1-Fluoro-4-(trifluoromethylthio)benzene: FAQs & Lab Guide
1-Fluoro-4-(trifluoromethylthio)benzene: FAQs & Lab Guide
1-Fluoro-4-(trifluoromethylthio)benzene is a fluorinated aromatic building block featuring both a fluorine substituent and a trifluoromethylthio (SCF3) group on a para-substituted benzene ring, making it a versatile electrophilic intermediate for pharmaceutical, agrochemical, and materials science research.
- Chemical Name
- 1-Fluoro-4-(trifluoromethylthio)benzene
- CAS Number
- 456-66-6
- Molecular Formula
- C7H4F4S
- Molecular Weight
- 196.16 g/mol
- Key Functional Groups
- Aryl fluoride, trifluoromethylthio (SCF3)
- Aladdin SKU
- F695733
- Recommended Storage
- Cool, dry, well-ventilated area; away from moisture and incompatible oxidizing agents
Chemical Identity and Physical Properties
1-Fluoro-4-(trifluoromethylthio)benzene (CAS 456-66-6) is a para-disubstituted benzene derivative carrying a fluorine atom at position 1 and a trifluoromethylthio (–SCF3) group at position 4. Its molecular formula is C7H4F4S with a molecular weight of approximately 196.16 g/mol. The compound is typically encountered as a colorless to pale-yellow liquid at room temperature. The presence of four fluorine atoms—one directly on the ring and three on the sulfur-bound carbon—confers strong electron-withdrawing character and high metabolic stability to the molecule. The –SCF3 group is known to significantly increase lipophilicity (log P contribution ~+1.0–1.4 unit relative to –H), which is exploited in medicinal chemistry for tuning membrane permeability and bioavailability of drug candidates.
Note: Specific physical constants such as boiling point, density, and refractive index should be confirmed against the certificate of analysis (CoA) supplied with each lot from Aladdin Scientific (SKU F695733).
Applications in Synthetic and Medicinal Chemistry
1-Fluoro-4-(trifluoromethylthio)benzene serves as a key electrophilic aromatic building block in nucleophilic aromatic substitution (SNAr) reactions. The fluorine atom at the para position, activated by the electron-withdrawing –SCF3 group, is susceptible to displacement by a range of nucleophiles including amines, alkoxides, and thiolates under mild to moderate conditions. This reactivity makes the compound valuable for constructing diaryl ethers, diaryl amines, and thioether-linked biaryl scaffolds encountered in pharmaceutical and agrochemical research.
In drug discovery, the –SCF3 moiety is increasingly used as a bioisostere for –CF3, –OCF3, or –SF5 groups, offering a distinct combination of lipophilicity, electron withdrawal, and steric profile. Compounds bearing the –SCF3 pharmacophore have been investigated in the context of CNS-active agents, antibacterials, and crop-protection molecules. The compound also acts as a precursor in transition-metal-catalyzed cross-coupling reactions aimed at installing the SCF3 group onto more complex scaffolds.
Handling, Storage, and Safety Considerations
As with all organofluorine reagents, appropriate laboratory precautions must be observed when working with 1-Fluoro-4-(trifluoromethylthio)benzene. Personal protective equipment including chemical-resistant gloves, lab coat, and safety goggles should be worn at all times. The compound should be handled in a well-ventilated fume hood to avoid inhalation of vapors. Skin and eye contact must be avoided.
For storage, keep the material in a tightly sealed container in a cool, dry, well-ventilated location away from heat sources, open flames, and incompatible oxidizing agents. Moisture should be excluded to maintain reagent quality over time. Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for complete hazard classifications, first-aid measures, disposal procedures, and regulatory information before use.
Specific GHS hazard categories, flash point, and LD50 values should be verified against the official SDS for SKU F695733.
Ordering and Quality Assurance at Aladdin Scientific
1-Fluoro-4-(trifluoromethylthio)benzene is available from Aladdin Scientific under SKU F695733. Each lot is supplied with a Certificate of Analysis (CoA) documenting purity, appearance, and key analytical data such as GC purity, NMR confirmation, and moisture content where applicable. Researchers are encouraged to review the CoA prior to use to ensure the material meets the specifications required for their application.
For bulk quantities, custom packaging, or specific purity grades, please contact the Aladdin Scientific sales team directly. Orders may be placed through the Aladdin Scientific website, by email, or through authorized distributors. For questions about shipping conditions, temperature-controlled delivery, or regulatory documentation for import/export, please consult the customer service team.
Frequently Asked Questions Overview
The following FAQs address the most common technical and practical questions received from researchers working with 1-Fluoro-4-(trifluoromethylthio)benzene. Topics include reactivity, compatibility with common reaction conditions, recommended analytical methods for purity assessment, and guidance on solvent selection. If your question is not addressed here, please contact Aladdin Scientific technical support for personalized assistance.
Frequently asked questions
What makes the fluorine atom in 1-Fluoro-4-(trifluoromethylthio)benzene reactive toward nucleophilic aromatic substitution?
The –SCF3 group at the para position is a powerful electron-withdrawing substituent that stabilizes the Meisenheimer complex intermediate formed during SNAr reactions. This electronic activation lowers the energy barrier for nucleophilic attack at the ipso carbon bearing the fluorine, making displacement by amines, alkoxides, and thiolates feasible under relatively mild conditions. Fluorine is also the preferred leaving group in SNAr among the halogens due to its high electronegativity, which facilitates formation of the anionic intermediate.
Which solvents are recommended for reactions involving 1-Fluoro-4-(trifluoromethylthio)benzene?
Polar aprotic solvents such as DMF, DMSO, NMP, and acetonitrile are commonly used for SNAr reactions with this substrate because they stabilize the anionic Meisenheimer intermediate without protonating the nucleophile. For transition-metal-catalyzed reactions, THF, dioxane, or toluene may be suitable depending on catalyst and ligand requirements. Protic solvents can be used in some cases but may require adjustment of reaction temperature and base. Always verify solvent compatibility with the specific nucleophile and catalyst system employed.
How should I assess the purity of 1-Fluoro-4-(trifluoromethylthio)benzene before use in sensitive reactions?
Gas chromatography (GC) with a flame ionization detector (FID) is the standard method for purity assessment of this volatile liquid reagent and is typically reported on the Aladdin Scientific CoA for SKU F695733. Complementary characterization by 1H NMR and 19F NMR is highly recommended, as 19F NMR is particularly sensitive to fluorinated impurities that may not be resolved by GC alone. Cross-referencing your analytical results with the lot-specific CoA before use in asymmetric synthesis or pharmaceutical intermediate preparations is strongly advised.
Is 1-Fluoro-4-(trifluoromethylthio)benzene stable under aqueous basic conditions?
The –SCF3 group can be susceptible to hydrolysis under strongly basic or strongly acidic aqueous conditions, potentially releasing fluoride and other degradation products. Under mildly basic conditions typically used in SNAr reactions (e.g., K2CO3 in DMF at moderate temperatures), the compound generally performs well. However, prolonged exposure to aqueous base at elevated temperatures should be avoided. Reaction conditions should be optimized and monitored by TLC or GC to detect any decomposition.
What are the key differences between the –SCF3 and –OCF3 groups in drug design, and why choose this building block?
Both –SCF3 and –OCF3 are strongly electron-withdrawing groups that enhance metabolic stability and lipophilicity; however, –SCF3 generally confers greater lipophilicity than –OCF3 due to the larger, more polarizable sulfur atom. The –SCF3 group also has a distinct steric and electronic profile that can modulate binding affinity and selectivity in a target-specific manner. Choosing 1-Fluoro-4-(trifluoromethylthio)benzene allows medicinal chemists to introduce both an aryl fluoride handle (for further functionalization via SNAr) and an –SCF3 pharmacophore in a single building block, streamlining library synthesis.
References
- Muller, K.; Faeh, C.; Diederich, F. Fluorine in Pharmaceuticals: Looking Beyond Intuition. Science 2007, 317, 1881–1886. doi:10.1126/science.1131943
- Leroux, F. R.; Manteau, B.; Vors, J.-P.; Pazenok, S. Trifluoromethyl ethers—synthesis and properties of an unusual substituent. Beilstein J. Org. Chem. 2008, 4, 13. doi:10.3762/bjoc.4.13
- Wencel-Delord, J.; Glorius, F. C–H bond activation enables the rapid construction and late-stage diversification of functional molecules. Nature Chem. 2013, 5, 369–375. doi:10.1038/nchem.1607
- Aladdin Scientific. Product Page: 1-Fluoro-4-(trifluoromethylthio)benzene, SKU F695733. Aladdin Scientific, Shanghai.
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