2-Bromo-4,6-difluorophenol - ≥98% , CAS No.98130-56-4

CAS: 98130-56-4 Cat. No.: B139503 Fórmula: C₆H₃BrF₂O Peso molecular: 208.99 Beilstein Registry Number: 6(4)1058 Número CE: 619-323-9

GRADE & PURITY ≥98%

Synonyms

MFCD00070752 | AS-58802 | 2-bromanyl-4,6-bis(fluoranyl)phenol | A845814 | B3004 | AM83207 | DTXSID50371252 | AKOS005257825 | BP-10933 | FT-0611436 | Phenol, 2-bromo-4,6-difluoro- | SY049460 | EN300-109212 | SCHEMBL1155741 | YDRZYJATKMBSJX-UHFFFAOYSA-N | 2

Storage

Argon charged,Room temperature

Shipped In

Normal

Specifications

Sinónimos

MFCD00070752 | AS-58802 | 2-bromanyl-4,6-bis(fluoranyl)phenol | A845814 | B3004 | AM83207 | DTXSID50371252 | AKOS005257825 | BP-10933 | FT-0611436 | Phenol, 2-bromo-4,6-difluoro- | SY049460 | EN300-109212 | SCHEMBL1155741 | YDRZYJATKMBSJX-UHFFFAOYSA-N | 2

Especificações e pureza

≥98%

Condições de armazenamento de armazenamento

Argon charged,Room temperature

Enviado em

Normal

Pureza

≥98%

Nomes e identificadores

Pubchem Sid

488192792

Pubchem Sid Url

https://pubchem.ncbi.nlm.nih.gov/substance/488192792

Sorrisos canónicos

C1=C(C=C(C(=C1F)O)Br)F

IUPAC Name

2-bromo-4,6-difluorophenol

InChIKey

YDRZYJATKMBSJX-UHFFFAOYSA-N

INCHI

1S/C6H3BrF2O/c7-4-1-3(8)2-5(9)6(4)10/h1-2,10H

SMILES isoméricas

C1=C(C=C(C(=C1F)O)Br)F

Peso molecular

208.99

Beilstein

6(4)1058

Reaxy-Rn

3245935

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=3245935&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Phenols
      • Subclass Halophenols
        • Level5 Fluorophenols
          • Level6 P-fluorophenols

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Phenols
• Subclass: Halophenols
• Intermediate Tree Nodes: Fluorophenols
• Direct Parent: P-fluorophenols
• Alternative Parents: O-fluorophenols O-bromophenols Fluorobenzenes Bromobenzenes Aryl fluorides Aryl bromides Organooxygen compounds Organofluorides Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 4-fluorophenol - 2-bromophenol - 2-fluorophenol - Bromobenzene - Fluorobenzene - Halobenzene - Aryl bromide - Aryl fluoride - Aryl halide - Monocyclic benzene moiety - Hydrocarbon derivative - Organic oxygen compound - Organooxygen compound - Organofluoride - Organobromide - Organohalogen compound - Aromatic homomonocyclic compound
• Descrição: This compound belongs to the class of organic compounds known as p-fluorophenols. These are fluorophenols carrying a iodine at the C4 position of the benzene ring.
• 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

Propriedades químicas e físicas

• Índice de refração: 1.54
• Ponto de inflamação (°F): 106°C(lit.)
• Ponto de inflamação (°C): 106 °C
• Ponto de ebulição (°C): 53 °C
• Peso molecular: 208.990 g/mol
• XLogP3: 2.500
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 207.934 Da
• Monoisotopic Mass: 207.934 Da
• Topological Polar Surface Area: 20.200 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 122.000
• 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

Not applicable. This listing is a chemical building block and is not supplied with biological application protocols (e.g., WB, IHC, IF, FC). For synthetic use, refer to the Reaction Conditions and Synthetic Utility sections for general laboratory guidance.

Biological Roles

This product is a small-molecule synthetic intermediate rather than a biomolecule.

• Item-specific biological role: None stated. For research use only.
• General context (literature): Halogenated phenols are not endogenous metabolites. Their biological interactions, when studied, relate to physicochemical properties (lipophilicity, acidity) rather than specific biochemical roles. The strong C–F bonds confer metabolic stability in designed molecules but the parent reagent itself is not known to participate in natural pathways.
• Use in biochemical research: Occasionally, halogenated phenolic scaffolds are incorporated into probe molecules or ligands to tune binding via halogen bonding or to adjust pKa/logP. 2-Bromo-4,6-difluorophenol can serve as a precursor to such derivatives, where the phenolic OH may be masked (ethers/esters) and the aryl bromide used for cross-coupling to elaborate pharmacophoric space.

No biological activity or mechanism is claimed for the catalog item itself. Any use involving biological systems should be confined to laboratory research with appropriate safety and waste controls.

Buffer Applications

Not typically applicable.

• This compound is a hydrophobic, halogenated phenolic building block, not a buffering agent. While phenols are weak acids, 2-bromo-4,6-difluorophenol is not used to prepare laboratory buffer systems and has poor aqueous solubility at neutral pH.
• For aqueous work, if dissolution is needed, researchers may prepare stock solutions in DMSO or MeCN and dilute into assays; buffering should be provided by standard biological buffers (e.g., phosphate, HEPES), not by this compound.

Green Alternatives

While 2-bromo-4,6-difluorophenol itself is the target building block, its use can be aligned with greener chemistry by optimizing solvent, reagents, and process conditions.

Greener process choices (literature guidance):

• Solvent selection
  • Prefer Bio-based/safer solvents where feasible: 2-MeTHF or CPME instead of THF/diethyl ether; propylene carbonate or dimethyl carbonate instead of DMF/NMP when compatible.
  • Aqueous/ethanol or water/dioxane mixtures for Suzuki–Miyaura can reduce hazardous solvent use.
• Catalysis and loadings
  • Employ ligand-enabled Pd catalysts effective at ppm–0.1 mol% levels, or Ni catalysts for aryl bromides to reduce precious metal footprints.
  • Use heterogeneous or recyclable catalysts (e.g., Pd/C in flow, supported Pd) with appropriate controls for leaching.
• Bases and additives
  • Favor inorganic bases with lower EHS concerns (K3PO4, K2CO3) over strong alkoxides when compatible.
• Energy efficiency
  • Microwave or flow synthesis can shorten cycle times and reduce energy consumption.
• Workup/waste
  • Minimize halogenated solvent use in chromatography; use ethyl acetate/hexanes or greener alternatives; implement aqueous crystallizations when possible.

Comparison snapshot (general):

• DMF/NMP (effective polar aprotics) vs 2-MeTHF/EtOAc (greener, but may reduce solubility/coupling rates)
• Toluene/dioxane (traditional for Pd coupling) vs water/ethanol or PEG-400 (greener, may require surfactants/phase-transfer)

Note: Select alternatives case-by-case; verify reaction performance and product quality. The supplied product is Argon charged; maintain inert handling while pursuing greener conditions.

Pharmaceutical Uses

No excipient or pharmacopeial role is specified for this catalog item. For research use only.

General context (non-clinical, literature):

• Role in pharmaceutical R&D: Halogenated phenols like 2-bromo-4,6-difluorophenol serve as versatile intermediates for assembling fluorinated aromatic motifs common in medicinal chemistry. The aryl bromide enables rapid diversification via cross-coupling, while the phenolic OH allows tuning of physicochemical properties through ether/ester pro-moieties.
• Manufacturing/formulation: The reagent itself is not used as an excipient. Any incorporation into drug substances would occur at the synthetic intermediate stage, followed by thorough purification and control per GMP if advancing to regulated development.

No therapeutic claims are made or implied for this product.

Physical Properties

Item-specific specifications for this lot are not provided in the Product Data. For exact values (mp, bp, density, assay), Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for 2-bromo-4,6-difluorophenol (for context only):

• Molecular formula: C6H3BrF2O (literature)
• Molecular weight: ~208.99 g/mol (literature, calculated from atomic weights)
• Physical state: Typically a solid or low-melting solid/oil for halogenated phenols; exact appearance Not specified for this item; refer to CoA/Spec Sheet.
• Acidity: Phenolic pKa is expected in the ~8.5–10 range (literature for substituted phenols). Ortho-bromine and meta-fluorines modestly stabilize the phenoxide, potentially lowering pKa relative to phenol.
• Solubility (qualitative, literature trends):
  • Water: Low due to aryl halogens; can dissolve under basic conditions as the phenoxide salt.
  • Organic: Good solubility anticipated in polar aprotic solvents (DMSO, DMF, acetone, acetonitrile) and moderately in ethers/esters/aromatics.
• Volatility: Low to moderate; aryl bromides/phenols generally have high boiling points and low vapor pressure relative to simple aromatics.
• Partitioning: LogP expected to be moderate (halogenated phenols commonly logP ~2–3), increasing with halogenation; specific value not confirmed.
• UV/Vis: Aromatic chromophore; shows typical phenolic UV absorption bands (literature) but low-UV-cutoff grade is not specified.

Note: Use these qualitative descriptors for planning only. Always consult the CoA/SDS for authoritative property data for the supplied lot.

Quality and Grades

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

How to interpret and select grades for this compound (general guidance):

• Research grade vs higher-purity grades
  • For most synthetic applications (e.g., cross-coupling), standard research grade is often adequate. Trace metal content can matter for sensitive catalysis; if catalyst poisoning is observed, consider higher-purity material or additional pre-treatment.
• HPLC grade/low-UV absorbance
  • Not typically applicable to solid building blocks; however, if using as an analytical reference standard, request documentation of purity by NMR/GC/HPLC.
• Stabilizers/inhibitors
  • Phenolic substrates generally do not require added stabilizers; mild oxidative discoloration over time is common. This item is supplied Argon charged to limit oxidative processes.
• Documentation to request/consult
  • CoA: assay (%), residual solvents, identity confirmation (1H/13C/19F NMR, MS), and water content (Karl Fischer) when relevant.
  • Spec Sheet: appearance, melting point range, and recommended storage.

Fitness for purpose (practical considerations):

• Cross-coupling: Assess halide purity (avoid Br/Cl scrambling) and confirm absence of protodehalogenation products.
• Medicinal chemistry/SAR: Seek narrow mp range and high spectral purity to minimize ambiguity in structure–activity relationships.
• Analytical standardization: If quantitative work is needed, request a purity-corrected assay value and uncertainty.

Reaction and Applications

As a multifunctional aryl bromide/phenol, 2-bromo-4,6-difluorophenol is a versatile intermediate for assembling fluorinated aromatic targets.

Key application families (literature/general):

• Cross-coupling at the aryl bromide
  • Suzuki–Miyaura: Installation of aryl/vinyl groups from boronic acids/esters. Ortho-bromide relative to OH can show directing effects; use Pd(0/II) catalysts (e.g., Pd(PPh3)4, Pd(dppf)Cl2) and bases like K3PO4 or Cs2CO3 in toluene/dioxane/H2O or DMF.
  • Buchwald–Hartwig amination: Convert Ar–Br to Ar–NR2 employing Pd catalysts and biaryl phosphines (e.g., XPhos, BrettPhos) with NaOtBu or Cs2CO3 in toluene or dioxane.
  • Negishi/Stille/Kumada: Alternative couplings when partner availability dictates; control for protodehalogenation.
• Phenolic derivatization
  • O‑alkylation: Williamson ether synthesis via in situ phenoxide (NaH, K2CO3) in DMF/acetone/MeCN.
  • O‑acylation/carbamate formation: Use acid chlorides/anhydrides or chloroformates with base (pyridine/NEt3) in DCM or THF.
  • Protection strategies: TBS, TBDPS, or benzyl groups can protect OH during metalation/coupling.
• Directed metalation/orthogonal functionalization
  • The phenol (or its silyl ether) can guide ortho‑lithiation under strong bases at low temperature, though the ortho position bearing Br is already occupied; consider deprotonation adjacent to F substituents with care.
• Late-stage fluorinated scaffold elaboration
  • Retains two C–F bonds, enabling synthesis of metabolically robust motifs for materials or discovery chemistry.

Applications in discovery/materials synthesis (general):

• Precursor to fluorinated biaryl phenols, diaryl ethers, and anilines for agrochemical or materials research where lipophilicity and electron-deficient aromatics are desired.

Reaction Conditions

Guidance below reflects literature norms for aryl bromides/phenols and should be optimized per substrate/partner. These are not item-specific specifications.

• Suzuki–Miyaura coupling (Ar–Br → Ar–Ar)
  • Catalyst: 0.5–2 mol% Pd(PPh3)4 or Pd(dppf)Cl2 (1–3 mol%).
  • Base: K3PO4, Cs2CO3, or K2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (3:1), toluene/H2O, or DMF; 60–100 °C, 2–16 h.
  • Notes: Protect phenol (e.g., as TBS ether) if boronate is base-labile; aqueous mixtures often improve turnover.
• Buchwald–Hartwig amination (Ar–Br → Ar–NR2)
  • Catalyst/ligand: Pd2(dba)3 (1 mol% Pd) with XPhos/BrettPhos (2–4 mol% ligand) or precatalysts.
  • Base/solvent: NaOtBu or Cs2CO3 in toluene or dioxane; 80–110 °C, 4–18 h.
  • Notes: Free phenol may bind/cause side O-arylation of amines; consider O-protection.
• Sonogashira coupling (Ar–Br → Ar–C≡C–R)
  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%), CuI (2–5 mol%).
  • Base/solvent: Et3N or iPr2NH in THF/MeCN; 25–70 °C, 2–12 h.
  • Notes: Phenol can be tolerated but protection improves chemoselectivity.
• O‑alkylation (Williamson ether synthesis)
  • Base: NaH (1.1–1.5 equiv) in DMF/THF at 0–25 °C; add alkyl halide (1.1–1.5 equiv); 1–4 h.
  • Alternative: K2CO3 (2–3 equiv) in acetone/MeCN under reflux for milder conditions.
• O‑acylation
  • Reagent: Acyl chloride/anhydride (1.1–1.5 equiv) with pyridine/Et3N in DCM or THF; 0–25 °C, 0.5–2 h.

Monitoring and workup:

• TLC/UPLC to track consumption; 19F NMR provides sensitive handles for substitution pattern integrity.
• Quench metal-catalyzed reactions with aqueous NH4Cl; charcoal treat to remove Pd/Ni; silica plug with EtOAc/hexanes.

Yields: Literature for analogous substrates commonly 60–95% under optimized conditions; actual results depend on partner/catalyst/solvent.

Safety and Handling

Item-specific GHS classification and hazard statements: Not specified for this item; refer to SDS for definitive hazard, precautionary statements, and pictograms.

General safety considerations for halogenated phenols and aryl bromides (literature/typical):

• Hazards
  • May cause skin and eye irritation; phenols can be corrosive at higher concentrations and may cause acute dermal toxicity upon prolonged contact.
  • Harmful if swallowed; avoid inhalation of dust/vapors.
  • Environmental hazard: Halogenated aromatics can be harmful to aquatic life; prevent release to the environment.
• Handling/PPE
  • Use in a chemical fume hood.
  • Wear appropriate PPE: lab coat, safety glasses or face shield, and chemical-resistant gloves (e.g., nitrile). Change gloves regularly.
  • Avoid skin contact with phenolic materials; promptly wash exposed skin.
• Incompatibilities and reactivity
  • Avoid strong oxidizers (risk of exothermic reaction/oxidation of phenol).
  • Avoid strong bases in the presence of alkylating agents; phenoxide formation enhances nucleophilicity.
  • Metals/metal salts may catalyze oxidative darkening of phenols; store under inert gas as provided.
• First aid (overview; follow SDS protocols)
  • Skin: Remove contaminated clothing, wash with soap and water.
  • Eyes: Rinse cautiously with water for several minutes; remove contact lenses if present and easy.
  • Inhalation: Move to fresh air; seek medical advice if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire safety
  • Combustible organic solid/liquid; use CO2, dry chemical, or foam. Phenols can emit toxic fumes (HBr, HF, CO/CO2) on combustion.

Always defer to the product SDS and your institutional EHS procedures.

Solvent Selection

This product is a halogenated phenolic building block (not a solvent). Solvent choice pertains to its dissolution and reactivity in synthesis/analysis.

General solvent compatibility (literature-informed):

• Likely good solubility: DMSO, DMF, NMP, acetone, acetonitrile, ethyl acetate, THF, dichloromethane, toluene.
• Limited solubility: Water at neutral pH; solubility increases under basic conditions via phenoxide formation (e.g., Na2CO3, K2CO3, NaOH).

Practical selection by use case:

• Cross-coupling at C–Br (Suzuki, Buchwald–Hartwig):
  • Polar aprotics (DMF, DMAc, NMP) or mixed aqueous-organic (dioxane/H2O, MeCN/H2O) often give high conversions with bases like K3PO4, Cs2CO3.
  • For more hydrophobic partners, toluene or dioxane with phase-transfer of base is common.
• Nucleophilic substitution on the phenol (ether/ester formation):
  • Use polar aprotics (DMF, DMSO, MeCN) when generating the phenoxide; for acylations, use DCM, THF, or toluene with base (pyridine, NEt3).
• SNAr on the aryl fluoride is typically disfavored here (fluorines are at positions less activated by strong –I/–M groups); focus transformations on C–Br or O–H.

Analytical preparation:

• Stock solutions for LC/MS or NMR: DMSO‑d6, acetone‑d6, CDCl3 commonly suitable; ensure complete dissolution and avoid basic deuterated solvents if the free phenol state is required.

Note: Optimize solvent with base/catalyst and partner electrophile/nucleophile; verify solubility at reaction temperature.

Storage and Reconstitution

• Item-specific storage (from Product Data)
  • Store at room temperature.
  • Supplied Argon charged; maintain an inert atmosphere (argon or nitrogen) after opening to limit oxidative discoloration and moisture uptake.
  • Shipped under normal conditions.
• General handling tips (literature/practice):
  • Keep container tightly closed in a dry, well-ventilated area. Protect from light and heat sources.
  • If long-term storage is planned, consider transferring to an amber vial with inert headspace; desiccant can help maintain dryness.
  • Phenolic reagents can slowly oxidize; minor darkening does not necessarily indicate loss of assay, but confirm by NMR/LC as needed.
• Reconstitution/solution preparation:
  • Not applicable for solids per se; to prepare stock solutions, dissolve in a suitable anhydrous organic solvent (e.g., DMSO, DMF, MeCN, THF, DCM, toluene) to the desired concentration. Filter (PTFE) if particulates are present.
  • For moisture-sensitive transformations, pre-dry the solvent and glassware; sparge solutions with inert gas if needed.
• Shelf life:
  • Not specified for this item; refer to CoA/Spec Sheet. As a rule, minimize exposure to air and base to preserve integrity over time.

Always follow the product label and SDS for definitive storage guidance.

Structure and Identity

Brief overview: 2-Bromo-4,6-difluorophenol is a halogenated phenolic building block combining an aryl bromide handle with a phenolic OH and two ring fluorines at the 4- and 6-positions.

• Item-specific (from Product Data)
  • SKU: B139503
  • Product name: 2-Bromo-4,6-difluorophenol
  • CAS: 98130-56-4
  • Storage conditions: Room temperature, Argon charged (as supplied)
  • Shipped in: Normal
  • InChIKey (as provided): 434604
• Literature identity (for reference; not item specifications)
  • Synonyms: 2-bromo-4,6-difluoro-phenol; 2-bromo-3,5-difluorophenol (IUPAC locant conventions place OH at C1)
  • Molecular formula (literature): C6H3BrF2O
  • Molecular weight (literature): ~208.99 g/mol
  • Expected SMILES (literature): Oc1c(Br)cc(F)cc1F (representative; formatting may vary by source)
  • InChIKey (literature): not confirmed here; consult a trusted database (e.g., PubChem CID 2736290)
• Structural features (general description)
  • Core: Monosubstituted phenol (phenyl bearing OH at C1)
  • Substituents: Bromine at ortho (C2) to OH; fluorines at meta positions relative to OH (C4 and C6). The ring thus bears three halogens/heteroatoms influencing electronics.
  • Functional groups: Phenolic hydroxyl (weakly acidic), aryl bromide (cross-coupling handle), two aryl C–F bonds (strongly deactivating/ortho–para directing effects absent for F; net ring deactivation toward EAS).
  • Stereochemistry: None (achiral, planar aromatic system).
  • 2D description: A benzene ring with OH at position 1; Br at position 2 (adjacent to OH); F at positions 4 and 6 (para to each other, meta to OH).

Synthetic Utility

Functional handles and reactivity (literature/general):

• Aryl bromide (C–Br)
  • Highly competent for Pd/Ni-catalyzed cross-coupling (Suzuki, Buchwald–Hartwig, Sonogashira, Heck). Ortho relationship to OH can influence oxidative addition and regioselectivity in downstream transformations.
• Phenolic OH
  • Readily derivatized to ethers (Williamson, Mitsunobu) and esters (acylation), enabling pro-moiety or protecting-group strategies (e.g., benzyl, silyl, carbonate protections).
  • Phenoxide can direct metalation or act as a nucleophile in SN2 reactions with suitable electrophiles.
• Ring fluorines (C–F)
  • Strong –I effect lowers ring electron density, often improving selectivity in cross-couplings by suppressing competitive electrophilic substitution and enhancing stability. They also modulate pKa/logP in target molecules.

Retrosynthetic leverage:

• Build fluorinated biaryls: Couple at C–Br first, then manipulate the phenolic position (protect/deprotect) to introduce side chains.
• Orthogonal functionalization: Protect OH → perform cross-coupling → deprotect → O‑functionalize, maintaining C–F groups intact.
• Late-stage diversification: Use aryl bromide to append heteroaryl moieties; convert phenol to carbonate/carbamate for further coupling to amines/alcohols.

Practical notes:

• Protect OH when base-sensitive partners or strong bases (NaH, tBuOK) are used to avoid competitive O‑alkylation.
• Monitor for protodebromination under forcing conditions; milder catalysts/temperatures help preserve the aryl bromide until intended transformation.

Target Specificity

Not applicable. This product is a small-molecule chemical reagent and does not possess biological target specificity (no antigen/epitope/clone/isotype). No assay reactivity spectrum is associated with this item.