4-Ethoxy-6-fluorocoumarin , CAS No.527751-30-0

CAS: 527751-30-0 Cat. No.: E1005845 Formula: C₁₁H₉FO₃ Molecular Weight: 208.19 PubChem CID: 688959

Storage

Room temperature

Specifications

Storage

Room temperature

Names and Identifiers

• Canonical Smiles: CCOC1=CC(=O)OC2=C1C=C(C=C2)F
• IUPAC Name: 4-ethoxy-6-fluorochromen-2-one
• InChIKey: ZBDYDCPYWZBECM-UHFFFAOYSA-N
• INCHI: 1S/C11H9FO3/c1-2-14-10-6-11(13)15-9-4-3-7(12)5-8(9)10/h3-6H,2H2,1H3
• Isomeric SMILES: CCOC1=CC(=O)OC2=C1C=C(C=C2)F
• PubChem CID: 688959
• Molecular Weight: 208.19

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Phenylpropanoids and polyketides
    • Class Coumarins and derivatives

• Kingdom: Organic compounds
• Superclass: Phenylpropanoids and polyketides
• Class: Coumarins and derivatives
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Coumarins and derivatives
• Alternative Parents: 1-benzopyrans Pyranones and derivatives Alkyl aryl ethers Benzenoids Aryl fluorides Vinylogous esters Heteroaromatic compounds Lactones Oxacyclic compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Coumarin - Benzopyran - 1-benzopyran - Alkyl aryl ether - Pyranone - Benzenoid - Pyran - Aryl fluoride - Aryl halide - Vinylogous ester - Heteroaromatic compound - Lactone - Organoheterocyclic compound - Oxacycle - Ether - Hydrocarbon derivative - Organohalogen compound - Organic oxide - Organic oxygen compound - Organofluoride - Organooxygen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as coumarins and derivatives. These are polycyclic aromatic compounds containing a 1-benzopyran moiety with a ketone group at the C2 carbon atom (1-benzopyran-2-one).
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Chemical and Physical Properties

• Molecular Weight: 208.180 g/mol
• XLogP3: 2.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 208.054 Da
• Monoisotopic Mass: 208.054 Da
• Topological Polar Surface Area: 35.500 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 288.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No manufacturer-validated application protocols are provided for this item in the Product Data.

General research guidance (non-specific):

• Preparation of stock solutions: Dissolve the compound in anhydrous DMSO to 10–50 mM. Vortex and, if needed, sonicate gently. Filter through a 0.22 µm PTFE syringe filter for particulate removal if required by your assay.
• Fluorescence measurements (if applicable): Prepare serial dilutions in spectroscopic-grade solvents. Record excitation/emission spectra to locate λmax for your derivative; coumarin maxima vary with substitution and solvent polarity. Avoid concentrations that induce inner-filter effects (typically <10 µM for absorbance <0.1 AU at λex).
• Reaction setup (SNAr): Charge dry vessel with substrate, nucleophile/base, and dry DMF/DMSO. Heat (80–130 °C) under N2 with stirring; monitor by LC/MS. Quench into water, extract with EtOAc, wash, dry, and purify by silica chromatography.

These are starting points only. Optimize for your specific research application.

Biological Roles

Item-specific biological data are not provided. The following information reflects general roles of coumarin scaffolds in biochemistry (non-clinical, for research context only):

• Natural occurrence: The coumarin core is found in numerous plant metabolites, where it can participate in UV absorption and defense chemistry.
• Fluorescence in biological assays: Coumarin derivatives are widely used as small-molecule fluorophores and solvatochromic probes to report on local polarity, viscosity, or microenvironment changes in proteins, membranes, and nucleic acids. Substitution patterns (e.g., at C-4 and C-7) strongly influence emission maxima and quantum yields; no item-specific photophysics are provided here.
• Enzyme-responsive probes: Coumarin ethers and esters are common masked reporters that release a fluorescent phenol or phenolate upon enzymatic cleavage (e.g., esterases, hydrolases). For this compound, the 4-ethoxy group is not a typical enzyme-labile handle but can be transformed synthetically to generate pro-fluorophores.
• Tagging/derivatization: The 6-fluoro substituent enables SNAr to install amines/thiols that can target biomolecules or introduce reactive handles (azides, alkynes) for bioorthogonal chemistry, creating coumarin-based reporters.

Note: No medical, diagnostic, or therapeutic use is implied. This product is for research use only, and any biological applications should be validated by the user under appropriate biosafety and ethical guidelines.

Buffer Applications

This compound is not a buffering agent and does not define a specific pH range. Therefore, there are no standard buffer recipes associated with 4-ethoxy-6-fluorocoumarin.

Practical notes for research contexts where aqueous systems are used:

• Solubilization: Prepare concentrated DMSO or DMF stocks and dilute into the target buffer (e.g., PBS, HEPES) to a final organic cosolvent content ≤1–2% v/v to minimize perturbation of biological systems.
• Detergency: If higher apparent solubility is required, small amounts of non-ionic surfactants (e.g., 0.01–0.05% Tween-20) or carrier proteins (e.g., BSA) may mitigate adsorption losses; validate for your assay.
• pH effects: Coumarin fluorescence can be pH-sensitive if a phenolic form is generated. This specific item bears a 4-ethoxy ether and thus lacks a readily ionizable phenol; however, synthetic conversion to a 4-hydroxy analog would introduce pH-dependent behavior (general literature note).

For electrophoresis or chromatography buffers, the compound more commonly serves as a small-molecule analyte/standard or probe rather than a buffer constituent.

Green Alternatives

Greener strategy considerations (general; non-spec to this item):

• Solvent choices:

  • Prefer EtOAc, 2-MeTHF, Me-THF, or dimethyl carbonate over chlorinated solvents where solubility and reactivity permit.
  • For polar aprotic needs, evaluate propylene carbonate or Cyrene (dihydrolevoglucosenone) as partial replacements for DMF/DMSO in SNAr or substitution chemistry; note viscosity and basicity differences.

• Energy and process:

  • Use microwave-assisted SNAr to reduce reaction times and energy consumption versus prolonged thermal heating (monitor for pressure buildup and lactone stability).
  • Apply flow chemistry for photochemical steps involving coumarins to improve photon efficiency and safety.

• Reagent selection:

  • When de-ethylating at C-4, consider HCl/EtOH or H2SO4/MeOH in controlled, catalytic quantities rather than stoichiometric halogenating agents; or explore Lewis acid–assisted methods that minimize corrosive waste.
  • Favor organocatalytic or base-mediated routes for nucleophile installation at C-6 over metal-catalyzed couplings when feasible.

Trade-offs (typical):

• Greener solvents may lower solubility, requiring higher temperature or longer times.
• Alternative dipolar aprotics (e.g., Cyrene, propylene carbonate) can complicate workup due to high boiling points; plan extractive or antisolvent crystallizations accordingly.

Summary table (general):

• CH2Cl2 → EtOAc/2-MeTHF: Reduced halogenated waste; may require more volume.
• DMF → Cyrene/propylene carbonate: Better EHS profile; higher viscosity and sometimes slower kinetics.

Pharmaceutical Uses

No pharmacopeial grade, excipient role, or clinical application is specified for this item; refer to CoA/Spec Sheet for any regulatory status.

General, non-clinical considerations for the scaffold in pharmaceutical research:

• Discovery chemistry: Substituted coumarins are used as fragments or privileged scaffolds in medicinal chemistry campaigns to explore structure–activity relationships due to their planarity and capacity for π–π interactions. The 6-fluoro group permits vector diversification via SNAr, enabling rapid analog generation.
• Analytical markers: Coumarin chromophores can facilitate LC/UV tracking in purification and stability studies, and may serve as fluorescent tags in preclinical assay development.
• Formulation studies (research-only): If used as a fluorescent tracer in model formulations, DMSO or PEG-based cosolvents can assist dissolution. Solid dispersions with PVP/VA or HPMC-AS are potential research strategies to modulate apparent solubility; these uses are exploratory and not for human administration.

Compliance note: This product is supplied strictly for research use only. It is not an API, not a GMP material, and is not intended for diagnostic, therapeutic, or human/animal consumption.

Physical Properties

Item-specific specs: Not specified for this item; refer to CoA/Spec Sheet.

Literature/estimated (general guidance; non-spec):

• Phase/appearance: Substituted coumarins of similar substitution are typically crystalline solids; specific appearance for this lot is not provided.
• Melting point: Not reported for this exact compound in the Product Data; related 4-alkoxy/halo-coumarins often melt in the ~80–180 °C range (literature, varies with substitution and purity).
• Boiling point: Not commonly reported due to thermal sensitivity of coumarin lactones; many decompose before boiling at 1 atm.
• Density: Not specified.
• Solubility profile (typical for coumarins; literature):
  • Good solubility in polar aprotic organics (DMF, DMSO, NMP), chlorinated solvents (DCM, CHCl3), moderately in esters (EtOAc) and ketones (acetone, MEK), limited in alkanes/hexanes; low aqueous solubility at neutral pH.
• Acid/base properties: The lactone is neutral; 4-ethoxy is an ether; no strongly ionizable groups. Hydrolysis generates the corresponding o-hydroxycinnamate under strong base/acid (literature).
• LogP/logS: Not specified for this exact compound; coumarins commonly show moderate lipophilicity (logP ~1.5–3, literature, substitution-dependent).
• Spectroscopic notes (general for coumarins): Strong UV absorption due to the conjugated lactone; fluorescence is common for coumarin scaffolds, with wavelengths strongly dependent on substitution and solvent polarity (no item-specific λmax provided).

Always verify working properties (solubility, phase behavior) empirically with the received lot.

Quality & Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on quality considerations for this compound class (general, not product-specific):

• Purity and assay: For fluorescence or photophysical studies, higher chemical purity and lower UV-absorbing impurities are important to minimize background and ensure reproducible quantum yields. When used as a building block, typical synthetic-grade material (>95% by HPLC/GC/NMR) is often sufficient; trace phenolic (de-ethylated) impurities can affect reactivity.
• Moisture and hydrolysis: Although the lactone is reasonably stable, strong acidic/basic residues or high moisture during storage can lead to hydrolysis. Verify Karl Fischer/moisture only if critical for your application; item-specific moisture limits are not provided here.
• Stabilizers: None are indicated in the Product Data. If stabilizers or inhibitors were used, they would be declared on the CoA/SDS. Absence of such a note does not guarantee absence; confirm on documentation if your use is sensitive.
• Analytical verification: Recommended identity confirmation by 1H/13C NMR and HRMS; purity by HPLC or GC (if thermally stable). Fluorine substitution facilitates 19F NMR for rapid identity checks.

Implication for method development: If employing this scaffold in fluorescence assays, consider sourcing lots with chromatographic purity data across UV wavelengths to ensure minimal baseline drift.

Reaction & Applications

Research-oriented applications (general to this scaffold; expand/extend beyond catalog note):

• Fluorophore scaffold: Coumarin cores are extensively used in fluorescent probe design. The 4-ethoxy group modulates electron-donating capacity at C-4, influencing photophysical properties, while the 6-fluoro substituent enables further diversification via SNAr to install amine/thiol/alkoxy nucleophiles (literature, structure–property dependent). No item-specific optical data are provided here.
• SNAr diversification at C-6: The aryl fluoride adjacent to the electron-deficient lactone facilitates displacement by nucleophiles under polar aprotic conditions and elevated temperatures. This allows rapid access to 6-amino, 6-alkoxy, or 6-thio analogs for library synthesis or probe optimization.
• Deprotection/derivatization at C-4: Acid-mediated O-dealkylation can unmask the 4-hydroxy group (common in anticoagulant and dye chemistry) enabling further O-alkylation or carbonate/carbamate formation.
• Cross-coupling alternatives: Although aryl fluorides are less reactive in Pd-catalyzed cross-couplings, pre-activation (e.g., via halogen exchange or directed metalation) can be explored; however SNAr is typically more practical for this substrate class.
• Photochemistry: Coumarin chromophores can undergo [2+2] photocycloadditions or photodimerization in specific contexts; such transformations depend strongly on substitution and conditions (use appropriate shielding if photostability is required).

Practical tips:

• Maintain anhydrous conditions for base-catalyzed SNAr to minimize lactone opening.
• Protect from strong base/acid when preservation of the lactone is essential; quench and neutralize carefully during workup.

Reaction Conditions

General literature-guided conditions for transformations of 4-ethoxy-6-fluorocoumarin (non-spec; optimize per lab):

• SNAr at C-6 (displacing F):

  • Nucleophiles: Primary/secondary amines, alkoxides (NaOR/KOR), thiolates (NaSR).
  • Solvents: DMF, DMSO, NMP; dry conditions recommended.
  • Base: For amines, none or mild base (DIPEA) can suffice; for O/S nucleophiles, use corresponding alkoxides/thiolates.
  • Temperature/time: 80–140 °C, 1–16 h; microwave heating (120–170 °C, 10–60 min) often effective.
  • Notes: Excess nucleophile can drive conversion; monitor by LC/MS. Avoid strong aqueous base to protect the lactone.

• 4-O-dealkylation (to 4-hydroxycoumarin):

  • Conditions A (protic acid): H2SO4 or HCl in MeOH/EtOH, reflux, 2–12 h; may proceed via transetherification followed by hydrolysis.
  • Conditions B (Lewis acid): BBr3 (1–3 eq) in CH2Cl2 at −78 to 0 °C then warm to RT, 1–4 h; quench cautiously to avoid lactone opening.
  • Notes: Monitor for overreaction or ring opening; work up under mildly acidic conditions to re-lactonize if needed.

• Electrophilic substitutions (less common due to deactivation):

  • Strong Lewis/Brønsted acids (e.g., AlCl3, TfOH) in inert solvents (DCM, nitrobenzene), 0–25 °C to reflux; regioselectivity varies.

• Purification: Silica gel chromatography using DCM/EtOAc or toluene/EtOAc gradients. Protect from strong base on silica.

All conditions are general literature guidance for substituted coumarins; validate on small scale and tailor to your substrate and equipment.

Safety & Handling

Regulatory/GHS (from Product Data):

• Signal word: Not specified for this item; refer to SDS.
• Hazard statements (H-codes): Not specified for this item; refer to SDS.
• GHS classification and pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance for substituted coumarins (not product-specific; consult SDS for authoritative data):

• Likely hazards: Organic aromatic lactones and aryl fluorides may cause skin/eye irritation and respiratory irritation upon dust generation. Avoid dust formation and inhalation.
• PPE: Lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to prevent inhalation of dust or vapors from solvents.
• Handling: Avoid strong acids/bases which can promote lactone hydrolysis or ether cleavage. Prevent prolonged exposure to light and heat to minimize photodegradation and discoloration typical of coumarin chromophores.
• Storage incompatibilities: Separate from strong oxidizers and strong nucleophiles if not intended for reaction. Keep dry—moisture can facilitate hydrolysis under basic or acidic conditions.
• First-aid overview: In case of skin/eye contact, rinse with plenty of water for at least 15 minutes and remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical advice. Provide SDS to responders.
• Spill/accident: Avoid raising dust; collect mechanically or with damp disposable towels; dispose according to institutional and local regulations.

Always defer to the product-specific SDS for definitive hazard classification and response measures.

Solvent Selection

Use-case driven solvent guidance (general for coumarin solids; non-spec):

• Polarity/miscibility: The compound is moderately lipophilic and typically dissolves well in polar aprotic solvents (DMSO, DMF, NMP) and in chlorinated solvents (DCM, chloroform). Esters (EtOAc), ketones (acetone, acetonitrile), and aromatics (toluene) often afford workable solubility. Poorly soluble in alkanes and water at neutral pH.
• Stock solutions for assays: DMSO stocks (10–50 mM) are common for coumarin probes due to stability and miscibility with aqueous buffers upon dilution (final DMSO ≤1–2% v/v recommended to limit biological interference, if applicable to your research system).
• Reaction media: For nucleophilic aromatic substitution (SNAr) at the 6-fluoro position, DMF/DMSO are preferred; for acid-catalyzed de-ethylation (to 4-hydroxy), protic acids in alcohols or acetic acid are typical. For electrophilic substitutions on the ring, non-polar or mildly polar aromatics (toluene, nitrobenzene) may be used with Lewis/Brønsted acid catalysts.
• Workup and crystallization: EtOAc/hexanes or DCM/MeOH mixtures often give effective trituration or crystallization windows for substituted coumarins (optimize empirically).

Comparison (general):

• DMSO vs DMF: DMSO offers higher solubility and easier handling for stock solutions; DMF is preferred for some high-temperature SNAr owing to lower viscosity. Both are polar aprotic and water-miscible.
• CH2Cl2 vs EtOAc: CH2Cl2 provides superior solubility and faster evaporation; EtOAc is a greener option when feasible.

Storage & Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

Best practices (general for coumarin solids; non-spec):

• Keep container tightly closed in a dry place. Protect from prolonged exposure to light to minimize photodegradation or discoloration typical of coumarin chromophores. Store away from strong acids/bases and oxidizers.
• If preparing solutions: Make anhydrous DMSO, DMF, or CH2Cl2 stock solutions. Aliquot into amber vials to reduce headspace and light exposure. For long-term storage of solutions, maintain at 2–8 °C or −20 °C depending on solvent stability; allow to equilibrate to room temperature before opening to prevent moisture ingress.
• Freeze–thaw: Solid form is generally robust to ambient cycles when kept dry. Avoid repeated freeze–thaw of solutions; prepare single-use aliquots.
• Reconstitution: If the solid agglomerates, gently warm the vial or add a minimal volume of a strong solvent (DMSO, DMF) to dissolve, then dilute to working solvent. Filter if particulate remains.

Always consult the product’s CoA and SDS for item-specific handling instructions. Research use only.

Structure & Identity

Brief description: 4-Ethoxy-6-fluorocoumarin is a substituted coumarin (1,2-benzopyran-2-one) bearing an ethoxy group at C-4 and a fluorine at C-6.

• Item-specific IDs (from Product Data):
  • CAS: 527751-30-0
  • PubChem CID: 688959
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/computed identity details (non-spec):
  • Core scaffold: Coumarin (benzopyran-2-one) lactone fused ring system
  • Functional groups: Lactone (cyclic ester), aryl fluoride (at C-6), aryl ether (4-ethoxy substituent)
  • Molecular formula (computed from name; literature inference): C11H9FO3
  • Molecular weight (computed; literature inference): ~208.19 g/mol
• 2D structural description (general):
  • The structure comprises a benzene ring fused to an α-pyrone (lactone) ring. At the C-4 position of the lactone ring, an ethoxy substituent (–O–CH2CH3) is attached. At the C-6 position on the benzene ring, a fluorine atom replaces hydrogen. The lactone carbonyl is conjugated with the aromatic system, affording a planar, highly conjugated chromophore characteristic of coumarins.

Notes: Exact connection tables (SMILES/InChI) and stereochemistry are not provided in the Product Data; consult the product CoA/SDS for definitive identifiers.

Synthetic Utility

Key reactive elements (general to this molecule):

• Aryl fluoride at C-6: Activated toward nucleophilic aromatic substitution by the adjacent electron-withdrawing lactone. Useful for installing amines, thiols, and alkoxides to fine-tune electronic and photophysical properties.
• 4-Ethoxy group: Functions as an electron-donating substituent, influencing ring electronics. Under acidic conditions it can be cleaved to afford the 4-hydroxycoumarin, a versatile synthon for etherification, carbonate formation, or linker attachment.
• Lactone (benzopyran-2-one): Generally robust but susceptible to base-promoted ring-opening. Can participate in further annulations or serve as a directing element for electrophilic substitution on the benzene ring.

Retrosynthetic value:

• Access via Pechmann-type condensations or Knoevenagel/lactonization strategies followed by regioselective halogenation/fluorination and O-alkylation at C-4, or by constructing the 6-fluoro coumarin first then introducing the ethoxy group.

Named/typical transformations (literature):

• SNAr at aryl-F in DMF/DMSO with alkoxides, thiolates, or primary/secondary amines, 60–140 °C.
• Friedel–Crafts-type electrophilic substitution on the benzene ring (less favored due to deactivation by lactone; requires strong Lewis acids and controlled conditions).
• Acidic dealkylation to 4-hydroxy (e.g., BBr3 for ethers in non-aqueous media, or protic acids under reflux—optimize to protect the lactone).

Utility summary: A compact, diversifiable coumarin chromophore suitable for building fluorescent probe libraries and SAR sets.

Target Specificity

Not applicable. This product is a small-molecule chemical, not a biological affinity reagent. No antigen/epitope, clone, isotype, or species reactivity information applies. For functional or binding studies using coumarin-tagged constructs, target specificity arises from the conjugated ligand, not from the coumarin core itself.