Triethyl Phosphite Research Articles

NaIO4/NH2OH-mediated Efficient Synthesis of Phosphoroamidates from Anilines and Triethyl Phosphite

AbstractA simple, efficient, and metal-free method was developed for the synthesis of phosphoroamidates. In essence, a mixture of sodium periodate (NaIO4) and hydroxylamine (NH2OH⸱HCl) was used in stoichiometric amounts to execute the phosphoramidation reaction of aromatic amines and triethyl phosphites at room temperature, in open air. This method offers a practical synthesis route to afford a diverse range of phosphoroamidates via the construction of P − N bonds, with excellent functional group compatibility and good yields under mild conditions.

Influence of the Sun on the night side of the Earth

Solar radiation breaks hydrogen bonds between water molecules, which prevents their self-organization and destroys water clusters. This may be accounted for by the influence of muons which are generated in the upper atmosphere by the solar wind. Muon flux is anisotropic and changes direction depending on the position of the Sun in the sky. For this reason, the rate of hydrolysis of triethyl phosphite in acetonitrile depends on geometric shape of the reaction solution, its position in space and changes during the day. For example, in three 5 mm NMR-tubes directed North-South, East-West and Vertically the distributions of the rates of this reaction are always different in the daytime. At noon, when the Sun is at its zenith, the rates are considerably higher in the horizontal tubes, and at sunrise and sunset when the Sun shines along the East-West line the rate is higher in the vertical tube. One might assume that at night when the Sun irradiates the opposite side of the Earth, this phenomenon should disappear, and the reaction rates should be the same in all directions. However, it turned out that at midnight the distribution of hydrolysis rates in multidirectional NMR-tubes is the same as at noon. This may indicate that on the night side of the Earth the influence of the Sun is inducing the appearance of some radiation vertically from underground. This phenomenon requires detailed study in different places on the Earth.

Synthesis of Mesylated and Tosylated α-Hydroxy-Benzylphosphonates; Their Reactivity and Cytostatic Activity.

α-Hydroxyphosphonates and their acylated and phosphorylated derivatives may be of significant biological activity including cytotoxic effects. To extend the pool of the potentially bioactive species, new methane- and arenesulfonyloxyphosphonates were synthesized by the sulfonylation of differently substituted α-hydroxy-benzylphosphonates using methanesulfonyl chloride or p-toluenesulfonyl chloride at 25 °C in the presence of triethylamine in toluene. The new sulfonyl derivatives were obtained in 54-80% yields. In the case of the 4- or 2-methoxy substituent in the aromatic ring, surprisingly the corresponding α-chlorophosphonates were the exclusive products, whose formation was explained assuming a quinoid intermediate and supported by theoretical calculations. With a 3-methoxyphenyl substituent, the expected mesylation of the hydroxy group took place. Attempted alcoholyses of the diethyl α-methanesulfonyloxy-benzylphosphonates with different substituents in the benzyl ring at ∼140 °C in the presence of triethylamine under microwave irradiation left the P-function intact under the conditions applied, instead, the mesyloxy group was substituted by an alkoxy unit in a selective new reaction. The α-alkoxy-benzylphosphonates were isolated in 60-77% yields. While α-chloro- or α-bromo-benzylphosphonates proved to be rather inefficient in the Michaelis-Arbuzov reaction with triethyl phosphite, according to a new possibility, the α-methansulfonyloxy-benzylphosphonates underwent an efficient Arbuzov fission using the phosphite in excess at 135 °C. The arylmethylenebisphosphonates were obtained in yields of 76-81%. Bioactivity studies with the members of the phosphonate library revealed pronounced in vitro cytostatic effect of the α-hydroxy- and α-mesyloxy-3,5-di-tert-butylbenzylphosphonates on human breast carcinoma cell culture with IC50 values of 16.4 and 28.0 μM, respectively. The mesyloxy species was also cytostatic on melanoma cells (IC50 = 34.9).

Coating of the Surface of 316L Stainless Steel with Hydroxyapatite Produced from Eggshell Using the Sol-Gel Method

In this study, the production of high-yield and purity calcium nitrate from eggshell, a biological waste, and the usability of the obtained calcium nitrate in the production of hydroxyapatite (HAP) by the sol-gel method were investigated. In addition, the obtained HAP was used to coat 316L steel using the dip coating method. For this purpose, calcium nitrate, which will be used as a precursor in HAP production, was produced from chicken eggshells with high calcium carbonate content. The surface of 316L stainless steel discs was coated with sol-gel obtained from a mixture of calcium nitrate and triethyl phosphite by dip-coating method. Then, the 316L discs were dried and heat treated at 500 °C to form HAP on their surfaces. XRD and SEM techniques were used for the characterization of the obtained HAP structure. Unlike previous studies, it has been shown that chicken eggshell, a biological waste, can be used to produce HAP, a biocompatible material, and the surface of 316L stainless steel can be coated with the produced HAP.

Synthesis of proton-conductive Perfluoro(Benzylphosphonic Acid)s via polymer side chain phosphorylation

Nafion™ utilizes -SO3H groups for proton conduction. Using an alternative proton-exchange functionality like -PO3H2, -COOH, etc., to replace -SO3H in ion conductive fluoropolymers has attracted significant attention. For example, composite membranes comprising Nafion™ and perfluoro(carboxylic acid) bearing a -COOH group on its side chains have been used in color-alkali cells to reduce unwanted electrolyte crossovers. In the present paper, we reported a new synthetic strategy for constructing novel -PO3H2-bearing fluoropolymers (FBP). Our method employs a ZnI2-promoted phosphorylation reaction of triethyl phosphite that converts benzyl alcohol on a side chain of a fluoropolymer into a benzylphosphodiester group, followed by trimethylsilyl chloride (TMSCl) hydrolysis to yield FBP. This strategy has enabled us to graft a fluoropolymer side chain directly with phosphonic acid. Although the in-plane proton conductivities of FBP fluoropolymers are lower than those of Nafion™ 115, most FBPs, especially Homo-FBP that has no fluoroalkyl ether group on its side chains, are significantly more stable against hydroxyl radical degradations in Fenton tests. This paper presents a new method for the synthesis of -PO3H2-containing fluoropolymers and our work also confirms a novel strategy for enhancing the long-term stability of a proton-conductive fluoropolymer in electrical devices—eliminating or reducing fluoroalkyl ether groups on the side chains of the polymer.

Stereodivergent Synthesis of the Four Stereoisomers of Diethyl 4-Hydroxyphosphopipecolate from Ethyl (R)-4-Cyano-3-hydroxybutanoate

The stereodivergent synthesis of all four stereoisomers of diethyl 4-hydroxyphosphopipecolate from the commercial chiral building block ethyl (R)-4-cyano-3-hydroxybutanoate is described. Key steps in the synthesis of the target compounds involve the triethyl phosphite nucleophilic addition to chiral N-acyliminium ion easily obtained from (R)-4-hydroxypiperidin-2-one, giving diethyl (2R,4R)- and (2S,4R)-4-hydroxyphosphopipecolate diastereoisomers, easily separable by column chromatography followed by the 4-hydroxy epimerization through a sequential oxidation and highly diastereoselective reduction strategy, affording the diethyl (2R,4S)- and (2S,4S)-4-hydroxy-phosphopipecolate, respectively, consistent with our recently found results. All synthesized compounds were thoroughly characterized.

Amine-catalyzed substitution in CpFe(CO)2I by phosphine and bisphosphine ligands.

We have found that amines significantly accelerate iodide substitution in CpFe(CO)2I (1) (Cp = η5-cyclopentadienyl) with phosphines and allow the synthesis of new complexes that are not available through reactions carried out without an amine. The reaction of equimolar amounts of 1 and triphenylphosphine in toluene containing DIPA afforded [CpFe(CO)2PPh3]+I- within 5 min at room temperature in 72% yield (90% after 24 h). DIPA and pyrrolidine gave the highest yields of the tested amines. We performed a similar reaction using model bisphosphines 1,3-bis(diphenylphosphino)ethane (dppe) and 1,1'-bis(diphenylphosphino)ferrocene (dppf). The products depended on the reagent ratio and bore the CpFe(CO)2 moiety coordinated to one or two phosphine phosphorus atoms. Chelates [CpFe(CO)(dppe)]+I- (4) and [Cp2Fe2(CO)4(dppe)]2+2I- (5) were formed in 72% and 98% yield, respectively. We also performed the DIPA-catalyzed reaction of 1 with triethyl phosphite and obtained the product of an Michaelis-Arbuzov-like rearrangement, CpFe(CO)2[P(O)(OCH2CH3)2] (11). All complexes were characterized with spectroscopic analysis by NMR, FT-IR, and ESI-MS, and by XRD for three complexes. To clarify the reaction mechanism, we performed theoretical calculations of the intermolecular interactions between 1 and amine molecules. We propose two possible reaction mechanisms to explain the formation of products.

Functionalization of the position 5 of thiopyran fragment of 4-(diethoxyphosphoryl)-4,7-dihydro-5 Н-thiopyrano[3,4-b]furan

Alkaline hydrolysis of ethyl 4-(diethoxyphosphoryl)-4,7-dihydro-5 Н -thiopyrano[3,4- b ]furan-5-carboxylate proceeded selectively at the ester group. The acid obtained formed the corresponding acid chloride when treated with thionyl chloride. The acid chloride was used for acylation of glycine, α- and β-alanine esters. Under the conditions of phase transfer catalysis this acid chloride formed acyl azide which under mild conditions undergoes rearrangement to isocyanate. The latter reacted with primary amines to give ureas, and with the amino acid esters in forms ureidoesters. Reducing of acid chloride with sodium borohydride led to the corresponding alcohol. It was converted to chloride which in the reactions with sodium azide and iodide gives usual substitution products. When treated with potassium thiocyanate it formed thiocyanate. Iodide in the reaction with triethyl phosphite gave the corresponding phosphonate. Oxidation of alcohols with Collins reagent and acetic acid-DMSO system was studied.

Synthesis and properties of bay-functionalized 9,9′-bifluorenylidene derivatives

Abstract Here, we disclose the effect of substitution at the bay-region of 9,9′-bifluorenylidene on its optical and electrochemical properties. Bay-brominated 9,9′-bifluorenylidene was synthesized by the reductive dimerization of 4,5-dibromofluorenone with triethyl phosphite. The subsequent Suzuki–Miyaura cross-coupling afforded arylated derivatives. X-ray diffraction analysis revealed that the bulky bay-substituents twist the overall structure through the relay of the steric repulsion from the bay-region to the fjord-region. The π-extension at the bay-region with tolyl and 4-dimethylaminophenyl groups increases the electron-donating ability, while the introduction of bromo groups enhances the electron-accepting ability.

An efficient triethyl phosphite-promoted one-pot synthesis of vicinal diamines from arylglyoxals and aniline derivatives

An effective protocol for synthesis of some new vicinal diamine derivatives is reported through a one-pot reaction between arylglyoxals and aniline derivatives promoted by triethyl phosphite as a reductive coupling reagent. All reactions were conducted in ethanol as solvent at room temperature and the stable solid products were obtained by simple filtering off the precipitated solids in high yields. The structures of all products were proved by 1H and 13C NMR and IR spectral and elemental analysis data.

Influence of the Sun on Water. Dependence on geometry of solution and its position in space

Hydrolytic reactions with the participation of water clusters are highly dependent on the geometric shape of the reaction solution and its position in space. For example, the hydrolysis of triethyl phosphite in acetonitrile occurs at different rates in three 5-mm NMR tubes directed North-South, East-West and Vertically, and this difference can be very large. The rate ratios between the tubes vary greatly during the day depending on the position of the Sun in the sky. The rate of hydrolysis in the East-West tube displays the largest daily fluctuations. This phenomenon might be well accounted for by the decomposition of water clusters by muons which are constantly generated in the upper atmosphere by the solar wind. Since the muon flux is anisotropic, its influence depends on the area of a reaction solution which is affected by muons. This phenomenon depends on variations in solar activity and the distribution of solar energy due to the rotation of the Earth around its axis and around the Sun. As a result, the rate of hydrolysis of triethyl phosphite in multidirectional tubes displays not only daily, but also large annual fluctuations. Thus, this chemical process may be used to determine solar activity at different locations on the Earth and track changes in the direction of the muon flux.

Synthesis and self-assembly properties of thiacrown-cyclized tetrathiafulvalene organogelators

A novel low-molecular-weight organogelator (1) based on thiacrown-cyclized tetrathiafulvalene has been synthesized through cross-coupling reaction of crown-fused 1,3-dithiole-2-one 3 and the thione 4 in the presence of triethyl phosphite. The molecular structure of 1 was fully characterized by nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and infrared spectroscopy. Gel-forming-ability experiments showed that the gelator could only form an opaque gel in dimethyl sulfoxide by sonication. The xerogel morphology observed by scanning electron microscopy showed an amorphous wrinkled structure. The gel exhibited varied responses to various external stimuli, including temperature, chemical oxidation, anions, and Na+ ions.

A convenient synthesis, in silico study and crystal structure of novel sulfamidophosphonates: Interaction with SARS-CoV-2

A one-pot synthetic strategy was developed for the synthesis of novel sulfamidophosphonates via a three-component Kabachnik-Fields reaction of sulfanilamide, triethyl phosphite, and various aldehyde using ultrasound irradiation. Seven organophosphorus derivatives were synthesized with high yields through this newly developed method. The target compounds were characterized by 1H, 31P, 13C NMR, and IR. The molecular structure of 4a was obtained by X-ray diffraction on the monocrystal. Crystal belongs to the orthorhombic system with space groups Pbca. Insight into the binding mode of the synthesized compounds (ligand) into the binding sites of SARS-CoV2 (PDF code: 5R80) was provided by docking studies, performed with the help of Maestro 9.0 docking software.

Total Synthesis of Loroxanthin

The first total synthesis of loroxanthin (1) was accomplished by Horner-Wadsworth-Emmons reaction of C25-apocarotenal 8 having a silyl-protected 19-hydroxy moiety with C15-phosphonate 25 bearing a silyl-protected 3-hydroxy-ε-end group. Preparation of apocarotenal 8 was achieved via Stille coupling reaction of alkenyl iodide 10 with alkenyl stananne 9, whereas phosphonate 25 was prepared through treatment of ally alcohol 23 with triethyl phosphite and ZnI2. The ally alcohol 23 was derived from the known (3R,6R)-3-hydroxy C15-aldehyde 20, which was obtained by direct optical resolution of racemate 20 using a semi-preparative chiral HPLC column.

Bioinspired Nanonetwork Hydroxyapatite from Block Copolymer Templated Synthesis for Mechanical Metamaterials.

Inspired by Mantis shrimp, this work aims to suggest a bottom-up approach for the fabrication of nanonetwork hydroxyapatite (HAp) thin film using self-assembled polystyrene-block-polydimethylsiloxane (PS-b-PDMS) block copolymer (BCP) with a diamond nanostructure as a template for templated sol-gel reaction. By introducing poly(vinylpyrrolidone) (PVP) into precursors of calcium nitrate tetrahydrate and triethyl phosphite, which limits the growth of forming HAp nanoparticles, well-ordered nanonetwork HAp thin film can be fabricated. Based on nanoindentation results, the well-ordered nanonetwork HAp shows high energy dissipation compared to the intrinsic HAp. Moreover, the uniaxial microcompression test for the nanonetwork HAp shows high energy absorption per volume and high compression strength, outperforming many cellular materials due to the topologic effect of the well-ordered network at the nanoscale. This work highlights the potential of exploiting BCP templated synthesis to fabricate ionic solid materials with a well-ordered nanonetwork monolith, giving rise to the brittle-to-ductile transition, and thus appealing mechanical properties with the character of mechanical metamaterials.

Synthesis of 1,2,3-Triazine Derivatives by Deoxygenation of 1,2,3-Triazine 1-Oxides.

A convenient, efficient, and inexpensive method has been developed for the synthesis of 1,2,3-triazine derivatives via deoxygenation of 1,2,3-triazine 1-oxide using trialkyl phosphites. Triethyl phosphite is more reactive than trimethyl phosphite, and both phosphites form their corresponding phosphates in these reactions. This procedure provides a range of aromatic and aliphatic substituted 1,2,3-triazine-4-carboxylate derivatives cleanly in high yields. Unexpected 1,2,4-triazine derivatives were also obtained as minor products during deoxygenation of 1,2,3-triazine-4-carboxylate 1-oxides having an aliphatic substituent at the 5-position.

(Digital Presentation) Electrochemical Phosphonylation of π-Conjugated Polymers

π-Conjugated polymers exhibit attractive optoelectronic properties because of their extended π-conjugation system along with main chains. Therefore, the introduction of functional groups into their main chains is a straightforward strategy to control their optoelectronic properties. In this context, post-functionalization is a practical methodology to install functional units. Among the post-functionalization methods, electrochemical post-functionalization is a promising fashion due to its outstanding abilities to transform aromatic C–H bonds of π-conjugated polymers into various functional units.1) For example, anodic chlorination of poly(3-hexylthiophene) (P3HT) has been reported (Fig. 1 (a)).2) However, functional groups available for this post-functionalization remain limited to those derived from nucleophilic dopants such as a chloride ion.Here, to expand the applicable functional groups for electrochemical post-functionalization, we attempted to develop the electrochemical phosphonylation of P3HT and poly(9,9-dioctylfluorene) (PFO) (Fig. 1 (b)). With the use of non-nucleophilic dopants and triethyl phosphite as neutral nucleophiles, we successfully achieved C–H phosphonylation of the main chains of these polymers. The introduced phosphonyl groups significantly affected the optoelectronic properties of P3HT and PFO. Particularly, phosphonylated PFO was found to show unique emitting properties.References1) S. Inagi, T. Fuchigami, Macromol. Rapid Commun., 2014, 35, 854.2) S. Hayashi, S. Inagi, K. Hosaka, T. Fuchigami, Synth. Met., 2009, 159, 1792. Figure 1

Optimization of formation of phase pure hydroxyapatite and fabrication of electrochemically stable HAP coatings on 316L SS for orthopedic applications

AbstractImpact of sintering temperature and aging time was investigated on purity and phase of hydroxyapatite powders synthesized through sol–gel process. Phase, composition, and morphology of the prepared hydroxyapatite powders were characterized using X‐ray diffraction (XRD), Fourier transform infrared (FT‐IR), and scanning electron microscopy (SEM)/energy dispersive spectroscopy (EDS). Plausible mechanism respective to the formation of HAP from the precursors Ca(NO3)2·4H2O and triethyl phosphite (TEP) by sol–gel process was determined from 31P NMR analysis. Further, the development of hydroxyapatite coatings on 316L SS metallic surfaces was done by varying the spin coating parameters such as spin speed, spin time, and sintering atmosphere, and their corrosion resistance behavior in SBF solution was evaluated by electrochemical impedance spectroscopy (EIS) and TAFEL polarization analysis. From the results, we inferred that the HAP coatings deposited on 316L SS surfaces at 3000 rpm/min under nitrogen atmosphere sintering have shown improved corrosion resistivity. The effect of aging time, sintering atmosphere, and spin speed was evaluated in terms of corrosion resistance behavior.

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

An efficient Cu-catalyzed strategy for the direct C–H amination of arenes in high yields using N-hydroxyphthalimide as the amidyl radical precursor under air is reported. A possible mechanism is proposed that proceeds via a radical reaction in the presence of CuBr and triethyl phosphite.

A green and novel method for the preparation of α-aminophosphonates using eggshell as catalyst. X-ray study

An efficient and eco-friendly green methodology is developed for the synthesis of series of α-aminophosphonate derivatives from diverse aldehydes, anilines and triethyl phosphite by using environmentally benign and cost-effective Eggshells as solid heterogeneous base catalyst. The reaction is conducted by the stepwise one pot condensation through Kabachnick–Fields addition reaction in ethanol at room temperature during 25–30 min. High yield, short reaction time, solvent-free condition, waste to wealth, and optimization with the design of experiment are the major advantages of this method. In addition, this study examines the influence of different solvents, temperature and the amount of catalyst on the yield of the reaction. A single crystal of (2S)- diethyl (phenyl) ((4-fluorophenyl)-aminophosphonate (3g) has been obtained after recrystallization from ethanol/dichloromethane (9/1) and selected for X-ray diffraction study. Compound 3g crystallizes in the monoclinic space group P21/c. The structure of the obtained compounds was confirmed by 1H, 13C, and 31P NMR spectroscopy, IR spectroscopy, as well as elemental analysis.