4-Fluoroindolin-2-one: Properties, Uses & Lab Guidelines

4-Fluoroindolin-2-one is a fluorine-substituted oxindole heterocycle that serves as a versatile synthetic building block in medicinal chemistry, enabling the construction of bioactive scaffolds through diverse functionalization reactions.

IUPAC Name

4-Fluoroindolin-2-one

Molecular Formula

C₈H₆FNO

Molecular Weight

151.14 g/mol

Core Scaffold

Oxindole (indolin-2-one) with 4-position fluorine substitution

Primary Application

Synthetic intermediate and building block in medicinal and heterocyclic chemistry

Recommended Storage

Cool, dry, well-ventilated area; sealed container away from light and moisture

SKU

F190779

Chemical Identity and Structure

4-Fluoroindolin-2-one belongs to the oxindole class of bicyclic heterocycles, consisting of a benzene ring fused with a five-membered lactam ring. The defining structural feature is a fluorine atom at the 4-position of the benzene ring, which is ortho to the nitrogen-containing lactam ring junction. This fluorine substitution modifies the electronic distribution across the aromatic system, increasing the electrophilicity of certain ring positions and altering the acidity of the lactam NH proton relative to the parent indolin-2-one.

The molecular formula is C₈H₆FNO with a molecular weight of approximately 151.14 g/mol. The compound contains a reactive lactam carbonyl group and an NH group, both of which serve as handles for further synthetic elaboration. The fluorine atom, being strongly electronegative, participates in hydrogen-bonding interactions with biological targets and is known in medicinal chemistry to improve metabolic stability and membrane permeability of drug candidates when introduced onto aromatic rings.

Research and Synthetic Applications

4-Fluoroindolin-2-one is primarily employed as a building block in the synthesis of pharmacologically relevant molecules. The oxindole scaffold is a privileged structure found in numerous natural products and approved pharmaceuticals, including kinase inhibitors and receptor modulators. Introduction of the 4-fluoro substituent is strategically used to modulate electronic properties, binding affinity, and physicochemical parameters of target molecules.

Key synthetic applications include: (1) N-alkylation and N-acylation at the lactam nitrogen to produce N-substituted fluorooxindoles for structure–activity relationship (SAR) studies; (2) C-3 functionalization, such as aldol condensation, Knoevenagel reactions, and nucleophilic additions, generating 3-substituted derivatives with potential biological activity; (3) Nucleophilic aromatic substitution (SNAr) exploiting the fluorine atom at C-4 as a leaving group when the ring is sufficiently activated, enabling the introduction of diverse nucleophiles; and (4) use as an intermediate in the preparation of spirooxindoles and fused heterocyclic systems relevant to anticancer and CNS drug discovery programs.

Safe Handling, Storage, and Disposal

Personal Protective Equipment (PPE): When handling 4-Fluoroindolin-2-one, wear appropriate PPE including nitrile gloves, a laboratory coat, and safety glasses or goggles. Work in a well-ventilated fume hood to minimize inhalation of dust or vapors. Avoid contact with skin, eyes, and mucous membranes.

Storage: Store the compound in a tightly sealed container in a cool, dry, and well-ventilated area, protected from light and moisture. Segregate from strong oxidizing agents, strong acids, and strong bases. Check the product's Safety Data Sheet (SDS) for specific hazard classifications and GHS pictograms prior to use. Typical short-term bench stability is acceptable under ambient conditions, but long-term storage under inert atmosphere at reduced temperature is recommended to prevent degradation.

Disposal: Dispose of waste material in accordance with local, national, and institutional regulations governing fluorine-containing organic compounds. Do not pour down the drain. Collect in appropriately labeled waste containers and arrange for collection by a licensed chemical waste contractor. Always consult the current SDS for the most up-to-date hazard and disposal information.

Quality, Purity, and Analytical Characterization

For research-grade applications, 4-Fluoroindolin-2-one should meet defined purity specifications. Aladdin Scientific's F190779 is supplied as a research-grade reagent; consult the product certificate of analysis (CoA) for the specific purity value (typically ≥95% by HPLC or GC) applicable to your lot.

Standard analytical techniques used to confirm identity and purity include:

• ¹H and ¹³C NMR spectroscopy: Key diagnostic signals include the lactam NH, aromatic protons, the C-3 methylene protons (appearing as a singlet near δ 3.5 ppm in ¹H NMR), and ¹⁹F NMR resonance confirming fluorine substitution.
• HPLC or GC analysis: Used to quantify purity and detect trace impurities or synthetic precursors.
• Mass spectrometry (MS): Confirms the molecular ion at m/z 151 consistent with the molecular formula C₈H₆FNO.
• Melting point determination: A sharp melting point consistent with literature values serves as an additional purity indicator.

Always request and review the CoA before use, especially for critical synthetic steps where impurities could affect reaction outcomes or downstream biological assays.

Frequently asked questions

What is the role of the fluorine substituent in 4-Fluoroindolin-2-one?

The fluorine atom at the 4-position modifies the electronic properties of the oxindole ring system, increasing electrophilicity at certain positions and altering the NH acidity. In medicinal chemistry contexts, fluorine substitution on aromatic rings is widely used to improve metabolic stability, enhance membrane permeability, and modulate binding affinity of derived drug candidates.

Can the fluorine atom in 4-Fluoroindolin-2-one be used as a leaving group in nucleophilic aromatic substitution?

Yes, under appropriate activation conditions the fluorine atom at C-4 can act as a leaving group in nucleophilic aromatic substitution (SNAr) reactions. Electron-withdrawing groups elsewhere on the ring or additional activation strategies are typically required to render the aromatic carbon sufficiently electrophilic for displacement. Reaction conditions should be optimized on a case-by-case basis.

How should 4-Fluoroindolin-2-one be stored to maintain its integrity?

Store 4-Fluoroindolin-2-one in a tightly sealed container in a cool, dry, and well-ventilated area, protected from light and moisture. For long-term storage, an inert atmosphere (nitrogen or argon) at reduced temperature is recommended. Always reseal the container promptly after use and consult the SDS for specific storage requirements for your lot.

What analytical methods confirm the identity and purity of 4-Fluoroindolin-2-one?

Identity and purity can be confirmed by a combination of ¹H, ¹³C, and ¹⁹F NMR spectroscopy, HPLC or GC purity analysis, mass spectrometry (molecular ion at m/z 151), and melting point determination. The certificate of analysis (CoA) provided with each lot from Aladdin Scientific contains lot-specific analytical data.

Is 4-Fluoroindolin-2-one suitable for use as a scaffold in drug discovery programs?

Yes, the oxindole scaffold is a privileged structure in medicinal chemistry, present in multiple approved drugs and biologically active natural products. The 4-fluoro substitution adds an additional handle for electronic tuning and SNAr chemistry, making 4-Fluoroindolin-2-one a useful starting point for the design of kinase inhibitors, receptor modulators, and other pharmacological targets.

References

1. Bhatt, M. V.; Periasamy, M. Oxindole in organic synthesis. Chemical Society Reviews, general reference on oxindole chemistry.
2. Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in medicinal chemistry. Chemical Society Reviews, 2008.
3. Aladdin Scientific product page for 4-Fluoroindolin-2-one, SKU F190779. Certificate of Analysis and Safety Data Sheet.

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