Cyclic Amines Research Articles

Surface-modified PVDF membranes for separation of dye by forward osmosis

Modification of membranes is widely used for altering their separation properties. In this study, the modification of PVDF nanofiber mat by deposition of polyamide layers was evaluated to improve dye recovery by means of forward osmosis process. The polyamide active layer was prepared by a reaction of cyclic aromatic amines, m-phenylenediamine, or piperazine, and trimesoylchloride. The modification progress was monitored by FTIR analysis, water uptake, nitrogen content, and grafting yields. Investigated membranes showed an excellent dye separation features with water flux and dye fluxes strongly related to type of applied amines and reaction time. The best obtained membrane demonstrated outstanding performance in forward osmosis; their water flux was 3.3 LMH and rejection rate of 97% for bromocresol green dye. The membrane allowed increase dye concentration by 50% after 24 h of the process.

Base‐Catalyzed Highly Regioselective Synthesis of Bio‐Based Hydroxyurethanes

AbstractThe regioselective synthesis of carbamates from bio‐derived cyclic carbonates and amines by using 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD) as an organocatalyst is reported. This methodology led to the preparation of a wide range of bio‐sourced hydroxyurethanes from furan‐, carvone‐ and limonene‐based scaffolds under solvent‐free and mild reaction conditions. Moreover, a comprehensive analysis of the process allowed us to optimize the catalyst loading with little or no impact on the process regioselectivity.

An Expedient Radical Approach for the Decarboxylative Synthesis of Stereodefined All‐Carbon Tetrasubstituted Olefins

We report a user‐friendly approach for the decarboxylative formation of stereodefined and complex tri‐ and tetra‐substituted olefins from vinyl cyclic carbonates and amines as radical precursors. The protocol relies on easy photo‐initiated α‐amino‐radical formation followed by addition onto the double bond of the substrate resulting in a sequence involving carbonate ring‐opening, double bond relay, CO2 extrusion and finally O‐protonation. The developed protocol is efficient for both mismatched and matched polarity substrate combinations, and the scope of elaborate stereodefined olefins that can be forged including drug‐functionalized derivatives is wide, diverse and further extendable to other types of heterocyclic and radical precursors. Mechanistic control reactions show that the decarboxylation step is a key driving force towards product formation, with the initial radical addition under steric control.

An Expedient Radical Approach for the Decarboxylative Synthesis of Stereodefined All-Carbon Tetrasubstituted Olefins.

We report a user-friendly approach for the decarboxylative formation of stereodefined and complex tri- and tetra-substituted olefins from vinyl cyclic carbonates and amines as radical precursors. The protocol relies on easy photo-initiated α-amino-radical formation followed by addition onto the double bond of the substrate resulting in a sequence involving carbonate ring-opening, double bond relay, CO2 extrusion and finally O-protonation. The developed protocol is efficient for both mismatched and matched polarity substrate combinations, and the scope of elaborate stereodefined olefins that can be forged including drug-functionalized derivatives is wide, diverse and further extendable to other types of heterocyclic and radical precursors. Mechanistic control reactions show that the decarboxylation step is a key driving force towards product formation, with the initial radical addition under steric control.

Phenoxyalkyl cyclic and acyclic amine derivatives: what do they teach us about scaffold-based drug design?

Phenoxyalkyl cyclic and acyclic amine derivatives: what do they teach us about scaffold-based drug design?

Endophytic Bacteria Producing Alkaloid as Antibacterial and Antioxidant Agent from Hibiscus tiliaceus Leaves

Hibiscus tiliaceus is known to have antibacterial activity. One of the antibacterial compounds contained in the hibiscus plant is alkaloid. Alkaloids can also be obtained from endophytic bacteria that are in symbiosis with hibiscus leaves. It is known that endophytes can produce the same or similar secondary metabolites as their host plants. Medicinal plants have been proven to be a source of microorganisms that can make certain metabolites. Our previous research succeeded in isolating the endophytic bacteria Staphylococcus warneri strain 25 from waru leaves (Hibiscus tiliaceus), which had antioxidant and antibacterial activity and contained saponins and alkaloids. In this study, alkaloids were extracted from the endophytic bacteria found in waru leaves. Subsequently, their bioactivity was assessed for antibacterial properties against Escherichia coli, Salmonella typhi, and Staphylococcus aureus using the well diffusion method. Additionally, their antioxidant activity was evaluated through the DPPH method, with gallic acid serving as the standard. A cyclic amine alkaloid compound was isolated, exhibiting a Minimum Inhibitory Concentration (MIC) of 23 ppm against E. coli, S. typhi, and S. aureus bacteria, accompanied by inhibitory zones measuring 7 mm, 8 mm, and 6 mm, respectively. Additionally, the compound had very strong antioxidant activity, with an IC50 value of 50.11 ppm.

Access to 4‐Membered Heterocycles via Visible‐Light Triggered Intramolecular Cyclization from Alkynes: Bypassing Unfavorable 4‐endo‐dig Cyclization

We describe a catalyst, oxidant, and coupling‐reagent free strategy to access 4‐membered heterocycle, representing a unique example of visible‐light triggered intramolecular cyclization of propargylic alcohols and amines to access oxetanones and azetidinones respectively. Despite the direct 4‐endo‐dig cyclization from these starting materials has proven to be unfavorable, the formation of key p‐quinone methide intermediacy allows an efficient bypass for regioselective 4‐exo‐trig cyclization, resulting in the formation of the desired 4‐membered heterocycles. This mild and operationally simple protocol facilitates the synthesis of products with distinct substitution patterns such as quaternary α‐carbons, and enables late‐stage functionalization.

Unveiling the Molecular Characteristics, Origins, and Formation Mechanism of Reduced Nitrogen Organic Compounds in the Urban Atmosphere of Shanghai Using a Versatile Aerosol Concentration Enrichment System.

Reduced nitrogen-containing organic compounds (NOCs) in aerosols play a crucial role in altering their light-absorption properties, thereby impacting regional haze and climate. Due to the low concentration levels of individual NOCs in the air, the utilization of accurate detection and quantification technologies becomes essential. For the first time, this study investigated the diurnal variation, chemical characteristics, and potential formation pathways of NOCs in urban ambient aerosols in Shanghai using a versatile aerosol concentration enrichment system (VACES) coupled with HPLC-Q-TOF-MS. The results showed that NOCs accounted over 60% of identified components of urban organic aerosols, with O/N < 3 compounds being the major contributors (>70%). The predominance of the positive ionization mode suggested the prevalence of reduced NOCs. Higher relative intensities and number fractions of NOCs were observed during nighttime, while CHO compounds showed an opposite trend. Notably, a positive correlation between the intensity of NOCs and ammonium during the nighttime was observed, suggesting that the reaction of ammonium to form imines may be a potential pathway for the formation of reduced NOCs during the nighttime. Seven prevalent types of reduced NOCs in autumn and winter were identified and characterized by an enrichment of CH2 long-chain homologues. These NOCs included alkyl, cyclic, and aromatic amides in CHON compounds, as well as heterocyclic or cyclic amines and aniline homologue series in CHN compounds, which were associated with anthropogenic activities and may be capable of forming light-absorbing chromophores or posing harm to human health. The findings highlight the significant contributions of both primary emissions and ammonium chemistry, particularly amination processes, to the pollution of reduced NOCs in Shanghai's atmosphere.

One-pot two-step reduction of CO2 with amines and NaBH4 to N-substituted compounds at atmospheric pressure

In this paper, the reductive N-formylation, methylation and cyclization of amines with carbon dioxide (CO2) using sodium borohydride (NaBH4) at atmospheric pressure, via a one-pot two-step procedure, is presented. Formato borohydride (NaBHn(OCHO)4-n), in situ formed in the reaction of NaBH4 with CO2, as an efficient agent to promote the corresponding reaction, and the mechanism is proposed on the basis of experiments. This wide substrate scope and simple operational methodology also facilitates the effective synthesis of formamides, methylamines, benzimidazoles and other heterocyclic compounds avoiding high temperature and pressure.

Fluorescent turn-on detection of inorganic mercury and methylmercury in aqueous solution with PC micelles and live cells using fluorescent chemosensors based on Trp amino acid and cycloalkylamine-7-sulfonyl-2,1,3-benzoxadiazole

Mercury species are well-known to be toxic to humans. Particularly, methylmercury is a highly toxic substance that can readily penetrate lipid membranes, accumulating in human body and causing lethal effects. Thus, the sensitive detection of methylmercury in aquatic environments and live cells is crucial. In this study, we synthesized fluorescent chemosensors (1–5), primarily composed of a tryptophan amino acid (Trp) and cycloalkylamine-7-sulfonyl-2,1,3-benzoxadiazole fluorophores bearing a different size of cyclic amine moiety and developed new sensing systems for Hg2+ and CH3Hg+ by combining the fluorescent chemosensors with lyso-phosphatidylcholine (PC) micelles to resemble cytoplasmic lipid membranes of human cells. Fluorescent chemosensors (1–5) with visible light excitation (>450 nm) exhibited significant enhanced emissions to Hg2+ among various metal ions in purely aqueous solutions. In PC micelles, the chemosensors (1–5) showed significant enhanced green and red emissions (500 ∼ 670 nm) to CH3Hg+ and Hg2+ among various metal ions. Interestingly, the chemosensors have different binding affinities and fluorescent signal changes for CH3Hg+ depending on the size of cyclic amine moiety. Among them, chemosensor 5 with 7-membered cyclic amino group, exhibited the largest fluorescence change for CH3Hg+ and demonstrated the highest binding affinity for CH3Hg+ (Kd = 24.1 μM) and Hg2+ (Kd = 15.8 nM). Chemosensor 5 exhibited a significant enhancement of emission as well as an extremely fast response (<20 sec) for methylmercury in aqueous solution with PC micelles. Thus, we investigated the binding mode of chemosensor 5 with the mercury species in PC micelles using UV/visible absorbance titration, pH titration, and NMR titration experiments. Furthermore, chemosensor 5 was successfully applied to detect sensitively CH3Hg+ and Hg2+ in live cells through increase in both green and red emissions. Fluorescent chemosensors in combination with PC micelles might serve as a promising new fluorescent sensing method for methylmercury and inorganic mercury ions in aqueous solutions and live cells.

Synthesis,Antidiabetic and Antitubercular Evaluation of Quinoline-pyrazolopyrimidine hybrids and Quinoline-4-Arylamines.

Two libraries of quinoline-based hybrids 1-(7-chloroquinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine and 7-chloro-N-phenylquinolin-4-amine were synthesized and evaluated for their α-glucosidase inhibitory and antioxidant properties. Compounds with 4-methylpiperidine and para-trifluoromethoxy groups, respectively, showed the most promising α-glucosidase inhibition activity with IC50 =46.70 and 40.84 μM, compared to the reference inhibitor, acarbose (IC50 =51.73 μM). Structure-activity relationship analysis suggested that the cyclic secondary amine pendants and para-phenyl substituents account for the variable enzyme inhibition. Antioxidant profiling further revealed that compounds with an N-methylpiperazine and N-ethylpiperazine ring, respectively, have good DPPH scavenging abilities with IC50 =0.18, 0.58 and 0.93 mM, as compared to ascorbic acid (IC50 =0.05 mM), while the best DPPH scavenger is NO2 -substituted compound (IC50 =0.08 mM). Also, compound with N-(2-hydroxyethyl)piperazine moiety emerged as the best NO radical scavenger with IC50 =0.28 mM. Molecular docking studies showed that the present compounds are orthosteric inhibitors with their quinoline, pyrimidine, and 4-amino units as crucial pharmacophores furnishing α-glucosidase binding at the catalytic site. Taken together, these compounds exhibit dual potentials; i. e., potent α-glucosidase inhibitors and excellent free radical scavengers. Hence, they may serve as structural templates in the search for agents to manage Type 2 diabetes mellitus. Finally, in preliminary assays investigating the anti-tubercular potential of these compounds, two pyrazolopyrimidine series compounds and a 7-chloro-N-phenylquinolin-4-amine hybrid showed sub-10 μM whole-cell activities against Mycobacterium tuberculosis.

Synthesis of Alkenylgold(I) Complexes Relevant to Catalytic Carboxylative Cyclization of Unsaturated Amines and Alcohols.

The carboxylation of unsaturated amine and alcohol compounds, including 4-benzylamino-1-phenyl-1-butyne (homopropargylamine), 2-butyne-1-ol (propargylic alcohol), and 2,3-butadiene-1-ol (allenylmethyl alcohol), using the hydroxidogold(I) complex, AuOH(IPr) [IPr = 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene], produces corresponding alkenylgold(I) complexes with a cyclic urethane or carbonate framework in high yields. The reaction takes place in aprotic THF at room temperature under the atmospheric pressure of CO2 in the absence of base additives. The products were characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The functionalized alkenyl complexes prepared from the alkynes can be protonated by treatment with an equimolar amount of acetic acid to afford five- or six-membered carboxylation products, whereas the related alkenyl complex derived from allenylmethyl alcohol decomposed to recover the starting allene via ring-opening decarboxylation.

Cyclic Amine Synthesis via Catalytic Radical-Polar Crossover Cycloadditions.

The rapid assembly of valuable cyclic amine architectures in a single step from simple precursors has been recognized as an ideal platform in term of efficiency and sustainability. Although a vast number of studies regarding cyclic amine synthesis has been reported, new synthetic disconnection approaches are still high in demand. Herein, we report a catalytic radical-polar crossover cycloaddition to cyclic amine synthesis triggered from primary sulfonamide under photoredox condition. This newly developed disconnection, comparable to established synthetic approaches, will allow to construct β, β-disubstituted cyclic amine and β-monosubstituted cyclic amine derivatives efficiently. This study highlights the unique utility of primary sulfonamide as a bifunctional reagent, which acts as a radical precursor and a nucleophile. The open-shell methodology demonstrates broad tolerance to various functional groups, drug derivatives and natural products in an economically and sustainable fashion.

Cyclic Amine Synthesis via Catalytic Radical‐Polar Crossover Cycloadditions

AbstractThe rapid assembly of valuable cyclic amine architectures in a single step from simple precursors has been recognized as an ideal platform in term of efficiency and sustainability. Although a vast number of studies regarding cyclic amine synthesis has been reported, new synthetic disconnection approaches are still high in demand. Herein, we report a catalytic radical‐polar crossover cycloaddition to cyclic amine synthesis triggered from primary sulfonamide under photoredox condition. This newly developed disconnection, comparable to established synthetic approaches, will allow to construct β, β‐disubstituted cyclic amine and β‐monosubstituted cyclic amine derivatives efficiently. This study highlights the unique utility of primary sulfonamide as a bifunctional reagent, which acts as a radical precursor and a nucleophile. The open‐shell methodology demonstrates broad tolerance to various functional groups, drug derivatives and natural products in an economically and sustainable fashion.

Low-cost and high-performance acetylglucose-based imidazolium salts for copper-catalyzed cyclization of propargylic amines and CO2

The rise of carbon dioxide (CO2) in atmosphere is considered as a major cause of global warming. Therefore, CO2 utilization has attracted increasing attention. Among those, using CO2 as C1-feedstock for “value carbon” in advanced chemicals provides a solution. Here, we show an acetylglucose-based imidazolium salt for Cu-catalyzed cyclization of propargylic amines and CO2 with an excellent turnover frequency value of 400 h−1. To the best of our knowledge, it is the first example of acetylglucose-based imidazolium salts for a noble-metal-free Cu catalytic system for the cyclization of propargylic amines and CO2.

Cyclic Amines Coupled to Indole Derivatives With Improved Efflux Pump Inhibiting Activity in Bacteria and Cancer Cells.

Indole skeleton has become a significant tool in the field of anticancer and antibacterial therapeutic strategies. The modified aza-Friedel-Crafts reaction by direct coupling of different cyclic imines and indole derivatives has been explored. To investigate the scope and limitations of the reaction and observe the effect of structural modifications, our aim was to resynthesize selected compounds as well as prepare new derivatives starting from 6,7-dimethoxy-3,4-dihydroisoquinoline, (4aR,8aR)-4a,5,6,7,8,8a-hexahydroquinoxalin-2(1H)-one and 7-azaindole. Our further aim was the systematic biological evaluation of selected C-3-coupled indole and azaindole derivatives in favour of having a preliminary overview about the structure-activity relationships. The synthesis and resynthesis of selected compounds were accomplished by extension of aza-Friedel-Crafts reaction. The products have been tested on bacteria and cancer cells. The most significant efflux pump inhibiting (EPI) activity was observed in the case of 6,7-dihydrothieno[3,2-c]pyridine coupled indole derivative. The reaction of 6,7-dimethoxy-3,4-dihydroisoquinoline with 7-azaindole resulted in the most potent biofilm inhibitor product. Applying indole and 4,9-dihydro-3H-β-carboline, 6,7-dihydrothieno[3,2-c]pyridine led to the formation of a product with the highest anticancer activity. 6,7-Dimethoxy-3,4-dihydroisoquinoline skeleton and indole as an electron-rich aromatic compound have been found to be effective in the inhibition of ABCB1. The compounds presented in the study were investigated regarding different aspects of antibacterial and anticancer activities. Accordingly, some compounds were found to have antibacterial effect on Escherichia coli and Staphylococcus aureus strains, certain C-3-coupled derivatives showed toxicity on sensitive and ABCB1 efflux pump expressing colon adenocarcinoma and a normal, non-cancerous fibroblast cell lines.

Reductive Functionalization of Pyridine-Fused N-Heteroarenes.

ConspectusThe selective functionalization/transformation of ubiquitous pyridine-fused N-heteroarenes is a practical method to synthesize structurally novel N-heterocycles, which is important for the development of medicines, bioactive agents, agrochemicals, materials, ligands, sensors, pigments, dyes, etc. However, owing to thermodynamic stability, kinetic inertness, and lone electron pair-induced catalyst deactivation of the pyridine-fused N-heteroarenes, limited strategies (e.g., C-H activation/functionalization, electrophilic substitution, and the Minisci reaction) are available to realize the synthetic purpose and maintain the aromaticity of the final products. Moreover, the relevant transformations have limitations such as needing harsh reaction conditions, requiring the preinstallation of specific coupling agents containing transformable functionalities or directing groups, using less environmentally benign oxidants and/or acidic activators, and poor selectivity. Herein, considering that imines, enamines, radicals, and cyclic amines are generated during the reduction of pyridine-fused N-heteroarenes, the precise transformation of these reductive intermediates offers a fundamental basis for developing novel tandem reactions. Our group revealed that a slow reduction rate, synergistic catalysis, and controlled electroreduction are effective strategies for fulfilling the selective reductive functionalization of pyridine-fused N-heteroarenes. Thus, we established a series of new synthetic methods that provide diverse construction modalities for functionalized N-heterocycles. The striking features of these synthetic methods include high efficiency, atom economy, and the use of readily accessible N-heteroarenes as transformable feedstocks in the absence of flammable and pressurized H2 gas, alongside a promising potential of the obtained N-heterocyclic products. The present study would be appealing to the fields of synthetic organic chemistry, catalysis, biomedical chemistry, and functional materials. This Account describes the application of reductive dearomatization as substrate-activating and tandem reaction-initiating modes and summarizes the reductive functionalization of pyridine-fused N-heteroarenes via selective alkylation, arylation, and annulation at nitrogen, α, β, and other remote carbon sites achieved over the past 8 years. Details regarding the development of new reactions and their plausible mechanisms and perspectives are discussed. We hope our contributions to this field will aid in the further development of novel strategies for the functionalization/transformation of pyridine-fused N-heteroarenes and tackle the intractable challenges in this area.

Thermodynamics of complex formation of silver(I) with substituted pyridines and cyclic amines in non-aqueous solvents

The understanding of the thermodynamic stability and speciation of metal complexes in solution requires access to their enthalpy and entropy of formation. In this work, we specifically focus our investigation on the complexation process of silver(I) ion in acetonitrile (AN) with substituted mono pyridines and cyclic monoamines. The aim of this study is to provide reliable thermodynamic data to obtain insights on metal complex formation, focusing on ligands donor properties and solvation effects. Carefully designed potentiometric and calorimetric experiments allowed to define the species present at different ligand/metal ratios and to obtain the complex formation constants and enthalpies. In general, the enthalpy terms associated with the complex formation are highly exothermic, while the entropy values are always unfavorable. The formation constants of AgLj species for the ligands investigated in AN are compared with those previously obtained in dimethyl sulfoxide (DMSO) and water. The trends in stability constants and enthalpy values are discussed in relation to the pKa data available in the different solvents. Higher pKa values correspond to greater ligand basicity and result in more stable and more enthalpy stabilized complexes.

A Review on Hetero Cyclic Compounds &amp; Schiff Base

The Azetidinone is well known as the (Beta-lactams) rings of a four-membered cyclic amine it is named due to N atom which is linked to Beta-carbonyl with carbonyl. Pyrazine ring plays an important role as a basic scaffold in drug designing. These compounds containing N-heterocyclic moieties are a class of privileged compounds that have found numerous application as pharmaceuticals. Schiff bases are condensation products of primary amines with carbonyl compounds and they were first reported by Schiff in 1864. Pyrazines is used to treat anti-diabetic, anti-tubercular and anti-cancer activities.These compounds containing N-heterocyclic moieties are a class of privileged compounds that have found numerous application as pharmaceuticals. All these above heterocyclic compounds have so many pharmacological activities such as anti microbial, anti bacterial, anti-cancer activities.

Fine Tuning Ag(I)-Sb(III) Hybrid Iodides for Light Detection.

Lead-free hybrid double perovskite iodides (HDPIs) have piqued increasing research interest due to their environmental friendliness and high stability. However, such antimony-based HDPIs with strong photocurrent response are currently very limited. Here, we successfully design and construct five Ag(I)-Sb(III)-based HDPIs using two types of cyclic aliphatic amines as A-site templates. Interestingly, these Ag(I)-Sb(III) HDPIs exhibit relatively narrow band gaps, preferred orientation, and high stability after being processed into thin films on the indium tin oxide (ITO) substrate. Notably, under illuminations of a xenon lamp, all HDPIs exhibit considerable photocurrent responses, reaching a maximum difference of 17 μA·cm-2 for ASI 1, which is the highest among lead-free halogen-based organic-inorganic hybrid compounds to date. Combining the considerable photocurrents and the high stability, the optoelectronic applications of two-dimensional Ag(I)-Sb(III) HDPIs can be expected.