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3-(4-fluoro-3-hydroxyphenyl)benzaldehyde (CAS No. 1261978-62-4): A Versatile Aryl Aldehyde with Emerging Biochemical Applications

3-(4-fluoro-3-hydroxyphenyl)benzaldehyde (CAS No. 1261978-62-4), an aryl aldehyde derivative featuring a fluorinated hydroxylated phenyl group conjugated to a benzaldehyde core, has recently garnered significant attention in chemical biology and drug discovery. This compound, characterized by its molecular formula C₁₀H₇FO₂ and molecular weight of 188.17 g/mol, exhibits unique electronic properties due to the electron-withdrawing fluorine atom at the para position and the electron-donating hydroxyl group at the meta position on the aromatic ring. These substituent interactions create a polarizable framework that facilitates diverse chemical reactivity patterns, making it an ideal candidate for exploring structure-property relationships in medicinal chemistry.

The synthesis of 3-(4-fluoro-3-hydroxyphenyl)benzaldehyde has evolved significantly with recent advancements in green chemistry methodologies. Traditional Friedel-Crafts acylation approaches have been supplanted by more efficient protocols involving palladium-catalyzed cross-coupling reactions under microwave-assisted conditions. A notable study published in the Journal of Organic Chemistry (DOI: 10.1021/acs.joc.3c00547) demonstrated a solvent-free synthesis route using solid-supported catalysts, achieving >95% yield while minimizing environmental footprint. The compound's stability under various reaction conditions has also been systematically evaluated, revealing its compatibility with both acidic and basic media when protected as an acetal derivative.

In biochemical studies, this fluorinated phenolic aldehyde exhibits remarkable antioxidant activity through dual mechanisms: direct radical scavenging via its phenolic hydroxyl group and redox cycling mediated by the aldehydic carbonyl moiety. Recent investigations by Kim et al. (Nature Communications, 2023) identified its ability to inhibit lipid peroxidation in neuronal cell cultures at submicromolar concentrations, suggesting potential applications in neurodegenerative disease research. The fluorine substitution enhances metabolic stability compared to non-fluorinated analogs, as evidenced by prolonged half-life measurements in liver microsome assays reported in Chemical Biology & Drug Design (Volume 99).

Clinical relevance is emerging from studies exploring its anti-inflammatory properties through modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. A collaborative research effort between MIT and Pfizer (published in Bioorganic & Medicinal Chemistry Letters, 2023) revealed that this compound selectively inhibits IKKβ phosphorylation without affecting other kinases, demonstrating therapeutic potential for autoimmune disorders such as rheumatoid arthritis and multiple sclerosis. The meta position of the hydroxyl group relative to fluorine creates a unique steric environment that prevents off-target effects observed in structurally similar compounds.

In oncology research, this compound has shown selective cytotoxicity against triple-negative breast cancer cells (MDA-MB-231 line) through induction of endoplasmic reticulum stress as described in Cancer Research (January 2024). The fluorine substituent enhances cellular uptake by interacting with specific membrane transporters while the benzaldehyde group forms Michael adducts with glutathione under intracellular conditions, triggering apoptosis via caspase-dependent pathways without significant toxicity to normal fibroblasts.

Structural studies using X-ray crystallography have elucidated its solid-state packing arrangements where π-stacking interactions between benzene rings are modulated by hydrogen bonding networks involving the hydroxyl group and carbonyl oxygen atoms (Acta Crystallographica Section C, 2023). This structural insight is critical for optimizing formulation strategies when developing drug delivery systems for targeted therapies.

The compound's photochemical properties have also been explored in recent solar-driven synthesis applications. Researchers at ETH Zurich demonstrated its utility as a photocatalyst for visible-light mediated C-H activation reactions using ruthenium-based sensitizers (Chemical Science, March 2024). The fluorine atom's electron-withdrawing effect enhances excited-state lifetimes while the aldehydic functionality serves as a reactive handle for subsequent functionalization steps.

In enzyme inhibition studies published in ACS Catalysis (July 2023), this compound was found to reversibly inhibit monoamine oxidase B (MAO-B) with an IC₅₀ value of 58 nM through non-covalent binding interactions involving both aromatic rings and hydrogen bonding networks formed with active site residues Tyr58 and Phe59. This selectivity profile distinguishes it from currently approved MAO inhibitors that often cause unwanted side effects through off-target binding.

Safety assessments conducted according to OECD guidelines indicate low acute toxicity profiles when administered orally or intraperitoneally in murine models (LD₅₀>5 g/kg). Dermatotoxicity studies revealed mild irritation potential only at concentrations exceeding therapeutic relevance (>5%), which aligns with standard safety profiles observed among phenolic aldehydes when properly formulated.

Ongoing research focuses on optimizing prodrug strategies where this aryl aldehyde scaffold is conjugated with polyethylene glycol moieties to improve solubility while maintaining pharmacological activity. Preliminary data from phase I preclinical trials suggest that these conjugates could enable targeted delivery via nanoparticle encapsulation techniques without compromising bioactivity upon cellular internalization.

The unique combination of structural features - including the fluorinated meta-hydroxyphenyl ring system and reactive carbonyl group - positions this compound as a promising lead molecule for developing multi-target therapeutics addressing complex pathologies such as neuroinflammation-associated disorders or treatment-resistant cancers. Its inherent stability under physiological conditions coupled with tunable reactivity makes it particularly amenable to combinatorial chemistry approaches aimed at generating novel bioactive derivatives.

• 1261917-96-7(2-fluoro-5-(3-hydroxyphenyl)phenol)
• 103438-85-3(4-Fluoro-3-hydroxybenzaldehyde)
• 405-05-0(3-Fluoro-4-hydroxybenzaldehyde)
• 544474-55-7(3-(2-Chloro-5-(trifluoromethyl)phenyl)benzaldehyde)
• 716344-20-6([1,1'-Biphenyl]-4-carboxaldehyde,3'-fluoro-4'-methoxy-)
• 1214367-64-2(2-fluoro-5-(4-fluorophenyl)phenol)
• 1203988-32-2(4-(3-fluoro-4-hydroxyphenyl)benzaldehyde)
• 1214328-95-6(2-fluoro-5-phenylphenol)
• 1261917-98-9(2-(4-fluoro-3-hydroxyphenyl)benzaldehyde)
• 1261963-47-6(2-fluoro-5-(3-methylphenyl)phenol)