3-Ethoxy-5-(trifluoromethyl)phenol - ≥95% , CAS No.1881320-95-1

CAS: 1881320-95-1 Cat. No.: E937560 Formula: C₉H₉F₃O₂ Peso molecolare: 206.160

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

Sorrisi canonici

CCOC1=CC(=CC(=C1)O)C(F)(F)F

IUPAC Name

3-ethoxy-5-(trifluoromethyl)phenol

InChIKey

JXUHJLXZHLDEFX-UHFFFAOYSA-N

INCHI

1S/C9H9F3O2/c1-2-14-8-4-6(9(10,11)12)3-7(13)5-8/h3-5,13H,2H2,1H3

Peso molecolare

206.160

Proprietà chimiche e fisiche

• Peso molecolare: 206.160 g/mol
• XLogP3: 2.800
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 206.055 Da
• Monoisotopic Mass: 206.055 Da
• Topological Polar Surface Area: 29.500 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 181.000
• 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 biological assay protocols (e.g., WB, IHC, IF, FC) are applicable to this small‑molecule building block. For synthetic applications, refer to the Reaction Conditions and Synthetic Utility sections for general laboratory procedures and starting parameters. Always adapt to your substrate and verify on small scale.

Biological Roles

This compound is a synthetic, fluorinated aromatic phenol and is not known as an endogenous metabolite.

• General observations (literature):
  • Phenolic groups can engage in hydrogen bonding and undergo Phase II metabolism (e.g., glucuronidation/sulfation) in biological systems; however, the presence of a CF3 group often increases lipophilicity and metabolic stability of the aromatic core.
  • CF3 substitution is used in medicinal chemistry to modulate pKa, permeability, and binding interactions, but such roles are highly context‑dependent on the final scaffold.
  • The ethoxy substituent further tunes electronics and sterics of the ring; ether linkages are generally stable under neutral conditions.

No specific biochemical pathways or targets are associated with 3‑ethoxy‑5‑(trifluoromethyl)phenol itself. Any biological testing should be designed and interpreted within the framework of research use only, adhering to institutional biosafety guidelines. For handling and disposal after biological assays, follow local regulations for fluorinated organics.

Buffer Applications

This material is an organic building block and is not used to prepare aqueous buffer systems. It lacks the polyprotic/defined pKa characteristics and water solubility typically required for buffering capacity.

• Guidance: If aqueous work is needed (e.g., bioconjugation on derivatives), select an appropriate buffer system (phosphate, Tris, HEPES, etc.) independent of this reagent. Confirm solubility or use co‑solvents (DMSO, EtOH) at low percentages to introduce derivatives into aqueous media.

Green Alternatives

Although this product is a building block rather than a solvent or reagent, greener choices can be made around its use, particularly in solvent and auxiliary selection.

• Greener solvent substitutions (literature/general):
  • Replace dichloromethane with ethyl acetate or 2‑MeTHF for extractions and some reactions when feasible.
  • Use 2‑MeTHF or CPME instead of THF (better renewability, improved phase separation, reduced peroxide concerns).
  • Prefer ethanol or isopropanol over methanol for recrystallizations/workups when solubility permits.
• Reagent choices:
  • For aryl triflation, use 2,6‑lutidine or pyridine alternatives with lower toxicity where compatible; consider aryl nonaflates only when needed (higher E‑factor).
  • O‑alkylation via phase-transfer catalysis in greener biphasic systems (e.g., toluene alternatives such as anisole or Cyrene in some cases) can reduce dipolar aprotic solvent usage.
• Workup/waste minimization:
  • Favor EtOAc/hexanes over DCM for chromatography; optimize gradients to reduce solvent volume.
  • Use 19F NMR for quick reaction screening to minimize repeated workups and waste.

Comparison snapshot (general):

• THF vs 2‑MeTHF: similar performance for O‑alkylation/Mitsunobu; 2‑MeTHF is bio‑based and often allows easier separations.
• DCM vs EtOAc: EtOAc is less hazardous and biodegradable; DCM offers higher capacity for some phenols but with significant environmental/health liabilities.

Always validate green substitutions on small scale to confirm yield/selectivity.

Pharmaceutical Uses

No pharmacopeial/excipient status or formulation role is provided for this item. It is supplied for research use only.

• Typical role in pharmaceutical R&D (literature/general):
  • Serves as a synthetic intermediate or fragment in the preparation of CF3‑aryl phenol–containing candidates for SAR exploration.
  • The phenol can be masked as a pro‑moiety (e.g., esters/ethers) during synthesis, then unveiled for target engagement studies.
• Manufacturing/formulation notes (general):
  • If incorporated into APIs or intermediates, specifications would be tightly controlled (purity, residual solvents, ID by NMR/MS/19F NMR). Such controls are project‑specific and not implied here.

No therapeutic claims are made or intended. For any GMP or regulatory use, obtain appropriate quality documentation and assess against internal specifications.

Physical Properties

Item-specific specifications were not provided for this product. Values below are general literature/computed expectations and are NOT product specifications.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: ~206.16 g/mol (computed from formula C9H9F3O2; literature/calculation)
• Boiling point / Melting point: Not widely reported for this exact substitution pattern (literature). Phenolic aryl ethers of similar size often present as low-melting solids or high-boiling oils.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (qualitative, literature):
  • Low aqueous solubility typical for CF3‑aryl phenols.
  • Readily soluble in organic solvents such as dichloromethane, ethyl acetate, acetone, THF, acetonitrile, and alcohols; highly soluble in DMF/DMSO.
• Acidity/basicity (literature): phenolic pKa typically ~9–10; CF3 substitution may slightly increase acidity relative to phenol.
• Lipophilicity (literature): CF3 and ethoxy increase hydrophobicity; expect moderate-to-high logP for an aryl phenol of this size.

For exact physical constants and acceptance criteria for this specific lot, please consult the Aladdin CoA/Spec Sheet.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• What grade typically implies (general guidance):
  • Research-grade aromatic building blocks are supplied at defined purity (often ≥95% by HPLC/GC/NMR) with identity confirmed by NMR/MS/HRMS as stated on the CoA.
  • If an inhibitor/stabilizer is used in phenolic materials, it will be declared; absence of such a note generally implies no added stabilizer. For this item, stabilizer information is not provided.
• Analytical controls commonly applied (general):
  • Identity: 1H/13C NMR, MS (ESI/APCI), possibly 19F NMR for CF3 confirmation.
  • Purity: HPLC/GC area %, residual solvent by GC, water by Karl Fischer (if applicable).
  • Appearance range and allowable impurities defined in the product specification.
• How to use the CoA/Spec Sheet:
  • Verify lot-specific purity and analytical data prior to critical applications (e.g., SAR studies, library synthesis).
  • Check for residual water/base-sensitive impurities if planning moisture‑ or base‑sensitive reactions (e.g., triflation).

For any regulatory, pharmacopoeial, or trace-metal requirements, consult the lot CoA; if not listed, request a custom specification.

Reaction and Applications

As a CF3‑substituted aryl phenol/ether, 3‑ethoxy‑5‑(trifluoromethyl)phenol serves as a versatile building block in discovery and materials synthesis. Typical laboratory uses (literature/general):

• Electrophile platform via aryl triflate formation: Convert the phenol to its triflate with Tf2O and a base (e.g., pyridine/2,6‑lutidine) to access a competent electrophile for Pd‑catalyzed cross‑couplings (Suzuki–Miyaura, Buchwald–Hartwig amination, Negishi, Stille).
• O‑Derivatization:
  • Alkylation: Phenoxide (K2CO3/K3PO4/NaH) reacts with alkyl halides or sulfonates to give diaryl/alkyl aryl ethers.
  • Acylation: Formation of esters (acid chlorides/anhydrides + base) for protection or as intermediates.
  • Mitsunobu etherification: Couples with primary alcohols under DEAD/DIAD and PPh3 to form aryl ethers when base-sensitive substrates are present.
• C–H functionalization strategies: Deprotonated phenol can direct ortho‑metalation (with suitable conditions/ligands), though the CF3 group deactivates the ring and influences regioselectivity.
• Late-stage introduction of CF3‑phenol motif: The preinstalled CF3 offers metabolic stability and lipophilicity tuning, valuable in SAR series and agro/materials applications.
• 19F NMR handle: CF3 group aids rapid reaction monitoring and purity profiling.

Practical tips:

• Keep water low for triflation/cross‑coupling sequences; dry solvents and bases improve yields.
• For base‑mediated O‑alkylations, control temperature to minimize C‑ vs O‑alkylation and avoid ether cleavage.
• When scaling, assess phenol/phenoxide phase behavior to avoid extraction losses.

Reaction Conditions

The following are general literature conditions for common transformations of CF3‑aryl phenols and should be optimized per substrate. They are not specifications for this item.

• Aryl triflate formation (for cross‑coupling):
  • Reagents: Tf2O (1.1–1.5 eq), 2,6‑lutidine or pyridine (2–3 eq).
  • Solvent: dry CH2Cl2 or toluene; 0 °C to rt, 0.5–2 h.
  • Workup: aqueous NaHCO3, extract with EtOAc/DCM; purify by silica (avoid strong base on silica to limit hydrolysis).
• Suzuki–Miyaura coupling (from aryl triflate):
  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd2(dba)3/XPhos.
  • Base: K3PO4, Cs2CO3, or K2CO3 (2–3 eq).
  • Solvent: dioxane/H2O, toluene/H2O, or 2‑MeTHF/H2O; 60–100 °C, 2–16 h.
• Buchwald–Hartwig amination (from aryl triflate):
  • Catalyst/ligand: Pd2(dba)3 with BINAP/BrettPhos or Pd(OAc)2/XPhos.
  • Base: NaOtBu or Cs2CO3; solvent: toluene, dioxane, or CPME; 80–110 °C.
• O‑Alkylation of the phenol:
  • Base: K2CO3 or Cs2CO3 (1.5–2 eq); electrophile: primary alkyl bromide/iodide or mesylate.
  • Solvent: MeCN or DMF; 25–80 °C, 2–16 h. Minimize water to suppress hydrolysis.
• Mitsunobu etherification:
  • Reagents: PPh3 (1.2 eq), DIAD/DEAD (1.2 eq); solvent: THF or toluene; 0 °C to rt, 2–12 h.

Monitoring and analysis:

• 19F NMR provides a sensitive handle for conversion/purity; LC‑MS for rapid screening.
• Control base strength and temperature to avoid competitive C‑alkylation or ether cleavage.

Safety and Handling

Item-specific hazard classification was not provided. Always consult the SDS for authoritative guidance. The notes below are general for substituted phenols and fluorinated aromatics.

• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.
• Likely hazards (general): Phenols are irritant/corrosive to skin and eyes; ingestion/inhalation harmful. Organic vapors may cause CNS effects at high concentrations. Avoid prolonged or repeated exposure.
• PPE (good laboratory practice): lab coat, safety goggles, appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of vapors/aerosols.
• Handling tips:
  • Avoid contact with bases or strong oxidizers unless required for reaction; phenoxides can be strongly reactive.
  • Prevent dust/aerosol generation; cap containers promptly to limit moisture/air exposure.
• Incompatibilities (general): strong oxidizing agents; strong bases can form phenolates; reactive acylating/alkylating agents may O‑derivatize.
• First aid overview (general):
  • Skin/eye contact: rinse with plenty of water for ≥15 min; remove contaminated clothing; seek medical attention if irritation persists.
  • Inhalation: move to fresh air; monitor breathing; seek medical attention if symptoms occur.
  • Ingestion: rinse mouth; do NOT induce vomiting; seek medical attention.
• Fire safety: Treat as combustible organic; use CO2, dry chemical, or foam. Combustion may release HF and other toxic fluorinated species—firefighters should use SCBA.

Defer to the current SDS for this catalog item for definitive hazards and response.

Solvent Selection

This compound is an aryl phenol/ether building block rather than a solvent. The notes below focus on dissolving/processing it for synthesis and purification.

• Polarity/miscibility (literature expectations):
  • Poorly soluble in water; freely soluble in common organic solvents (DCM, EtOAc, acetone, THF, MeCN, alcohols) and polar aprotics (DMF/DMSO).
• Practical choices by operation:
  • Reaction media: THF, 2‑MeTHF, MeCN, dioxane, toluene, DCM, DMF/DMSO depending on transformation (e.g., triflation in DCM; Mitsunobu in THF/THF‑toluene; O‑alkylation in DMF/MeCN).
  • Workup: Partition with EtOAc/MTBE/hexanes against aqueous washes. Phenols may need mild base wash to remove acidic impurities—avoid losing product to aqueous phase if deprotonated.
  • Purification: Normal-phase silica with hexanes/EtOAc or DCM/MeOH gradients; 19F NMR can help track fractions.
• Small comparison (literature/general):
  • DCM vs EtOAc: DCM offers rapid extractions but with environmental concerns; EtOAc is greener and often sufficient.
  • THF vs 2‑MeTHF: 2‑MeTHF can be a drop‑in replacement in many steps with improved sustainability and easier phase splits.

Always confirm solubility and stability in the chosen solvent at reaction temperature and scale; avoid prolonged basic aqueous contact to limit phenoxide formation and extraction losses.

Storage and Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• General handling:
  • Keep container tightly closed under an inert headspace if possible, especially for long‑term storage, to limit oxidative discoloration typical of phenols.
  • Protect from excessive heat and direct sunlight. Store in a dry place to avoid moisture uptake and phenoxide formation during opening.
• Stability considerations (general): Phenolic compounds are typically stable at ambient conditions when dry and protected from light/air; avoid prolonged exposure to strong bases or oxidants.
• Reconstitution/solubilization (general guidance):
  • For stock solutions, dissolve in dry organic solvents such as DMSO, DMF, THF, MeCN, EtOAc, or ethanol. Filter (PTFE syringe filter) if particulates are present.
  • For biological assays requiring aqueous media, prepare concentrated DMSO or ethanol stocks and dilute into buffer to ≤1–2% organic cosolvent, checking for precipitation.

For lot-specific stability, retest period, and packaging details, consult the Aladdin CoA/Spec Sheet. Research use only, as stated in the product description.

Structure and Identity

3-Ethoxy-5-(trifluoromethyl)phenol is a substituted phenol bearing an electron‑withdrawing CF3 group and an ethoxy ether on the aromatic ring (meta/meta′ relative to the phenolic OH).

• Item-specific identifiers (from Product Data)
  • CAS: 1881320-95-1
  • CID: 125116184
  • InChIKey: 172952
  • SKU: E937560
• Literature/computed identifiers (general reference; not item-specific specifications)
  • Molecular formula (computed from structure name): C9H9F3O2
  • Molecular weight (computed): ~206.16 g/mol
  • Representative SMILES (literature): OC1=CC(=CC(=C1)OCC)C(F)(F)F
• Structural features (general description)
  • Functional groups: phenolic OH, aryl ether (ethoxy), and a trifluoromethyl substituent.
  • Ring system: mono-substituted benzene core with two additional substituents (total three ring substituents).
  • Electronics: CF3 strongly deactivates and meta-directs; phenol (in neutral form) is weakly activating/ortho–para directing; the net pattern yields differentiated reactivity across positions.
  • 2D description in words: A benzene ring bearing an OH group, an –OCH2CH3 group two carbons away (meta to OH), and a –CF3 group para to the ethoxy and meta to the OH (i.e., 1-hydroxy,3-ethoxy,5-trifluoromethyl arrangement).

Synthetic Utility

Key functional elements and their reactivity (literature/general):

• Phenolic OH:
  • Converts to aryl triflate (Tf2O/base) enabling Pd‑catalyzed cross‑couplings (Suzuki, Buchwald–Hartwig, Negishi, Stille).
  • Undergoes O‑alkylation/acylation; Mitsunobu coupling with alcohols to form aryl ethers under neutral-to-mildly basic conditions.
  • Protection as silyl (TBS/TBDPS), benzyl, or carbonate groups facilitates multi‑step sequences.
• CF3 group:
  • Strong –I/–M effects decrease ring electron density, influencing regioselectivity and suppressing electrophilic substitution at adjacent positions; serves as a robust 19F NMR tag.
• Ethoxy substituent:
  • Contributes to solubility/lipophilicity; can participate in intramolecular H‑bond acceptor interactions in targets; typically inert under many coupling conditions.

Retrosynthetic value:

• The phenol can serve as a linchpin: transform to aryl electrophiles (triflates) or nucleophiles (via directed ortho‑metalation on protected phenol derivatives).
• Late‑stage functionalization: leveraging the phenolic handle allows diversification to ethers, esters, carbamates, and sulfamates without perturbing CF3.

Operational considerations:

• Maintain anhydrous conditions for triflation and subsequent cross‑couplings.
• Base choice matters: weak bases (K2CO3/Cs2CO3) for O‑alkylation vs stronger bases (NaH) for sluggish alkylating agents; monitor by 19F NMR for rapid decision‑making.

Target Specificity

Not applicable. This product is a small‑molecule building block, not a biological macromolecule or affinity reagent. No target specificity data (antigen/epitope, clone, isotype, species reactivity) are associated with this item.