1,1-Difluoro-2-propanone
[CAS# 431-05-0]

Identification

• Classification: Chemical reagent >> Organic reagent >> Fatty ketone (including enol)
• Name: 1,1-Difluoro-2-propanone
• Synonyms: 1,1-Difluoroacetone; 1,1-Difluoropropan-2-one
• Molecular Formula: C₃H₄F₂O
• Molecular Weight: 94.060
• CAS Registry Number: 431-05-0
• EC Number: 688-420-6
• SMILES: CC(=O)C(F)F

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*, 1.164 g/mL (Expl.)
• Boiling point: 45.3±25.0 ºC 760 mmHg (Calc.)^*, 46.1 - 47.1 ºC (Expl.)
• Flash point: 1.6±17.3 ºC (Calc.)^*
• Index of refraction: 1.302 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS02;GHS07 DangerGHS02;GHS02
• Hazard Statements: H225-H226-H315-H319-H335
• Precautionary Statements: P210-P233-P240-P241-P242-P243-P261-P264-P264+P265-P271-P280-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319
Flammable liquids	Flam. Liq.	3	H226
Skin irritation	Skin Irrit.	2	H315
Flammable liquids	Flam. Liq.	2	H225

Discovory and Applicatios

1,1-Difluoro-2-propanone is a small fluorinated ketone with the molecular formula CF₂CHCOCH₃. It belongs to the class of geminal difluoroketones, in which two fluorine atoms are attached to the same carbon atom adjacent to a carbonyl group. The introduction of the difluoromethyl group significantly alters the electronic properties of the molecule, increasing the electrophilicity of the carbonyl carbon and stabilizing adjacent intermediates. The compound is typically a colorless liquid under standard conditions and is reactive due to the combined effects of the carbonyl and difluoromethyl functionalities.

The discovery of 1,1-difluoro-2-propanone is linked to the mid-20th century development of organofluorine chemistry, when chemists sought to explore the influence of fluorine substitution on carbonyl compounds. Fluorinated ketones like this one were of particular interest due to their enhanced chemical stability, altered acidity of adjacent protons, and unique reactivity in nucleophilic and condensation reactions. The compound provides a versatile platform for introducing difluoromethyl groups into more complex organic molecules.

In synthetic chemistry, 1,1-difluoro-2-propanone is used as a building block for the preparation of fluorinated intermediates. Its carbonyl group allows for reactions such as nucleophilic addition, condensation, and reduction, while the difluoromethyl group stabilizes resulting products and influences reactivity. This makes the compound valuable for synthesizing difluoromethylated alcohols, amines, and heterocycles, which are important in medicinal chemistry and agrochemical applications.

In pharmaceutical research, derivatives of 1,1-difluoro-2-propanone are used to incorporate difluoromethyl groups into drug candidates. The difluoromethyl moiety can act as a bioisostere for hydroxyl or methyl groups, enhancing metabolic stability, lipophilicity, and overall pharmacokinetic properties. The ketone functionality allows selective modification and derivatization, making it useful for the preparation of enzyme inhibitors, antiviral agents, and other bioactive compounds.

In agrochemicals, 1,1-difluoro-2-propanone has been employed as an intermediate for the synthesis of herbicides, fungicides, and insecticides. The electron-withdrawing difluoromethyl group enhances chemical stability and biological activity, enabling the design of compounds with improved efficacy and environmental persistence.

The compound also finds application in materials science and specialty chemical synthesis. Fluorinated intermediates derived from 1,1-difluoro-2-propanone are used to introduce difluoromethyl groups into polymers, coatings, and other functional materials, where fluorination improves hydrophobicity, thermal stability, and chemical resistance.

The development and use of 1,1-difluoro-2-propanone highlight its role as a versatile fluorinated building block in modern chemistry. Its unique combination of a reactive carbonyl group and a stabilizing difluoromethyl substituent makes it an important tool in organic synthesis, pharmaceutical development, agrochemical production, and materials science. The compound exemplifies how selective fluorination can enhance reactivity, stability, and functional utility in small organic molecules.

References

2017. Characterization of two carbonyl reductases from Ogataea polymorpha NBRC 0799. Applied Microbiology and Biotechnology, 101(24).
DOI: 10.1007/s00253-017-8668-8

2007. Trimethylsilyl Trifluoromethanesulfonate as a Metal-Free, Homogeneous and Strong Lewis Acid Catalyst for Efficient One-Pot Synthesis of a-Aminonitriles and Their Fluorinated Analogues. Synlett, 2007(16).
DOI: 10.1055/s-2007-985594

2016. Synthesis of LpxC Inhibitor LP-058. Synfacts, 12(07).
DOI: 10.1055/s-0035-1562373