Ethyl 4,4-difluoroacetoacetate
[CAS# 352-24-9]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Ethyl 4,4-difluoroacetoacetate
• Synonyms: Ethyl 4,4-difluoro-3-oxobutanoate
• Molecular Formula: C₆H₈F₂O₃
• Molecular Weight: 166.12
• CAS Registry Number: 352-24-9
• EC Number: 206-519-0
• SMILES: CCOC(=O)CC(=O)C(F)F

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.375, Calc.^*
• Boiling Point: 170.1±30.0 °C (760 mmHg), Calc.^*, 162 °C (Expl.)
• Flash Point: 55.7±19.4 °C, Calc.^*, 68 °C (Expl.)

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

Safety Data

• Hazard Symbols: GHS02;GHS07 Warning
• Risk Statements: H226-H315-H319
• Safety Statements: P210-P233-P240-P241-P242-P243-P264-P264+P265-P280-P302+P352-P303+P361+P353-P305+P351+P338-P321-P332+P317-P337+P317-P362+P364-P370+P378-P403+P235-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Flammable liquids	Flam. Liq.	3	H226
Eye irritation	Eye Irrit.	2A	H319
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Serious eye damage	Eye Dam.	1	H318
Skin sensitization	Skin Sens.	1	H317

Discovery and Applications

Ethyl 4,4-difluoroacetoacetate is an organic compound belonging to the class of β-diketones, with two fluorine atoms attached to the carbon atom in the 4-position of the acetoacetate structure. It is primarily used in organic synthesis due to its functional group reactivity, particularly its ability to undergo nucleophilic substitution and enolate chemistry.

The compound has found applications in the field of organic chemistry as a versatile intermediate for the synthesis of various fluorinated organic molecules. The presence of the difluoromethyl group imparts distinct chemical properties that make it useful in reactions where fluorine's electronegativity and unique electronic properties are advantageous. It can act as a key building block in the synthesis of fluorinated compounds, which are highly relevant in pharmaceutical, agrochemical, and material science industries.

One major application of ethyl 4,4-difluoroacetoacetate is in the synthesis of fluorine-containing heterocycles. The compound can undergo reactions such as the Michael addition and nucleophilic substitution, which are often employed in the design of bioactive molecules. By incorporating the fluorine atoms into the structure of these heterocycles, researchers can enhance the stability, bioavailability, and specific interaction properties of the resulting compounds.

Ethyl 4,4-difluoroacetoacetate is also used in the synthesis of fluorinated analogs of biologically active molecules, including those used in drug discovery. The introduction of fluorine atoms into organic molecules is known to affect the biological activity of these compounds, influencing their pharmacokinetic properties, such as absorption, distribution, metabolism, and excretion. This makes ethyl 4,4-difluoroacetoacetate an important tool in the design of pharmaceutical agents with improved efficacy or selectivity.

Additionally, the compound has been employed in the development of agrochemicals, where fluorine-containing intermediates play a significant role in creating compounds with increased potency or resistance to degradation. The incorporation of the difluoromethyl group enhances the chemical stability and biological activity of these agents, allowing them to be more effective in pest control or plant protection.

The utility of ethyl 4,4-difluoroacetoacetate in synthetic chemistry and its role in enhancing the properties of final products continue to make it a valuable reagent in organic synthesis. Its applications in pharmaceuticals and agrochemicals are well-documented, and it remains an important intermediate for the development of fluorine-containing compounds across multiple industries.

References

2017. Synthesis of fungicidally active succinate dehydrogenase inhibitors with novel difluoromethylated heterocyclic acid moieties. Monatshefte für Chemie - Chemical Monthly, 148(12).
DOI: 10.1007/s00706-017-2101-y

2020. Synthesis of pyrazole-4-carboxamides as potential fungicide candidates. Molecular Diversity, 25(3).
DOI: 10.1007/s11030-020-10127-w

2024. Design, Synthesis, Antifungal and Antibacterial Activities of Novel Difluoromethyl Pyrazole Derivatives. Russian Journal of General Chemistry, 94(4).
DOI: 10.1134/s1070363224040248