Diethyl phosphite
[CAS# 762-04-9]

Identification

• Classification: Organic raw materials >> Inorganic acid ester
• Name: Diethyl phosphite
• Synonyms: Diethyl hydrogen phosphonate
• Molecular Formula: C₄H₁₁O₃P
• Molecular Weight: 138.10
• CAS Registry Number: 762-04-9
• EC Number: 212-091-6
• SMILES: CCO[P+](=O)OCC

Properties

• Density: 1.072 g/mL
• Melting point: -70 °C
• Boiling point: 50-51 °C (2 mmHg)
• Refractive index: 1.407-1.409
• Flash point: 74 °C
• Water solubility: miscible (hydrolysis)

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H315-H317-H318-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P272-P280-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-P319-P321-P332+P317-P333+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Serious eye damage	Eye Dam.	1	H318
Skin sensitization	Skin Sens.	1B	H317
Eye irritation	Eye Irrit.	2	H319
Skin sensitization	Skin Sens.	1	H317
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovery and Applications

Diethyl phosphite is an organophosphorus compound with the chemical formula (C₂H₅O)₂P(O)H. It is a colorless, oily liquid with a characteristic odor and is classified as a phosphonic acid ester. The molecule consists of two ethoxy groups bonded to a central phosphorus atom, which also carries a double-bonded oxygen and a hydrogen atom, forming a phosphite structure.

The compound was first synthesized in the 19th century during investigations into organophosphorus chemistry. Its production typically involves the alcoholysis of phosphorus trichloride with ethanol under controlled conditions, yielding diethyl phosphite along with hydrogen chloride as a byproduct. The reaction must be carefully managed to prevent overreaction or the formation of unwanted side products.

Diethyl phosphite is widely used as a reagent and intermediate in organic and organophosphorus chemistry. One of its key features is the presence of a reactive P–H bond, which allows it to participate in a variety of transformations, such as the Pudovik reaction (a base-catalyzed addition of phosphites to carbonyl compounds) and the Abramov reaction (nucleophilic addition to aldehydes or ketones). These reactions are commonly used in the synthesis of α-hydroxy phosphonates, which are valuable building blocks in medicinal and agrochemical compounds.

In the field of medicinal chemistry, diethyl phosphite has served as a precursor for the synthesis of biologically active phosphonate analogs of amino acids, nucleotides, and peptidomimetics. These compounds often exhibit enhanced metabolic stability and bioavailability due to the phosphonate group's resistance to enzymatic hydrolysis, making them attractive as antiviral, antibacterial, or anticancer agents.

Diethyl phosphite is also employed in the production of flame retardants. Its ability to form phosphorus-containing polymers or react with halogenated compounds makes it suitable for applications in materials science, especially in the development of fire-resistant coatings and additives. Additionally, it finds use in the synthesis of organophosphorus ligands and catalysts for transition metal chemistry.

In coordination chemistry, derivatives of diethyl phosphite can act as ligands for metal complexes, particularly when modified to include additional donor atoms. These complexes are studied for their catalytic properties in various organic transformations, including hydrogenation, hydroformylation, and cross-coupling reactions.

Diethyl phosphite has also been utilized as a reducing agent. The P–H bond can participate in the reduction of certain organic and inorganic substrates under mild conditions. For instance, it has been reported to reduce azo compounds and nitro groups in some specific synthetic contexts, offering an alternative to more conventional reducing agents.

In analytical chemistry, diethyl phosphite can be used in derivatization techniques for the detection and quantification of reactive carbonyl compounds, such as aldehydes and ketones. It reacts with these analytes to form stable phosphonate derivatives, which are easier to detect by chromatographic or spectroscopic methods.

In industrial settings, diethyl phosphite is produced and handled in bulk quantities for use in pesticide and plasticizer synthesis. It serves as a starting material for the production of phosphonates that act as chelating agents, scale inhibitors, and biocides. These applications are especially important in water treatment, agricultural formulations, and detergents.

Although diethyl phosphite is a valuable chemical intermediate, it must be handled with care. It is flammable and may react with oxidizing agents. Exposure to the vapor or liquid can cause irritation to the eyes, skin, and respiratory tract. Inhalation or ingestion in large amounts can be harmful. Therefore, its use in laboratories and industry is accompanied by safety protocols including the use of gloves, goggles, and fume hoods.

In conclusion, diethyl phosphite is a versatile and well-characterized compound in organophosphorus chemistry. Its unique reactivity, especially the nucleophilic and reducing nature of the P–H bond, underpins a wide array of applications ranging from organic synthesis and medicinal chemistry to industrial formulations and materials science. Its significance continues to grow as research explores new uses for phosphonate-containing compounds.

References

1960. Acceptor-donor concepts applied to extraction. Journal of Structural Chemistry.
DOI: 10.1007/bf00748856

2023. Nanocellulose from agro-waste: a comprehensive review of extraction methods and applications. Reviews in Environmental Science and Bio/Technology.
DOI: 10.1007/s11157-023-09643-6

2023. Flame-retardant epoxy resin: synergistic effect between aluminum diethylphosphinate and piperazine pyrophosphate. Iranian Polymer Journal.
DOI: 10.1007/s13726-023-01238-w