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
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.
Certificati (CoA, COO, BSE/TSE e tabella di analisi)
C of A & Other Certificates(BSE/TSE, COO):
Analytical Chart:
Proprietà chimiche e fisiche
Peso molecolare
217.240 g/mol
XLogP3
2.900
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
2
Exact Mass
217.09 Da
Monoisotopic Mass
217.09 Da
Topological Polar Surface Area
35.300 Ų
Heavy Atom Count
16
Formal Charge
0
Complexity
224.000
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
Calcolatori di soluzioni
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Recensioni
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Application Protocols
Not applicable. No biological assay protocols (e.g., WB, IHC, IF, FC) or dilutions are defined for this small-molecule building block. For synthetic applications, refer to the Reaction Conditions and Synthetic Utility sections for representative guidance.
Biological Roles
Item-specific: None specified for this product; it is sold for research use only.
General context (literature/general knowledge; not product-specific claims)
4-(2-Fluorophenoxy)-2-methylaniline is a synthetic aromatic amine/diaryl ether without a known endogenous biological role. Such scaffolds are common in medicinal chemistry campaigns as fragments or intermediates because anilines can engage in hydrogen bonding and the aryl–F motif can influence metabolic stability and binding orientation.
Any biological activity would be context-dependent on the broader structure into which this building block is incorporated. No assumptions should be made about bioactivity, toxicity, or pharmacokinetics of this discrete compound without dedicated study.
Usage note
For biochemical screening or probe development, prepare well-characterized stocks (e.g., in DMSO) and confirm identity/purity by NMR/LC–MS prior to assays. Adhere strictly to “For research use only” guidance.
Buffer Applications
This product is an organic building block, not a buffering agent. It does not serve as a conventional buffer component for aqueous pH control. If aqueous handling is needed (e.g., for biological assays), the free base may be protonated to form anilinium salts that are more water-soluble, but dedicated buffer systems (PBS, HEPES, citrate, etc.) should be used for pH control.
Green Alternatives
While the compound itself is a fixed building block, greener choices can be made for its use in synthesis, workup, and purification.
Greener solvent swaps (literature guidance)
Replace THF with 2-MeTHF when feasible: similar polarity, better safety/renewable sourcing, easier phase separation.
Prefer EtOAc or IPA over DCM for extractions and reactions where kinetics and solubility allow.
Use CPME or cyclohexyl methyl ether in place of dioxane/toluene for certain Pd-catalyzed couplings due to lower peroxide formation tendency and better recyclability (monitor peroxides regardless).
Consider water/Me-THF biphasic or micellar media (e.g., TPGS-750-M) for amide couplings and Buchwald–Hartwig reactions, reducing organic solvent load.
Reagent considerations
Amide couplings: T3P or CDI can offer cleaner byproduct profiles vs carbodiimide/HOBt systems; avoid azabenzotriazoles if energetic-safety or waste is a concern.
Catalysis: Employ ligand-enabled Pd catalysis at ppm levels or Ni-catalyzed alternatives to reduce precious metal content; recover catalysts via supported systems where practical.
Workup/purification
Prioritize crystallization or trituration over silica chromatography. When chromatography is needed, use heptane/EtOAc gradients instead of hexane/DCM.
Energy and safety
Leverage flow chemistry for hazardous steps (e.g., lithiation/halogen exchange on the aryl fluoride) to improve thermal control and minimize solvent volumes.
Tradeoffs: Greener solvents may reduce rates/solubility; a brief solvent screen is recommended to balance EHS with throughput.
Pharmaceutical Uses
Item-specific: No pharmacopeial grade or excipient designation is specified for this item; refer to CoA/Spec Sheet. For research use only.
General formulation/manufacturing context (literature; not therapeutic claims)
Role as an intermediate: Substituted anilines and diaryl ethers are common intermediates in small-molecule drug discovery and scale-up, enabling rapid diversification via acylation, urea/sulfonamide formation, and cross-couplings. The 2-fluorophenoxy group provides conformational control and can modulate lipophilicity in target compounds.
Salt handling: Where anilines are formulated for processing, transient salt formation (e.g., HCl, mesylate, tosylate) may assist crystallization or enable polymorph control during isolation of downstream targets.
Purity considerations: For GMP-relevant development, typical controls include residual Pd/Ni (if used), residual solvents, aromatic amine impurities, and potential aniline N-oxide formation upon storage. These controls are not specified for this research item.
Note: This product is not an approved excipient and is not intended for human or veterinary use.
Physical Properties
Item-specific (from Product Data)
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 values (reference only; not item specifications)
Acid–base: primary aniline (typical pKa of anilinium conjugate acid ~4.5–5.5, literature general range; exact value for this substituted aniline not established here).
Polarity/solubility (qualitative, literature general):
Expected to be sparingly soluble in water as a neutral free base; readily soluble in common organic solvents (e.g., dichloromethane, ethyl acetate, THF, toluene, MeOH, DMSO). Formation of the anilinium salt (e.g., HCl) typically increases aqueous solubility.
LogP: Not established here for this exact structure; consult cheminformatics calculation if required.
BP/MP, density, refractive index, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.
General notes
The presence of an aryl–O–aryl ether and a fluorine substituent typically increases hydrophobicity relative to unsubstituted aniline (literature trend).
Salt formation (HCl, TsOH) can aid handling and purification of basic anilines (literature practice).
Quality and Grades
Item-specific
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 (general guidance)
Research or synthetic grade materials are typically suitable for discovery chemistry, library synthesis, and process scouting. When chromatography-grade (HPLC/GC) is offered, it implies stringent limits on UV-absorbing impurities or low-bleed for analytical work.
For heteroatom-containing aromatic amines, relevant quality markers can include residual metals (if made via Pd-catalysis), halide content, related diaryl ether impurities, and aniline oxidation products. Unless listed, these are not specified for this item.
Documentation and release testing
Request the Certificate of Analysis (CoA) for batch-specific purity, assay method (e.g., qNMR, HPLC), water content (Karl Fischer), and residual solvent profile, where available.
If your application is moisture- or metal-sensitive (e.g., cross-coupling), consider an in-lab pre-treatment (e.g., base wash, filtration through basic alumina) as appropriate and verify by your analytical suite (NMR, LC/MS).
Reaction and Applications
Role in synthesis
Nucleophilic aniline: The primary amine participates in acylation (amides, carbamates, ureas), sulfonylation (sulfonamides), and imine formation with aldehydes/ketones. It is also a partner in C–N cross-couplings (e.g., Buchwald–Hartwig) to form diarylamines or arylated anilides (literature).
Electrophilic aromatic substitution (EAS): The aniline-directing effects activate the remaining meta positions (relative to –NH2) on the proximal ring; with ortho (2-) methyl and para (4-) aryloxy occupied, nitration/sulfonation/halogenation often occurs at the 3- or 5-positions under controlled conditions (literature trend). The methyl group adds steric bias.
Aryloxy/fluoro handle: The 2-fluorophenyl moiety can undergo lithium–halogen exchange (e.g., with n-BuLi at low temperature) to access functionalization adjacent to the ether oxygen; directed ortho-metalation is sometimes facilitated by the ether oxygen (literature). Direct SNAr of the aryl fluoride is generally disfavored without additional ring activation.
Named/representative transformations (literature)
Amide coupling: HATU, HBTU, EDCI/HOAt/HOBt, T3P in DMF, DCM, or 2-MeTHF; bases such as DIPEA, NMM, or collidine.
Carbamate/urea formation: CDI or phosgene-equivalents; isocyanate route; triphosgene for poly-urea frameworks.
Buchwald–Hartwig amination: Pd2(dba)3 or Pd(OAc)2 with ligands (XPhos/BrettPhos/RuPhos) and NaOtBu or Cs2CO3; solvents toluene/dioxane/CPME.
Electrophilic acylation on ring: Friedel–Crafts conditions often require protection of –NH2 (e.g., acyl, Boc) to control reactivity/chemoselectivity.
Applications
Discovery/medchem scaffold: Combines an aniline donor site with a lipophilic diaryl ether and a metabolically interesting aryl–F element.
Materials/intermediates: Useful as a precursor to dyes, UV-absorbing motifs, or cross-coupling substrates where positional substitution patterns are critical (literature general use of substituted anilines/diaryl ethers).
Reaction Conditions
General literature guidance for reactions involving 4-(2-fluorophenoxy)-2-methylaniline (not product specifications):
Amide coupling
Reagents: HATU or EDCI (0.9–1.2 equiv) with HOAt/HOBt or Oxyma; base DIPEA (2–3 equiv).
Solvent: DMF, DCM, THF, 2-MeTHF, or MeCN.
Temperature/time: 0–25 °C, 1–16 h. Typical isolated yields for clean substrates: 70–95% (literature ranges).
Urea/carbamate formation
CDI (1.1–1.5 equiv) in THF/DMF at 0–25 °C; or react with isocyanates directly in DCM/THF at 0–25 °C.
Buchwald–Hartwig N-arylation
Catalyst/ligand: Pd2(dba)3 (1–2 mol%) or Pd(OAc)2 (1–3 mol%) with XPhos/BrettPhos/RuPhos (2–6 mol%).
Base: NaOtBu, KOtBu, or Cs2CO3 (2–3 equiv).
Solvent: toluene, dioxane, CPME, tAmylOH.
Temperature: 80–110 °C; 4–18 h. Typical yields: 60–90% depending on partners/ligands.
Diazotization/Sandmeyer on the aniline ring
Conditions: NaNO2/HCl (aq) at 0–5 °C to form diazonium, then CuX-mediated substitution (Ar–X). Protect ether if needed. Careful temperature control for safety.
Lithiation of the 2-fluorophenyl moiety
Lithium–halogen exchange: n-BuLi (1.1–1.5 equiv) in THF or Et2O at –78 to –40 °C, then quench with electrophiles (DMF for aldehyde, B(OR)3 for boronate, CO2 for acid). Compete with ortho-lithiation directed by the ether oxygen—conduct small-scale screens.
Workup tips
For basic products, wash organics with dilute acid to remove unreacted amine, then basify and extract if isolating the free base. Neutralize silica with 1–2% Et3N for chromatography of amines.
Safety and Handling
Item-specific hazard information
GHS classification: Not specified for this item; refer to SDS.
Signal word: Not specified for this item; refer to SDS.
Hazard statements (H-codes): Not specified for this item; refer to SDS.
Pictograms: Not specified for this item; refer to SDS.
General safety guidance for aromatic anilines and diaryl ethers (literature; not product-specific)
Potential hazards: Many anilines are harmful if swallowed or absorbed through skin and may cause skin/eye irritation or methemoglobinemia upon significant exposure. Avoid inhalation of dust/vapors and skin contact. Diaryl ethers are generally of low volatility but can be irritating.
PPE: Use appropriate gloves (e.g., nitrile), lab coat, eye protection. Handle in a fume hood to minimize exposure.
Storage incompatibilities: Keep away from strong oxidizers and strong acids/bases that may cause unwanted reactions (e.g., aggressive nitration/oxidation). For free-base anilines, avoid long-term exposure to air/oxidants and light that can promote coloration/oxidation.
First aid (overview; defer to SDS):
Inhalation: move to fresh air; seek medical attention if symptoms persist.
Skin/eye contact: rinse with plenty of water for at least 15 minutes; remove contaminated clothing; seek medical advice.
Ingestion: rinse mouth; do not induce vomiting unless directed by medical personnel; obtain medical attention.
Fire safety: Combustible organic; use CO2, dry chemical, or foam. Thermal decomposition may release irritating fumes (e.g., NOx, HF-containing species from fluorinated aromatics).
Always consult the product-specific SDS for authoritative hazard classifications and response measures.
Solvent Selection
This product is a solid organic building block, not a solvent. Selection here refers to solvents suitable for manipulating and reacting 4-(2-fluorophenoxy)-2-methylaniline.
Polarity/miscibility considerations (general)
As a moderately lipophilic aniline, it is typically soluble in polar aprotic and many less polar organic solvents: DCM, EtOAc, THF, 2-MeTHF, acetone, MeCN, toluene, DMF/DMAc, DMSO, MeOH/EtOH (literature general behavior for substituted anilines/diaryl ethers).
Aqueous solubility is expected to be low for the free base; solubility increases upon protonation (e.g., in dilute HCl) for salt manipulations and extractions.
Typical use scenarios
Amide couplings: DMF, DCM, THF, MeCN, or 2-MeTHF are commonly selected depending on coupling reagent and base.
N-arylation (Buchwald–Hartwig): toluene, dioxane, CPME, or tAmylOH with Pd catalysts and strong bases.
Electrophilic acylation/sulfonylation: DCM or toluene with base (e.g., pyridine, DIPEA) at 0–25 °C.
Quick comparison (general)
DCM vs EtOAc: DCM offers rapid dissolution and ease of workup; EtOAc is a greener alternative with higher polarity but slower rates for some reactions.
THF vs 2-MeTHF: similar solvating power; 2-MeTHF provides better phase separation and greener profile (see Green Alternatives).
Always verify solvent compatibility with reagents/catalysts and desired selectivity.
Storage and Reconstitution
Item-specific
Storage Conditions: Room temperature (per Product Data).
Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
General handling guidance (literature/general)
Store tightly closed in a dry, inert atmosphere (desiccator or with desiccant) to limit aniline oxidation and moisture uptake. Protect from prolonged light exposure.
If long-term storage is intended, consider filling headspace with nitrogen/argon and using amber glass.
Prepare stock solutions in dry organic solvents such as DMSO, DMF, THF, MeOH, or DCM depending on downstream use. Typical screening stocks: 10–100 mM in DMSO for medchem workflows.
For aqueous operations, form the anilinium salt in situ by adding a stoichiometric acid (e.g., HCl in dioxane) to enhance water compatibility, then neutralize as needed after reaction.
Stability notes
Avoid strong oxidizers and strong acids/bases during storage. Monitor for discoloration as an indicator of oxidation; purify if necessary prior to critical use.
Always consult the product’s CoA and SDS for lot-specific guidance and regulatory information. For research use only.
Structure and Identity
Brief description: 4-(2-Fluorophenoxy)-2-methylaniline is an aniline building block bearing an ortho-methyl substituent and a para-aryloxy substituent in which the distal ring is ortho-fluorinated. The scaffold combines a nucleophilic aniline (–NH2) with an aryl–O–aryl ether and a fluorinated aryl handle.
Item-specific (from Product Data)
Product name: 4-(2-Fluorophenoxy)-2-methylaniline
CAS: 946699-47-4
CID: 26190288
InChIKey: 100552 (as provided)
SMILES: Not specified for this item; refer to CoA/Spec Sheet.
Literature/computed identity (for reference; not item specifications)
Expected molecular formula (from structure name): C13H12FNO (computed)
Calculated average molecular weight: ~217.24 g/mol (computed from formula)
Monoisotopic mass: ~217.0903 Da (computed)
Structural features:
Ring systems: two benzene rings linked by an ether oxygen (aryl–O–aryl, “diaryl ether”).
Functional groups: primary aniline (–NH2) at C-1 of the proximal ring, methyl at C-2, aryloxy at C-4; distal ring bears fluorine at its 2-position relative to the ether oxygen.
2D description: Proximal aniline ring substituted with –NH2 (position 1), –CH3 (position 2), and –O–Ar (position 4). The distal ring is a 2-fluorophenyl group bonded via oxygen.
Stereochemistry: none (achiral, no stereocenters).
General notes
The aniline nitrogen is basic/nucleophilic and can be protected, acylated, or engaged in cross-couplings.
The aryl fluoride provides a handle for metal–halogen exchange or directed lithiation adjacent to the ether oxygen (literature).
Synthetic Utility
Functional group reactivity
Primary aniline (–NH2): readily acylated to amides/carbamates, converted to ureas/thioureas, or transformed to imines/enamines. It can undergo diazotization (–N2+) for subsequent Sandmeyer-type substitutions (e.g., Ar–Cl, –CN) on the aniline ring; protection (Boc, Cbz, acyl) helps manage chemoselectivity.
Aromatic substitution pattern: With –CH3 at C-2 and –OAr at C-4, electrophilic substitution is biased toward the 3- and 5-positions; sterics may favor one site over the other. Directed metalation strategies can further differentiate positions.
Aryl fluoride handle: Suitable for lithium–halogen exchange (e.g., n-BuLi, –78 to –40 °C) enabling subsequent trapping with electrophiles (formylation, borylation). SNAr at the 2-F position is typically poor unless additional electron-withdrawing substituents are introduced.
Ether linkage: Generally inert to many conditions; however, strong Lewis acids (BBr3, AlCl3) can cleave aryl–O–aryl ethers—useful for deprotection/diversification but requires caution.
Cross-coupling and diversification
N-arylation with aryl halides/triflates (Buchwald–Hartwig) to form tertiary anilines.
C–H functionalization on the aniline ring (e.g., Cu/Pd-catalyzed direct arylation), often after N-acyl protection to enhance selectivity.
Formation of sulfonamides/sulfinamides as handles for further transformations (e.g., directed ortho-metalation via sulfonamide).
Purification/handling
Free-base anilines may tail on silica; pre-treat silica with 1–2% Et3N or isolate as crystalline salts and basify.
Oxidation to colored species can occur on standing; store under air-tight conditions and minimize light exposure (general practice).
Target Specificity
Not applicable. This product is a small-molecule chemical building block, not a biological probe, antibody, or enzyme inhibitor with defined target specificity. No antigen/epitope, isotype, or species reactivity information is relevant.
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