Phenol, dichloro-4-methyl- - ≥95% , CAS No.33963-35-8

CAS: 33963-35-8 Cat. No.: P1039273 Formula: C₇H₆Cl₂O Molecular Weight: 177.020

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifications & Purity

≥95%

Storage

Room temperature

Purity

≥95%

Names and Identifiers

• Canonical Smiles: CC1=C(C(=C(C=C1)O)Cl)Cl
• IUPAC Name: 2,3-dichloro-4-methylphenol
• InChIKey: MCCTUAKNFRUXLR-UHFFFAOYSA-N
• INCHI: 1S/C7H6Cl2O/c1-4-2-3-5(10)7(9)6(4)8/h2-3,10H,1H3
• Molecular Weight: 177.020

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Halobenzenes
        • Level5 Chlorobenzenes
          • Level6 Dichlorobenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Halobenzenes
• Intermediate Tree Nodes: Chlorobenzenes
• Direct Parent: Dichlorobenzenes
• Alternative Parents: Para cresols O-chlorophenols M-chlorophenols Toluenes 1-hydroxy-2-unsubstituted benzenoids Aryl chlorides Organooxygen compounds Organochlorides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 1,2-dichlorobenzene - 3-halophenol - 2-halophenol - 3-chlorophenol - 2-chlorophenol - P-cresol - 1-hydroxy-2-unsubstituted benzenoid - Toluene - Phenol - Aryl halide - Aryl chloride - Hydrocarbon derivative - Organic oxygen compound - Organohalogen compound - Organochloride - Organooxygen compound - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
• 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

Chemical and Physical Properties

• Molecular Weight: 177.020 g/mol
• XLogP3: 3.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 0
• Exact Mass: 175.98 Da
• Monoisotopic Mass: 175.98 Da
• Topological Polar Surface Area: 20.200 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 118.000
• 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 assay/application protocols are provided for this small-molecule reagent. Typical laboratory uses are covered under Reaction & Applications, Synthetic Utility, and Reaction Conditions. If using in materials fabrication, catalysis, or analytical method development, validate concentration, solvent, and temperature parameters empirically and consult the primary literature.

Biological Roles

This product is a small halogenated phenolic compound primarily intended as a synthetic building block. Item-specific biological data are not provided.

General literature context for chlorinated phenols (not item-specific and not implying use in humans/animals):

• Phenolic OH enables hydrogen bonding and acid–base interactions with proteins and membranes; chlorination generally increases lipophilicity and can enhance membrane partitioning.
• Many chlorinated phenols act as enzyme inhibitors or protonophores at sufficient concentrations, disrupting energy metabolism in microorganisms; such properties underpin their historical use as biocidal agents. These effects are concentration- and structure-dependent and are not application recommendations.
• Biotransformation typically occurs via phase I hydroxylation or dechlorination followed by phase II conjugation (glucuronidation/sulfation) in biological systems; persistence increases with degree of halogenation.

No clinical, diagnostic, or therapeutic claims are made. For research use only.

Buffer Applications

This compound is not a buffering reagent and is not typically used to prepare biological or analytical buffer systems. If pH-switchable solubility is desired (via phenolate formation), see the Solvent Selection and Reaction & Applications sections for guidance on basic aqueous conditions to transiently solubilize phenols.

Green Alternatives

• Considerations:

  • Chlorinated phenols carry inherent environmental persistence and aquatic toxicity concerns. When feasible, assess whether a non-halogenated phenolic analog or an alternative protecting/activating strategy could meet your synthetic objective.

• Possible greener choices (context-dependent):

  • Replace halogenated phenols with cresols or guaiacols if halogen functionality is not essential to downstream steps.
  • For O-alkylation media, prefer bio-based ethers/esters (e.g., 2-MeTHF, EtOAc) over chlorinated solvents.
  • Use carbonate bases and aqueous micellar catalysis where compatible to reduce solvent burden.

• Comparison snapshot (general literature guidance):

  • Feedstock hazard: chlorinated phenols > non-halogenated phenols.
  • Solvent greenness: 2-MeTHF/EtOAc > THF/DMF/DMAc > DCM/chloroform.
  • Workup: pH-switchable extraction useful; minimize halogenated waste streams via solvent selection.

• Trade-offs:

  • Removing aryl chlorides may limit cross-coupling handles or alter target bio-physical properties.
  • Greener solvents may impact solubility and rate; optimization is often required.

Adopt life-cycle thinking: solvent selection, energy input (room-temperature catalysis), and waste minimization typically yield the greatest green gains.

Pharmaceutical Uses

No pharmacopeial or excipient status is specified for this item; refer to CoA/Spec Sheet if applicable. In general terms (literature context only), phenolic compounds and some chlorinated cresol derivatives have historically been explored as preservatives or intermediates in the manufacture of actives; however, such uses are highly structure-specific and regulated.

For this SKU:

• Formulation role, excipient grade, residual solvent limits, and bioburden specifications: Not specified for this item; refer to CoA/Spec Sheet.
• Any GMP or compendial compliance: Not specified for this item; refer to CoA/Spec Sheet.

Aladdin Scientific supplies reagents strictly for research and laboratory use; no claims are made regarding suitability for therapeutic, diagnostic, or clinical applications.

Physical Properties

• Item-specific measured specifications (BP, MP, density, etc.): Not specified for this item; refer to CoA/Spec Sheet.

• General/literature expectations for dichloro-methylphenols (guidance only; may vary by isomer):

  • Phase at ambient conditions: typically low-melting solids or viscous oils depending on substitution pattern (literature).
  • Water solubility: low, increased upon basification to the corresponding phenolate (literature).
  • Organic solubility: generally miscible or highly soluble in alcohols (MeOH, EtOH), ketones (acetone, MEK), esters (EtOAc), ethers (THF, MTBE), and chlorinated solvents (DCM, chloroform) (literature).
  • Acid/base behavior: phenolic pKa generally lower (more acidic) than unsubstituted phenol due to inductive effects of chlorine; exact pKa depends on isomer (literature).
  • Volatility: reduced vs non-chlorinated phenols; may exhibit appreciable vapor pressure when warmed (literature).

• Optical/refractive properties, UV cutoff, residual water/peroxides/metals: Not specified for this item; refer to CoA/Spec Sheet.

Note: Use the above as planning guidance only; consult the item’s CoA/SDS for definitive properties relevant to your application.

Quality & Grades

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

• Guidance on typical grades for small organic reagents (general):

  • Analytical/Reagent grade: controlled for common impurities suitable for general synthesis and analysis.
  • High-purity (≥98–99%): preferred for mechanistic studies or when trace impurities bias reactivity.
  • Chromatography (HPLC/GC) grade solvents are defined by low non-volatile residue/UV absorbance; not applicable to this solid unless offered as a solution.

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

• What to check on receipt:

  • Appearance vs CoA, assay/purity method (GC/HPLC/qNMR), limits on phenolic water, halogenated byproducts, and any stabilizers.
  • If critical to your work, request batch-specific UV-Vis absorbance or residual solvent profiles.

• Trace specifications (water ppm, peroxides, metals, UV cutoff): Not specified for this item; refer to CoA/Spec Sheet.

Reaction & Applications

• Functional reactivity (general for dichloro-methylphenols):

  • O-Functionalization: Efficient Williamson ether synthesis (alkyl halides/sulfates, base) and esterification (acyl chlorides/anhydrides, base or DMAP/EDC systems).
  • Electrophilic aromatic substitution (EAS): The phenolic –OH activates ortho/para positions; chloro substituents are deactivating but ortho/para-directing. Net reactivity depends on substitution pattern—nitration, sulfonation, or Friedel–Crafts may require controlled conditions.
  • Cross-coupling leverage: Aryl C–Cl bonds can participate in Pd-catalyzed couplings (Suzuki–Miyaura, Buchwald–Hartwig) using modern catalysts/ligands (e.g., Pd–NHC, bulky phosphines) after appropriate protection of the phenol if needed.
  • Metal–halogen exchange: Directed lithiation or Cl–Li exchange at low temperature can provide access to functionalized derivatives; protect the phenol (e.g., as silyl/benzyl ether) to avoid proton quench.

• Practical tips:

  • Dry the substrate and solvent; phenols can retain moisture via hydrogen bonding. If base-sensitive steps are planned, consider phenol protection (TBS, MOM, benzyl).
  • For O-alkylation, minimize C-alkylation by using mild bases (K2CO3/Cs2CO3) in polar aprotic solvents and phase-transfer catalysts as needed.
  • When targeting C–C couplings on aryl chlorides, use activated catalysts, elevated temperatures, and polar, high-boiling solvents (dioxane, toluene, DMAc) with bases such as K3PO4 or Cs2CO3 (literature guidance).

• Research contexts:

  • Serves as a halogenated phenolic building block for materials, agrochemical intermediates, and probe molecules where tunable acidity and lipophilicity are desired.

Note: No medical or clinical uses are implied; for research and laboratory applications only.

Reaction Conditions

General literature guidance for halogenated phenols (optimize for your substrate; not item-specific specifications):

• O-alkylation (Williamson ether synthesis):

  • Base: K2CO3 or Cs2CO3 (1.2–2.0 eq) for SN2 with primary alkyl halides/tosylates.
  • Solvent: Dry DMF, MeCN, or acetone; 20–80 °C; 2–16 h. Phase-transfer (TBAB) can enhance rates in biphasic toluene/H2O with NaOH.

• O-acylation (esters/carbonates):

  • Reagents: Acyl chlorides/anhydrides (1.1–1.5 eq) with pyridine/Et3N or catalytic DMAP; solvents: DCM, THF, or toluene; 0–25 °C, 0.5–4 h.
  • Steglich esterification: EDC or DCC, DMAP, in DCM or EtOAc at 0–25 °C.

• Cross-coupling on aryl C–Cl:

  • Suzuki–Miyaura: Aryl/alkenyl boron (1.2–1.5 eq), Pd(PPh3)4 or Pd-PEPPSI/NHC (1–3 mol%), base (K3PO4, Cs2CO3), solvent (1,4-dioxane, toluene, DMAc), 80–120 °C, 4–24 h.
  • Buchwald–Hartwig amination: Amine (1.2 eq), Pd2(dba)3 + bulky phosphine (BrettPhos, XPhos) or Pd–NHC, strong base (NaOtBu, Cs2CO3), toluene/DME/DMAc, 80–120 °C.

• Halogen–lithium exchange / directed metalation:

  • t-BuLi or n-BuLi in THF/Et2O at −78 to −40 °C, then electrophile quench (e.g., DMF, CO2, B(OMe)3). Protect phenol to avoid proton transfer.

• Electrophilic substitutions:

  • Nitration/sulfonation typically require mild conditions due to phenolic activation but are moderated by chloro deactivation; temperature control critical for regioselectivity.

Reported yields vary widely with isomer, catalyst, and protection strategy. Conduct small-scale screens to identify optimal ligand/base/solvent combinations.

Safety & Handling

• GHS classification, signal word, hazard and precautionary statements, and pictograms: Not specified for this item; refer to the product SDS for authoritative hazard communication.

• General hazards for chlorinated phenols (literature/experience-based):

  • Can be corrosive/irritating to skin, eyes, and respiratory tract; phenols may be absorbed through skin.
  • Potential acute toxicity and environmental hazard (toxic to aquatic life) typical of halogenated phenols.
  • May release HCl and other toxic fumes upon thermal decomposition/combustion.

• Handling recommendations (good laboratory practice):

  • Work in a fume hood; avoid inhalation and skin contact. Wear appropriate PPE: lab coat, nitrile gloves (change regularly), splash goggles.
  • Prevent environmental release; collect waste as halogenated organic waste.
  • Avoid contact with strong oxidizers and strong bases unless generating phenolates intentionally; phenolates can be caustic and highly reactive.

• First aid (general guidance; defer to SDS):

  • Skin: Immediate decontamination with copious water and soap; remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes; seek medical attention.
  • Inhalation: Move to fresh air; obtain medical attention if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.

Always consult the current SDS for this specific SKU before use.

Solvent Selection

• Polarity and miscibility (general behavior of chlorinated phenols):

  • Poorly soluble in water at neutral pH; forms water-soluble phenolates in basic aqueous media (e.g., NaOH, carbonate) enabling biphasic extraction strategies.
  • Good solubility in polar protic and aprotic organics (MeOH, EtOH, i-PrOH, acetone, acetonitrile, ethyl acetate) and ethers (THF, MTBE). Often highly soluble in chlorinated solvents (DCM, chloroform).

• Choosing solvents for synthesis/purification:

  • For O-alkylation/esterification: dry acetone/DMF/MeCN/THF with a soluble base (K2CO3, Cs2CO3) to form the phenolate in situ.
  • For acylations (Schotten–Baumann): biphasic toluene or DCM / aqueous base aids neutralization of HCl.
  • For crystallization: employ anti-solvent methods (e.g., dissolve in EtOAc or hot ethanol, precipitate with hexanes/water depending on ionization state).
  • For extractions: switch solubility via pH control (extract into organic at low pH; into aqueous at high pH as phenolate).

• Comparison notes (general):

  • Versus non-chlorinated cresols: chlorinated analogs are often less water-soluble and more lipophilic, benefiting organic-phase handling but complicating aqueous workups.
  • Versus phenol: higher acidity (easier deprotonation), similar solvent choices but often lower volatility.

All solvent choices should consider compatibility with bases and the phenolic functionality; verify solubility empirically for your specific isomer.

Storage & Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Container: Store tightly closed in an appropriate amber glass bottle if possible to limit light exposure; use PTFE-lined caps for phenolic reagents.
• Atmosphere: Keep in a dry environment; reseal promptly to minimize moisture uptake and oxidation.
• Incompatibilities: Avoid strong oxidizers; segregate from strong bases unless intentionally generating phenolates.
• Stability: Phenolic compounds are generally stable at ambient conditions; monitor for discoloration or odor changes indicative of degradation or contamination.
• Reconstitution/solution prep: Dissolve in a compatible organic solvent (e.g., EtOAc, THF, MeOH, DCM) as required by the application. For aqueous handling, adjust to basic pH to form the water-soluble phenolate, then neutralize post-use if needed.
• Freeze–thaw: Not typically applicable to solids; for stock solutions, store in sealed vials under inert gas if long-term storage is planned and avoid repeated freeze–thaw by aliquoting.

Always refer to the batch-specific CoA/SDS for definitive storage and stability guidance.

Structure & Identity

• Item-specific identifiers from Product Data:

  • Product name: Phenol, dichloro-4-methyl- (a halogenated cresol)
  • CAS: 33963-35-8
  • CID: 12311536 (reference identifier)
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Structural class and features (general chemistry context):

  • Phenolic aromatic bearing one hydroxyl group (–OH) on a benzene ring.
  • Two chloro substituents (–Cl) and one methyl group (–CH3) on the ring (i.e., a dichloro-methylphenol; specific substitution pattern is defined by the CAS but is not restated here).
  • Functional groups: phenol (weakly acidic, capable of hydrogen bonding), aryl chlorides (potential handles for cross-coupling or metal–halogen exchange), and a methyl group (weakly activating/ortho–para directing, benzylic site for oxidative or radical chemistry).

• 2D description (general):

  • A monosubstituted phenolic ring with three additional ring substituents: two chlorines and one methyl group. The phenolic OH can engage in intra- and intermolecular hydrogen bonding; chlorines increase lipophilicity and acidity (inductive withdrawal), while the methyl group modestly increases electron density at ortho/para positions.

• Stereochemistry: Not applicable (achiral aromatic).

Synthetic Utility

• Phenolic handle:

  • Readily converted to aryl ethers (Williamson), aryl esters (acyl chlorides/anhydrides or Steglich conditions), and carbonate/urethane derivatives.
  • Can be protected as silyl ethers (TBS/TBDPS), benzyl ethers, or carbonates to mask acidity and direct reactivity.

• Aryl chloride functionality:

  • Serves as a platform for Pd-catalyzed cross-couplings (Suzuki–Miyaura, Negishi, Buchwald–Hartwig amination). Modern catalyst systems enable C–Cl activation; phenol may require protection under strong basic conditions.
  • Enables directed metalation or halogen–lithium exchange at low temperature for subsequent electrophile trapping (e.g., formylations, carboxylations, borylations).

• Ring electronics and directing effects:

  • The –OH group donates electron density (activating, o/p-directing), while –Cl groups are deactivating but o/p-directing; methyl is weakly activating. Net site-selectivity in EAS or metalation steps depends on the specific substitution pattern (defined by the CAS) and protecting-group strategy.

• Retrosynthetic value:

  • A versatile phenolic/aryl chloride linchpin for assembling libraries with tunable polarity and lipophilicity by orthogonal modification at O and C–Cl sites.
  • Useful precursor to polyaryl architectures, aryl amines/ethers, and benzylic derivatives via selective functionalization.

Plan sequences to exploit orthogonality: O-derivatization first, then C–Cl activation (or vice versa) with appropriate protection to manage chemo- and regioselectivity.

Target Specificity

Not applicable. This SKU is a small-molecule organic reagent, not a biological macromolecule or antibody. No antigen/epitope, species reactivity, or isotype information applies.