A convenient method to access long-chain and functionalised mixed methylphosphonate esters and their application in the synthesis of ionic liquids

A new method to synthesise long-chain and functionalised methylphosphonate esters and the corresponding ionic liquids is reported. The synthesis comprises the formation of dialkyl methylphosphonate esters in a S(N)2 reaction followed by the use of these esters as alkylating agents to form the corresponding, new alkyl methylphosphonate ILs.     

The specificity of reductive dechlorination in the polychloropyridine series. Synthesis of 2,3,5-trichloro- and of 2,3,5,6-tetrachloropyridine

The high specificity of the reduction system zinc and ammonium salts in dimethyl methylphosphonate as solvent is demonstrated in several reductive dechlorination reactions of polychloropyridines. The reduction of pentachloropyridine with zinc/ammonium chloride system in dimethyl methylphosphonate yielded solely 2,3,5,6-tetrachloropyridine. Similarly, the reduction of 2,3,4,5-tetrachloropyridine with zinc and the tetramethylammonium salt of methyl methylphosphonate furnished exclusively 2,3,5-trichloropyridine. A synthetic procedure for the preparation of the new ammonium salts of methyl methylphosphonate is given.     

Some properties of bis(4,6-dimethyl-2-pyrimidyl)methylphosphonate

It has been established that bis(4,6-dimethyl-2-pyrimidyl)methylphosphonate (I) is capable of forming a crystalline hydrate with five molecules of water. Compound I reacts with dimethyl sulfate, forming a complex mixture of products from which dimethyl methylphosphonate, 1,4,6-trimethyl-5-sulfo-2-pyrimidinone, the betaine 1,3,4,6-tetramethyl-2-oxodihydropyrimidinium-2-sulfonate, and 4,6-dimethyl-2-hydroxypyrimidine methylphosphonate have been isolated.     

DIMETHYL METHYLPHOSPHONATE AS METHYLATING REAGENT

Abstract

The methylating properties of dimethyl methylphosphonate have been investigated. Aromatic mono- and polycarboxylic acids were converted into their methyl esters by heating with dimethyl methylphosphonate. Similarly phenols or amines gave their respective O- or N-methyl derivatives. The sodium salts of sulfinic acids also reacted yielding sulfones in high yield.     

NMR chemical shift and J coupling parameterization and quantum mechanical reference spectrum simulation for selected nerve agent degradation products in aqueous conditions

The spectral parameters of selected nerve agent degradation products relevant to the Chemical Weapons Convention, namely, ethyl methylphosphonate, isopropyl methylphosphonate, pinacolyl methylphosphonate and methylphosphonic acid, were studied in wide range of pH conditions and selected temperatures. The pH and temperature dependence of chemical shifts and J couplings was parameterized using Henderson–Hasselbalch‐based functions. The obtained parameters allowed calculation of precise chemical shifts and J coupling constants in arbitrary pH conditions and typical measurement temperatures, thus facilitating quantum mechanical simulation of reference spectra in the chosen magnetic field strength for chemical verification. Copyright © 2017 John Wiley & Sons, Ltd.     

Stereospecific Grignard-Activated Solid Phase Synthesis of DNA Methylphosphonate Dimers

Stereoregular R(p) or S(p) DNA methylphosphonate dimers have been synthesized on a solid phase support. A deprotected 5'-hydroxyl-N(2)-isobutanoyldeoxyguanosine 3'-O-succinate coupled to high-loaded polyethylene glycol (PEG) coated polystyrene beads (HLP) was activated with a Grignard reagent, t-BuMgCl. After activation was complete, a pure diastereoisomer of 5'-(dimethoxytrityl) N-benzoyldeoxynucleoside 3'-(p-nitrophenyl methylphosphonate) p-nitrophenyl ester (R(p) or S(p)) was added. Coupling of the activated 5'-hydroxyl to the 3'-methylphosphonate ensued, releasing nitrophenol, yielding the R(p) or S(p) dimer, respectively. The dimers were then cleaved from the solid support, deprotected, and purified, yielding methylphosphonate DNA dimers of defined stereochemistry.     

Concise and stereocontrolled syntheses of phosphonate C-glycoside analogues of β-d-ManNAc and β-d-GlcNAc 1-O-phosphates

Diethyl C-(2-deoxy-2-acetamido-β-d-mannopyranosyl)methylphosphonate and dimethyl C-(2-deoxy-2-acetamido-β-d-glucopyranosyl)methylphosphonate were stereoselectively prepared from N-acetyl d-glucosamine. Routes to such compounds starting from d-GlcNAc have been problematic, but we have found short and efficient implementations of this highly desirable transformation.     

Synthesis of sterically hindered phenol-containing phosphorylated isatin derivatives

Addition of isatin to the exocyclic double bond of dimethyl (3,5-di-tert-butyl-4-oxocyclohexa-2,5-dienylidene)methylphosphonate gave dimethyl (3,5-di-tert-butyl-4-hydroxyphenyl)(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methylphosphonate. Its subsequent functionalization in reactions with thiosemicarbazide and 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionohydrazide yielded isatin derivatives containing several pharmacophoric fragments.     

Synthesis of phosphorus‐containing dipeptide mimetics via the Kabachnik–Fields reaction

The synthesis of three novel dimethyl (2‐(4,4‐dimethyl‐2,5‐dioxoimidazolidin‐1‐ylamino)‐ 2‐oxoethylamino)methylphosphonate, dimethyl (1‐ (4,4‐dimethyl‐2,5‐dioxoimidazolidin‐1‐ylamino)‐4‐ methyl‐1‐oxopentan‐2‐ylamino)methylphosphonate, and dimethyl (1‐(4,4‐dimethyl‐2,5‐dioxoimidazolidin‐ 1‐ylamino)‐1‐oxo‐3‐phenylpropan‐2‐ylamino)methylphosphonate, respectively, is reported. The newly synthesized compounds were prepared via the Kabachnik–Fields reaction. Their structures have been characterized by elemental analysis, IR, and NMR (¹H, ¹³C, and ³¹P) spectra. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:669–672, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20731     

High-sensitivity determination of the degradation products of chemical warfare agents by capillary electrophoresis–indirect UV absorbance detection

Capillary electrophoresis coupled with indirect UV absorbance detection was employed for the determination of the chemical warfare agent degradation products: methylphosphonic acid, ethyl methylphosphonate, isopropyl methylphosphonate, and pinacolyl methylphosphonate. Glutamic acid was used as a buffering agent at its isoelectric point (pH 3.22). In its zwitterionic form, glutamic acid does not act as a competing co-anion in the system, thus providing buffering capacity while maintaining high sensitivity. The indirect probe (phenylphosphonic acid) concentration was lowered to 1 mM from the 10 mM in previous literature studies, further enhancing sensitivity. Detection limits of 2 μM were achieved with hydrodynamic injection and up to 100-fold lower using electrokinetic injection. The increased buffering capacity of this system over previous methods led to migration time reproducibility RSD values of 0.18 to 0.22%. This represents a 10-fold improvement in reproducibility over previous studies with comparable or improved sensitivity.     

TiO2 photocatalytic degradation of dimethyl- and diethyl- methylphosphonate, effects of catalyst and environmental factors

Dimethyl methylphosphonate (DMMP) and diethyl methylphosphonate (DEMP) are readily mineralized by photoexcited titanium dioxide (TiO₂). Intermediate products include low molecular weight organic acids and methylphosphonic acid. Complete mineralization yields phosphate and carbon dioxide. The photoactivities of different types of TiO₂ were investigated. The decomposition kinetics of DMMP and effects of DMMP and catalyst concentration, sonication, solar irradiation, oxygen concentration, temperature, and hydrogen peroxide on the rate of decomposition are reported. The degradation rates increase with simultaneous sonication, addition of hydrogen peroxide, and at higher temperatures.     

Separation of diastereomers of methylphosphonate dinucleotides

A chiral derivatizing agent, 1-menthyl chloroformate, has been used as a 3′-OH blocking group to facilitate the resolution of diastereomers of methylphosphonate dinucleotides by silica gel column chromatography.     

The enantio- and diastereoselective synthesis of the first phospho-statine derivative

The title compound was synthesized by the diastereoselective addition of the lithium or sodium anion of dimethyl methylphosphonate to $\text{N}$-trityl-L-phenylalaninal.     

Crystal and molecular structure of (±)-diphenyl-4′-chlorophenyl-[(2-hydroxy-1,1-dimethylethyl)amino]methylphosphonate

We have synthesized (±)-diphenyl-4′-chlorophenyl-[(2-hydroxy-1,1-dimethylethyl)amino]methylphosphonate and studied it by X-ray diffraction.     

Synthesis of deoxynucleoside methylphosphonates via a phosphonamidite approach

Deoxynucleoside methylphosphonamidites 1 have been synthesized as building monomers for the stepwise synthesis of methylphosphonate analogs of oligonucleotides.     

Supramolecular Complexes of Diglycidyl Methylphosphonate with Calix[4]resorcinolarene

Various-composition supramolecular complexes of calix[4]resorcinolarene with diglycidyl methylphosphonate were synthesized in organic solvents. The products have well-defined melting points, they are cleaved by acetylation, but remain unchanged on treatment with triethylamine.     

Real‐time trace detection and identification of chemical warfare agent simulants using recent advances in proton transfer reaction time‐of‐flight mass spectrometry

This work demonstrates for the first time the potential of using recent developments in proton transfer reaction mass spectrometry for the rapid detection and identification of chemical warfare agents (CWAs) in real‐time. A high‐resolution (m/Δm up to 8000) and high‐sensitivity (～50 cps/ppbv) proton transfer reaction time‐of‐flight mass spectrometer (PTR‐TOF 8000 from Ionicon Analytik GmBH) has been successfully used to detect a number of CWA simulants at room temperature; namely dimethyl methylphosphonate, diethyl methylphosphonate, diisopropyl methylphosphonate, dipropylene glycol monomethyl ether and 2‐chloroethyl ethyl sulfide. Importantly, we demonstrate in this paper the potential to identify CWAs with a high level of confidence in complex chemical environments, where multiple threat agents and interferents could also be present in trace amounts, thereby reducing the risk of false positives. Instantaneous detection and identification of trace quantities of chemical threats using proton transfer reaction mass spectrometry could form the basis for a timely warning system capability with greater precision and accuracy than is currently provided by existing analytical technologies. Copyright © 2009 John Wiley & Sons, Ltd.     

STEREOSELECTIVITY IN THE SYNTHESIS OF DIADENYLYL METHYLPHOSPHONATE

Stereoselectivity was found during the coupling reaction to form 2', 5'-and 3', 5'-linked diadenylyl methylphosphonate.     

The Synthesis and Bioactivity of Dimethyl (2,3- Dihydrobenzo[b][1,4]Dioxin-6-Yl)(Aryl Amino)Methylphosphonates

Abstract

A new series of α-aminophosphonates have been synthesized by a one-pot three-component reaction of 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde, various amines, and dimethyl phosphite by using nano-TiO₂ as a catalyst under solvent-free conditions at 50°C. The major advantages of the present method are high yields, short reaction times, recyclable catalyst, and solvent-free reaction conditions. Among these new structurally diversified set of α-aminophosphonates, dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(3-nitrophenylamino) methylphosphonate and dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(4-fluoro-3-nitro-phenyl-amino) methylphosphonate have shown higher antioxidant activity in diphenyl picryl hydrazyl (DPPH) scavenging, reducing power assay, and lipid peroxidation methods.     

Straightforward and Scalable Synthesis of Diethyl Fluoro-(phenylsulfonyl)methylphosphonate

A process is described for the synthesis of diethyl fluoro(phenylsulfonyl)methylphosphonate which is easily and safely performed on a multi-kilogram scale.