Ethyl 4,4,4-trifluoroacetoacetate
[CAS# 372-31-6]

Identification

• Classification: Chemical reagent >> Organic reagent >> Ester >> Ethyl ester compound
• Name: Ethyl 4,4,4-trifluoroacetoacetate
• Synonyms: Ethyl 3-oxo-4,4,4-trifluoroacetoacetate; Ethyl 4,4,4-trifluoro-3-oxobutanoate
• Molecular Formula: C₆H₇F₃O₃
• Molecular Weight: 184.11
• CAS Registry Number: 372-31-6
• EC Number: 206-750-7
• SMILES: CCOC(=O)CC(=O)C(F)(F)F

Properties

• Density: 1.259
• Melting point: -39 °C
• Boiling point: 131 °C (709 mmHg)
• Refractive index: 1.375-1.378
• Flash point: 28 °C
• Water solubility: 10 g/L (20 °C)

Safety Data

• Hazard Symbols: GHS02;GHS07 Warning
• Risk Statements: H226-H302-H315-H412
• Safety Statements: P210-P233-P240-P241-P242-P243-P264-P270-P273-P280-P301+P317-P302+P352-P303+P361+P353-P321-P330-P332+P317-P362+P364-P370+P378-P403+P235-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	3	H226
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Serious eye damage	Eye Dam.	1	H318
Flammable liquids	Flam. Liq.	2	H225

• Transport Information: UN 3272

Discovery and Applications

Ethyl 4,4,4-trifluoroacetoacetate is a fluorinated compound that has attracted significant interest in the fields of organic chemistry and medicinal chemistry due to its unique structural features and versatile applications. The discovery of this compound can be traced back to research efforts aimed at developing fluorinated analogs of acetoacetate, which are known for their enhanced chemical reactivity and biological activity. The introduction of trifluoromethyl groups into organic molecules often imparts distinctive properties that can be harnessed for various synthetic applications.

The synthesis of ethyl 4,4,4-trifluoroacetoacetate typically involves the fluorination of acetoacetate derivatives or the use of fluorinated precursors. One common synthetic route includes the reaction of ethyl acetoacetate with a suitable fluorinating agent, which results in the formation of the trifluoroacetic moiety at the 4-position. This synthetic approach allows for the efficient production of the compound, facilitating further exploration of its reactivity and potential applications.

In medicinal chemistry, ethyl 4,4,4-trifluoroacetoacetate has been studied for its potential as a building block in the synthesis of biologically active compounds. The presence of the trifluoromethyl group enhances the lipophilicity and metabolic stability of the derivatives, making them attractive candidates for drug development. Research has indicated that derivatives of ethyl 4,4,4-trifluoroacetoacetate exhibit significant activity against various biological targets, including enzymes and receptors, suggesting potential therapeutic applications.

Furthermore, the compound has found utility in the synthesis of fluorinated pharmaceuticals. The incorporation of trifluoromethyl groups in drug candidates has been shown to improve their pharmacokinetic properties, making them more effective and selective in targeting specific diseases. Ethyl 4,4,4-trifluoroacetoacetate serves as a valuable intermediate in the synthesis of these advanced materials, highlighting its importance in modern drug discovery.

In addition to its applications in medicinal chemistry, ethyl 4,4,4-trifluoroacetoacetate is utilized in agrochemical research. Its unique chemical properties make it suitable for developing new herbicides and pesticides that can effectively target specific plant pathways while minimizing adverse effects on non-target species. The fluorinated nature of the compound often enhances its efficacy and selectivity, making it a promising candidate for further exploration in agricultural chemistry.

Overall, ethyl 4,4,4-trifluoroacetoacetate represents a significant advancement in the realm of fluorinated compounds, with implications in both pharmaceuticals and agrochemicals. Its discovery has paved the way for novel synthetic pathways and the development of effective therapeutic agents, underscoring the importance of fluorinated compounds in contemporary chemical research.

References

2024. Influence of the sulfonyl group on the biological activity of 2-sulfonarylhydrazinylidene 1,3-dicarbonyl compounds. Russian Chemical Bulletin, 73(6).
DOI: 10.1007/s11172-024-4294-7

2023. Cyclization of ethyl 4,4,4-trifluoroacetoacetate and cycloheptanone with dinucleophiles in the design of new alkaloid-like structures. Russian Chemical Bulletin, 72(12).
DOI: 10.1007/s11172-023-4098-1

2023. Multicomponent Cyclization of Ethyl Trifluoroacetoacetate with Acetaldehyde and 1,3-Diamines to Hetero-Fused Pyridines. Russian Journal of Organic Chemistry, 59(12).
DOI: 10.1134/s1070428023120126