Dialkyl Phosphonates Research Articles

Facile synthesis of diphosphoryl acetylenes through copper-catalyzed cross coupling

Organic molecules containing 1,2-diphosphonate moiety are of great value in organic synthesis. Diphosphoryl acetylenes (or named as ethyne-1,2-diyldiphosphonates) are a class of molecules utilized for synthesis of diverse phosphorus compounds applicable in multiple fields. However, present stoichiometric methods for the preparation of diphosphoryl acetylenes generally requires multiple steps or harsh conditions. Herein, we report a facile synthesis of diphosphoryl acetylenes, in which the readily available ethynyl phosphonates couple with dialkyl phosphonates through cheap copper catalysis. A series of diphosphoryl acetylenes in symmetric or unsymmetric fashions are facilely prepared. This protocol demonstrates advantages of mild reaction conditions, inert atmosphere-free, cheap catalyst, base-free, and high efficiency to serve as a practical method for synthesis of diphosphoryl acetylenes.

Synthesis, anti-microbial, and docking studies of functionalized chromenyl phosphonates using ionic liquid catalyst.

Synthesis of functionalized chromenyl phosphonates by the reaction among 2-hydorxybenzaldehydes, dicyanoethane, and dialkyl phosphonates that was promoted by choline hydroxide ionic liquid catalyzes the simultaneous, Knoevenagel, Pinner, and phospha-Michael reactions, under neat condition at room temperature. Important phosphorus-containing compounds can be produced at a reasonable cost because of the mild reaction conditions and the inexpensive promoter choline hydroxide. Furthermore, the desired products can be obtained without the need for any extraction or chromatography steps. An alternate technique for the simple and high-yield synthesis of functionalized chromenyl phosphonates is offered by this protocol. The synthesized compounds were studied by anti-microbial activity and docking studies. The title compounds molecular docking investigations demonstrated their efficacy as therapeutic agents against DNA Gyrase B and Aspergillus niger endoglucanase in both antibacterial and antifungal inhibition, and they identified compounds 4a, 4d, 4l, 4p, and 4q as promising candidates for microbial treatment, with binding affinities ranging from -6.9 to -7.4kcal/mol.

Dialkyl(5-ethyl-2-hydroxyphenyl)phosphonates as extractants for the selective recovery of lithium from alkaline media

Dialkyl(5-ethyl-2-hydroxyphenyl)phosphonates as extractants for the selective recovery of lithium from alkaline media

Synthesis and Anticancer Activity of Phosphinoylated and Phosphonoylated N-Heterocycles Obtained by the Microwave-Assisted Palladium Acetate-Catalyzed Hirao Reaction.

A literature survey showed that different derivatives with the 9-phenyl-9H-carbazole or the dihydroindoline scaffold may be of biological activity including cytotoxic effect. Driven by this experience, P-functionalized derivatives of these N-heterocycles were synthesized. Three N-heterocycles, 9-(4-bromophenyl)-9H-carbazole, 3-bromo-9-phenyl-9H-carbazole and 1-(5-bromoindolin-1-yl)ethan-1-one, were coupled with dialkyl phosphites and diarylphosphine oxides using Pd(OAc)2 (10 %) as the catalyst precursor and triethylamine as the base in ethanol under microwave irradiation. The excess of the Y2 P(O)H reagent (Y=alkoxy, aryl) (30 %) served as the P-ligand in its trivalent tautomeric form (Y2 POH), hence there was no need for the usual P-ligands meaning cost and environmental burden. Hence, the presented method is a "green" approach that proved to be more efficient than the preparation by the traditional method. The products, dialkyl phosphonates and tertiary phosphine oxides obtained in 58-84 % yields were characterized, one of them also by single crystal X-ray analysis, and were subjected to in vitro biological activity evaluation. A (carbazol)yl-phenylphosphonate, an N-phenyl-(carbazol)yl-phosphonate, a (carbazol)yl-phenylphosphine oxide and an N-phenyl-(carbazol)ylphosphine oxide revealed a significant cytotoxic activity on A549 human non-small-cell lung carcinoma and MonoMac-6 acute monocytic leukemia cancer cells. The cytotoxic effect was significant as compared to that of the reference compounds.

Dialkyl phosphonate with carboxylic acid as antiwear additives for ester-base lubricants

Ester-base oils are commonly used in environmentally adapted lubricants (EALs) because of their biodegradability. However, their antiwear performance is difficult to improve using the conventional lubricant additives developed for mineral-base oils. In this study, dialkyl phosphonates with various functional groups were designed as antiwear additives for ester-base oils. The antiwear performances of these phosphonates were evaluated using four-ball tests. The results suggest that dialkyl phosphonate with carboxylic acid (DAPA) has better antiwear performance in ester-base oils than that of other phosphonates and conventional phosphorus additives. Remarkably, DAPA exhibits better antiwear performance under severe test conditions in ester-base oils than in poly-alpha olefin. X-ray photoelectron spectroscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy were used to study the chemical compositions of steel surfaces after friction and better understand the antiwear mechanism of DAPA, particularly in ester-base oils.

Solvent-free visible-light-mediated α-phosphorylation and Csp3-H activation of tertiary and secondary amines at room temperature in the presence of cadmium sulfide nanophotocatalyst.

Recently, the synthesis of organic compounds via Csp3-H activation is an important target for organic and medicinal chemists. On the other hand, visible-light-mediated organic synthesis is an attractive method, which is dependent on the capability of the reagent or photocatalyst to take up solar energy. Thus, the discovery and development of novel, Milde, simple, and effective manners using visible-light-induced photocatalysts have gained great interest in synthetic organic chemistry. Herein, cadmium sulfide (CdS) nanophotocatalyst has been successfully used for the reaction of tertiary and secondary amines with trialkyl phosphites or dialkyl phosphonates for the synthesis of dialkyl ((alkyl(aryl)amino)alkyl)phosphonate, dialkyl (2-benzyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate, and dialkyl ((3,4-dihydroquinolin-1(2H)-yl)(aryl)methyl)phosphonate derivatives. Using this novel procedure, all desirable products were prepared in good yields and relatively short reaction times under solvent-free conditions at room temperature (more benignant conditions) with the usage of visible-light irradiation as an easily available, inexpensive, safe, and renewable energy source.

Furan ring opening reaction for the synthesis of 2,5-dicarbonyl-3-ene-phosphates.

Furan ring opening reactions are essential in organic synthesis, enabling the incorporation of diverse functional groups and the construction of complex molecular structures. A highly efficient and practical method for synthesizing 2,5-dicarbonyl-3-ene-phosphates from readily available biomass furan and dialkyl phosphonates is reported. The reaction, catalyzed by FeCl3, demonstrated wide substrate scope and high synthetic efficiency. Gram-scale synthesis was achieved, and a one-pot reaction provided a quick access route to the desired compounds. Additionally, a successful Diels-Alder reaction highlighted the versatility of the methodology.

Nickel-Catalyzed Defluorophosphonylation of Aryl Fluorides.

A Ni-catalyzed cross-coupling reaction between aryl fluorides and dialkyl phosphonates [HP(O)(OR)2] (R = secondary alkyl groups) in the presence of potassium tert-butoxide as a base is reported. The reaction converted various aryl fluorides into the corresponding aryl phosphonates even when electron-donating substituents were present on the aromatic ring. The combined experimental and computational studies suggested Ni-K+ cooperative action of a Ni(0) complex chelated with a strongly electron-donating ion-bridged dimeric phosphite ligand system [P(OR)2O-K+]2 that facilitates turnover-limiting C-F bond oxidative addition of aryl fluorides.

Metal-free synthesis of indenone derivatives from ortho-alkynylaryl ketones mediated by the combination of dialkyl phosphonates and CBr4

A novel metal-free synthesis of indenone derivatives mediated by CBr4 and diethyl phosphonate is reported. The methodology has a relatively wide substrate scope and is suitable to access a π-extended indenone and an s-indacene-1,5-dione derivative as well.

Synthesis and biological evaluation of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates

This study reports the design and synthesis of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates as potential antitumor agents against A549 (lung cancer), DU-145 (prostate cancer), PC-3 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer), cell lines evidenced from the in vitro antitumor studies performed by MTT assay (across 10–30 μM concentrations). The structural eminence of these synthesized molecules has emanated by designing the structural core by uniting the chromene, pyrimidine and phosphonate moieties into one, which has augmented their novelty and made them unreported. Further the deep structural activity relationship study investigations articulated that the title compounds are promising drug-like compounds and potential inhibitor of histidine amino acid residue present on the respective enzymatic proteins [3QJZ (A549), 3VHE (DU-145), 3V49 (PC-3), 3F81 (HeLa), & 3R7Q (MCF-7)] of the cell lines screened and are identified as responsible for the multi-faceted antitumor activities predicted in vitro. The obtained results were further supported by molecular docking studies, QSAR, ADMET, and bioactivity studies which have supported them as potential BBB penetrable molecules and proficient CNS active neuro-protective agents during drug delivery.

General and Efficient C–P Bond Formation by Quantum Dots and Visible Light

General and Efficient C–P Bond Formation by Quantum Dots and Visible Light

Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B).

This work describes, for the first time, the synthesis of dialkyl (2-arylquinolin-8-yl)phosphonate derivatives. The preparation was carried out through a direct and simple process as a multicomponent Povarov reaction of aminophenylphosphonates, aldehydes, and styrenes and subsequent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or, alternatively, by a cycloaddition reaction between phosphonate aldimines and acetylenes. Based on phosphonate group structural characteristics, considered as phosphorous isosteres of carboxylic heterocycles, they may present interesting biological properties related to cell proliferation. In the current report, a new series of dialkyl (2-arylquinolin-8-yl)phosphonates have been synthesized and their antiproliferative effect evaluated on different human cancer and embryonic cells, as well as on Leishmania infantum parasites, a eukaryotic protist responsible for visceral leishmaniasis. Thereby, the antitumor effect was assessed in human lung adenocarcinoma cells (A549), human ovarian carcinoma cells (SKOV3), and human embryonic kidney cells (HEK293) versus the non-cancerous lung fibroblasts cell line (MRC5). On the other hand, the antileishmanial activity was tested against both stages of L. infantum cell cycle, namely free-living promastigotes and intramacrophage amastigotes, using a primary culture of Balb/c splenocytes to calculate the selectivity index. Besides the antiproliferative and antileishmanial capacities, their behavior as topoisomerase 1B inhibitors has been evaluated as a possible mechanism of action.

Copper-Catalyzed Enaminone C(sp2)-N Bond Phosphonation for Stereoselective Synthesis of Alkenylphosphonates.

A direct enaminone C-N bond coupling functionalization that generates a new C-P bond using dialkyl phosphonate for the efficient and stereoselective synthesis of (E)-alkenylphosphonates is reported. The reactions toward target products proceed well with a broad scope, disclosing a valuable new synthetic application of enaminones by the interesting C(sp2)-N bond elaboration.

Dialkyl (2-oxopropyl)phosphonates in the synthesis of phosphorylated heterocycles

This minireview summarizes data on the use of dialkyl (2-oxopropyl)phosphonates in the synthesis of phosphorylated heterocycles. Convenient methods for the synthesis of reagents and examples of their use in the Paal–Knorr, Dimroth, Gewald, Knoevenagel–Fries, Fischer, Friedlander, and Beirut reactions are analyzed.

Synthesis of Novel Coumarin Derivatives Bearing Phosphor Ester Motifs and Evaluation of their Antioxidant Activities

phosphoramidate, phosphoranylidenetriazene, and azaphosphole derivatives can be respectively formed when the substituted azidocoumarin 1 reacted with trialkylphosphites (TAP), dialkylphosphonates (DAP), and tris(dialkylamino)phosphines. The known triazinedione was revealed to be a side product in the reactions of carbaldehyde 1 with TAP and tris(dialkylamino)-phosphines. In the same context, when the starting coumarin 16 was allowed to react with P (III) reagents, chromen phosphoramidates and chromen phosphoric triamide derivatives were obtained via Staudinger reaction. Contrary to that pathway, phosphoranylidenetriazen chromen derivative could be isolated and identified when coumarin 16 was allowed to react with tris(diethylamino)-phosphine. The antioxidant activities of 6-newly products were evaluated. The results showed that two from the six screened compounds exhibited good antioxidant activities.

The McKenna reaction - avoiding side reactions in phosphonate deprotection.

The McKenna reaction is a well-known and popular method for the efficient and mild synthesis of organophosphorus acids. Bromotrimethylsilane (BTMS) is the main reagent in this reaction, which transforms dialkyl phosphonate esters into bis(trimethylsilyl)esters, which are then easily converted into the target acids. However, the versatile character of the McKenna reaction is not always used to its full extent, due to formation of side products. Herein, demonstrated by using model examples we have not only analyzed the typical side processes accompanying the McKenna reaction, but also uncovered new ones. Further, we discovered that some commonly recommended precautions did not always circumvent the side reactions. The proposed results and recommendations may facilitate the synthesis of phosphonic acids.

Copper-catalyzed O-alkenylation of phosphonates.

Copper catalysis allows the direct oxygen alkenylation of dialkyl phosphonates with alkenyl(aryl)iodonium salts with selective transfer of the alkenyl group. This novel methodology proceeds with a wide range of phosphonates under mild conditions and gives straightforward access to valuable enol phosphonates in very good yields.

Features of the Identification of Trialkyl Phosphites in Reaction Mixtures and Their Characterization by Gas Chromatography–Mass Spectrometry

The interaction of aliphatic alcohols ROH with phosphorus trichloride in the absence of bases leads to the formation of exclusively dialkyl phosphonates (RO)2PHO. To obtain trialkyl phosphites (RO)3P, insufficiently described to date, the pH of the reaction mixtures was adjusted by adding N,N-dimethylaniline (pKa 5.1 ± 0.1). The identification of trialkyl phosphites directly in reaction mixtures without preparative isolation implies a joint consideration of their mass spectra and gas chromatographic retention indices, provided that all other components of such mixtures are identified. The need to comply with this condition has led to the identification of several homologues of a previously uncharacterized series of 2-alkoxy-1,3,2-dioxaphospholanes, formed from a random admixture of ethylene glycol. The use of such combined mass spectrometric parameters as homologous increments of retention indices helps to distinguish trialkyl phosphites from isobaric dialkyl phosphonates; the compounds of both series belong to the homologous group of y = 12, y ≡ M(mod14). Despite the absence of molecular ion signals in the electron ionization (EI) mass spectra, the molecular weights of trialkyl phosphites can be estimated. In addition, a comparison of the homologous increments of retention indices shows that, compared with dialkyl phosphonates, trialkyl phosphites are significantly less polar.

Comparative gas chromatographic/mass spectrometric characterization of di- and trialkyl phosphites.

Homologous series of alkyl esters of phosphorus-containing acids, namely, dialkyl phosphonates (synonym: dialkyl phosphites) and trialkyl phosphites, were characterized by electron ionization (EI) mass spectra and gas chromatographic retention indices (GC RI) on semi-standard non-polar stationary phases. It is confirmed that GC/MS characterization of any sets of homologues should not be restricted to independent registration of these analytical parameters. Their joint processing in the form of so-called homologous increments of GC RIs means, firstly, a novel way of evaluating the chromatographic polarity of analytes and, secondly, a new algorithm for the prediction of their molecular weights if no peaks of molecular ions are registered in the mass spectra. A standard GC/MS technique, including determination of GC RIs on semi-standard nonpolar stationary phases in temperature-programmed regime and electron ionization (EI) mass spectra was used. A total of 31 dialkyl phosphonate homologues and 37 trialkyl phosphite homologues were characterized by EI mass spectra and GC RIs for the first time. Joint processing of these analytical parameters allows the calculation of so-called homologous increments of GC RIs, which are useful parameters for evaluating the chromatographic polarity of analytes and predicting their molecular weights. GC/MS characterization of any sets of homologues should not be restricted to independent registration of the mass spectra and chromatographic retention parameters. Their joint processing in the form of so-called homologous increments of GC retention indices means, firstly, a novel way of evaluating the chromatographic polarity of analytes and, secondly, a new algorithm for predicting their molecular weights.

Biocatalytic Promiscuity of Lipases in Carbon‐Phosphorus Bond Formation

AbstractA promiscuous lipase‐catalyzed carbon‐phosphorus bond formation is presented. The developed enzymatic Pudovik‐Abramov reaction of various aromatic and aliphatic aldehydes with dialkyl phosphonates provides biologically and pharmacologically relevant α‐hydroxy phosphonates with the yields from 11 % to 85 %. The developed protocol proceeds in the presence of porcine pancreas lipase under environmentally sustainable conditions. The influence of the reaction conditions including enzyme origin, organic solvent, and temperature on the reaction course was examined. The developed protocol is applicable to a range of aldehydes, including synthetically relevant heterocyclic furfural and 2‐thiophenecarbaldehyde.