Triethyl phosphite
[CAS# 122-52-1]

Identification

• Classification: Organic raw materials >> Inorganic acid ester
• Name: Triethyl phosphite
• Synonyms: Phosphorous acid triethyl ester
• Molecular Formula: C₆H₁₅O₃P
• Molecular Weight: 166.16
• CAS Registry Number: 122-52-1
• EC Number: 204-552-5
• SMILES: CCOP(OCC)OCC

Properties

• Density: 0.969 g/mL (Expl.)
• Melting point: -112 °C (Expl.)
• Boiling point: 159.8±8.0 °C 760 mmHg (Calc.)^*, 156 °C (Expl.)
• Flash point: 54.1±18.7 °C (Calc.)^*, 54.4 °C (Expl.)
• Solubility: water: slightly soluble (Expl.)
• Refraction index: 1.413 (Expl.)

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

Safety Data

• Hazard Symbols: GHS02;GHS07 Warning
• Risk Statements: H226-H302-H315-H317-H319-H332-H335-H412
• Safety Statements: P210-P233-P240-P241-P242-P243-P261-P264-P264+P265-P270-P271-P272-P273-P280-P301+P317-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P333+P317-P337+P317-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	3	H226
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Skin sensitization	Skin Sens.	1	H317
Skin sensitization	Skin Sens.	1B	H317
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H312
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Reproductive toxicity	Repr.	2	H361
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H412
Specific target organ toxicity - single exposure	STOT SE	2	H371

• Transport Information: UN 2323

Discovery and Applications

Triethyl phosphite is an organophosphorus compound with the molecular formula C₆H₁₅PO₃. Structurally, it consists of a phosphorus atom bonded to three ethoxy groups (–OCH₂CH₃), forming a trialkyl phosphite ester. It is a colorless, flammable liquid with a mild, characteristic odor and is soluble in most organic solvents while having limited solubility in water.

Triethyl phosphite is widely used as a reagent in organic synthesis. Its nucleophilic phosphorus center allows it to react with alkyl halides, acyl halides, and other electrophiles. One of its primary applications is in the **Michaelis–Arbuzov reaction**, in which triethyl phosphite reacts with alkyl halides to produce diethyl phosphonates. These phosphonates are important intermediates in the synthesis of pharmaceuticals, agrochemicals, and other organophosphorus compounds.

Beyond the Michaelis–Arbuzov reaction, triethyl phosphite can be used in the preparation of phosphinates, phosphonates, and related derivatives through nucleophilic substitution or addition reactions. Its liquid form at room temperature, relatively low toxicity, and stability under standard laboratory conditions make it convenient for handling in both academic and industrial settings.

Triethyl phosphite is typically synthesized by reacting phosphorus trichloride with ethanol, substituting the chlorine atoms with ethoxy groups. The reaction requires careful control of temperature and moisture to avoid side reactions and to ensure high-purity product. Standard safety precautions must be observed, as the compound is flammable and reacts with strong oxidizing agents.

Overall, triethyl phosphite is a versatile organophosphorus reagent, notable for its nucleophilic reactivity and utility in forming phosphorus-containing intermediates. Its role in the Michaelis–Arbuzov reaction and other synthetic transformations makes it an essential reagent in organic and organophosphorus chemistry.

References

2018. Rhenium and technetium complexes of thioamide derivatives of pyridylhydrazine that bind to amyloid-β plaques. Journal of Biological Inorganic Chemistry, 23(6).
DOI: 10.1007/s00775-018-1590-4

2017. Synthesis of Lactones and Other Heterocycles. Topics in Current Chemistry, 375(2).
DOI: 10.1007/s41061-017-0108-9