3-(2-Fluorophenoxy)benzyl Bromide - ≥95% , CAS No.242812-04-0

CAS: 242812-04-0 Cat. No.: B300628 Fórmula: C₁₃H₁₀BrFO Peso molecular: 281.13 Número CE: 670-969-8

GRADE & PURITY ≥95%

Synonyms

A877973 | MFCD00059914 | 3'-Bromomethyl-2-fluorodiphenyl Ether; | DTXSID40372076 | 1-(bromomethyl)-3-(2-fluorophenoxy)benzene | PS-9873 | 3'-Bromomethyl-2-fluorodiphenyl Ether | SCHEMBL1191537 | FWAHWPGVFDHNCH-UHFFFAOYSA-N | FT-0706534 | F0236 | 3-Methyl-

Storage

Store at 2-8°C

Shipped In

Wet ice

Specifications

Sinónimos

A877973 | MFCD00059914 | 3'-Bromomethyl-2-fluorodiphenyl Ether; | DTXSID40372076 | 1-(bromomethyl)-3-(2-fluorophenoxy)benzene | PS-9873 | 3'-Bromomethyl-2-fluorodiphenyl Ether | SCHEMBL1191537 | FWAHWPGVFDHNCH-UHFFFAOYSA-N | FT-0706534 | F0236 | 3-Methyl-

Especificações e pureza

≥95%

Condições de armazenamento de armazenamento

Store at 2-8°C

Enviado em

Wet ice

Este produto requer transporte de cadeia fria. Serviços terrestres e outros serviços econômicos não estão disponíveis.

Pureza

≥95%

Nomes e identificadores

• Pubchem Sid: 488192897
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/488192897
• Sorrisos canónicos: C1=CC=C(C(=C1)OC2=CC=CC(=C2)CBr)F
• IUPAC Name: 1-(bromomethyl)-3-(2-fluorophenoxy)benzene
• InChIKey: FWAHWPGVFDHNCH-UHFFFAOYSA-N
• INCHI: 1S/C13H10BrFO/c14-9-10-4-3-5-11(8-10)16-13-7-2-1-6-12(13)15/h1-8H,9H2
• SMILES isoméricas: C1=CC=C(C(=C1)OC2=CC=CC(=C2)CBr)F
• Peso molecular: 281.13
• Reaxy-Rn: 19195284
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=19195284&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Diphenylethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Diphenylethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diphenylethers
• Alternative Parents: Diarylethers Phenoxy compounds Phenol ethers Benzyl bromides Fluorobenzenes Aryl fluorides Organofluorides Organobromides Hydrocarbon derivatives Alkyl bromides
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Diphenylether - Diaryl ether - Phenoxy compound - Phenol ether - Benzyl bromide - Benzyl halide - Halobenzene - Fluorobenzene - Aryl halide - Aryl fluoride - Ether - Alkyl halide - Organooxygen compound - Organofluoride - Organobromide - Organohalogen compound - Alkyl bromide - Hydrocarbon derivative - Organic oxygen compound - Aromatic homomonocyclic compound
• Descrição: This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
• 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

• Sensibilidade: Heat sensitive
• Peso molecular: 281.120 g/mol
• XLogP3: 4.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 279.99 Da
• Monoisotopic Mass: 279.99 Da
• Topological Polar Surface Area: 9.200 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 212.000
• 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. No assay/application protocols (e.g., WB, IHC, IF, FC) are relevant for this small-molecule reagent. For practical use, see Reaction Conditions and Synthetic Utility for representative organic synthesis procedures.

Biological Roles

• Item-specific biological/biochemical roles: None specified; this product is supplied for research and synthetic laboratory use only.

• General considerations (not therapeutic/clinical)

  • As a benzylic bromide, it is an alkylating agent and can react with biological nucleophiles (thiols, amines). This chemical reactivity underpins its hazard profile but does not imply any physiological function.
  • The 2‑fluorophenoxy substituent is a common motif in medicinal chemistry for tuning potency and metabolic stability; accordingly, this reagent may be used to append that motif to candidate scaffolds during SAR campaigns.

No endogenous biological role is known or expected for this synthetic intermediate.

Buffer Applications

Not typically applicable. This compound is a hydrophobic, reactive benzylic bromide used as an electrophile in organic synthesis, not a buffering agent. For aqueous work, see Reaction & Applications and Solvent Selection for biphasic/phase-transfer strategies.

Green Alternatives

While this product is the electrophile itself, greener choices concern solvent and base selection and process design.

• Greener solvent options (vs traditional choices)

  • 2‑MeTHF or CPME vs THF/DMF: better safety (lower peroxide formation than THF, less reproductive toxicity than DMF), good SN2 performance.
  • MeCN (with careful recovery) vs DMF/DMSO: lower boiling point simplifies solvent recycling and reduces energy cost.
  • Propylene carbonate or Cyrene (where compatible) can replace DMF/NMP in some alkylations, though viscosity and solubility may limit rates.

• Base/catalyst considerations

  • Solid carbonates (K2CO3/Cs2CO3) under phase-transfer conditions reduce need for strong bases and minimize waste salts in homogeneous phase.
  • Aqueous NaOH with PTC in toluene/CPME reduces polar aprotic solvent load.

• Comparison snapshot (general)

  • DMF: high performance, but reproductive toxin; challenging solvent removal.
  • MeCN: good performance, flammable, toxic but manageable; easier workup.
  • 2‑MeTHF/CPME: bio-based/safer, hydrophobic; sometimes slower reactions but improved extraction and lower E-factors.

Trade-offs should be evaluated via small-scale screening to balance rate, selectivity, safety, and environmental impact.

Pharmaceutical Uses

• Item-specific pharmacopeial/excipient status: Not specified for this item; refer to CoA/Spec Sheet.

• General context (non-clinical)

  • Used as a synthetic intermediate to introduce a 3‑(2‑fluorophenoxy)benzyl substituent into discovery compounds. Such benzyl groups can modulate lipophilicity, binding interactions, and metabolic stability in medchem workflows.
  • Potential roles in process development include quaternization to generate benzyl ammonium salts (phase-transfer catalysts) or formation of pro-moieties in early formulation studies; however, this reagent itself is not an excipient and is for research use only.

Physical Properties

• Item-specific specifications

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed reference values (for context; not item specifications)

  • Molecular formula: C13H10BrFO (from structure)
  • Formula weight (average): 281.12 g/mol (computed)
  • Exact mass (monoisotopic, 79Br): 279.989 g/mol (computed)
  • Physical state at RT: benzylic bromides of this mass are typically liquids or low-melting solids (literature generalization; confirm on CoA).
  • Solubility profile (general): expected good solubility in chlorinated solvents (CH2Cl2, CHCl3), aromatic hydrocarbons (toluene), and polar aprotic media (DMF, DMSO, MeCN); very low solubility in water (general diaryl ether/benzyl bromide behavior).
  • Volatility: moderate; benzylic bromides may have appreciable vapor; handle in fume hood.

Notes

• Where precise values (bp/mp, density, refractive index, UV cutoff) are critical, consult the product’s CoA/SDS or characterize in-house. No item-specific physical constants are provided here.

Quality and Grades

• Item-specific status

  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Stabilizers/Inhibitors: Not specified for this item; refer to CoA/Spec Sheet.

• Interpreting grade for this compound class (general guidance)

  • For a benzylic bromide electrophile used in synthesis, common grades include: synthetic grade (suitable for routine alkylations), >95% or >98% purity for discovery/medchem, and HPLC-grade criteria if low UV background is essential (rarely specified for reagents of this type).
  • Stabilizers are typically not required; however, storage under inert gas and dry conditions helps minimize hydrolysis to benzyl alcohol or formation of trace HBr.

• Recommended quality controls (best practice)

  • Identity: 1H/13C NMR (benzylic CH2 typically ~4.3–4.6 ppm), IR (C–Br stretch weak, aryl ether ~1240–1270 cm−1), HRMS.
  • Purity: GC or HPLC; monitor for benzyl alcohol and debrominated impurities.
  • Water content: Karl Fischer optional if using moisture-sensitive bases; specification not provided for this item.

Always consult the Aladdin CoA for lot-specific assay, residual solvents, and impurity profile before use in critical steps.

Reaction and Applications

This benzylic bromide is a versatile electrophile for installing the 3-(2-fluorophenoxy)benzyl motif onto nucleophiles.

• Representative transformations (literature/general)

  • N‑Alkylation: tertiary and secondary amines to give benzyl ammonium salts or tertiary amines; imidazoles/azoles under mild base.
  • O‑Alkylation: phenoxides and alcohols to form benzyl ethers; careful control minimizes competing C‑alkylation for phenolates.
  • S‑Alkylation: thiolates to thioethers; typically fast at rt in polar aprotic media.
  • C‑Alkylation: active methylene compounds (e.g., malonates, β‑ketoesters) under phase-transfer or strong base conditions.
  • Quaternization: formation of benzyl quaternary ammonium or phosphonium salts (phase-transfer catalysts, Wittig precursors).

• Strategic use in synthesis

  • Late-stage diversification: introduces a lipophilic, aryl‑fluoro diaryl ether handle impacting electronics and conformational bias.
  • Probe/tag installation: enables incorporation of this benzyl group onto heterocycles, peptides (via side-chain nucleophiles), or polymers.

• Practical tips

  • Order of reactivity (benzylic electrophiles): I > Br >> Cl; bromide offers a good balance of reactivity and handling.
  • Bases: K2CO3/Na2CO3 (O‑alkylation in MeCN/acetone), Cs2CO3 (heteroaryl N‑alkylation), NaH/t‑BuOK (more forcing), or PTC (BnX + aq. NaOH, toluene, TBAB).
  • Minimize over‑alkylation by using limiting equivalents of electrophile and slow addition.
  • Monitor by TLC/LC: benzylic UV chromophore gives strong response at 254 nm.

Note: No manufacturer application notes were provided; the above reflects common use-cases for benzylic bromides.

Reaction Conditions

General literature guidance for benzylic bromide alkylations (optimize per substrate):

• O‑Alkylation of phenols/alcohols

  • Base/solvent: K2CO3 or Cs2CO3 in MeCN or acetone; alternatively NaH in THF/2‑MeTHF for hindered alcohols.
  • Temperature/time: rt to 60 °C, 1–16 h.
  • Notes: Add electrophile last; use slight excess (1.1–1.3 equiv) or inverse addition to control over‑alkylation.

• N‑Alkylation of heterocycles/amines

  • Base/solvent: DIPEA or Na2CO3 in MeCN/DMF; for weakly nucleophilic azoles, Cs2CO3 in DMF or DMSO.
  • Temperature/time: rt to 50 °C, 2–18 h.
  • Notes: For tertiary amine quaternization, use neat or concentrated MeCN; monitor exotherm.

• S‑Alkylation of thiols

  • Base/solvent: NaH or K2CO3 in MeCN, acetone, or DMF.
  • Temperature/time: 0 °C to rt, 0.5–4 h (typically fast).

• Phase-transfer conditions (for weak nucleophiles)

  • System: Toluene or CPME with 50% aq. NaOH, TBAB/TEAB as PTC.
  • Temperature/time: 20–60 °C, 2–8 h; vigorous stirring to ensure mass transfer.

• Workup/purification

  • Quench residual electrophile with a nucleophile (e.g., Et3N/Na2S2O3) before aqueous workup to reduce lachrymatory vapors.
  • Purify by silica gel chromatography; benzylic products typically elute with 10–30% EtOAc/hexanes or DCM/MeOH systems.

• Expected outcomes

  • SN2 reactions of benzylic bromides typically afford good to excellent yields (60–95%) under optimized conditions (literature generalization).

Safety and Handling

• Item-specific hazard fields

  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements: Not specified for this item; refer to SDS.
  • GHS Classification/Pictograms: Not specified for this item; refer to SDS.

• General safety profile for benzylic bromides (literature/general)

  • Benzylic bromides are strong alkylating agents; many are potent irritants/lacrimators and can cause severe eye/skin irritation and respiratory discomfort. Avoid inhalation of vapors and contact with skin/eyes.
  • May cause sensitization or acute toxicity upon significant exposure; handle in a certified fume hood.

• PPE and engineering controls

  • Minimum PPE: lab coat, nitrile gloves (change frequently), splash goggles or face shield when charging.
  • Use in a fume hood; avoid open handling. For larger scale, consider dual gloves and respirator readiness per institutional policy.

• Incompatibilities and reactivity (general)

  • Reacts with strong nucleophiles/bases; can quaternize amines and alkylate thiols/alkoxides.
  • Hydrolysis to the corresponding benzyl alcohol in aqueous/alkaline media; avoid moisture if purity is critical.
  • Avoid strong oxidizers and strong Lewis acids that may promote side reactions.

• First-aid overview (general guidance; defer to SDS)

  • Skin/eye contact: Immediate decontamination with copious water for ≥15 min; remove contaminated clothing; seek medical evaluation.
  • Inhalation: Move to fresh air; monitor breathing; seek medical attention.
  • Ingestion: Rinse mouth; do not induce vomiting; urgent medical attention required.

• Waste disposal

  • Collect halogenated organic waste according to local regulations. Neutralize reactive residues with suitable nucleophiles only in controlled conditions.

Solvent Selection

This reagent is a benzylic bromide electrophile; solvent choice should maximize nucleophilicity while controlling elimination and side reactions.

• Polarity and miscibility (general behavior)

  • Expected to dissolve well in polar aprotic solvents (DMF, DMSO, NMP, MeCN, acetone) and common organics (THF, toluene, CH2Cl2, EtOAc). Poorly water-soluble.

• Choosing solvents by reaction class

  • SN2 alkylation of O/N/S nucleophiles: MeCN, acetone, DMF, DMSO, or 2-MeTHF (for greener choice). These enhance nucleophilicity and minimize ion pairing.
  • Phase-transfer alkylation: biphasic toluene or CH2Cl2 with aqueous base and a quaternary ammonium catalyst.
  • SN1 or solvolysis (less common here): polar protic or strongly ionizing media (HFIP/TFE) but risk of rearrangements/cations.
  • Avoid strongly basic, high-temperature protic solvents if elimination or hydrolysis is a concern.

• Comparative notes

  • MeCN vs DMF: MeCN is easier to remove and greener; DMF offers higher polarity but can form dimethylamine under strong base and elevated temp.
  • THF vs 2-MeTHF/CPME: ethers aid solubility; 2-MeTHF/CPME provide improved stability toward peroxides and better phase behavior for workup.
  • DMSO: powerful but can promote side oxidations with strong bases; malodor upon contact with thiols after reaction.

Dry, oxygen-free solvents are recommended to limit hydrolysis and byproduct formation.

Storage and Reconstitution

• Item-specific storage

  • Store at 2–8 °C (from Product Data). Shipments are on wet ice.

• Handling and in-use guidance (general best practices for benzylic bromides)

  • Keep container tightly closed in a dry, well-ventilated place. Minimize headspace and consider storing under inert gas (N2/Ar) to limit hydrolysis.
  • Protect from moisture and prolonged light exposure. Use anhydrous techniques when charging to base-containing media.
  • If long-term storage is needed, aliquot into amber vials to reduce repeated warming cycles; avoid frost-free refrigerators that cycle humidity.

• Reconstitution

  • Supplied neat (typical for this class). If a solution is desired, prepare fresh anhydrous stock in an appropriate solvent (e.g., MeCN, DMF, DCM, THF) immediately before use. Label with solvent, concentration, and date; store cold and use promptly.

Always refer to the product’s CoA and SDS for lot-specific stability, impurity evolution, and safety recommendations.

Structure and Identity

A benzylic bromide bearing a diaryl ether scaffold: a meta-(phenoxy) substituent on one ring and an ortho-fluoro on the phenoxy ring. Highly activated benzylic carbon (–CH2Br) adjacent to an aromatic ring facilitates nucleophilic substitution.

• Item-specific identifiers (from Product Data)

  • SKU: B300628
  • CAS: 242812-04-0
  • CID: 2737454
  • InChIKey: 93675 (as provided)
  • Storage: 2–8 °C; shipped on wet ice
  • Research Use: For research use only

• Structure descriptors (literature/computed; for reference)

  • Preferred name: 3-(2-Fluorophenoxy)benzyl bromide
  • Molecular formula: C13H10BrFO (literature/stoichiometry)
  • Molecular weight (average): ~281.12 g/mol (computed from formula)
  • Canonical SMILES (literature): Fc1ccccc1Oc1cccc(CBr)c1
  • 2D structure (verbal): Two phenyl rings linked by an ether oxygen. The “distal” ring bears F at the ortho position relative to O. The “proximal” ring bears a benzylic bromomethyl (–CH2Br) substituent meta to the ether oxygen.
  • Key functional groups/features: benzylic bromide (strong electrophile), aryl–O–aryl diaryl ether, aryl fluoride (electron-withdrawing), two π-systems.

• Stereochemistry: None (achiral, no stereocenters).

Synthetic Utility

• Electrophilic handle

  • The benzylic –CH2Br is highly activated by the adjacent aromatic ring, enabling rapid SN2 reactions with a broad range of nucleophiles (RO–, RS–, R2NH/RNH–, enolates, azoles, and heteroaryl anions).

• Functional group compatibility (general)

  • Tolerant of many neutral and mildly basic conditions. Avoid strong nucleophiles that may induce ether cleavage under forcing conditions. The aryl fluoride is robust and typically inert under alkylation conditions, enabling orthogonal chemistry.

• Protecting-group strategies

  • Temporary benzylation of alcohols/phenols/thiols is feasible; subsequent deprotection by hydrogenolysis is typically not viable due to the diaryl ether motif, but oxidative or radical debenzylation strategies may be optimized depending on substrate.

• Retrosynthetic value

  • Serves as a convergent point: prepare the benzylated target by nucleophile derivatization rather than late-stage diaryl ether formation, which can be more challenging.

• Downstream elaborations

  • After alkylation, benzylic oxidation (e.g., to aldehyde/acids) or radical bromination is possible on derived substrates; the intact aryl–O–aryl unit persists under many conditions.

Target Specificity

Not applicable. This product is a small-molecule chemical reagent, not a biological targeting agent (e.g., antibody, enzyme inhibitor with validated target panel). No antigen/epitope, species reactivity, clone, or isotype data apply.