2,2,2-Trifluoroethyl formate
[CAS# 32042-38-9]

Identification

• Classification: Organic raw materials >> Organic fluorine compound
• Name: 2,2,2-Trifluoroethyl formate
• Synonyms: TFEF
• Molecular Formula: C₃H₃F₃O₂
• Molecular Weight: 128.05
• CAS Registry Number: 32042-38-9
• EC Number: 628-307-0
• SMILES: C(C(F)(F)F)OC=O

Properties

• Density: 1.3±0.1 g/cm³, Calc.^*, 1.317 g/mL (Expl.)
• Index of Refraction: 1.3, Calc.^*
• Boiling Point: 33.7±40.0 ºC (760 mmHg), Calc.^*, 59-60 ºC (Expl.)
• Flash Point: -17.7±19.6 ºC, Calc.^*, 7 ºC (Expl.)

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

Safety Data

• Hazard Symbols: GHS02;GHS07;GHS08 Danger
• Hazard Statements: H225-H302-H315-H319-H335
• Precautionary Statements: P210-P233-P240-P241-P242-P243-P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Flammable liquids	Flam. Liq.	2	H225
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315

• Transport Information: UN 1993

Discovory and Applicatios

2,2,2-Trifluoroethyl formate is an organic compound belonging to the class of formate esters. Its molecular formula is C₃H₃F₃O₂, and it exists as a colorless liquid with a characteristic odor. The compound features a trifluoroethyl (-CF₃CH₂) group attached to a formyl (-HCOO) functional group, and the presence of fluorine atoms significantly alters its chemical and physical properties compared to non-fluorinated analogs.

Fluorinated organic compounds have been studied extensively since the mid-20th century due to their unique reactivity and applications in various fields, including pharmaceuticals, agrochemicals, and materials science. 2,2,2-Trifluoroethyl formate was synthesized as part of research into fluorinated esters for use as synthetic intermediates. One of the common synthetic methods involves the reaction of trifluoroethanol (CF₃CH₂OH) with formic acid (HCOOH) or its derivatives, typically in the presence of an acid catalyst. Alternatively, the compound can be obtained through transesterification reactions, where a formate ester reacts with 2,2,2-trifluoroethanol under suitable conditions.

The electron-withdrawing effect of fluorine influences the ester’s stability, reactivity, and solubility. The compound exhibits moderate volatility, making it suitable for reactions requiring controlled evaporation. Hydrolysis of 2,2,2-trifluoroethyl formate can occur under both acidic and basic conditions, yielding trifluoroethanol and formic acid. This reactivity is relevant in organic transformations where selective deprotection or functional group modification is required. Additionally, it can participate in esterification and transesterification reactions, enabling its use as an intermediate in complex synthesis pathways.

2,2,2-Trifluoroethyl formate is used as a reagent in organic synthesis, particularly in the introduction of trifluoroethyl (-CF₃CH₂) groups into target molecules. This modification is valuable in medicinal chemistry, where fluorinated compounds often exhibit enhanced metabolic stability, bioavailability, and receptor-binding affinity. The trifluoroethyl moiety contributes to altering lipophilicity, which can be beneficial in drug design.

The compound is also used in the synthesis of fluorinated agrochemicals, where the incorporation of fluorine atoms improves the efficacy and persistence of active ingredients. Additionally, fluorinated esters such as 2,2,2-trifluoroethyl formate serve as precursors for the development of advanced materials, including specialty polymers and coatings.

In industrial settings, 2,2,2-trifluoroethyl formate finds applications in fine chemical production and specialized solvent systems. Its volatility and chemical behavior make it suitable for processes requiring selective ester hydrolysis or controlled decomposition. Researchers have explored its use in catalyst development and reaction optimization, where fluorinated esters provide unique advantages in selectivity and efficiency.

The compound’s role in fluoroorganic chemistry has been expanding as new methodologies are developed for fluorine incorporation in pharmaceuticals and functional materials. Its compatibility with a range of chemical reactions, including nucleophilic substitution and reduction, supports its continued use in synthetic organic chemistry.

Like other formate esters, 2,2,2-trifluoroethyl formate requires careful handling to prevent hydrolysis and degradation. Proper storage conditions include keeping it in tightly sealed containers away from moisture and strong acids or bases. Although its toxicity profile is not extensively documented, exposure should be minimized by using appropriate personal protective equipment (PPE), including gloves and safety goggles.

The compound should be handled in well-ventilated areas, as its vapors may be irritating to the respiratory system. In case of accidental exposure, immediate measures such as flushing the affected area with water and seeking medical attention are recommended.

2,2,2-Trifluoroethyl formate is a valuable compound in synthetic chemistry, offering applications in pharmaceuticals, agrochemicals, and material sciences. Its distinctive properties, influenced by the presence of fluorine, contribute to its utility as an intermediate in organic synthesis. Continued research into fluorinated esters and their reactivity ensures its ongoing relevance in modern chemical applications.

References

2017. N-Heterocyclic Carbene Catalyzed Transformylation. Synthesis, 49(17).
DOI: 10.1055/s-0036-1588449

2011. Chirped Pulse Fourier Transform Microwave Study of 2,2,2-Trifluoroethyl Formate. The journal of physical chemistry. A, 115(32).
DOI: 10.1021/jp2047129