Phosphite Research Articles

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.

Tribochemical Mechanisms of Trimethyl and Triethyl Phosphite on Oxidized Iron in Ultrahigh Vacuum

The surface chemistry of model lubricant additives, trimethyl phosphite (TMPi) and triethyl phosphite (TEPi), is studied on oxidized iron in ultrahigh vacuum (UHV) and the results compared with the gas-phase lubrication of TEPi on oxidized iron in a UHV tribometer. Oxide films are grown on a polycrystalline iron substrate and characterized by X-ray photoelectron spectroscopy (XPS) and assigned to the formation of an Fe3O4 film. Measurements of the friction coefficient and contact resistance of the oxide films show that the oxide film remains intact while rubbing in UHV at a normal load of 0.29 N. It is found that phosphite esters adsorb on the oxide by electron donation to the phosphorus atom, with a binding energy that increases in the order tributyl phosphite > TMPi > TEPi, and correlates well with the location of the vacant lowest-occupied molecular orbital (LUMO) energy. The phosphite esters decompose via sequential P‒O bond scission to form adsorbed alkoxy species, which then react on the surface either by hydrogen addition to form the corresponding alcohol, or by hydrogen abstraction to yield an aldehyde. XPS studies of the surface shows that essentially no carbon remains after the TMPi has reacted, while a small amount of carbon is present when TEPi has decomposed. On heating, the phosphite esters convert to phosphate species. Gas-phase lubrication experiments in the presence of 1 × 10−7 Torr of gas-phase TEPi reveal that the friction coefficient is significantly reduced, where the friction reduction is found to increase with increasing reaction temperature. The friction reduction correlates well with the proportion of phosphate product formed in the film and indicates that the formation of phosphate tribofilm is primarily responsible for reducing friction. However, friction is also reduced for a reaction at ~ 300 K, lower than the temperature at which the adsorbed phosphite ester reacts, suggesting that its rate of decomposition could be accelerated by interfacial shear.

Synthesis of S -Alkyl Phosphorothioates from Alkyl Cholorides, Phosphites and Sulfur Powder

Synthesis of S -Alkyl Phosphorothioates from Alkyl Cholorides, Phosphites and Sulfur Powder

Analysis of the aqueous solubility of trialkyl phosphates, dialkyl alkylphosphonates, dialkylphosphites and alkyl dialkylphosphinates

Linear free energy relationship (LFER) analysis based on the molar intrinsic volume (Vx), McGowan hydrophile‒lipophile balance (HLB) and cumulative Kabachnik constants (Σσϕ) of considered solutes has been performed for the solubility of trialkyl phosphates, dialkyl alkylphosphonates, dialkyl phosphites and alkyl dialkylphosphonates in pure water (called also as their aqueous solubility). The descriptors mentioned above are known for all considered solutes and are strongly correlated with their aqueous solubility. From the correlation found for trialkyl phosphates, dialkyl alkylphosphonates and dialkyl phosphites it follows that the mean contribution of each methylene group in their structure (Δlog Sw) is a constant for these homologous series and equal to − 0.41. It means that within of homologous series the aqueous solubility of succeeding solutes decreases regularly. The established increment has been further used as a tool for the preliminary selection of solutes whose aqueous solubility at 25 °C is in agreement with this condition. The adequate model (further denoted as AR model) based on the accessible data of temperature effects upon the aqueous solubility of tributyl phosphate, dibutyl butylphosphonate and butyl dibutylphosphinate has been formulated and then tested with positive results for the other solutes whose solubility is known at a selected constant temperature, e.g. at 25 °C. It should noticed, however, that in this case there are some serious restrictions. First, the interpretation and formulation of conclusions for the solutes which aqueous solubility is known at one selected temperature (e.g. 25 °C) or if it has been determined at a few temperatures only, should be made with care. Second, the obtained results with AR model cannot be used for prediction of temperature effects upon the aqueous solubility of such solutes. Simultaneously, the results obtained with AR model have been compared with those following from the modified Abraham model. Such comparison has been possible due to a significant progress in the different application of Abraham model for several organophosphorus derivatives as monobasic dialkyl- and diarylphosphoric acids, dialkyl- and diphenylphosphinic acids, trialkyl- and triaryl phosphates, dimethyl methylphosphonate, dialkylphosphites and some of trialkyl- and triarylphosphine oxides, respectively.

New Developments on the Hirao Reactions, Especially from "Green" Point of View.

Background: The Hirao reaction discovered ca. 35 years ago is an important P–C coupling protocol between dialkyl phosphites and aryl halides in the presence of Pd(PPh3)4 as the catalyst and a base to provide aryl phosphonates. Then, the reaction was extended to other P-reagents, such as secondary phosphine oxides and H-phosphinates and to other aryl and hetaryl derivatives to afford also phosphinic esters and tertiary phosphine oxides. Instead of the Pd(PPh3)4 catalyst, Pd(OAc)2 and Ni-salts were also applied as catalyst precursors together with a number of mono- and bidentate P-ligands.Objective: In our review, we undertook to summarize the target reaction with a special stress on the developments attained in the last 6 years, hence this paper is an update of our earlier reviews in a similar topic.Conclusions: “Greener” syntheses aimed at utilizing phase transfer catalytic and microwave-assisted approaches, even under “P-ligand-free. or even solvent-free conditions are the up-to date versions of the classical Hirao reaction. The mechanism of the reaction is also in the focus these days.

Mn(III)-Mediated C-H Phosphorylation of Indazoles with Dialkyl Phosphites.

A direct and efficient Mn(III) acetate-mediated phosphorylation of 2H-indazoles with dialkyl phosphites has been achieved under mild reaction conditions. A series of phosphorylated products with a wide range of functional groups were obtained in moderate to good yields. A radical mechanism has been proposed for the present protocol.

Cu-Catalyzed Direct C-P Bond Formation through Dehydrogenative Cross-Coupling Reactions between Azoles and Dialkyl Phosphites.

A direct dehydrogenative cross-coupling of azoles [C(sp2)-H] with dialkyl phosphites [P(O)-H] to access 2-phosphonated azoles using Cu(I)/Cu(II) as catalyst and K2S2O8/di- tert-butylperoxide as oxidant has been achieved. A remarkable advantage over reported procedures includes that oxazoles, imidazoles, benz(ox/othi/imid)azoles, and indole are found to react under optimized reaction conditions to provide corresponding adducts in high yields. The mechanistic insight of cross-coupling was obtained by deuterium kinetic isotope effect studies.

Microwave-Assisted Kabachnik⁻Fields Reaction with Amino Alcohols as the Amine Component.

In this paper, the microwave (MW)-assisted catalyst-free and mostly solvent-free Kabachnik–Fields reaction of amino alcohols, paraformaldehyde, and various >P(O)H reagents (dialkyl phosphites, ethyl phenyl-H-phosphinate, and secondary phosphine oxides) is reported. The synthesis of N-2-hydroxyethyl-α-aminophosphonate derivatives was optimized in respect of the temperature, the reaction time, and the molar ratio of the starting materials. A few by-products were also identified. N,N-Bis(phosphinoylmethyl)amines containing a hydroxyethyl group were also prepared by the double Kabachnik–Fields reaction of ethanolamine with an excess of paraformaldehyde and secondary phosphine oxides. The crystal structure of a 2-hydroxyethyl-α-aminophosphine oxide and a bis(phosphinoylmethyl)ethanolamine was studied by X-ray analysis.

Intercalations and Characterization of Zinc/Aluminium Layered Double Hydroxide-Cinnamic Acid

Cinnamic acid (CA) is known to lose its definite function by forming into radicals that able to penetrate into the skin and lead to health issues. Incorporating CA into zinc/aluminum-layered double hydroxides (Zn/Al-LDH) able to reduce photodegradation and eliminate close contact between skin and CA. Co-precipitation or direct method used by using zinc nitrate hexahydrate and aluminium nitrate nonahydrate as starting precursors with addition of various concentration of CA. The pH were kept constant at 7 ± 0.5. Fourier Transform Infrared-Attenuated Total Reflectance (FTIR-ATR) shows the presence of nanocomposites peak 3381 cm–1 for OH group, 1641 cm–1 for C=O group, 1543 cm–1 for C=C group and 1206 cm–1 for C–O group and disappearance of N–O peak at 1352 cm–1 indicates that cinnamic acid were intercalated in between the layered structures. Powder X-Ray Diffraction (PXRD) analysis for Zn/Al-LDH show the basal spacing of 9.0 Ǻ indicates the presence of nitrate and increases to 18.0 Ǻ in basal spacing in 0.4M Zn/Al-LDH-CA. CHNS analysis stated that 40 % of cinnamic acid were being found and intercalated in between the interlayer region of the Zn/Al-LDH with higher thermal stability. Field Emission Scanning Electron Microscope (FESEM) images of 0.4 M Zn/Al-LDH-CA shows that the nanocomposites are in more compact, flaky non porous, large agglomerates with smooth the surfaces of the intercalated compound. Controlled release was successful with 80 % release in phosphite anion and 70 % release carbonate anion. The cinnamic acid was successfully inserted between the interlayer regions of Zn/Al-LDH with slow release formulation.

Phosphine-catalyzed bishydrophosphorylation of electron-deficient alkynes

Tertiary phosphines (n-Bu3P, Ph3P) efficiently catalyze the vicinal bis-addition of dialkyl phosphites and diaryl phosphine oxides to alkynoates though the tandem α-umpolung/β-Michael addition. This reaction offers a simple metal-free method for gram-scale preparation of practically useful bisphosphonates and bisphosphine oxides under mild conditions with high atom economy and selectivity.

Microwave-assisted synthesis of phosphonic and phosphinic esters and phosphine oxides by the Hirao reaction

Phosphinic- and phosphonic esters, as well as phosphine oxides can be easily obtained by P–C coupling reactions of aryl- and vinyl halides with dialkyl phosphites, H-phosphinates and secondary phosphine oxides in the presence of mostly Pd catalysts. The use of the microwave (MW) technique allows the realization of the Hirao reaction more efficiently, economically and environmentally-friendly.

Nano Sb2O3 catalyzed green synthesis, cytotoxic activity, and molecular docking study of novel α-aminophosphonates

Green synthesis of a series of novel dialkyl (aryl substituted)(2-fluoro-4-((2-methylcarbamoyl)pyridine-4-yl)oxy)phenyl)amino)methyl)phosphonates is accomplished by a simple and an efficient one pot three component reaction of 3-(4-amino-3-fluorobenzyl)-N-methylbenzamide with different substituted aromatic aldehydes and dialkyl phosphite in the presence of nano Sb2O3 catalyst under solvent free conditions at 40–50 °C to obtain the title compounds. Excellent isolated product yields are obtained (85–95%) with high purity within shorter reaction times (30–60 min). The title compounds are characterized by IR, 1H, 13C, 31P-NMR and mass spectral data. The synthesized compounds are screened for their anticell-proliferation activity on seven cell lines, Control cells–HEK293 (human embryonic kidney), DU-145 (human prostate adenocarcinoma), MCF-7 (human ER+/PR+/Her2− breast cancer), MDA-MB-231 (human ER−/PR−/Her2− breast cancer), Mia-Paca-2 (human pancreatic carcinoma), HeLa (human cervical cancer) cells as well as HepG2 (human hepatocellular carcinoma) cancer cell lines using Sulforhodamine B (SRB) assay method. Docking studies were carried out for all these synthesized compounds against topoisomerase-II by using Auto dock method. Doxorubicin was taken as standard. Compounds 4a, 4c, 4d, 4e, 4h, 4i, 4k, and 4l exhibited higher cytotoxic activity than the standard doxorubicin.

The typical crystal structures of a few representative α-aryl-α-hydroxyphosphonates.

The crystal structures of seven α-aryl-α-hydroxyphosphonates synthesized by the Pudovik reaction of substituted benzaldehydes and dialkyl phosphites, namely dimethyl [(hydroxy)(phenyl)methyl]phosphonate, C9H13O4P, dimethyl [(3,4-dimethoxyphenyl)(hydroxy)methyl]phosphonate, C11H17O6P, dimethyl (1-hydroxy-1-phenylethyl)phosphonate, C10H15O4P, dimethyl [1-hydroxy-1-(4-nitrophenyl)ethyl]phosphonate, C10H14NO6P, dibenzyl [hydroxy(2-nitrophenyl)methyl]phosphonate, C21H20NO6P, dibenzyl [(3-chlorophenyl)(hydroxy)methyl]phosphonate, C21H20ClO4P, and dibenzyl [hydroxy(4-methylphenyl)methyl]phosphonate, C22H23O4P, were studied to gain a better understanding of the organization in this type of molecule in the solid state. The crystals obtained for this series of compounds show a balance between C-OH...O=P chain-linked packing and the dimeric types of hydrogen-bond bridges of intermolecular pairs of such functions. The description is based on primary graph-set descriptors. Using graph-set descriptors one level deeper (i.e. secondary graph sets of the C-H...O type) revealed a similarity in the graph-set descriptors, suggesting a fine interplay of substituent- and shape-dependent effects on strong-weak interactions. It seems that the formation of chains or dimers is governed not only by the presence of a tertiary Cα atom, but also by the nature and crowding of the ortho substituents of the α-aryl group.

Copper-catalyzed one-pot synthesis of alkynylphophonates

Copper is found to be an effective catalyst for the preparation of alkynylphophonates. A novel copper-catalyzed one-pot synthesis of alkynylphophonates from terminal alkynes and dialkyl phosphites is developed which involves the haloalkynes intermediates. This method provides a unique and alternative approach to the well-documented oxidative coupling or arylpropiolic acid strategies.

Ultrasonic irradiation used in synthesis of aminophosphonates

Ultrasound technique represents a green method for the synthesis of different class of compounds. In this review, the progress in the synthesis of aminophosphonates, an important class of phosphorus derivatives having biological applications, under sonication, with or without catalysts or solvents, is presented. Aminophosphonates were obtained in very good yield from amines, aldehydes (ketones), and dialkyl or trialkyl phosphites under ultrasound. Ultrasound had a notable effect on the reaction conditions, the purity and yield of obtained compounds. Aminophosphonates which cannot be obtained by traditional methods were obtained when ultrasound is used.

Copper-promoted dehydrogenative cross-coupling reaction of dialkyl phosphites with sulfoximines

Synthesis of sulfoximine derived phosphoramidates was achieved in good to excellent yields from NH-sulfoximines and dialkyl phosphites.

Efficient light harvesting with a nanostructured organic electron-transporting layer in perovskite solar cells.

Nanostructures have proved to be advantageous in light harvesting, improving the power conversion efficiency (PCE) of photovoltaic devices. However, the reported light-harvesting nanostructures all require extra processing beyond that for device fabrication, with multiple steps for nano-patterned structures or plasmonic nano-particles. Here we synthesized a conjugated polymer PFPDI which could simply form a nanostructured film on perovskite by spin coating. PFPDI possesses a perylene diimide-based backbone and phosphite ester pendants, which makes it a robust electron-transporting material (ETM) in perovskite solar cells. Furthermore, the perovskite solar cells with PFPDI as the electron-transporting layer (ETL) exhibited a higher light-harvesting efficiency compared to the standard phenyl-C61-butyric acid methyl ester (PCBM) devices. The JSC of the PFPDI device was enhanced from 19.71 mA cm-2 to 23.43 mA cm-2. SEM images and reflectance spectra confirmed that the PFPDI formed ditch-like nanostructures on perovskite film and induced a better light-harvesting efficiency. Further research indicated that the interaction of P[double bond, length as m-dash]O with Pb was essential to the formation of the nanostructures of PFPDI on perovskite. Therefore, our work not only offers an efficient organic ETM, but also opens up new horizons for simply constructing nanostructures with light-harvesting ability in photovoltaic devices.

Cobalt-Catalyzed Oxidative Phosphonylation of α-Amino Acid Derivatives and α-Amino Ketones for α-Aminophosphonates.

A novel and efficient direct oxidative phosphonylation of α-amino ketones and α-amino acid derivatives with dialkyl phosphites by the catalysis of a cobalt salt under air is disclosed. A variety of α-amino ketones and α-amino acid derivatives underwent the reaction well with dialkyl phosphites to produce the desired α-aminophosphonates. This protocol not only provides an alternative synthetic route for the preparation of diverse α-aminophosphonates but also avoids the use of potentially explosive peroxide agents.

Utilization of 1,3-Dioxolanes in the Synthesis of α-branched Alkyl and Aryl 9-[2-(Phosphonomethoxy)Ethyl]Purines and Study of the Influence of α-branched Substitution for Potential Biological Activity

Syntheses of α-branched alkyl and aryl substituted 9-[2-(phosphonomethoxy)ethyl]purines from substituted 1,3-dioxolanes have been developed. Key synthetic precursors, α-substituted dialkyl [(2-hydroxyethoxy)methyl]phosphonates were prepared via Lewis acid mediated cleavage of 1,3-dioxolanes followed by reaction with dialkyl or trialkyl phosphites. The best preparative yields were achieved under conditions utilizing tin tetrachloride as Lewis acid and triisopropyl phosphite. Attachment of purine bases to dialkyl [(2-hydroxyethoxy)methyl]phosphonates was performed by Mitsunobu reaction. Final α-branched 9-[2-(phosphonomethoxy)ethyl]purines were tested for antiviral, cytostatic and antiparasitic activity, the latter one determined as inhibitory activity towards Plasmodium falciparum enzyme hypoxanthine-guanine-xanthine phosphoribosyltransfesase. In most cases biological activity was only marginal.

Phosphite Esters: Reagents for Exploring S-Nitrosothiol Chemistry.

The reactions between S-nitrosothiols and phosphite esters, including P(OPh)3, P(OBn)3, and P(OEt)3, were studied. Two different conjugated adducts, thiophosphoramidates and phosphorothioates, were formed, depending on the structures of the S-nitrosothiol substrate (e.g., primary vs tertiary). These reactions proceeded under mild conditions, and the reaction mechanisms were studied using experiments and calculations.