3-Cyclobutylphenol - ≥95% , CAS No.211495-49-7

CAS: 211495-49-7 Cat. No.: C1308549 Fórmula: C₁₀H₁₂O Peso molecular: 148.2 Número CE: 884-422-8

GRADE & PURITY ≥95%

Storage

Room temperature

Shipped In

Normal

Specifications

Especificações e pureza

≥95%

Condições de armazenamento de armazenamento

Room temperature

Enviado em

Normal

Pureza

≥95%

Nomes e identificadores

Sorrisos canónicos

C1CC(C1)C2=CC(=CC=C2)O

IUPAC Name

3-cyclobutylphenol

InChIKey

KGAOBXXXNFRSSW-UHFFFAOYSA-N

INCHI

1S/C10H12O/c11-10-6-2-5-9(7-10)8-3-1-4-8/h2,5-8,11H,1,3-4H2

Peso molecular

148.2

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Phenols
      • Subclass 1-hydroxy-4-unsubstituted benzenoids

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Phenols
• Subclass: 1-hydroxy-4-unsubstituted benzenoids
• Intermediate Tree Nodes: Not available
• Direct Parent: 1-hydroxy-4-unsubstituted benzenoids
• Alternative Parents: 1-hydroxy-2-unsubstituted benzenoids Benzene and substituted derivatives Organooxygen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 1-hydroxy-4-unsubstituted benzenoid - 1-hydroxy-2-unsubstituted benzenoid - Monocyclic benzene moiety - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Aromatic homomonocyclic compound
• Descrição: This compound belongs to the class of organic compounds known as 1-hydroxy-4-unsubstituted benzenoids. These are phenols that are unsubstituted at the 4-position.
• 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

• Peso molecular: 148.200 g/mol
• XLogP3: 3.000
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 1
• Exact Mass: 148.089 Da
• Monoisotopic Mass: 148.089 Da
• Topological Polar Surface Area: 20.200 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 129.000
• 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 validated bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule reagent. For synthetic applications, refer to the Reaction Conditions and Synthetic Utility sections for practical procedures and conditions.

Biological Roles

Item-specific biological/biochemical roles are not defined for this compound (research chemical; not endogenous).

General context (literature/biochemistry):

• Phenolic functionality: Phenols can participate in hydrogen bonding and weak acid–base equilibria near physiological pH only when deprotonated (phenoxide), which generally requires basic environments (typical phenol pKa ~10, literature). The neutral phenol is largely unionized at neutral pH, contributing to membrane partitioning.
• Redox/antioxidant behavior: Simple phenols can undergo oxidation to phenoxy radicals or quinone-like species under oxidative conditions; this underlies generic antioxidant assay responses (e.g., DPPH scavenging), although activity is highly structure dependent.
• Metabolism (xenobiotic perspective): Alkylphenols in vivo are often subject to Phase I hydroxylation/oxidation on the ring or side chain, followed by Phase II conjugation (glucuronidation, sulfation) at the phenolic OH. These are general xenobiotic pathways and not specific to this item.

This product is supplied strictly for research use only and is not intended for human or animal diagnostic, therapeutic, or clinical applications.

Buffer Applications

3-Cyclobutylphenol is not a buffering reagent and is not typically used to prepare laboratory buffer systems. Its pKa (phenolic OH, typical phenols ~10; literature) is unsuitable for common biological buffer ranges, and its low water solubility further limits applicability.

For aqueous experimental systems requiring this compound, dissolve in a compatible co-solvent (e.g., DMSO, ethanol) and dilute into buffer while monitoring final organic content to maintain biological assay integrity.

Green Alternatives

Greener choices around 3-cyclobutylphenol typically concern solvent and reagent selection, as the substrate itself is fixed. The goals are to reduce hazard, improve atom economy, and minimize waste.

• Solvent substitutions (literature best practices):

  • Replace chlorinated solvents (DCM, chloroform) with ethyl acetate, 2-MeTHF, CPME, or toluene where feasible.
  • Use aqueous ethanol or isopropanol for extractions and recrystallizations when solubility allows.

• Base/reagent choices:

  • For O-alkylation, K2CO3 in acetone or acetonitrile is a milder, greener alternative to NaH in DMF/DMSO.
  • Employ catalytic acylations (DMAP-catalyzed) with less hazardous acyl donors; avoid stoichiometric pyridine when possible.

• Workup/waste minimization:

  • Favor solid-supported reagents (e.g., PS-carbodiimide) to simplify purification.
  • Implement telescoped sequences (e.g., in situ phenoxide generation and immediate coupling) to reduce solvent use.

Comparison snapshot (general):

| Use case | Conventional | Greener alternative | Trade-offs | |---|---|---|---| | O-alkylation solvent | DMF/DMSO | Acetone, MeCN, 2-MeTHF | May need higher temp or longer time | | Deprotonation base | NaH | K2CO3, Cs2CO3 | Reduced basicity; scope narrower | | Acylation medium | DCM + pyridine | EtOAc or MeCN + Et3N/DMAP | Rate/selectivity changes |

Note: Always validate alternatives at small scale; solubility and rates vary with substrate and electrophile.

Pharmaceutical Uses

No pharmacopeial grade, excipient role, or formulation specifications are provided for this item. It is not typically used as a pharmaceutical excipient.

Research/manufacturing context (general):

• Synthetic intermediate: Phenolic building blocks like 3-cyclobutylphenol may serve as intermediates in the synthesis of drug candidates or fine chemicals via O-derivatization (ethers, esters, carbonates) or conversion to aryl electrophiles (e.g., triflates) for cross-coupling.
• Pre-formulation studies: In medicinal chemistry, such fragments are sometimes evaluated for physicochemical property modulation within a scaffold series (research use only).

Compliance note: This product is supplied for research use only and is not intended for use in humans or as an active pharmaceutical ingredient or excipient in commercial drug products.

Physical Properties

Item-specific physical specifications (e.g., exact BP/MP, density, refractive index, UV cutoff) are not provided in the Product Data for SKU C1308549. When required for method development or safety assessments, consult the product CoA/SDS for definitive values.

Literature/general property context (for reference; not item specifications):

• Phase and appearance: Phenolic aromatics of this size are often low-melting solids or high-boiling liquids; the cyclobutyl group increases hydrophobicity relative to phenol.
• Acid–base: Phenolic OH is a weak acid (typical phenol pKa ~10; literature), enabling formation of phenoxide salts with bases (NaH, K2CO3, NaOH).
• Polarity/solubility: Expected poor water solubility but good solubility in polar aprotic organics (DMSO, DMF, acetone, acetonitrile) and in alcohols/ethers; limited solubility in alkanes compared to fully aliphatic arenes due to H-bonding capability.
• LogP: Substituted phenols with small alkyl rings generally exhibit moderate to high lipophilicity; cyclobutyl increases logP versus phenol (qualitative, literature trend).
• Boiling/melting: Alkylphenols typically boil well above 200 °C at 1 atm; exact values depend on substitution pattern (literature trend only).

Not specified for this item; refer to CoA/Spec Sheet for:

• Boiling point, melting point, density, refractive index, water content, and UV cutoff.

Quality and Grades

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

Interpretation and context (general guidance for phenolic building blocks):

• Research-grade vs. high-purity: For synthesis and screening, typical quality parameters include assay by GC/GC–MS or 1H NMR, water content (Karl Fischer), residual solvents, and chromatographic purity. When using in catalysis or medicinal chemistry, trace impurities can influence reaction outcomes or SAR; request a CoA if these are critical.
• Low-UV/LC grade: If chromatographic analysis at low wavelengths is required, low-UV absorbing solvent residues and stabilizer-free materials are preferred. Phenols can show significant absorbance below ~280 nm; baselines may be improved with HPLC-grade eluents.
• Stabilizers: None specified for this product. Phenolic stabilizers (e.g., BHT) are occasionally added to oxidizable aromatics; if absence of stabilizer is required (e.g., polymerization or radical chemistry), confirm by CoA.
• Metals/ions: No metal specifications are provided. For metal-sensitive cross-couplings or organometallic steps, consider pre-purifying (e.g., silica plug) and verifying by ICP if necessary.

Documentation: For this SKU, consult the lot-specific CoA/SDS for assay, impurity profile, residual solvents, and any stabilizer declaration.

Reaction and Applications

As a meta-substituted phenol, 3-cyclobutylphenol serves as a versatile building block in organic synthesis, enabling O-functionalization, protection/deprotection strategies, and directed aromatic substitution.

• O-Functionalization:

  • Alkylation: Formation of ethers via phenoxide (K2CO3/acetone or NaH/THF/DMF). Mitsunobu etherification offers complementary scope with primary/secondary alcohols.
  • Acylation/Carbonate/Carbamate formation: Acyl chlorides or anhydrides (Et3N or pyridine base) to give aryl esters; chloroformates for carbonates; CDI or triphosgene for carbamates/urethanes.
  • Sulfonate activation: Conversion to aryl triflates/mesylates of the phenolic oxygen permits subsequent cross-couplings (e.g., Pd-catalyzed C–O to C–C coupling using aryl triflates).

• Aromatic chemistry (directing effects): The phenolic OH is strongly ortho/para directing and activating for EAS (nitration, halogenation, Friedel–Crafts acylation). With a meta cyclobutyl substituent (weakly activating/deactivating through hyperconjugation/inductive effects), regioselectivity is predominantly governed by the phenolic OH.

• Ring-specific considerations:

  • The cyclobutyl group is ring-strained; under strong acidic or radical conditions it can undergo ring-opening or rearrangement—optimize conditions to preserve it.
  • Benzylic oxidation adjacent to the aryl–cyclobutyl bond can occur with harsh oxidants; milder conditions are advised.

• Applications:

  • Intermediates for agro/functional materials and as fragments in medicinal chemistry SAR exploration where a compact, lipophilic meta-substituent modulates potency and ADME-relevant properties (research use only).

Reaction Conditions

General literature guidance for phenol derivatization (optimize per substrate and scale):

• O-Alkylation (Williamson ether synthesis):

  • Base: K2CO3 (2–3 equiv) in acetone or acetonitrile, reflux 4–24 h; or NaH (1.1–1.5 equiv) in THF/DMF at 0–25 °C then add alkyl halide, 1–6 h.
  • Typical outcomes: Primary halides often high yields; secondary lower; avoid elimination-prone substrates.

• Mitsunobu etherification:

  • Reagents: DIAD or DEAD (1.1–1.5 equiv), PPh3 (1.2–1.5 equiv), ROH (1.5–2.0 equiv), THF or toluene, 0–25 °C, 2–16 h.
  • Notes: Inverts alcohol stereocenter; works well with primary/secondary alcohols.

• Acylation to esters/carbonates:

  • Acyl chloride/anhydride (1.1–1.5 equiv), base (Et3N or pyridine, 2–3 equiv), DCM/MeCN, 0–25 °C, 1–4 h.
  • Carbonates via CDI or p-nitrophenyl chloroformate in DCM/THF, 0–25 °C.

• Triflation (to aryl triflate):

  • Tf2O (1.1–1.3 equiv), base (2,6-lutidine or pyridine, 2–3 equiv), DCM at −78 to 0 °C; quench and purify. Subsequent Pd-catalyzed Suzuki: Pd(dppf)Cl2 (1–3 mol%), boronic acid (1.2–1.5 equiv), K3PO4 or K2CO3 (2–3 equiv), dioxane/H2O or toluene/H2O, 60–90 °C, 2–12 h.

• Protection:

  • Silylation (TBSCl, imidazole, DMF), 25–50 °C, 2–6 h. Benzylation (BnBr/K2CO3, acetone, reflux). Deprotection: TBAF (for silyl), H2/Pd (for Bn), mild acid (for MOM/Ac).

• Workup/purification tips:

  • Neutralize residual base/acids carefully; phenols can emulsify—brine and gentle swirling help. Add 0.1–1% Et3N to silica eluent to minimize tailing of phenolic species.

All conditions are literature-style generalizations; verify and tune for your specific electrophiles/nucleophiles and scale.

Safety and Handling

GHS classification, pictograms, and H-statements are not specified for this item in the Product Data. Always consult the SDS for authoritative hazard and response information.

General safety profile of substituted phenols (literature/generic guidance):

• Hazards: Many phenols cause skin and eye irritation and may be harmful if swallowed or inhaled. Avoid aerosol/mist generation.
• PPE: Use lab coat, safety glasses or chemical splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Work in a chemical fume hood.
• First aid (overview; follow SDS/local protocols):
  • Inhalation: Move to fresh air; seek medical advice if symptoms persist.
  • Skin: Remove contaminated clothing; wash with soap and water.
  • Eyes: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; seek medical attention for persistent irritation.
  • Ingestion: Rinse mouth; do not induce vomiting unless directed by medical personnel.
• Incompatibilities/Reactive tendencies: Strong oxidizers (risk of exotherm/oxidation), strong bases (quantitative deprotonation to phenoxide; exothermic with strong bases such as NaH), acylating/alkylating agents (react readily with the phenolic OH). Avoid prolonged contact with reactive metals when strong base is present (phenoxide complexation).
• Handling practices: Keep container tightly closed. Prevent exposure to heat sources and direct sunlight. Use clean, dry tools and anhydrous solvents when generating phenoxide salts.

Storage per Product Data: Store at room temperature. Ship under normal conditions.

Solvent Selection

3-Cyclobutylphenol is a moderately lipophilic phenol. Solvent choice should balance solubility of the neutral phenol versus its phenoxide, and compatibility with the intended transformation.

• Polarity and miscibility (general expectations):

  • High solubility: DMSO, DMF, NMP, acetone, acetonitrile, ethanol/methanol, THF, 2-MeTHF, ethyl acetate.
  • Moderate solubility: Toluene, CPME, dichloromethane (DCM), MTBE.
  • Low solubility: Alkanes (hexanes/heptane) unless co-solvent is present.
  • Aqueous: Poorly water-soluble in the neutral form; phenoxide salts dissolve better in water/alcohol-water mixtures.

• Selection by task:

  • Deprotonation/alkylation: Polar aprotics (DMF, DMSO, acetonitrile) or acetone with K2CO3. NaH-mediated O-alkylation commonly in THF, DMF, or DMSO.
  • Acylation/silylation: DCM, THF, or acetonitrile with a base (pyridine, DIPEA, imidazole).
  • Electrophilic aromatic substitution (EAS): Nonpolar to moderately polar solvents (toluene, DCM, nitromethane) depending on electrophile.
  • Purification: Normal-phase silica with hexanes/ethyl acetate or toluene/EtOAc; phenols may tail—add 0.1–1% Et3N to mobile phase if needed.

• Comparison notes:

  • 2-MeTHF/CPME can replace THF/MTBE for greener profiles while maintaining solubility of phenols.
  • For aqueous workups, salting out is effective; convert to phenoxide to shift partitioning into aqueous, then re-acidify for extraction.

Storage and Reconstitution

• Storage (from Product Data): Room temperature. Ship under normal conditions.
• Container: Store tightly closed in a clean, dry, inert container. Protect from moisture and prolonged exposure to light/air to minimize slow oxidation typical of phenols.
• Inert atmosphere: Not required by specification; however, for extended storage or for highly air/moisture-sensitive transformations, consider blanketing with dry nitrogen/argon after opening.
• Reconstitution/solubilization: Provided as a neat compound (appearance not specified). Dissolve in an appropriate organic solvent prior to use (e.g., DMSO, THF, MeCN, EtOAc, alcohols). For aqueous assays, prepare a concentrated stock in DMSO or ethanol and dilute into buffer, keeping final organic content low (commonly ≤1–2%).
• Freeze–thaw: Not applicable to neat solids/liquids. If preparing stock solutions, store aliquots to avoid repeated freeze–thaw and check for precipitation before use.
• Stability checks: Prior to critical steps, verify integrity by 1H NMR or GC/LC to rule out adventitious oxidation or contamination, especially after long-term storage.

Research Use Note: For research use only.

Structure and Identity

3-Cyclobutylphenol is a meta-substituted phenol featuring a cyclobutyl ring attached to the aromatic ring and a phenolic hydroxyl group.

• Item identifiers (from Product Data)

  • SKU: C1308549
  • CAS: 211495-49-7
  • InChIKey: 179182 (as provided; format atypical — see CoA/SDS for confirmation)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identity details (for reference; not item specifications)

  • Preferred name: 3-Cyclobutylphenol (m-cyclobutylphenol)
  • Molecular formula (literature): C10H12O
  • Molecular weight (literature): 148.20 g/mol
  • Representative SMILES (literature): c1cc(ccc1O)C2CCC2 (meta-cyclobutyl substituent)
  • Structural features: one phenyl ring bearing a phenolic OH (weakly acidic, H-bond donor/acceptor) and a saturated 4-membered cyclobutyl ring (ring strain, nonpolar character). No heteroatoms beyond one oxygen; no stereocenters; planar aromatic core with an sp3 alkyl substituent.

• 2D structure description (literature): A benzene ring with an OH group at position 1 and a cyclobutyl group at position 3 (meta). The phenolic oxygen is para to one C–C bond and ortho to two ring carbons; the cyclobutyl is a puckered 4-membered alicyclic substituent attached via a benzylic C–C bond.

Synthetic Utility

Key functional group: phenolic OH (weak acid, nucleophile as phenoxide). The meta cyclobutyl substituent is a compact, lipophilic group that can modulate sterics and electronics without introducing heteroatoms.

• Transformations from the phenolic OH:

  • Ether formation: Williamson O-alkylation (phenoxide + alkyl halide/sulfate); Mitsunobu etherification with alcohol partners.
  • Ester/carbonate/carbamate: React with acyl/haloformates or CDI/urazine-based coupling reagents to introduce protective or functional groups.
  • Sulfonate activation: Aryl triflates (Tf2O/Et3N or pyridine, −20 to 0 °C) enable Pd-catalyzed cross-couplings (Suzuki–Miyaura, Negishi, Stille) converting the C–O to C–C/O/N bonds.
  • Protective groups: Silyl (TBS/TIPS), benzyl, or MOM protection to control chemoselectivity during multi-step sequences; deprotect under standard conditions (TBAF, hydrogenolysis, mild acid).

• Aromatic functionalization:

  • EAS directed by –OH: Nitration (AcOH/HNO3 at low temp), halogenation (NBS/NCS with catalysts), sulfonylation; regioselectivity driven mainly by the activating OH group.
  • Directed ortho-metalation (DoM) adjacent to –O-protecting groups (e.g., O-alkyl/O-silyl) can allow access to ortho-substituted derivatives using s-BuLi/TMEDA at low temperature.

• Considerations for the cyclobutyl group:

  • Preserve ring integrity by avoiding strongly acidic or radical conditions that promote ring opening.
  • Oxidation on the benzylic position is possible with harsh oxidants—prefer selective electrophiles/conditions.

Overall, 3-cyclobutylphenol is a practical handle for assembling meta-cyclobutyl aryl architectures across medicinal and materials chemistry.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological targeting reagent (e.g., antibody, ligand with defined biomolecular target). No antigen/epitope, isotype, or species reactivity data are relevant.

Perguntas frequentes

What is the purity of this product?

This product is supplied at ≥95% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

How is this product shipped?

This product ships under standard ambient conditions. No temperature-controlled packaging is required.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 211495-49-7, the molecular formula is C10H12O, and the molecular weight is 148.2 g/mol. InChIKey KGAOBXXXNFRSSW-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.