Secondary Aliphatic Amines Research Articles

Catalytic Cycloisomerization-Oxidative Cyclization Reaction Sequence of Enyne Diesters Derived from 2-Propargyloxyarylaldehydes.

Enyne diesters derived from 2-propargyloxyarylaldehydes are converted into 2-oxopyranochromenes via In(OTf)3-catalyzed cycloisomerization and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated oxidative cyclization reaction sequence in one pot. The process possesses broad substrate scope and good functional group compatibility and generates various 4-(hetero)aryl-substituted 2-oxopyranochromenes in 32-79% yields (over two steps). 2-Oxopyranochromenes undergo selective decarboxylation under Krapcho conditions. When treated with aliphatic secondary amines in DMF, 2-oxopyranochromenes undergo decarboxylative amination at ambient temperature to generate 2-amino-substituted functionalized chromenes in good yields.

Heterogeneous visible-light photoredox catalysis with NiCl2@g-C3N4 for induced C(sp2)-H/N[sbnd]H cross-dehydrogenative coupling

A novel photoactive NiCl2@g-C3N4 catalyst system, which effectively drives C(sp2)-H/NH bond formation between quinolin-2(1H)-ones, primary and secondary aliphatic amines under blue light irradiation. The NiCl2@g-C3N4 composite with a NiCl2 loading of 0.7wt% had the highest photoactivity, and the calculated band gap energy value is 2.56 eV The nickel ion could act as an electron acceptor enhancing carrier separation and transfer efficiency, greatly enhanced the photoreaction efficiency of g-C3N4. Preliminary mechanistic studies indicate upon visible light irradiation, the photo-generated electrons and holes act as oxidants, thereby generating amine radicals in the absence of external chemical oxidants. This provides a straightforward and efficient approach for directly 3-aminating quinoxalines-2(1H)-ones. Moreover, the heterogeneous catalyst can be recycled at least six times without significant activity loss.

Amine Exchange of Aminoalkylated Phenols as Dynamic Reaction in Benzoxazine/Amine-Based Vitrimers.

Bisfunctional benzoxazine and polyether diamine-based polymers show Arrhenius-like stress-relaxation varying with stoichiometry and polymerization temperatures proving vitrimeric behavior. Molecular structural investigations reveal the presence of different aminoalkylated phenols occurring at varying ratios depending on polymer composition and polymerization conditions. The vitrimeric mechanism is found to involve an amine exchange reaction of aminoalkylated phenols in an equilibrium reaction like a nucleophilic substitution reaction. As determined by molecular studies and dissolution experiments in reactive solvents, aliphatic and aromatic primary as well as aliphatic secondary amines in the polybenzoxazine structure can act as nucleophiles in reaction with electrophilic methylene bridges. Thus, aminoalkylated phenols proved to be a relevant structural motif resulting in a vitrimeric polybenzoxazine due to amine exchange reaction.

Photoredox cross-dehydrogenative C(sp2)-C(sp3) coupling of heteroarenes with secondary amines through 1,5-HAT.

The functionalization of α-C(sp3)-H bonds in amines has become a focal point of contemporary research. Here, we report a new approach utilizing photocatalysis α-C(sp3)-H bond functionalization in alicyclic and aliphatic secondary amines facilitated by intramolecular 1,5-hydrogen atom transfer (HAT). This finding unlocks a sustainable method for rapidly constructing complex heterocyclics via cross-dehydrogenative C-C coupling of protected amines and nitrogen-containing heterocycles. This protocol boasts broad applicability to various substrates, exhibits tolerance to numerous functional groups, and supports the late-stage modification of drug molecules.

Tandem Protocol for Diversified Deuteration of Secondary Aliphatic Amines under Mild Conditions.

Deuteration of amine compounds has been widely of concern because of its practical role in organic reaction mechanisms and drug research; however, only limited deuteration label methods are accessible with D2O as a deuterium source. Herein, we propose a convenient deuteration protocol, including preparing D2 by the AlGa activation method, using PtRu nanowires as catalysts, and utilizing the elementary step in the couple reaction involving an imine unit, to realize the rapid preparation of a secondary amine with a diversified deuteration label. The self-coupling between nitriles not only provides a symmetric secondary amine with four α-D atoms but also produces high-valued ND3 in an atomic-economic way.

Well-defined nanomagnetic nitrilotriacetic acid complex of Cu(ii) supported on silica-coated nanosized magnetite: a new highly efficient and magnetically separable catalyst for C-N bond formation.

A nitrilotriacetic acid (NTA) complex of Cu(ii) supported on silica-coated nanosized magnetite Fe3O4@SiO2-Pr-DEA-[NTA-Cu(ii)]2 was prepared as a new well-defined magnetically separable nanomaterial and fully characterized via IR, XRD, FESEM, TEM, TGA, DLS, BET, VSM, solid-state UV-vis spectroscopy, EDX, ICP-OES, and FESEM-EDX map analyses. Thereafter, it was successfully applied as a new easily magnetically separable and reusable heterogeneous nanocatalyst for the Buchwald-Hartwig C-N bond formation reaction in DMF at 110 °C. Using this method, various kinds of nitrogen heterocycles, such as imidazoles, 2-methyl-1H-imidazole, benzimidazole, indole, and 10H-phenothiazine as well as aliphatic secondary amines such as piperidine, piperazine, morpholine, dimethylamine, and diethylamine, were reacted with aryl halide compounds, and the desired products were obtained with good to excellent yields. In all cases, the applied catalyst could be recovered easily and rapidly using an external magnet and reused 7 times without significant loss of catalytic activity.

Green, facile synthesis and evaluation of unsymmetrical carbamide derivatives as antimicrobial and anticancer agents with mechanistic insights

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9–23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds. All the synthesized compounds were tested as antimicrobial agents against some clinically bacterial pathogens such as Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compounds 15, 16, 17, 19 and 22 showed potent antimicrobial activity with promising MIC values compared to the positive controls. Moreover, compounds 15 and 22 provide a potent lipid peroxidation (LPO) of the bacterial cell wall. On the other hand, we investigated the anti-proliferative activity of compounds 9–23 against selected human cancerous cell lines of breast (MCF-7), colon (HCT-116), and lung (A549) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and pro-apoptotic protein markers. The results of MTT assay revealed that compounds 10, 13, 21, 22 and 23 possessed highly cytotoxic effects. Out of these, three synthesized compounds 13, 21 and 22 showed cytotoxicity with IC50 values (13, IC50 = 62.4 ± 0.128 and 22, IC50 = 91.6 ± 0.112 µM, respectively, on MCF-7), (13, IC50 = 43.5 ± 0.15 and 21, IC50 = 38.5 ± 0.17 µM, respectively, on HCT-116). Cell cycle and apoptosis/necrosis assays demonstrated that compounds 13 and 22 induced S and G2/M phase cell cycle arrest in MCF-7 cells, while only compound 13 had this effect on HCT-116 cells. Furthermore, compound 13 exhibited the greatest potency in inducing apoptosis in both cell lines compared to compounds 21 and 22. Docking studies indicated that compounds 10, 13, 21 and 23 could potentially inhibit enzymes and exert promising antimicrobial effects, as evidenced by their lower binding energies and various types of interactions observed at the active sites of key enzymes such as Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of K. pneumenia and Gyrase B of B. subtilis. Moreover, 13, 21, and 22 demonstrated minimal binding energy and favorable affinity towards the active pocket of anticancer receptor proteins, including CDK2, EGFR, Erα, Topoisomerase II and VEGFFR. Physicochemical properties, drug-likeness, and ADME (absorption, distribution, metabolism, excretion, and toxicity) parameters of the selected compounds were also computed.

One-Pot Synthesis of Silver/Zirconium Nanoparticles Using Sargassum tenerrimum for the Evaluation of Their Antibacterial and Antioxidant Activities.

The global health threat posed by worldwide antimicrobial resistance necessitated immediate multisectoral action by the scientific community to achieve sustainable development goals. Silver and zirconium nanoparticles (Ag/ZrO-NPs), known for their antimicrobial properties, have the potential to combat pathogens effectively, making them versatile for various applications across different fields. This study aims to synthesize and characterize Sargassum tenerimum-mediated Ag/ZrO-NPs and evaluate their antioxidant and antibacterial efficacy against multidrug resistant (MDR) pathogens. The synthesis of Ag/ZrO-NPs using the one-pot green synthesis method was conducted and followed by using characterization techniques, namely, UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), X-ray diffraction analysis (XRD), and energy-dispersive X-ray analysis (EDX). The antibacterial activity was assessed using the agar well diffusion method, and antioxidant activity was determined using the DPPH(2,2-diphenyl-1-picrylhydrazyl) method. Statistical analysis was analyzed using the IBM SPSS Statistics for Windows, version 21.0 (released 2012, IBM Corp., Armonk, NY). The green-synthesized Ag/ZrO-NPs exhibited acolor change from dark brown to creamy white, indicating the successful reduction of the nanoparticles. UV-analysis peaks were observed at 310-330 nm, while the FT-IRanalysis showed the peaks at various wavelengths, such as 648.9 cm-1 (alkyne C-H bond), 1041.14 cm-1 (aliphatic fluoro compounds, C-F stretch), 1382.54 cm-1 (dimethyl -CH3), 1589.6 cm-1 (primary amine, N-H bond), and 3353.8 cm-1 (aliphatic secondary amine, N-H stretch). The crystallinity of the nanoparticles was determined to be 59.5%, while the remaining 40.5% exhibited an amorphous structure.The SEM image revealed the spherically agglomeratedstructure of the nano-ranged size Ag/ZrO-NPs. The EDX analysis indicated the presence of elemental compositions Zr (16.2%), Ag (18.8%), and C (28.7%)in the green-synthesized Ag/ZrO-NPs. These nanoparticles demonstrated significant antibacterial activity against Pseudomonas aeruginosa, Enterococcus faecalis, and Methicillin-resistant Staphylococcus aureus (MRSA). The moderate antibacterial activity against E. coli showed thesignificant antioxidant activity in a dose-dependent manner. The green-synthesized Ag/ZrO-NPs showed notable antibacterial and antioxidant activity. In future aspects, it may be used as a potential drug after completion of in-vivo and in-vitro studies.

NMI-SO2Cl2-Mediated Amide Bond Formation: Facile Synthesis of Some Dihydrotriazolopyrimidine Amide Derivatives as Potential Anti-Inflammatory and Anti-Tubercular Agents.

Facile access to some novel biologically relevant dihydrotriazolopyrimidine carboxylic acid-derived amide analogues using NMI/SO2Cl2, and aromatic and aliphatic primary and secondary amines, is reported herein. The role of N-methylimidazole (NMI) as the base and sulfuryl chloride (SO2Cl2) as the coupling reagent has been effectively realized in accessing these molecules in good to excellent yields. The feasibility of the developed protocol has also been extended to the gram-scale synthesis of N-benzylbenzamide in a 75% yield from benzoic acid and benzyl amine. The newly synthesized compounds were tested via in vitro anti-inflammatory and anti-tubercular activity studies. The compounds 6aa and 6be were found to be the most active anti-inflammatory agents, whereas 6cb and 6ch were found to exhibit promising anti-tubercular potency when compared to other synthesized molecules. The structure-activity relationship (SAR) studies revealed the importance of the presence of electron-donating functionalities in enhancing the anti-inflammatory potential of the newly synthesized molecules. However, the presence of electron-withdrawing substituents was found to be significant for improving their anti-tubercular potency.

Direct synthesis of branched amines enabled by dual-catalyzed allylic C─H amination of alkenes with amines.

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

An improved Simon reaction method to discriminate between methamphetamine and false-positive substances.

The conventional methamphetamine (MA) detection method using the Simon reaction can be affected by false positives owing to compounds similar to aliphatic secondary amines. In this study, we examined the new Simon reaction to improve the qualitative accuracy of MA detection to discriminate substances that give false positives in a conventional Simon reaction. After the conventional Simon reaction for MA and false positives (N-isopropylbenzylamine (NIP-BA), N-methylbenzylamine (NMe-BA), L-proline (Pro), and L-hydroxyproline (HYP)), which are colored blue, di-tert-butyl dicarbonate (t-Boc) reagent was added, and color tone changes were observed. When t-Boc was added to the false positives (NIP-BA, NMe-BA, Pro, and HYP), the colors of MA, Pro, and HYP changed to purple; NIP-BA changed to blue; and NMe-BA changed to light pink after 3 min. These results suggested that MA can be differentiated from NIP-BA and NMe-BA. Furthermore, the solid-phase chromogenic method was examined, and it was confirmed that MA could be differentiated from Pro and HYP. The method developed in this study should increase the accuracy of MA appraisal at crime scenes and contribute to the reduction of misclassifications arising from false-positive substances.

X‐Ray Crystallography and Antimicrobial Activity of Synthetic Cyanoguanidinophenytoin Cocrystals

AbstractA novel series of 1 : 1 cocrystals of 2‐cyanoguanidinophenytoin (CNG‐DPH) with primary, secondary, and tertiary aliphatic amines has been presented through this work. The antimicrobial activities of all new CNG‐DPH‐amine cocrystals were studied. The existence of cocrystals has been proven through crystal structure results. The 5‐Oxo‐4,4‐diphenylimidazolidin‐2‐ylidenecyanamide‐piperidine cocrystal (10) is located in an orthorhombic crystal system, and the cocrystal is connected via the N−H−N hydrogen bond between the cyanide group and the piperidine molecule. Hirshfeld surface analysis authenticated supramolecular contacts. Ring puckering analysis revealed a chair stereochemistry at the 6‐membered piperidine. The crystal packing has been stabilized through intermolecular forces, hydrogen bonds, and interactions within the gravity center of rings (Cg). The antimicrobial activities of the newly synthesized compounds were only effective against Gram‐positive bacteria, demonstrating that the antibacterial spectrum of these compounds was restricted. In vitro cytotoxicity of the synthesized cocrystals was assessed in normal cells, giving the highest half‐maximal inhibitory concentration (IC50) ratio (637.63 μg/ml) and the lowest value (181.98 μg/ml).

Convenient and versatile method of 8-amino-6-(2-R-thiazol-4-yl)-1,7-naphthyridines synthesis

On the base of 3-formylpicolinic acid by two successive heterocyclizations (the formation of a pyrone fragment by the cyclization of chloroacetone with the carboxyl and formyl groups; and the construction of the thiazole cycle through the bromination of the acetyl fragment and following interaction with thioamides), 6-(2-(phenyl/thiophen-2-yl)thiazole-4-yl)-8H-pyrano[3,4-b]pyridin-8-ones were obtained; and then the pyrone fragment was converted to pyridone by the action of ammonia under high pressure. When such 6-(2-R-thiazol-4-yl)-1,7-naphthyridin-8(7H)-ones reacted with triflic anhydride, O-sulfonylation of the pyridone fragment occurred, after that triflate group was easily substituted by secondary cyclic aliphatic amines. Thus, a number of new 8-amino-6-(2-R-thiazol-4-yl)-1,7-naphthyridines – previously inaccessible heterocyclic derivatives with promising biological activity – were obtained.

Copper-catalyzed carbonylative multi-component borylamidation of alkenes for synthesizing γ-boryl amides with CO as both methylene and carbonyl sources.

A multi-component carbonylation reaction is an efficient strategy for the synthesis of valuable carbonyl compounds from simple and readily available substrates. However, there remain challenges in carbonylation reactions where two CO molecules are converted to different groups in the target product. Considering the merit of complex amides, we reported here a copper-catalyzed multi-component borylamidation for the synthesis of γ-boryl amides. This method provides access to a wide range of functional γ-boryl amides from alkenes, amines, B2pin2, and CO with good yields and excellent diastereomeric ratios. Notably, two CO molecules were converted to methylene and carbonyl groups in the target amides. A series of amines were successfully involved in the transformation, including arylamines, aliphatic amines, and hydrochloride salts of secondary aliphatic amines.

Insights into the formation of halonitromethanes from dimethylamine involving bromide ion during UV/chloramine disinfection

Aliphatic amines are vital precursors of halonitromethane (HNMs), which pose a potential hazard to water safety. Bromide ions (Br−) have been reported to exert a significant effect on HNMs formation. However, the formation of HNMs from secondary aliphatic amine during UV/chloramine disinfection in the presence of Br− has rarely been studied. Hence, this work selected dimethylamine (DMA) as the model precursor and focused on the mechanism and impact factors of HNMs formation involving Br− during UV/chloramine disinfection. The results indicated that after adding 2 mg/L Br−, the total concentration of HNMs at 4 min increased up to 1.86-fold compared with adding 0.3 mg/L Br−. Moreover, brominated (chlorinated)-HNMs (Br(Cl)-HNMs) were gradually transformed into brominated-HNMs (Br-HNMs) with increased Br− concentration. While Br-HNMs would be transformed into Br(Cl)-HNMs with the increase of monochloramine concentration. The peak values of HNMs were promoted with the increase of DMA concentration but inhibited with the increase of pH. Notably, tribromonitromethane was the dominant species of HNMs involving Br− during UV/chloramine disinfection. The possible formation pathways of HNMs from DMA involving Br− during UV/chloramine disinfection were deduced. Finally, it was discovered that the formation of HNMs in real water was basically consistent with that in simulated water. The findings of this research are beneficial for comprehending the formation mechanism of HNMs from aliphatic amines and provide scientific measures to minimize the HNMs production during UV/chloramine disinfection.

Synthesis of α,β-diamino acid derivatives by acid-catalyzed Aza-Michael addition of N-phthalyldehydroalanine with different amine

A series of α,β-diamino acid derivatives were synthesized from N-phthalyldehydroalanine with different amines by acetic acid catalytic Aza-Michael additions. This reaction achieves C–N bond formation with good functional group tolerance. Under optimized conditions, the desired products of most aromatic and secondary aliphatic amines were obtained in moderate to good yields under mild conditions. The electronic effect and steric effect play the important roles to the reactivity of amines.

GC-MS and FTIR analyses of bioactive compounds present in ethanol leaf extract of Sida acuta from Imo State, Nigeri

Medicinal plants are vital to human and community health. This work aimed at using gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared (FTIR) to determine the phytochemical contents of ethanol leaf extract of Sida acuta from Imo State, Nigeria. Leaves of Sida acuta were collected, washed, air-dried, and pulverized. Pulverized leaves were extracted in 100% ethanol at 70°C in a water bath. Bioactive compounds from the extract were analyzed using Agilent Technologies GC equipment and Buck Scientific M530 USA FTIR. The GC-MS Screening of the plant’s extract revealed the presence of seventy-one (71) phytocompounds including gamma-terpinene (1.11%), p-cymene (0.29%), linalool (2.45%), alpha-cubebene (0.11%), alpha-copaene (1.34%), aromadendrene (6.21%), humulene (1.90%), alpha-selinine, guaiol (0.58%), phytol (0.11%), butyl-2-ethylhexylphthalate (0.32%), 1,2-benzenedicarboxylic acid (0.40%), 1-docosene (0.36%), 1,4-dichlorobenzene (0.22%), (e)-.beta.-farnesene (10.87%), and piperine (0.61%), which are reported to exhibit various biological activities. The FTIR analysis of the plant extract revealed functional groups such as Primary (1°) and Secondary (2°) amines, alkanes, alkenes, alkyl halides, carboxylic acids, allenes, aromatics, aliphatic amines, esters, ethers, phenols, and aldehydes. Cross-referencing the phytocompounds with literature revealed a variety of biological functions, including antibacterial, antifungal, anti-inflammatory, anticancer, antimutagenic, antioxidant, antitumor, and others. It may be concluded that Sida acuta contains bioactive compounds with anti-microbial, anti-inflammatory, anti-oxidant, hepatoprotective, and anti-carcinogenic properties, with (E). beta.-farnesene being the most abundant (10.87%).

Yttrium‐Catalyzed Intermolecular Anti‐Markovnikov Hydroamination and Sequential Intermolecular Hydroamination/Endocyclization of Vinylsilanes

AbstractThe intermolecular anti‐Markovnikov hydroamination of vinylsilanes was achieved utilizing five silyl‐substituted ortho‐terphenoxide yttrium complexes. The highest activity was observed for the most sterically encumbered triphenylsilyl‐substituted complex. Excellent activity and complete anti‐Markonikov selectivity were obtained for a variety of benzylic and aliphatic primary and secondary amines. Interestingly, the reaction with 2‐picolylamine produced the hydroaminoalkylation product rather than the hydroamination product. Reaction of dimethyldivinylsilane resulted in a range of 1,4‐azasilinanes via sequential hydroamination/endocyclization in good yields.

An investigation to compare the shear strength of the adhesive joint of unidirectional CFRP after KrF excimer laser treatment in normal atmosphere, argon and underwater environments

Unidirectional CFRP was treated by KrF laser in normal atmosphere, argon and underwater environments, before adhesive bonding. KrF laser removed the top resin layer and exposed the carbon fibres. Porosity and holes were generated around exposed carbon fibres after argon environment treatments and flakes-like-surface-structure was generated after underwater treatments with two-step method. KrF laser treatments increased Sq and Sdr values. Sdr was more influential for adhesive joint shear strength. These laser treatments in all environments transformed secondary and tertiary aliphatic amines to primary and secondary aliphatic amines, respectively. SLSS study confirmed that the highest shear strength of 35.78 MPa which was 45% higher than the untreated joint, was achieved after underwater treatment. Normal atmosphere and argon environment treatments resulted in 31.74 and 31.95 MPa, respectively. Adhesive failure which occurred after argon environment treatments, reduced after normal atmosphere treatments. Underwater treatments resulted in cohesive failure and thin layer cohesive failure.

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on "in-out" structure, and theoretical calculations of non-covalent interactions.

Resorcin[4]arenes (R[4]A) are macrocyclic compounds with a cavity structure. Despite a relatively small cavity, these compounds are capable of forming complexes with small organic molecules. The current paper focuses on the synthesis of complexes between R[4]A and secondary aliphatic amines (sec-amines). Through NMR spectroscopy, it was observed that "in-out" complexes are formed depending on the solvent. It was also found that the stoichiometry of the formed complexes depends on the size of the amine molecule. The automated interaction sites screening (aISS) made it possible to generate molecular ensembles of complexes. The geometry of the ensembles was first optimized with the r2scan-3c functional and, finally, the structure with the lowest energy, with the functional PBE0-D4/mTZVPP/CPCM. The Hartree-Fock plus London dispersion (HFLD) method was used for the study of non-covalent interactions (NCI). The calculations lead to the conclusion that a reduction in electrostatic interactions and an increase in exchange and dispersion interactions in CHCl3 in relation to DMSO are the driving forces behind the placement of sec-amine molecules into the R[4]A cavity and the formation of "in" type complexes.