1,1-Difluoroacetone: Properties, Uses & Handling FAQs

1,1-Difluoroacetone is a gem-difluorinated ketone building block widely employed in organofluorine synthesis to introduce a difluoromethyl ketone motif into target molecules.

Chemical Name

1,1-Difluoroacetone

Molecular Formula

C₃H₄F₂O

Molecular Weight

94.06 g/mol

CAS Number

430-54-6

Functional Class

Gem-difluoro ketone (organofluorine reagent)

Key Application

Fluorinated building block in medicinal and synthetic chemistry

Storage Condition

Store sealed in a cool, dry, well-ventilated location away from ignition sources

What Is 1,1-Difluoroacetone and Why Is It Used in Research?

1,1-Difluoroacetone (CAS 430-54-6; MW 94.06 g/mol; formula C₃H₄F₂O) is the simplest gem-difluorinated methyl ketone. The two fluorine atoms are located on the carbon alpha to the carbonyl, creating a strongly electron-withdrawing environment that modulates both reactivity and the physicochemical properties of derivatives.

In synthetic and medicinal chemistry, the gem-CF₂ group is valued for its metabolic stability, increased lipophilicity relative to the corresponding hydroxymethyl analogue, and its ability to serve as a bioisostere of carbonyl or hydroxyl groups. As a low-molecular-weight, bifunctional building block, 1,1-Difluoroacetone enables the rapid incorporation of a difluoromethyl ketone fragment into complex molecules via condensation, aldol-type, or nucleophilic addition reactions.

Key Chemical Properties of 1,1-Difluoroacetone

The presence of two electronegative fluorine atoms on the methylene carbon adjacent to the ketone carbonyl confers several distinctive properties:

• Enhanced electrophilicity: The carbonyl carbon is more electrophilic than in unsubstituted acetone, making the compound more reactive toward nucleophiles.
• Hydration tendency: Like other gem-difluoro ketones, 1,1-Difluoroacetone exhibits a greater degree of hydrate formation in aqueous solution compared with non-fluorinated analogues.
• Acidity of alpha protons: The remaining methyl group retains enolizable protons, allowing base-mediated condensation chemistry.
• Volatility: The compound is a low-boiling liquid; the exact boiling point should be confirmed from the certificate of analysis supplied with the product.

These properties collectively make 1,1-Difluoroacetone a versatile electrophilic fluorine-containing synthon.

Typical Synthetic Applications

Researchers employ 1,1-Difluoroacetone in several reaction classes:

1. Fluorinated heterocycle synthesis: Condensation with nitrogen or sulfur dinucleophiles affords difluoromethyl-substituted five- and six-membered heterocycles relevant to drug discovery.
2. Aldol and Knoevenagel-type reactions: The activated methyl group can participate in condensations with aldehydes under basic catalysis to produce α,β-unsaturated gem-difluoro ketone intermediates.
3. Nucleophilic additions: Grignard reagents, organolithiums, and other hard nucleophiles add efficiently to the electrophilic carbonyl, delivering fluorinated tertiary alcohols.
4. Reductive amination: The ketone can be reductively aminated to incorporate a difluoromethyl-bearing amine motif.

These transformations make the compound particularly attractive in early-stage drug discovery and agrochemical research, where introduction of gem-CF₂ groups can favorably modulate ADMET properties.

Safe Handling, Storage, and Regulatory Considerations

Because 1,1-Difluoroacetone is a volatile, low-boiling organic compound, appropriate precautions are essential:

• Personal Protective Equipment (PPE): Use chemical-splash goggles, nitrile gloves, and a lab coat. Conduct all manipulations inside a fume hood.
• Inhalation risk: Vapors may cause respiratory irritation; ensure adequate ventilation at all times.
• Flammability: The compound is expected to be flammable given its low molecular weight and ketone functionality; keep away from open flames and hot surfaces.
• Storage: Store tightly sealed in a cool, dry, well-ventilated area, segregated from strong oxidizers and bases.
• Disposal: Follow local and institutional regulations for halogenated organic waste disposal.

Always consult the Safety Data Sheet (SDS) supplied by Aladdin Scientific before use. Specific GHS hazard classifications should be verified in the current SDS, as regulatory designations may vary by jurisdiction.

Ordering, Specification, and Quality Information

Aladdin Scientific offers 1,1-Difluoroacetone under SKU D303714. When ordering or evaluating the product, consider the following:

• Purity: Check the Certificate of Analysis (CoA) for lot-specific purity data determined by GC or NMR. Contact our technical support team if a particular purity grade is required for your application.
• Packaging: Available pack sizes are listed on the product page; select an appropriate quantity to minimise repeated freeze-thaw or open-close cycles that could affect quality.
• Documentation: SDS, CoA, and specification sheets are available for download from the Aladdin Scientific website or on request from customer service.
• Lead time and shipping: As a specialty fluorochemical, confirm stock availability and shipping conditions (cold-chain requirements if applicable) at time of order.

For bulk quantities, custom purity grades, or application-specific technical enquiries, please contact Aladdin Scientific customer support directly.

Frequently asked questions

What is the CAS number and molecular formula of 1,1-Difluoroacetone?

1,1-Difluoroacetone has CAS number 430-54-6, molecular formula C₃H₄F₂O, and a molecular weight of 94.06 g/mol. It belongs to the class of gem-difluorinated ketones.

How should 1,1-Difluoroacetone be stored to maintain its quality?

The compound should be stored tightly sealed in a cool, dry, and well-ventilated location, away from heat sources, open flames, and strong oxidizers. Consult the current SDS and CoA from Aladdin Scientific for lot-specific recommendations, including any cold-storage requirements.

What reactions can 1,1-Difluoroacetone participate in as a synthetic building block?

1,1-Difluoroacetone is a versatile electrophilic fluorine building block. It can undergo nucleophilic addition with Grignard reagents or organolithiums, base-mediated aldol or Knoevenagel condensations via its methyl group, reductive amination, and condensation with dinucleophiles to form fluorinated heterocycles. These reactions are exploited in drug discovery and agrochemical synthesis.

Is 1,1-Difluoroacetone safe to handle on the open bench?

No. Due to its volatility, potential flammability, and capacity to cause respiratory and skin irritation, 1,1-Difluoroacetone should always be handled inside a fume hood with appropriate PPE including gloves, goggles, and a lab coat. Always review the SDS before use.

Why is the gem-CF₂ group introduced by 1,1-Difluoroacetone useful in drug discovery?

The gem-difluoro (CF₂) motif is metabolically stable, can act as a bioisostere of carbonyl or hydroxyl groups, and modulates lipophilicity and membrane permeability of drug candidates. These features can improve pharmacokinetic profiles and binding selectivity, making fluorinated building blocks like 1,1-Difluoroacetone highly sought after in medicinal chemistry programs.

Where can I find the Certificate of Analysis and Safety Data Sheet for SKU D303714?

The Certificate of Analysis (CoA) and Safety Data Sheet (SDS) for 1,1-Difluoroacetone (SKU D303714) are available for download on the Aladdin Scientific product page or can be requested directly from our customer service team. Always use the lot-specific CoA to confirm purity and identity before use.

References

1. O'Hagan, D. Understanding organofluorine chemistry. An introduction to the C–F bond. Chemical Society Reviews, 2008, 37, 308–319. doi:10.1039/b711844a
2. Meanwell, N. A. Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design. Journal of Medicinal Chemistry, 2018, 61, 5822–5880. doi:10.1021/acs.jmedchem.7b01788
3. Gouverneur, V.; Seppelt, K. Introduction: Fluorine Chemistry. Chemical Reviews, 2015, 115, 563–565. doi:10.1021/cr500686b

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.