Synthesis Of Α-aminophosphonates Research Articles

A new protocol for the one-pot synthesis of α-aminophosphonates using hydroxyapatite-supported palladium as a solid and reusable catalyst

Abstract The rational design of a new method has been reported for the synthesis of α-aminophosphonates from alcohols, amines, and phosphonates using palladium-supported hydroxyapatite (Pd-HAP) as a catalyst. This synthetic protocol involves alcohol oxidation to aldehyde over Pd-HAP followed by condensation with amine and phosphonates to form α-aminophosphonates in one pot. The catalyst demonstrated excellent catalytic activity for up to four cycles without any appreciable activity loss. This strategy provides advantages such as heterogeneous catalyst, mild reaction conditions, simple experimental and work-up procedure, high yield, low cost, alcohol use instead of unstable aldehyde, and environmental friendliness.

Synthesis and molecular docking study of α-aminophosphonates as potential multi-targeting antibacterial agents

Antibacterial compounds that reduce extracellular polymeric substances (EPS) are needed to avoid bacterial biofilms in water pipelines. Herein, green one-pot synthesis of α-aminophosphonates (α-Amps) [A-G] was achieved by using ionic liquid (IL) as a Lewis acid catalyst. The synthesized α-Amp analogues were tested against different bacteria such as Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The representative [B] analogue showed an efficient antibacterial effect with MIC values of 3.13 μg/mL for E. coli, P. aeruginosa, and 6.25 μg/mL for B. subtilis. Additionally, a strong ability to eliminate the mature bacterial biofilm, with super-MIC values of 12.5 μg/mL for E. coli, P. aeruginosa, and 25 μg/mL for B. subtilis. Moreover, bacterial cell disruption by ROS formation was also tested, and the compound [B] revealed the highest ROS level compared to other compounds and the control, and efficiently destroyed the extracellular polymeric substances (EPS). The docking study confirmed strong interactions between [B] analogue and protein structures with a binding affinity of −6.65 kCal/mol for the lyase protein of gram-positive bacteria and −6.46 kCal/mol for DNA gyrase of gram-negative bacteria. The results showed that α-Amps moiety is a promising candidate for developing novel antibacterial and anti-biofilm agents for clean water supply.

TBAPMNP as an Effective and Recyclable Heterogeneous Catalyst for Single-Pot Three Component Synthesis of α-Aminophosphonates through Kabachnik–Fields Reaction

TBAPMNP as an Effective and Recyclable Heterogeneous Catalyst for Single-Pot Three Component Synthesis of α-Aminophosphonates through Kabachnik–Fields Reaction

Direct Synthesis of α-Aminophosphonates from Amines, Alcohols, and White Phosphorus

Direct Synthesis of α-Aminophosphonates from Amines, Alcohols, and White Phosphorus

The Last Decade of Optically Active α-Aminophosphonates.

α-Aminophosphonates and related compounds are important due to their real and potential biological activity. α-Aminophosphonates may be prepared by the Kabachnik-Fields condensation of oxo compounds, amines and dialkyl phosphites, or by the aza-Pudovik addition of the same P-reagents to imines. In this review, the methods that allow for the synthesis of α-aminophosphonates with optical activity are surveyed. On the one hand, optically active catalysts or ligands may induce enantioselectivity during the Kabachnik-Fields reaction. On the other hand, asymmetric catalysis during the aza-Pudovik reaction, or hydrogenations of iminophosphonates, may prove to be a useful tool. Lastly yet importantly, it is possible to start from optically active reagents that may be associated with diastereoselectivity. The "green" aspects of the different syntheses are also considered.

Pvp-based deep eutectic solvent polymer: Sustainable Brønsted-Lewis acidic catalyst in the synthesis of α-aminophosphonate and bisindole

Polymeric deep eutectic solvents (PDESs) have emerged for augmentation of the functions of deep eutectic solvents (DESs) as a sustainable material class. Considering the common synthetic limitation of PDESs to the in-situ polymerization of deep eutectic monomers, herein, we have implemented linear polyvinylpyrrolidone (PVP) to develop a simple-to-prepare, atom-economical, cost-effective, and eco-friendly Brønsted-Lewis acidic PDES via ZnCl2 and a quaternization procedure. The prepared PDES was characterized by SEM, EDS, elemental mapping, FT-IR, and TGA techniques. This method enables physicochemical tunation of the PDES by altering the molar ratio of ZnCl2 to PVP monomer repeating units. The PDES was used as a heterogeneous catalyst to promote greener approaches towards biologically significant scaffolds via a multicomponent reaction of aldehydes, amines, and tri(alkyl/aryl)phosphites to synthesize secondary and tertiary α-aminophosphonates (APs), in addition to a carbon–carbon bond-forming reaction to synthesizing bis(indolyl)methanes (BIMs) from aldehydes and indolyl compounds. PDESs proved to be highly efficient catalysts for these transformations, providing mild and high-yielding green protocols for an extensive library of both APs and BIMs. The desired compounds from either transformation group were obtained shortly with good to excellent yields (15–120 min for APs and 100–200 min for BIMs). Examination with BIMs revealed that the protocol is amenable to large-scale production without significant loss of efficiency. In addition, the stability of the PDES catalyst was confirmed from five successful recycles, in which no significant decrease in the activity was monitored.

2-Hydroxymethyl-18-crown-6 as an efficient organocatalyst for α-aminophosphonates synthesized under eco-friendly conditions, DFT, molecular docking and ADME/T studies

Eco-friendly and simple procedure has been developed for the synthesis of α-aminophosphonates that act as topoisomerase II α-inhibiting anticancer agent, using 2-hydroxymethyl-18-crown-6 as an unexpected homogeneous organocatalyst in multicomponents reaction of aromatic aldehyde, aniline and diethylphosphite in one pot via Kabachnik–Fields reaction. This efficient method proceeds with catalytic amount, transition metal-free, at room temperature within short reaction time, giving the α-aminophosphonates derivatives (4a–r) in high chemical yields (up to 80%). Theoretical DFT calculations of three compounds (4p, 4q and 4r) were carried out in a gas phase at CAM-B3LYP 6-31G (d,p) basis set to predict the molecular geometries and chemical reactivity descriptors. The frontier orbital energies (HOMO/LUMO) were described the charge transfer and used to predict structure-activity relationship study. Molecular electrostatic potential (MEP) has also been analyzed. Molecular docking studies are implemented to analyze the binding energy and compared with Adriamycin against 1ZXM receptor which to be considered as antitumor candidates. In silico pharmacological ADMET properties as Drug likeness and oral activity have been carried out based on Lipinski’s rule of five. Communicated by Ramaswamy H. Sarma

Synthesis of α-Amino Phosphonates and Phosphines via Hydrosilylation and Iron-Catalyzed Phosphonylation

Key words iron catalysis - α-amino phosphonates - tertiary amides - hydrosilylation - phosphonylation

Organocatalytic Direct Enantioselective Hydrophosphonylation of N-Unsubstituted Ketimines for the Synthesis of α-Aminophosphonates

We report an organocatalyzed direct enantioselective hydrophosphonylation of N-unsubstituted ketimines that affords N-unprotected α-tetrasubstituted α-aminophosphonates without protection/deprotection steps. The reaction is suitable for N-unsubstituted isatin-derived and trifluoromethyl ketimines, affording products in high yields with excellent enantioselectivity. Applications of the reaction and a proposed transition state model are also described.

Synthesis of α-Aminophosphonates by Umpolung-Enabled Cu-Catalyzed Regioselective Hydroamination

A copper-catalyzed regioselective hydroamination of α,β-unsaturated phosphonates has been developed to form corresponding α-aminophosphonates of interest in medicinal chemistry. The introduction of an umpolung, electrophilic amination strategy with the hydroxylamine derivative is the key to achieving the α-amination regioselectivity, which is otherwise difficult under the conventional nucleophilic hydroamination conditions with the parent amine. Asymmetric synthesis with a chiral bisphosphine ligand and application to a related silylamination reaction are also described.

Sequential KOtBu/FeCl3-catalyzed reductive phosphonylation of tertiary amides for the synthesis of α-amino phosphonates and phosphines.

A simple, mild and efficient sequential KOtBu/FeCl3-catalyzed reductive phosphonylation of tertiary amides is herein described. This process first involved the KOtBu-catalyzed selective semi-reduction of tertiary amides to hemiaminal intermediates by TMDS (1,1,3,3-tetramethyldisiloxane) and then the FeCl3-catalyzed nucleophilic addition of the hemiaminal intermediates to phosphonates, which allowed the straightforward synthesis of α-amino phosphonates in moderate to good yields. This method applied well to amides and lactams that bear no strong acidic α-hydrogens, and various functional groups, including methoxy, methylthio, cyano, halogen, and heterocycles, could be tolerated.

An ultra-sound assisted synthesis of α-aminophosphonates from benzyl halides via sequential Kornblum and Kabachnik-fields reaction

An ultrasound-assisted simple, easy and straightforward method for the synthesis of α-aminophosphonates has been developed via Kornblum/Kabachnik-fields reaction. The method involves in situ generation of an aldehyde intermediate from benzyl halides via oxidative dehalogenation followed by coupling with aryl amine and trialkyl phosphite in a one-pot three component manner under ultrasonic irradiations. The developed method is compatible with various functionalities and the desired products are obtained in good to excellent yield under mild conditions.

In silico ADMET, molecular docking study, and nano Sb2O3-catalyzed microwave-mediated synthesis of new α-aminophosphonates as potential anti-diabetic agents

Abstract An efficient and greener method is developed for the synthesis of α-aminophosphonates via Kabachnik–Fields reaction in solvent free condition using microwave irradiation technique. For all of the compounds, an in silico ADMET and molecular docking study was conducted to get insight on the drug likeliness behavior as well as their ability to block the enzyme α-amylase. The compounds with significant binding affinity and significant pharmacokinetic characteristics were produced. The newly produced compounds were spectroscopically analyzed to confirm their structure, and in vitro α-amylase inhibitory activity was also tested for all of them. The compounds 8j (half-maximal inhibitory concentration (IC50), 100.5 ± 0.2 μg·mL−1) showed better inhibitory activity than the reference drug, acarbose. The compounds 8d (IC50, 108.6 ± 0.2 μg·mL−1), 8g (IC50, 110.9 ± 0.3 μg·mL−1), 8h (IC50, 115.0 ± 0.1 μg·mL−1), and 8f (IC50, 118.9 ± 0.2 μg·mL−1) have been reported to exhibit significant inhibition toward the target enzyme. All the leftover compounds displayed modest to excellent inhibition through IC50 values in the range from 122.3 ± 0.3 to 154.3 ± 0.6 μg·mL−1 while comparing with the reference drug, Acarbose (IC50, 103.2 ± 0.7 μg·mL−1). The results disclosed that the majority of these compounds exhibit significant α-amylase inhibitory activity.

Synthesis of α-Aminophosphonates Derivatives by Using Novel Nano-Catalyst through Kabachnik-Fields Reaction

The novel Nano-catalyst (PAni-Mn) as the first multifunctional catalyst is described for efficient synthesis of α-Aminophosphonates by Kabachnik-Field reaction. This reaction is a Multicomponent reactions in which three- components i e. substituted aldehyde, aniline and dialkylphosphite are combining to form α-Aminophosphonates. The four α-Aminophosphonates were synthesized in good to high yield under solvent free condition at room temperature. The novel Nano-catalyst i.e. Doped Polyaniline with Manganese (PAni-Mn) has been synthesized first and characterized by elemental analysis FT-IR, SEM, TEM, X-ray diffraction technique. This catalyst provides high surface area, increase catalytic activity, easily separated and recycled. It increases the yield of α-Aminophosphonates. α-Aminophosphonates are bioisosteres of amino acids analogous, which has important application in Industrial, Agricultural and Medicinal field, due to their biological and physical properties, They are also use full as synthetic intermediates..

Heterogeneous catalyst SiO2-LaCl3·7H2O: characterization and microwave-assisted green synthesis of α-aminophosphonates and their antimicrobial activity.

Silica-supported lanthanum (III) chloride (SiO2-LaCl3·7H2O) was prepared and characterized by infrared spectroscopy, X-ray diffraction analysis, scanning electron microscope, energy-dispersive X-ray spectroscopy, thermogravimetric analysis and differential thermal analysis techniques. The catalytic activity of this silica-supported lanthanum (III) chloride was investigated in a one-pot three-component Kabachnik-Fields reaction. A library of new α-aminophosphonates was prepared employing various benzothiazole and thiadiazole amines, different substituted aldehydes and diethylphosphite under solvent-free conditions using conventional/microwave methods with good to excellent yields (85-97%). The advantages of this catalyst are that it is environmentally benign, economically inexpensive, and easy to prepare, gives high yields and high purity is less time-consuming, offers easy purification is reusable and enables products to be obtained by simple recrystallization without column chromatography.

Nano TiO2/SiO2: An Efficient and Reusable Catalyst for the Synthesis of α-aminophosphonates

Nano TiO2/SiO2 acts as a Lewis acid, which is Nano TiO2 supported on SiO2 was found to be an effective and reusable catalyst for the Kabachnik–Fields reaction of benzhydrylamine, substituted benzaldehyde and dialkyl phosphites using ethyl alcohol as solvent, when stirred for 1hr at room temperature. Convesion of 88-94% were obtained.

Facile Synthesis of Iron-Based MOFs MIL-100(Fe) as Heterogeneous Catalyst in Kabachnick Reaction

An effective technique was proposed for the synthesis of novel α-aminophosphonates: a three-component one-pot condensation reaction of aniline, aromatic aldehydes, and triphenyl phosphite in the presence of (MIL-100(Fe)) as a heterogeneous catalyst. Initially, MIL-100(Fe) was synthesized using H3BTC and ferric nitrate at low temperature and atmospheric pressure. Further, MIL-100(Fe) was characterized using various techniques such as XRD, BET surface area, scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR), and thermogravimetric analysis (TGA). Herein, MIL-100(Fe) showed exceptional catalytic performance for the synthesis of α-aminophosphonate and its derivatives compared with conventional solid catalysts, and even homogeneous catalysts. The study demonstrated that MIL-100(Fe) is an ecofriendly and easily recyclable heterogeneous catalyst in Kabachnick reactions for α-aminophosphonate synthesis, with high yield (98%) and turnover frequency (TOF ~ 3.60 min−1) at room temperature and a short reaction time (30 min).

An efficient nano-FGT catalyzed green synthesis of α-aminophosphonates and evaluation of their antioxidant, anti-inflammatory activity and molecular docking studies

A green and efficient one-pot has been developed for the synthesis of a series of new diethyl-(((2,3-dihydrobenzo[b][1, 4] dioxin-6yl)amino)(substituted phenyl)methyl) phosphonates (4a-k) by the Kabachinik-Fields reaction of 2,3-dihydrobenzo[b] [1, 4]dioxin-6-amine (1) with various substituted aldehydes (2a-k) and diethyl phosphite (3) using nano ferrite supported glutathione (nano FGT) as catalyst under microwave irradiation and solvent free conditions. The synthesized compounds were evaluated for their antioxidant (DPPH & FRAP) and anti-inflammatory activity studies. Compounds 4b (naphthyl) and 4k (9-anthracenyl) showed highest antioxidant activity than that of standard ascorbic acid in DPPH method. Whereas compounds 4f (3-nitrophenyl), 4h (3-phenoxyphenyl) and 4k (9-anthracenyl) exhibited low IC50 values than that of standard ascorbic acid in and in Ferric Reducing Antioxidant Power (FRAP) studies. Compounds 4a, 4b, 4h, 4i, and 4k have shown strong anti-inflammatory activity against LPS induced cell death in RAW 264.7 cell lines. Molecular docking studies were also carried out against COX-2 showed high binding energies that are in support of their high anti-inflammatory activity. Being the most bioactive compound (4k) stands as promising next future anti-oxidant and anti-inflammatory agent.

Synthesis of α-amino phosphonates catalyzed by copper-based metal organic frameworks

In this paper we report a novel and straightforward method for the synthesis of α-amino phosphonates via three-component reaction of amines, aldehydes, and triethyl phosphite in the presence of Cu2(BDC)2DABCO (Cu-MOF) as a recyclable heterogeneous catalyst. The chemical structures of the all synthesized compounds were confirmed by NMR, IR and CHN analysis.

LaCl3⋅7H2O as an Effective Catalyst for the Synthesis of α-Aminophosphonates under Solvent-Free Conditions and Docking Simulation of Ligand Bond Complexes of Cyclin-Dependent Kinase 2

The α-amino phosphonates find a wide spectrum of applications in medicinal, industrial, and agricultural chemistry. The most simple and straight forward synthetic technique for the formation of α-amino phosphonates is the Kabachnik–Fields reaction (an MCR) which involves the one-pot, three-component coupling of an aldehyde or ketone (carbonyl compound), amine and phosphite ester. The development of computational approaches as another tool for determining the features of chemicals has been a content of intensive research. In the current research, the AutoDock 4.0 package was employed for docking synthetic compounds into a protein, cyclin-dependent kinase 2 with the flexible side chain of TYR15. Cyclin-dependent kinase 2 (CDK2) is a member of an extremely conserved family of protein kinases that regulate the eukaryotic cell cycle. The lowest energy poses obtained in docking simulations of dimethyl ((4-nitrophenyl)(phenylamino)methyl) phosphonate were attained with the CDK2 model. This inhibitor has investigated the chemical effects on conformational behavior of CDK2.