Trimethyl phosphonoacetate
[CAS# 5927-18-4]

Identification

• Classification: Organic raw materials >> Organic phosphine compound
• Name: Trimethyl phosphonoacetate
• Synonyms: (Dimethoxyphosphinyl)-acetic acid methyl ester; Methyl (dimethoxyphosphoryl)acetate
• Molecular Formula: C₅H₁₁O₅P
• Molecular Weight: 182.11
• CAS Registry Number: 5927-18-4
• EC Number: 227-663-0
• SMILES: COC(=O)CP(=O)(OC)OC

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*, 1.263 g/mL (Expl.)
• Index of Refraction: 1.408, Calc.^*, 1.437 (Expl.)
• Boiling Point: 311.0±0.0 °C (760 mmHg), Calc.^*, 265-268 °C (Expl.)
• Flash Point: 109.7±42.9 °C, Calc.^*, 110 °C (Expl.)

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

Trimethyl phosphonoacetate is a notable organophosphorus compound that plays a significant role in organic synthesis, particularly in the preparation of biologically active molecules and other complex organic structures. This compound, characterized by the presence of a phosphonate group attached to an acetate moiety, was first synthesized in the mid-20th century as chemists sought versatile intermediates for organic synthesis. Since its discovery, trimethyl phosphonoacetate has become an invaluable reagent in the chemical industry due to its unique reactivity and the phosphorus atom's ability to influence the properties of organic molecules.

One of the most prominent applications of trimethyl phosphonoacetate is in the synthesis of phosphonates and phosphoramidates, which are essential classes of compounds in medicinal chemistry. Its ability to act as a phosphorylating agent facilitates the incorporation of phosphorus into organic frameworks, thereby enhancing the biological activity of the resulting molecules. This is particularly relevant in drug development, where the addition of phosphonate groups can improve the pharmacokinetic properties, such as solubility and bioavailability, of pharmaceutical agents. Numerous studies have demonstrated that compounds containing phosphonate moieties exhibit increased antiviral, anticancer, and antibacterial activities compared to their non-phosphonated counterparts.

In the realm of medicinal chemistry, trimethyl phosphonoacetate serves as a key intermediate in the synthesis of various bioactive molecules. For instance, it has been employed in the synthesis of nucleotide analogs, which can act as effective inhibitors of viral replication by mimicking natural nucleotides. These analogs can integrate into the viral genome, thereby disrupting the replication process. Additionally, trimethyl phosphonoacetate is utilized in the synthesis of peptide and nucleoside analogs, where it plays a crucial role in forming phosphodiester bonds. The incorporation of phosphonate groups into these compounds can enhance their stability against enzymatic degradation, making them promising candidates for therapeutic applications.

Furthermore, trimethyl phosphonoacetate has applications beyond medicinal chemistry. In agricultural chemistry, it is utilized in the development of herbicides and insecticides. The introduction of phosphonate functionalities into agrochemical formulations has led to increased efficacy and specificity against target pests and weeds. Researchers have been exploring how trimethyl phosphonoacetate can be used to create more effective and environmentally friendly agricultural products, as phosphonates can sometimes exhibit lower toxicity to non-target organisms compared to traditional chemical classes.

The versatile nature of trimethyl phosphonoacetate extends to its role in the synthesis of various phosphorus-containing materials, including flame retardants and polymer additives. Its ability to modify the properties of polymers makes it valuable in materials science, where it contributes to the development of advanced materials with enhanced thermal and fire resistance.

In conclusion, trimethyl phosphonoacetate is a vital compound in the fields of organic synthesis, medicinal chemistry, and agricultural science. Its unique structure and reactivity allow for the incorporation of phosphorus into a variety of organic frameworks, leading to the development of bioactive molecules with improved therapeutic properties. As research continues, the potential applications of trimethyl phosphonoacetate are likely to expand further, highlighting its significance as a versatile building block in chemical synthesis.

References

2021. Applications of the Horner-Wadsworth-Emmons Olefination in Modern Natural Product Synthesis. Synthesis, 53(20).
DOI: 10.1055/a-1493-6331

2021. A Straightforward, Purification-Free Procedure for the Synthesis of Ando and Still-Gennari Type Phosphonates. Synthesis, 54(3).
DOI: 10.1055/a-1628-7586

2018. Synthesis and Electrophysical Properties of Methanofullerene with C1-Geminal Dimethoxyphosphoryl and Methoxycarbonyl Groups. Russian Journal of Organic Chemistry, 54(9).
DOI: 10.1134/s1070428018090257