Ethyl dimethylphosphonoacetate
[CAS# 311-46-6]

Identification

• Classification: Chemical reagent >> Organic reagent >> Carboxylic anhydride
• Name: Ethyl dimethylphosphonoacetate
• Synonyms: Ethoxycarbonylmethylphosphonic acid dimethyl ester; Phosphonoacetic acid P,P-dimethyl ethyl ester
• Molecular Formula: C₆H₁₃O₅P
• Molecular Weight: 196.14
• CAS Registry Number: 311-46-6
• EC Number: 206-222-6
• SMILES: CCOC(=O)CP(=O)(OC)OC

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 268.7 ºC 760 mmHg (Calc.)^*
• Flash point: 98.9 ºC (Calc.)^*
• Index of refraction: 1.414 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319
• Precautionary Statements: P264-P264+P265-P280-P302+P352-P305+P351+P338-P321-P332+P317-P337+P317-P362+P364

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

Ethyl dimethylphosphonoacetate is an organophosphorus compound with the molecular formula C₅H₁₁O₄P. Structurally, it consists of a phosphonate group bearing two methyl substituents connected via a methylene bridge to an ethyl ester of acetic acid. This combination of a stabilized phosphonate group and an ester functionality imparts distinctive reactivity, making it a useful reagent in carbon–carbon bond-forming reactions. The compound is typically a colorless to pale yellow liquid, soluble in organic solvents and sparingly soluble in water.

The primary application of ethyl dimethylphosphonoacetate is in the Horner–Wadsworth–Emmons reaction, a variant of the Wittig olefination. In this reaction, the methylene group adjacent to the phosphonate is deprotonated to form a stabilized carbanion, which then reacts with aldehydes or ketones to generate α,β-unsaturated esters. The phosphonate group stabilizes the anion, allowing reactions under milder conditions and often providing high stereochemical selectivity.

Ethyl dimethylphosphonoacetate is also used as a building block in the synthesis of heterocycles, pharmaceuticals, and agrochemicals. The ester functionality allows for subsequent transformations, such as hydrolysis to a carboxylic acid or reduction to an alcohol, providing versatility in multistep syntheses.

Synthetically, the compound can be prepared by the reaction of diethyl methylphosphonate with ethyl bromoacetate or through other alkylation strategies involving phosphonate esters. Handling requires standard laboratory precautions, as it is flammable and reacts with strong bases used to generate the reactive carbanion.

Overall, ethyl dimethylphosphonoacetate is a versatile organophosphorus reagent valued for its nucleophilic reactivity and stability. Its role in the Horner–Wadsworth–Emmons reaction and related transformations makes it a key reagent in the synthesis of unsaturated esters and other carbon–carbon bonded frameworks in organic chemistry.

References

2017. Asymmetric Synthetic Strategies of (R)-(-)-Baclofen: An Antispastic Drug. Synthesis, 49(20).
DOI: 10.1055/s-0036-1590938