Methyl trifluoroacetate
[CAS# 431-47-0]

Identification

• Classification: Chemical reagent >> Organic reagent >> Ester >> Methyl ester compound
• Name: Methyl trifluoroacetate
• Synonyms: methyl 2,2,2-trifluoroacetate
• Molecular Formula: C₃H₃F₃O₂
• Molecular Weight: 128.05
• CAS Registry Number: 431-47-0
• EC Number: 207-074-5
• SMILES: COC(=O)C(F)(F)F

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*, 1.273 g/mL (Expl.)
• Melting point: -78 ºC (Expl.)
• Boiling point: 40.2±3.0 ºC 760 mmHg (Calc.)^*, 43 - 43.5 ºC (Expl.)
• Flash point: -7.2 ºC (Calc.)^*, -7 ºC (Expl.)
• Solubility: water 8 g/L (Expl.)
• Index of refraction: 1.298 (Calc.)^*, 1.29 (Expl.)

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

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS07;GHS09 DangerGHS02
• Hazard Statements: H225-H314-H317-H318-H411
• Precautionary Statements: P210-P233-P240-P241-P242-P243-P260-P261-P264-P264+P265-P272-P273-P280-P301+P330+P331-P302+P352-P302+P361+P354-P303+P361+P353-P304+P340-P305+P354+P338-P316-P317-P321-P333+P317-P362+P364-P363-P370+P378-P391-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	2	H225
Skin corrosion	Skin Corr.	1B	H314
Serious eye damage	Eye Dam.	1	H318
Skin sensitization	Skin Sens.	1	H317
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - single exposure	STOT SE	2	H371

• Transport Information: UN 2924

Discovory and Applicatios

Methyl trifluoroacetate is a fluorinated ester with the molecular formula CF₃COOCH₃. It is the methyl ester of trifluoroacetic acid and was developed as part of the expansion of organofluorine chemistry in the mid-20th century. The trifluoromethyl group is strongly electron-withdrawing, which increases the electrophilicity of the carbonyl carbon and alters the chemical reactivity compared with non-fluorinated esters. Methyl trifluoroacetate is typically a colorless liquid with good solubility in organic solvents and is sensitive to hydrolysis under acidic or basic conditions.

The primary application of methyl trifluoroacetate is in organic synthesis as a reagent for introducing the trifluoroacetyl group into nucleophilic substrates such as amines, alcohols, and thiols. This reaction yields trifluoroacetamides, esters, and thioesters, which serve as valuable intermediates in the preparation of pharmaceuticals, agrochemicals, and specialty chemicals. The trifluoromethyl group modifies the electronic and steric properties of the resulting molecules, often enhancing chemical stability, lipophilicity, and metabolic resistance.

In pharmaceutical chemistry, methyl trifluoroacetate is used to synthesize trifluoromethylated derivatives of drug candidates. The trifluoroacetyl moiety improves pharmacokinetic properties such as absorption, distribution, and metabolic stability. It has been applied in the preparation of enzyme inhibitors, antiviral agents, and central nervous system therapeutics, where the trifluoromethyl group enhances potency and chemical robustness. Its ester functionality allows controlled reactions under mild conditions, facilitating selective functionalization without affecting other sensitive groups.

In agrochemical research, methyl trifluoroacetate is utilized to prepare fluorinated herbicides, fungicides, and insecticides. The trifluoromethyl group increases chemical and thermal stability, environmental persistence, and lipophilicity, improving the biological activity and efficacy of final products. The ester’s reactivity allows efficient introduction of trifluoroacetyl groups into precursor molecules, streamlining the synthesis of bioactive compounds.

In materials science, methyl trifluoroacetate has been applied in the synthesis of specialty polymers and fluorinated fine chemicals. The trifluoromethyl group enhances hydrophobicity, thermal stability, and chemical resistance of materials, while the ester functionality enables selective incorporation into monomers or polymer backbones. This contributes to improved performance in coatings, membranes, and other high-performance applications.

Analytical chemistry also benefits from methyl trifluoroacetate. It is used as a derivatization reagent for polar compounds in gas chromatography and mass spectrometry. Trifluoroacetyl derivatives formed with this ester are more volatile and thermally stable, facilitating better separation and detection of analytes such as amino acids, peptides, and other biologically relevant molecules.

The discovery and continued use of methyl trifluoroacetate highlight its importance as a versatile fluorinated reagent. Its combination of strong electrophilicity, chemical stability, and reactivity makes it a valuable intermediate in modern organic synthesis, supporting advances in pharmaceuticals, agrochemicals, materials science, and analytical chemistry. The compound demonstrates how fluorination can enhance the functional utility of simple ester molecules in research and industrial applications.

References

2023. Reaction mechanism of methyl trifluoroacetate (CH3TFA) with lithium polysulfides (Li2S6) in gas and solvent phase. Theoretical Chemistry Accounts, 142(10).
DOI: 10.1007/s00214-023-03039-z

2023. Economically viable co-production of methanol and sulfuric acid via direct methane oxidation. Communications Chemistry, 6(1).
DOI: 10.1038/s42004-023-01080-4

2012. Recent Developments on the Trifluoromethylation of (Hetero)Arenes. Chemistry � An Asian Journal, 7(7).
DOI: 10.1002/asia.201200211