounds showed moderate activity with reasonable IC50 values in the micromolar range compared to Doxorubicin.

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.

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.

Catalytic kinetic resolution of helical polycyclic phenols via an organocatalyzed enantioselective dearomative amination reaction.

Despite the considerable potential applications for helically chiral molecules across various sectors, their catalytic asymmetric synthesis remains nascent and has seen very limited advancement compared to that of central and axial chiral compounds, primarily owing to the scarcity of available starting materials and the immense challenges associated with achieving stereochemical control. Herein, we report an innovative approach to the facile synthesis and catalytic kinetic resolution of uniquely structured and stereochemically complex helical polycyclic phenols by using a steric hindrance-regulated enantioselective dearomative amination reaction. The distinguished aspects of this method include the exceptional stability of the dearomatized products and impressive versatility of the recovered substrates in the construction of enantioenriched helical frameworks. This work showcases that the strategic incorporation of appropriate steric groups near the reaction site of an electron-rich aromatic compound can indeed enable an interrupted Friedel-Crafts reaction, thus opening an alternate avenue for the study of dearomatization in nonfunctionalized arenes.

Single Step Synthesis of Non-symmetric Azoarenes Using Buchwald-Hartwig Amination.

Aromatic azo compounds stand as a highly sought-after class of substances owing to their extensive array of applications across various fields. Despite their significance, their synthesis often presents challenges, requiring either multistep reactions or being restricted to specific substrate types. In this study, we are showing the universality and mechanistic aspects of a one-step approach for synthesis of nonsymmetrical azoarenes via the Buchwald-Hartwig amination reaction of (pseudo)haloaromatics with arylhydrazines, conducted in the presence of atmospheric oxygen. This reaction protocol yields products in up to 85% yield and is compatible with a wide class of substituents, making it highly adaptable. Notably, the inclusion of BINAP as a ligand plays a pivotal role in achieving favorable outcomes. This study not only offers a versatile solution to a long-standing synthetic challenge but also provides experimental and computational insights into the mechanisms driving the reaction.

Design and Evaluation of Azaspirocycles as RNA binders.

This study presents efficient synthetic pathways for preparing novel azaspirocycles. These methodologies involve functionalizing key bicyclic hydrazines with a substituent on one of their bridgehead carbon atoms. The desired spirocyclic cores were successfully obtained through double reductive amination reactions, intramolecular cyclizations, and cleavages of the N-N bond. The isolated molecules possess unique three-dimensional structures, suggesting potential applications in medicinal chemistry and drug discovery. With the growing interest in targeting nucleic acids as a complementary approach to protein-targeting strategies for developing novel active compounds, we investigated the potential of the synthesized azaspirocycles as RNA binders. As a proof of concept, we highlight the promising activity of some compounds as strong binders of HIV-1 TAR RNA and inhibitors of Tat/TAR interactions.

Fe‐Catalyzed α‐C(sp3)−H Amination of N‐Heterocycles

AbstractNitrogen‐heterocycles are privileged structures in both marketed drugs and natural products. On the other hand, C−H amination reactions furnish unconventional and straightforward approaches for the construction of C−N bonds. Yet, most of the known methods rely on precious metal catalysts. Herein we report a site‐selective intermolecular C(sp3)−H amination of N‐heterocycles, catalyzed by inexpensive FeCl2, which allows the functionalization of a wide range of pharmaceutically relevant cyclic amines. The C−H amination occurs site‐selectively in α‐position to the nitrogen atom, even when weaker C−H bonds are present, and furnishes Troc‐protected aminals or amidines. The method employs the N‐heterocycle as limiting reagent and is applicable to the late‐stage functionalization of complex molecules. Its synthetic potential was further illustrated through the derivatization of α‐aminated products and the application to a concise total synthesis of the reported structure for senobtusin. Mechanistic studies allowed to propose a plausible reaction mechanism involving a turnover‐limiting Fe‐nitrene generation followed by fast H atom transfer and radical rebound.

Non‐Isocyanate Carbamate Acrylates: Synthesis, Characterization, and Applications in UV 3D Printing

ABSTRACTIn this paper, two synthetic routes for non‐isocyanate carbamate acrylates (CAs) were explored. Four amino alcohols reacted with ethylene carbonate respectively forming carbamate alcohols. Additionally, carbamate amines were synthesized through the reaction of diethylene glycol with dimethyl carbonate, followed by the reaction of 4‐methylcyclohexane‐1,3‐diamine. Five kinds of CAs were synthesized via oxa‐Michael addition of carbamate alcohols and aza‐Michael reactions of carbamate amines with neopentyl glycol diacrylate (NPGDA), respectively. The resulting intermediates and final CAs were characterized by electrospray ionization high‐resolution mass spectrometry (ESI‐HRMS), 1H NMR, and FT‐IR spectroscopy. The photopolymerization kinetics of the CAs were investigated using FT‐IR spectroscopy. Under UV irradiation and initiation by 1 wt% 2‐isopropylthioxanthone (ITX) for 30 s, the double bond conversion of the CAs synthesized by oxa‐Michael addition were over 95%. The resulting CAs can be UV cured to form a transparent film with a gel content of 90%–95%, a hardness of 4–5 H, and a flexibility of 1 mm. A formulation consisting of 79 wt% CA2, 20 wt% NPGDA, and 1 wt% ITX was applied for 3D printing to produce various models with smooth surfaces, high precision, and excellent flexibility.

Fe-Catalyzed α-C(sp3)-H Amination of N-Heterocycles.

Nitrogen-heterocycles are privileged structures in both marketed drugs and natural products. On the other hand, C-H amination reactions furnish unconventional and straightforward approaches for the construction of C-N bonds. Yet, most of the known methods rely on precious metal catalysts. Herein we report a site-selective intermolecular C(sp3)-H amination of N-heterocycles, catalyzed by inexpensive FeCl2, which allows the functionalization of a wide range of pharmaceutically relevant cyclic amines. The C-H amination occurs site-selectively in α-position to the nitrogen atom, even when weaker C-H bonds are present, and furnishes Troc-protected aminals or amidines. The method employs the N-heterocycle as limiting reagent and is applicable to the late-stage functionalization of complex molecules. Its synthetic potential was further illustrated through the derivatization of α-aminated products and the application to a concise total synthesis of the reported structure for senobtusin. Mechanistic studies allowed to propose a plausible reaction mechanism involving a turnover-limiting Fe-nitrene generation followed by fast H atom transfer and radical rebound.

Chemical and Solvent-Based Recycling of DGEBA-Based Epoxy Thermoset and Carbon-Fiber Reinforced Epoxy Composite Utilizing Imine-Containing Secondary Amine Hardener.

Epoxy systems are essential in numerous industrial applications due to their exceptional mechanical properties, thermal stability, and chemical resistance. Yet, recycling epoxy networks and reinforcing materials in epoxy composites remains challenging, raising environmental concerns. The critical challenge is the recovery of well-defined molecules upon depolymerization. To address these issues, an innovative strategy is developed utilizing imine-containing secondary amine hardener (M1). The reaction of M1 with DGEBA produced high-performance epoxy thermoset P1, which exhibits Young's modulus of 2.18 GPa and tensile strength of 63.4 MPa, and excellent stability in neutral aqueous conditions. Upon carbon-fiber reinforcement, Young's modulus and tensile strength are significantly elevated to 10.99GPa and 328.3MPa, respectively. The reactive secondary amine functionalities enabled the tailored network to display a well-defined growth pattern, yielding only well-defined molecules and intact carbon fibers upon acidic depolymerization. Consequently, the recycled polymers retained properties identical to those of P1. Notably, it is discovered that despite the cross-linked nature of the epoxy networks, complete dissolution in dichloromethane facilitated straightforward solvent-based recycling, allowing the recovery of undamaged carbon fibers and an epoxy thermoset with properties matching the virgin material. Presented novel monomer design and approach showcased two important and efficient recycling options for epoxy systems.

Synthesis of Novel Phenylalanine Carboxamides Derivatives Bearing Sulfonamides Functionality and Their Molecular Docking, In Vitro Antimalarial, and Antioxidant Properties

AbstractA new series of phenylalanine‐derived carboxamides with sulfonamide functionality is designed, synthesized, and assessed for their in silico studies, in vitro antimalarial, and antioxidant activities. The interaction of 4‐nitrobenzene sulfonyl chloride with phenylalanine in a basic aqueous solution yielded an intermediate ((4‐nitrophenyl)sulfonyl)phenylalanine. The reaction of various cyclic amines with the intermediate, utilizing phenylboronic acid as the coupling agent, yielded the carboxamides derivatives. The derived‐carboxamides passed in silico test and fulfilled all the allowed ranges for molecular descriptors. Optimization was achieved before compounds were deployed as ligands in molecular docking studies using density functional theory utilizing the functional B3LYP and the basis set 6–31G**. The docking experiments were done on the active site of FKBP35 binding domain of Plasmodium falciparum for antimalarial impact whereas that of antioxidants was performed on the active site of PDB ID:IXAN. The computational antimalarial and antioxidant study demonstrated that the compounds displayed a high binding affinity with the target protein residues via hydrogen bonding, π‐π, π‐alkyl, π‐sigma, and π‐cation bonding interactions. Additionally, the new compounds were evaluated for in vitro antimalarial and antioxidant properties. The screening findings suggest that the new compounds exhibit effective antimalarial and antioxidant action compared to traditional medicines.

A new one-pot microwave-assisted synthesis and structural analysis of 6,N2,N4-trisubstituted 1,3,5-triazine-2,4-diamines

The substituted 1,3,5-triazine-2,4-diamine motif is a well-recognised scaffold for the construction of bioactive compounds. To improve the synthetic accessibility of these compounds and expand their molecular diversity, a convenient one-pot, two-step method for the synthesis of 6,N2,N4-trisubstituted 1,3,5-triazine-2,4-diamines was developed. The three-component acid-catalysed reaction of arylaldehydes, amines, and N-arylcyanoguanidines under microwave irradiation resulted in the dihydrotriazine ring closure. The subsequent microwave irradiation of the reaction mixture after treatment with a base afforded fully aromatic 6,N2,N4-trisubstituted 1,3,5-triazine-2,4-diamines as products of dehydrogenative aromatisation. The method was rather general, tolerated structural variations of all reactants and afforded a high chemical diversity of products. The molecular structure and intermolecular interactions in the crystal of N2-phenyl-4-morpholino-6-(4-methylphenyl)-1,3,5-triazine-2-amine as a representative example were studied using X-ray crystallography and molecular Hirshfeld surface analysis. The crystal packing was stabilised by two one-dimensional motifs: hydrogen bonding between the secondary amino group and morpholine moiety oxygen and π-π stacking interactions, common for the electron-deficient 1,3,5-triazine ring.

TFA-Catalyzed cascade annulation of thioamides with aromatic hydrazides/amines: an internal oxidant-triggered protocol to diverse N-heterocycles

An internal oxidant-triggered highly efficient protocol for the synthesis of diverse N-heterocycles (benzothiazoles, benzoxazoles, quinazolines, and 1,3,4-oxadiazoles) by TFA-catalyzed cascade annulation of thioamides with aromatic hydrazides or ortho-functionalized arylamines is described. In this transformation, thioamides act as a “C1” source as well as an internal oxidant, constructing a C=N double bond and a C-X (O/S/N) bond. The protocol is characterized by simple operation, metal-free conditions, broad substrate scope, good yields, and gram-scale synthesis. In addition, products can be further modified by Buchwald-Hartwig amination reactions, to a series of novel fluorescent compounds, which exhibit significant fluorescence performance with large Stokes shifts.

Functionalized iminodiacetic acid pectin/montmorillonite hydrogel for enhanced adsorption of 4-nitrophenol from simulated water: An integrated approach of response surface optimization and non-linear modeling

This research focuses on the modification of pectin through an amination reaction, followed by the development of a novel iminodiacetic acid-functionalized pectin/montmorillonite hydrogel nanocomposite (IMAP/MMT) using gamma radiation. This composite was investigated as an adsorbent for 4-nitrophenol removal from aqueous solutions. Central composite design was utilized for numerical optimization, identifying the maximum adsorption capacity under optimal conditions [0.8 g/L; 52 min;4 pH, 73 mg/L). A decrease in Qm (330.19 to 273.96 mg/g) with increasing temperature indicated an exothermic adsorption process, supported by the calculated ΔH° value of −28.39 kJ/mol. Analysis of pH, FTIR, and XPS results revealed that the primary mechanisms for 4-nitrophenol uptake include hydrogen bonding, π-π interactions, and n-π interactions. Additionally, the Temkin and D-R isotherms, along with ΔH° values, confirmed the physical nature of the adsorption process, as evidenced by bT (0.70–0.86 kJ/mol) and E (0.74–0.82 kJ/mol) values. The IMAP/MMT composite exhibited superior adsorption selectivity, efficient performance in real water, and good reusability, with a rate of 79.4 % maintained for up to five cycles, highlighting its potential for practical applications as an effective adsorbent. Overall, the findings suggest that IMAP/MMT can serve as an environmentally and economically sustainable material for the removal of 4-nitrophenol from wastewater.

Synthesis of 6- or 8-Carboxamido Derivatives of Imidazo[1,2-a]pyridines via a Heterogeneous Catalytic Aminocarbonylation Reaction.

Imidazo[1,2-a]pyridines and especially their amide derivatives exhibit a wide range of favourable pharmacological properties. In this work, Pd-catalysed carbonylation was used for the first time for the introduction of the carboxamide moiety into positions 6 or 8. A recyclable Pd catalyst, with palladium immobilised on a supported ionic liquid phase decorated with pyridinium ions, was used efficiently for the conversion of 6- or 8-iodo derivatives to the products. In the case of 6-iodo derivatives, a competing mono- and double carbonylation could be observed in the reactions of aliphatic amines as nucleophiles, but under the proper choice of reaction conditions, good-to-excellent selectivities could be achieved towards either the corresponding amides or α-ketomides. The heterogeneous catalyst showed excellent recyclability and low Pd-leaching.

Thiazolo[5,4‐d]Thiazole‐Linked Conjugated Porous Organic Polymers for Visible Light‐Driven C−N Bond Formation Reactions

AbstractDue to their unique semiconducting properties, conjugated porous organic polymers (CPOPs) have garnered significant interest in various photocatalysis applications. In this study, we synthesize three thiazolo[5,4‐d]thiazole (TzTz)‐linked CPOPs with three polyaryl rigid cores of benzene (CPOP1), pyrene (CPOP2), and triazine (CPOP3). We investigated their efficacy in catalyzing visible light‐driven C−N bond formation reactions, including C−N cross‐couplings between aryl bromides and amines and amination reactions from aryl bromides and sodium azides. Among the three, only CPOP2, combined with NiCl2 or Ni(dtbbpy)Cl2, effectively facilitated these transformations. Notably, CPOP2 exhibited photocatalytic activities approximately six times higher than its small molecular counterpart C1 in both reactions. The CPOP catalyst was easily recovered through centrifugal separation and reused for five catalytic cycles with minimal loss of activity. Theoretical calculations revealed that the deliberate structural design of polyaryl moieties could effectively tune the energy gap, which is crucial for the photocatalytic activity in organic reactions. This study, therefore, demonstrates a novel application of TzTz‐linked CPOPs for heterogeneous photocatalytic organic transformations.