Diethyl P-(hydroxymethyl)phosphonate

Clear colorless to yellow viscous liquid

In the 500 ml in the reaction bottle, adding phosphorous acid diethyl ester 76.6 kg (0.554 µM), paraformaldehyde 20g (0.667 µM, adding 15percent the amount of), K2CO3 244g (1.765 µM, adding 15percent the amount of) and 277 ml toluene, raising the temperature to 60 °C to about, waiting a few minutes later, observed obvious of the exothermic phenomenon, start to continue to batch add residual paraformaldehyde, about 15min adjustments. Then 60 °C continue to thermal insulation 2h. In the preservation process continuously add the remaining K2CO3, make the PH=7.5 - 8. After the reaction, filtration, pressure reducing recovery toluene, results in the hydroxy methylphosphonic acid diethyl ester thick 92.1g, gas chromatographic detection content of 96percent or more, yield is up to 95percent. Directly used for the next step reaction. In the 1L in the reaction bottle, adding alpha phosphonic acid diethyl ester 78.8g (0.472 µM), toluene 278 ml and triethylamine 90g (0.889 µM). The temperature is not more than 30 °C lower, dropping to the toluene sulfonyl chloride 90g (0.472 µM) of the 166 ml toluene solution, 1h after finishing dripping, raising the temperature to 60 °C insulation 5h. HPLC display the completion of reaction (toluene sulfonyl chloride residue to _AOMARKENCODELTX0AO _ 0.5percent) after, washed with water (277 ml × 2 times) toluene organic layer, is decompressed and the majority of the solvent toluene, to obtain light yellow liquid, cooling to obtain solid paratoluene sulfonyl oxygen methoxy phosphine acid diethyl ester 130.5g, yield 87percent.To a reactor containing an inert atmosphere, such as nitrogen, Diethyl phosphite (81.0 g, 0.586 mol, 1.0 eq.) Was added, Triethylamine (63.2 g, 0.625 mol, 1.1 eq.), Paraformaldehyde (22.4 g, 0.746 mol, 1.3 eq.), Stirring. Refluxed at 90 ° C for 8 h until completion of the reaction, only trace diethyl phosphite or no diethyl phosphite was detected by TLC monitoring and distillation under reduced pressure gave 59.2 g of product in a yield of 60percentTo a reactor containing an inert atmosphere (e.g., nitrogen), (81.0 g, 0.586 mol, 1 eq) of diethyl phosphonate, triethylamine (63.2 g, 0.625 mol, 1.1 eq.), Paraformaldehyde (22.4 g, 0.746 mol, 1.3 eq.) were added , stirred and refluxed at 90 ° C for 8 h until completion of the reaction. According to TLC monitoring, only trace amounts of diethyl phosphite or undetectable diethyl phosphite and distilled under reduced pressure to give 59.2 g of product in 60percent yieldConvenient replacement by adding anhydrous ethanol in a glass autoclave (51 kg, 1107 mol) and phosphorous acid diethyl ester (22 kg, 159 . 3mol), stirring, mixing complete, the kettle is opened, into the poly-formaldehyde (5.5 kg, 61 . 06 mol) and triethylamine (1.4 kg, 13 . 84 mol), heating to 40 °C reaction 0.5-1 hours, in 50-65 °C reaction the 5 hours, slightly cold to 30-40°C, with 0.3 kg of diatomaceous earth filtration out the solid, and using 2 kg after anhydrous ethanol eluviation, combined filtrate and showering liquid, 55 °C decompression concentrating ethanol, adding toluene concentration after the completion of (18 kg, 195 . 35 mol), continue to concentrated, after steaming dry ethanol cooling to 30 °C, lower the temperature to -10 ° C the following, dropping triethylamine (15.2 kg, 150 . 21mol), and added in batches to toluene sulfonyl chloride (24.5 kg, 128 . 51mol), dropping process temperature control -3 to -10 °C, after dripping stirring for 1 hour, heating to 19-25°C, thermal insulation reaction 2.5-3.5 hours, until the reaction is complete, by adding 18 kg of water, stirring water washing, by adding 5 kg anhydrous sodium sulfate, mixing and drying 6 hours, filtering, the filtrate in the 65 °C within concentrated under reduced pressure, the solvent concentration, the residue as paratoluene sulfonyl oxygen methyl phosphine acid diethyla ester thick, to continue to improve temperature (to 152 °C, 2-3mmHg) reduced pressure distillation, the vapor substance obtained 30.14 kg of toluene sulfonyl oxygen methyl phosphine acid diethyla ester high-quality goods, ≥ 99percent purity, the yield is 137percent.

Α and β-Dialkoxyphosphoryl isothiocyanate for anti-proliferation research; Dendritic polyglycerol anion for synthesis of L-selectin inhibitors; Phosphate for synthesis of anti-HIV-1 activity; For the synthesis of homogenous and copolymers of phosphorylated norbornene; for the study of the inhibition of FBPase by containing thiazole phosphonic acid; used as Mitsunobu reaction reagent

Flame retardants

Molecular Weight:168.13
XLogP3:-0.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:168.05514589
Monoisotopic Mass:168.05514589
Topological Polar Surface Area:55.8
Heavy Atom Count:10
Complexity:115
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes