Diethyl (hydroxymethyl)phosphonate Chemical Properties

Boiling point:

124-126 °C/3 mmHg (lit.)

Density 

1.14 g/mL at 25 °C (lit.)

refractive index 

n20/D 1.444(lit.)

Flash point:

>230 °F

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

form 

Viscous Liquid

pka

13.00±0.10(Predicted)

color 

Clear colorless to yellow

Water Solubility 

500g/L at 20℃

InChI

InChI=1S/C5H13O4P/c1-3-8-10(7,5-6)9-4-2/h6H,3-5H2,1-2H3

InChIKey

RWIGWWBLTJLKMK-UHFFFAOYSA-N

SMILES

P(CO)(=O)(OCC)OCC

CAS DataBase Reference

3084-40-0(CAS DataBase Reference)

NIST Chemistry Reference

Diethyl hydroxymethylphosphonate(3084-40-0)

EPA Substance Registry System

Phosphonic acid, (hydroxymethyl)-, diethyl ester (3084-40-0)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

37/39-26-36-37

WGK Germany 

3

TSCA 

Yes

HS Code 

29319090

MSDS

• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS
• Language:English Provider:ALFA

Diethyl (hydroxymethyl)phosphonate Usage And Synthesis

Chemical Properties

Clear colorless to yellow viscous liquid

Uses

Diethyl hydroxymethylphosphonate acts as a reactant for synthesis of α And β-dialkoxyphosphoryl isothiocyanate used in antiproliferative studies, dendritic polyglycerol anions for L-selectin inhibition, phosphonates for anti-HIV-1 activity, homo and copolymers of phosphonated norbornenes, Mitsunobu reactions. It is involved in studies of FBPase inhibition by phosphonic acid-containing thaizoles.

reaction suitability

reaction type: C-C Bond Formation

Synthesis

1. In a 500 ml reaction flask, 76.6 g (0.554 moles) of diethyl phosphite, 20 g (0.667 moles added at 15%) of paraformaldehyde, 244 g (1.765 moles added at 15%) of potassium carbonate and 277 ml of toluene were added sequentially. The reaction mixture was heated to 60° C. After exothermic phenomena were observed, the remaining paraformaldehyde was added in batches and the addition process took about 15 minutes. 2. The reaction was continued at 60°C for 2 hours, during which time the remaining potassium carbonate was added in batches, maintaining the pH of the reaction system between 7.5 and 8. 3. Upon completion of the reaction, filtration was performed, and toluene was recovered by distillation under reduced pressure to obtain diethyl hydroxymethylphosphonate crude product of 92.1 g. The purity was detected by gas chromatography as ≥96%, and the yield was 95%. The product can be directly used in the next step of the reaction. 4. In a 1 liter reaction flask, 78.8 g (0.472 mol) of diethyl α-phosphonate, 278 mL of toluene and 90 g (0.889 mol) of triethylamine were added. Maintaining the temperature not lower than 30°C, 166 mL of toluene solution of toluene sulfonyl chloride 90 g (0.472 mol) was slowly added dropwise to the reaction vial, and the reaction was continued for 1 hour after the dropwise addition was completed. 5. The reaction system was warmed up to 60°C and the reaction was kept warm for 5 hours until high performance liquid chromatography (HPLC) showed that toluenesulfonyl chloride residue was ≤0.5%. 6. After the reaction was completed, the organic layer of toluene was washed twice with 277 ml of water, most of the toluene was removed by distillation under reduced pressure, a light yellow liquid was obtained, and 130.5 g of solid diethyl p-toluenesulfonyl oxymethoxyphosphonate was precipitated after cooling, with a yield of 87%.

References

[1] Tetrahedron Letters, 2016, vol. 57, # 30, p. 3349 - 3353
[2] Patent: CN106699814, 2017, A. Location in patent: Paragraph 0017-0019
[3] Journal of Organometallic Chemistry, 2005, vol. 690, # 10, p. 2472 - 2481
[4] Tetrahedron Letters, 1986, vol. 27, # 13, p. 1477 - 1480
[5] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 11, p. 1477 - 1482

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