2-Bromo-4-methylphenol - ≥96% , CAS No.6627-55-0

CAS: 6627-55-0 Cat. No.: B141113 Formule: C₇H₇BrO Poids moléculaire: 187.04 Beilstein Registry Number: 6405 Numéro CE: 229-595-7

GRADE & PURITY ≥96%

Synonyms

DTXSID8074574 | p-Cresol, 2-bromo- (6CI,7CI,8CI); 2-Bromo-4-methylphenol; 2-Bromo-4-cresol; 2-Bromo-p-cresol; 3-Bromo-4-hydroxytoluene; NSC 60115 | p-CRESOL, 2-BROMO- | BB 0262339 | EINECS 229-595-7 | NSC 60115 | 2-Bromo-4-methylphenol, 96% | BRN 1859036

Storage

Room temperature,Argon charged

Shipped In

Normal

Specifications

Synonymes

DTXSID8074574 | p-Cresol, 2-bromo- (6CI,7CI,8CI); 2-Bromo-4-methylphenol; 2-Bromo-4-cresol; 2-Bromo-p-cresol; 3-Bromo-4-hydroxytoluene; NSC 60115 | p-CRESOL, 2-BROMO- | BB 0262339 | EINECS 229-595-7 | NSC 60115 | 2-Bromo-4-methylphenol, 96% | BRN 1859036

Spécifications et pureté

≥96%

Conditions de stockage de stockage

Room temperature,Argon charged

Expédié en

Normal

Pureté

≥96%

Noms et identifiants

Pubchem Sid

504753109

Pubchem Sid Url

https://pubchem.ncbi.nlm.nih.gov/substance/504753109

Sourires canoniques

CC1=CC(=C(C=C1)O)Br

IUPAC Name

2-bromo-4-methylphenol

InChIKey

MTIDYGLTAOZOGU-UHFFFAOYSA-N

INCHI

1S/C7H7BrO/c1-5-2-3-7(9)6(8)4-5/h2-4,9H,1H3

Isomères SMILES

CC1=CC(=C(C=C1)O)Br

WGK Allemagne

3

RTECS

GO6868200

Poids moléculaire

187.04

Beilstein

6405

Reaxy-Rn

1859036

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=1859036&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Phenols
      • Subclass Cresols

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Phenols
• Subclass: Cresols
• Intermediate Tree Nodes: Not available
• Direct Parent: Para cresols
• Alternative Parents: O-bromophenols Toluenes Bromobenzenes 1-hydroxy-2-unsubstituted benzenoids Aryl bromides Organooxygen compounds Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 2-halophenol - 2-bromophenol - P-cresol - Bromobenzene - Halobenzene - 1-hydroxy-2-unsubstituted benzenoid - Toluene - Aryl halide - Aryl bromide - Monocyclic benzene moiety - Organohalogen compound - Organic oxygen compound - Organobromide - Organooxygen compound - Hydrocarbon derivative - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as para cresols. These are compounds containing a para cresol moiety, which consists of a benzene ring bearing one hydroxyl group at ring positions 1 and 4.
• 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

Propriétés chimiques et physiques

• Sensibilité: air sensitive
• Indice de réfraction: 1.578
• Point d'éclair (°F): >110°C(230°F)
• Point d'éclair (°C): >110°C(230°F)
• Point d'ébullition (°C): 213-214°C
• Point de fusion (°C): 16°C
• Poids moléculaire: 187.030 g/mol
• XLogP3: 2.400
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 0
• Exact Mass: 185.968 Da
• Monoisotopic Mass: 185.968 Da
• Topological Polar Surface Area: 20.200 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 94.900
• 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 biological assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic use, refer to the Reaction Conditions and Synthetic Utility sections for representative procedures and optimization tips.

Biological Roles

This product is intended strictly for research use; no clinical or diagnostic use is implied.

• General biochemical context (literature)
  • Phenolic rings are common motifs in natural products and biomolecules, contributing to hydrogen bonding, redox behavior, and π–π interactions with proteins and nucleic acids.
  • Halogenation (bromine) modulates lipophilicity and polarizability, influencing membrane affinity and binding through halogen bonding.
  • The para-methyl group subtly increases electron density and can affect metabolic oxidation patterns in phenolic scaffolds.
• Research implications
  • 2-Bromo-4-methylphenol can serve as a probe-like scaffold for SAR studies where the bromide is a synthetic handle for rapid diversification (e.g., replacing Br with aryl, amine, or boron groups) while assessing the role of a phenolic hydrogen bond donor.
  • The phenolic pKa (~10 for related compounds; literature) allows pH-dependent ionization studies relevant to transport or partitioning models.

No specific biological targets or activities are assigned to this item. Any biological testing should be designed and interpreted by qualified researchers under appropriate institutional approvals.

Buffer Applications

This compound is not a buffering reagent and is not typically used to prepare laboratory buffer systems.

• Practical note
  • The phenolic OH is weakly acidic (literature pKa for similar phenols ~10), but this does not make it suitable as a buffering agent in physiological pH ranges.
  • For pH control, choose established buffer systems (e.g., phosphate, Tris, HEPES) appropriate to your application.

Green Alternatives

While 2-bromo-4-methylphenol is a substrate rather than a solvent, greener choices can be made in its use and in alternative disconnections.

• Greener solvent choices (for typical reactions)

  • Prefer 2-MeTHF, EtOAc, MeOH/EtOH, water/ethanol mixtures, or Cyrene where compatible, in place of dioxane, DMF, or NMP.
  • Use toluene or 2-MeTHF instead of chlorinated solvents when possible; reserve DCM only for critical steps.

• Alternative coupling strategies

  • C–H functionalization (literature): Direct arylation of p-cresol derivatives can obviate prefunctionalization with bromine, reducing halogenated waste; requires catalyst optimization and may have scope limitations.
  • Aryl triflates vs bromides: Phenol-to-triflate enables high reactivity; although not inherently greener, it may improve step economy and yields, reducing rework/waste.

• Base and workup considerations

  • Aqueous K2CO3/Na2CO3 in ethanol/water for Suzuki couplings can replace stronger inorganic bases; biphasic systems simplify separation.
  • Replace phase-transfer halogenated solvents with greener alternatives (e.g., PEG-400, propylene carbonate) when feasible.

Small comparison (general)

• THF vs 2-MeTHF: similar polarity; 2-MeTHF has bio-based sourcing and easier aqueous separations; may require adjusted temperatures due to higher bp.
• Dioxane vs toluene: dioxane offers solubility and miscibility with water but has worse health/environmental profile; toluene is less polar but often adequate with tuned ligands.

Trade-offs exist; choose conditions that balance safety, waste minimization, and performance without compromising selectivity.

Pharmaceutical Uses

No pharmacopeial excipient status or formulation grade is specified for this item; it is supplied for research and chemical synthesis only.

• Potential roles in pharmaceutical R&D (general)
  • Synthetic intermediate: The aryl bromide enables formation of diverse biaryl/aryl–heteroatom linkages common in API scaffolds, while the phenol can be protected, etherified, or esterified.
  • Probe/library synthesis: A handle for parallel synthesis to explore structure–property relationships by modifying the aryl position bearing bromine and derivatizing the phenol.
• Manufacturing considerations
  • If used in GMP pathways, the route would require qualification of impurity profiles and residual metals/solvents per ICH guidelines; this catalog item is not designated for GMP use unless explicitly stated on the CoA.

No therapeutic claims are made or implied. This product is for research use only.

Physical Properties

Only item-specific values listed in Product Data may be treated as specifications. The following are literature/general properties for reference; verify against the CoA/SDS for this lot.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting/boiling point: Not specified for this item; refer to CoA/Spec Sheet. (Literature: aryl bromophenols of similar substitution often melt near ambient and boil >230 °C under reduced pressure; exact values vary by isomer.)
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (general behavior, literature):
  • Organics: Readily soluble in common organic solvents (e.g., dichloromethane, ethyl acetate, THF, acetone, toluene, alcohols) due to aromatic core and moderate polarity of the phenol.
  • Water: Sparingly soluble; phenolic OH provides limited aqueous solubility, enhanced in basic media via phenolate formation.
• Acid–base: Phenolic pKa typically ~10 for p-cresol derivatives (literature); deprotonation enables nucleophilic O-alkylation/acylation.
• Partitioning: Phenolic aryl bromides generally show moderate lipophilicity (logP in the 2–3 range, literature for close analogs); check lot-specific data if needed.

Note: Do not treat these literature values as specifications. For exact numeric properties (mp, bp, density, water content, UV cutoff, metal impurities), see the item-specific CoA/Spec Sheet.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• What “grade” implies (general guidance)
  • Research grade: Suitable for most synthetic and discovery workflows; impurity profile acceptable for general lab use.
  • High-purity/analytical grades (if specified on CoA) support sensitive applications (e.g., catalyst screening, spectroscopy) where trace impurities can bias outcomes.
• Stabilizers/inhibitors
  • Not specified for this item; refer to CoA/Spec Sheet. Phenolic materials are typically shipped without stabilizers; inert-atmosphere packaging limits oxidative discoloration.
• Documentation
  • Each lot should be supported by a Certificate of Analysis listing assay/purity, identity (NMR/IR/HRMS where available), and key residuals if applicable. For any unlisted parameter (water, metals, UV cutoff), consider requesting an extended spec.
• Practical notes for this substrate
  • For cross-coupling and metalation chemistry, low halogen exchange and minimal phenolic impurities are important; if your application is catalyst-sensitive, request recent CoA and consider in-house KF or GC for verification.

Reaction and Applications

2-Bromo-4-methylphenol couples a reactive aryl bromide with a handleable phenolic OH, enabling orthogonal transformations.

• Halogen-driven transformations
  • Suzuki–Miyaura coupling: Convert the Ar–Br into biaryl frameworks using aryl/alkenyl/alkyl boron partners. Phenol can be protected (e.g., as TBS) to prevent O-arylation.
  • Buchwald–Hartwig amination: Install anilines or diarylamines using Pd catalysts/ligands; phenol protection recommended in many cases.
  • Miyaura borylation: Generate the corresponding boronic ester (pinacol boronate) from the bromide for subsequent diversification.
  • Carbonylation (Pd-catalyzed): Access aryl esters/amides under CO; the phenol can serve as a nucleophile after protection/deprotection planning.
• Phenol-driven transformations
  • Williamson ether synthesis: O-alkylation to aryl ethers after base activation (NaH, K2CO3, Cs2CO3).
  • Ester formation: Acyl chloride/anhydride coupling to aryl esters; used as protecting groups or intermediates.
  • Triflation: Conversion to aryl triflate (after methylation or direct from phenol via Tf2O/pyridine) to create an alternative, highly reactive coupling handle.
• Directed metalation and orthogonal strategies
  • Metal–halogen exchange (e.g., with n-BuLi or i-PrMgCl•LiCl) gives aryl lithium/magnesium species for formylation, carboxylation, or electrophile trapping; protect the phenol (e.g., as silyl ether) to avoid acid–base quench.
  • Electrophilic substitution elsewhere on the ring is influenced by the methyl/phenol directing effects; nitration, sulfonylation, and halogenation require selectivity control.
• Applications
  • Intermediate for brominated cresyl ethers/esters, ligands, fine chemicals, and materials monomers where a phenolic motif is retained or elaborated.

Note: Selectivity between O- vs C-coupling must be managed by protection, base choice, and catalyst/ligand selection.

Reaction Conditions

General literature guidance; optimize for your specific system. Values below are not item specifications.

• Suzuki–Miyaura coupling (Ar–Br to biaryl)

  • Catalyst: Pd(dppf)Cl2·DCM (1–3 mol%) or Pd2(dba)3 (1 mol%) with suitable phosphine ligand (SPhos/XPhos).
  • Base: K3PO4, K2CO3, or Cs2CO3 (2–3 equiv); aqueous or anhydrous depending on solvent.
  • Solvent: 1,4-dioxane/H2O, 2-MeTHF/H2O, or toluene/EtOH/H2O.
  • Temperature/time: 60–100 °C, 2–16 h.
  • Notes: Protect phenol when O-arylation competes; weaker bases and bulky ligands favor C–C coupling.

• Buchwald–Hartwig amination (Ar–Br to aryl amine)

  • Catalyst/ligand: Pd2(dba)3 (1 mol%) + BrettPhos or RuPhos; or Pd-PEPPSI for Ni options.
  • Base: NaOtBu, KOtBu, or Cs2CO3 (1.5–2.0 equiv).
  • Solvent: Toluene, 2-MeTHF, or dioxane.
  • Temperature: 80–110 °C.
  • Tip: Phenol protection often required to suppress aryl O-arylation.

• Miyaura borylation (Ar–Br to Ar–B(pin))

  • Catalyst: Pd(dppf)Cl2 (1–3 mol%) or Pd(OAc)2 with dtbpy (Ni variant).
  • Reagents: B2pin2 (1.2–1.5 equiv), KOAc (2–3 equiv).
  • Solvent: 1,4-dioxane or 2-MeTHF.
  • Temperature: 70–90 °C, 4–12 h.

• Metal–halogen exchange and electrophile trapping

  • Reagent: n-BuLi (1.0–1.2 equiv) at −78 to −20 °C in dry THF/Et2O; protect phenol beforehand (e.g., TBS) to prevent quenching.
  • Electrophiles: CO2 (to acid), DMF (to aldehyde), I2/Br2 (to dihalides), trialkyl borates (to boronic acids).

Always monitor by TLC/GC/LC, and rigorously exclude moisture/air for metalations and Pd/Ni couplings.

Safety and Handling

• GHS/Signal Word/Pictograms/H-statements: Not specified for this item; refer to SDS for authoritative hazard classification.
• Anticipated hazards (general, based on structure; defer to SDS):
  • May cause skin and eye irritation; phenols can be harmful if absorbed through skin.
  • Aryl bromides are generally combustible organic liquids/solids; avoid ignition sources.
• Personal protective equipment
  • Use chemical-resistant gloves (e.g., nitrile), lab coat, and safety glasses or face shield.
  • Handle in a fume hood to avoid inhalation of vapors or dust.
• Storage incompatibilities and precautions
  • Store away from strong oxidizers and strong bases/acids that may induce undesired reactions.
  • Phenols can slowly oxidize; exclusion of air helps minimize discoloration and impurity growth.
• First-aid overview (consult SDS for detail)
  • Skin: Wash with soap and water; remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes; remove contact lenses if present.
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth; seek medical attention.
• Fire-fighting measures (general)
  • Use dry chemical, CO2, or foam. Combustion may produce CO/CO2 and HBr.
• Stability/Peroxides
  • Phenolic aryl bromides are not peroxide-forming like ethers; primary concern is oxidative darkening/polymerization in air over time. Store under inert gas as specified (argon-charged).

Always refer to the product’s SDS for definitive safety, handling, and disposal guidance.

Solvent Selection

This item is a small-molecule building block rather than a solvent. The guidance below addresses solvent choice when using 2-bromo-4-methylphenol in synthesis.

• Polarity and solubility considerations (general)
  • The substrate is typically soluble in moderately polar aprotic solvents (THF, 2-MeTHF, dioxane, DMF, DMAc, NMP) and in less polar media (toluene, DCM, EtOAc). Aqueous solubility is low but increases upon deprotonation to the phenolate.
• Typical solvent choices by transformation
  • Cross-coupling (Suzuki–Miyaura, Buchwald–Hartwig): 1,4-dioxane, toluene, or THF/2-MeTHF, often with aqueous base (biphasic or homogenous with alcohol/water).
  • Metal–halogen exchange/aryllithium generation: Dry THF or diethyl ether at −78 to −20 °C.
  • O-alkylation/acylation (Williamson, Schotten–Baumann variants): Polar aprotics (DMF, DMSO, acetone, MeCN) with inorganic base; biphasic conditions (toluene/aqueous base) also common.
  • Protection of phenol (silylation): Anhydrous DCM, THF, or MeCN.
• Comparison notes
  • 2-MeTHF can replace THF in many cases, offering higher boiling point and greener profile; solubility of bases and salts may differ.
  • Dioxane is excellent for coupling but is classified as a potential carcinogen; consider toluene or 2-MeTHF when feasible.
• Practical tips
  • Remove dissolved oxygen for Pd-catalyzed couplings (sparge or freeze–pump–thaw) if air-sensitive catalysts/ligands are used.
  • Ensure complete deprotonation of the phenol when targeting O-alkylation; heterogeneous bases may require phase-transfer catalysts.

Storage and Reconstitution

• Item-specific storage and shipping

  • Storage conditions: Room temperature, Argon charged (as provided). Keep container tightly closed under inert gas to minimize oxidative discoloration and degradation.
  • Shipped in: Normal (as provided).

• General handling guidance

  • Minimize headspace oxygen; reseal under argon or nitrogen after each use. Use dry transfer techniques if employing air/moisture-sensitive reactions.
  • Protect from prolonged light and heat sources. Avoid contact with strong oxidizers and strong bases/acids during storage.

• Reconstitution/dissolution

  • Solubility: Readily dissolves in common organic solvents such as dichloromethane, ethyl acetate, THF/2-MeTHF, acetone, toluene, and alcohols (literature). Sparingly soluble in water; soluble upon deprotonation with base.
  • Preparation of stock solutions: For reaction setup, prepare solutions at convenient molarity (e.g., 0.1–1.0 M) in anhydrous solvent; store short-term under inert atmosphere at ambient temperature. For longer-term solutions, refrigerate under inert gas and protect from moisture.

• Stability notes

  • Phenolic compounds can slowly oxidize, leading to darkening; inert-gas storage reduces this risk. No known peroxide formation issues.
  • If solidification or crystallization occurs near room temperature, gently warm to dissolve (exact mp not specified for this item; refer to CoA/Spec Sheet).

Always consult the product CoA and SDS for definitive storage and handling instructions.

Structure and Identity

Brief description: 2-Bromo-4-methylphenol is a brominated p-cresol derivative bearing a phenolic OH, a para-methyl group, and an ortho-bromine. It serves as a versatile aryl-bromide/phenol building block for cross-coupling and derivatization chemistry.

• Item-specific identifiers (from Product Data)

  • SKU: B141113
  • Product name: 2-Bromo-4-methylphenol
  • CAS: 6627-55-0
  • CID: 23109
  • InChIKey: 227970 (as provided; full InChIKey not specified for this item; refer to CoA/Spec Sheet.)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Core structural features (general chemistry description)

  • Ring system: Monosubstituted phenyl ring bearing three substituents overall (phenolic OH at C1, Br at C2, CH3 at C4 relative to OH).
  • Functional groups: Phenol (acidic Ar–OH), aryl bromide (C(sp2)–Br), methyl (weakly activating, ortho/para-directing).
  • Substitution pattern: 2-bromo, 4-methyl relative to the phenolic OH (i.e., 4-methyl-2-bromophenol).
  • Stereochemistry: None (achiral, planar aromatic).

• Empirical formula and formula mass

  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet. (Literature: C7H7BrO)
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (Literature: ~187.03 g/mol)

• 2D structure in words

  • A benzene ring with an OH at position 1, a Br atom ortho to the OH (position 2), and a methyl group para to the OH (position 4).

Synthetic Utility

• Orthogonal reactivity
  • Ar–Br: amenable to Pd-catalyzed cross-couplings (Suzuki, Stille, Negishi, Sonogashira), Ni-catalyzed couplings, borylation, and carbonylation.
  • Ar–OH: enables ether/ester synthesis, sulfonylation (e.g., tosylate/mesylate), carbonate formation, or conversion to aryl triflate for enhanced cross-coupling reactivity.
• Protection strategies
  • Common: TBS/TBDPS silyl ethers (imidazole, DMF; or TBSCl, Et3N), benzyl ethers (BnBr/NaH), and methyl ethers (MeI/Ag2O or Me2SO4/K2CO3). Deprotection after C–C/C–N bond formation restores phenol.
• Retrosynthetic value
  • Provides an aryl electrophile embedded in a p-cresol framework; enables late-stage diversification to access libraries of brominated/biaryl cresol analogs.
• Functional group interconversions
  • Oxidation of the para-methyl to acid/aldehyde (e.g., KMnO4, SeO2) while managing the phenol via protection.
  • Sandmeyer-like routes are unnecessary due to preinstalled bromide; however, halogen exchange (Br→I via Finkelstein variants on aryl systems is non-trivial; alternative is dihalogenation/iododebromination under specific conditions, literature).
• Compatibility notes
  • Phenol can chelate metals and inhibit some catalysts; protection or base selection (e.g., carbonate vs alkoxide) may be required to favor C-coupling over O-coupling.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological macromolecule or affinity reagent. No antigen, epitope, clone, isotype, or species reactivity applies.

Foire aux questions

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 6627-55-0, the molecular formula is C7H7BrO, and the molecular weight is 187.04 g/mol. InChIKey MTIDYGLTAOZOGU-UHFFFAOYSA-N.