2,6-Dichlorophenol - 10mM in DMSO , CAS No.87-65-0

CAS: 87-65-0 Cat. No.: D660567 Formula: C₆H₄Cl₂O Molecular Weight: 163 Beilstein Registry Number: 1447806 EC Number: 201-761-3

GRADE & PURITY 10mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Soluble in alcohol, ether, petroleum ether, benzene and water. Low toxicity, 50% lethal dose (rat, oral) 2940mg/kg. Irritating to eyes and skin.Organic synthesis, gas chromatography to compare samples.

Specifications

Specifications & Purity

10mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Names and Identifiers

Isomeric SMILES

C1=CC(=C(C(=C1)Cl)O)Cl

WGK Germany

2

RTECS

SK8750000

UN Number

2020

Packing Group

III

Molecular Weight

163

Beilstein

1447806

Reaxy-Rn

1447806

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=1447806&ln=

Chemical and Physical Properties

• Sensitivity: Moisture sensitive
• Boil Point(°C): 219-220°C
• Melt Point(°C): 67-69°C

Application Protocols

No assay-specific protocols (WB, IHC, IF, FC, etc.) are applicable to this small-molecule reagent. For synthetic uses, see Reaction Conditions and Application notes provided in Reaction & Applications and Synthetic Utility.

Biological Roles

Item-specific biological data: Not specified for this item; research use only.

General context (literature):

• 2,6-Dichlorophenol is not a known endogenous metabolite and has no constructive biological role in living systems. As a chlorinated phenol, it may interact nonspecifically with lipid membranes and proteins due to its hydrophobicity and acidity.
• Phenols can undergo phase II metabolism (e.g., glucuronidation, sulfation) in vivo; chlorination often slows oxidative biodegradation relative to phenol.
• Environmental toxicology literature highlights that certain chlorophenols exhibit aquatic toxicity and persistence; specific thresholds and regulatory classifications vary by jurisdiction and must be consulted in official databases.

This information is provided for general biochemical context. No clinical or therapeutic claims are made; this product is for research use only.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare biochemical buffers. As a weak acid (phenol), its pKa and poor aqueous solubility make it unsuitable for controlled buffering in common lab systems. For relevant usage, see Reaction & Applications and Synthetic Utility.

Green Alternatives

While 2,6-dichlorophenol is a useful building block, chlorinated phenols carry environmental concerns (persistence, aquatic toxicity). Consider greener strategies when feasible (general guidance):

• Substrate/route choices:
  • Use less-halogenated or non-halogenated phenolic precursors when chlorine substituents are not required in the final target.
  • Employ catalytic C–H functionalization of phenol/anisole to install para substituents directly, avoiding pre-halogenated starting materials.
• Solvent optimization around this substrate:
  • Replace chlorinated solvents with greener options (e.g., EtOAc, 2-MeTHF, CPME) where compatible.
  • For cross-coupling, aqueous micellar media (e.g., TPGS-750-M) or bio-based solvents (Cyrene, propylene carbonate) can be explored.
• Comparison snapshot (general):
  • 2,6-dichlorophenol vs phenol: The former affords para-selectivity but introduces halogenated waste; the latter is greener but leads to isomer mixtures unless directed methods are used.
  • Dioxane vs CPME/2-MeTHF as coupling solvents:
    • Dioxane: effective but with health/peroxide concerns.
    • CPME/2-MeTHF: bio-based options with broad utility, easier drying, and better safety profiles; may require condition re-optimization.
• Waste minimization:
  • Capture phenolate-containing aqueous waste and treat as hazardous; avoid uncontrolled neutralization that generates heat.

Trade-offs are project-specific; assess EHS impacts alongside synthetic efficiency.

Pharmaceutical Uses

Item-specific pharmacopeial/excipient status: Not specified for this item; refer to CoA/Spec Sheet.

General notes (non-clinical, formulation/manufacturing context only):

• 2,6-Dichlorophenol is primarily a synthetic intermediate and is not commonly employed as a pharmaceutical excipient. In medicinal chemistry, it may be used as a building block to access para-substituted phenolic cores with defined steric profiles.
• Impurity control: Chlorinated phenols may appear as process-related impurities in some syntheses and are typically tightly controlled due to safety and sensory concerns; validated analytical methods (GC, HPLC, GC–MS) are recommended for trace detection.
• Handling in process development: Where used, closed handling systems and rigorous containment are advisable to mitigate operator exposure and environmental release.

No therapeutic claims are made; this product is offered strictly for research and laboratory synthesis.

Physical Properties

Item-specific specifications (grade-specific cutoffs, impurity limits, etc.): Not specified for this item; refer to CoA/Spec Sheet.

Literature/general physicochemical data for 2,6-dichlorophenol (for reference only; not product specifications):

• Appearance: typically a crystalline solid (literature)
• Melting point: ~68–70 °C (literature)
• Boiling point: ~218–220 °C at 1 atm (literature)
• Density (solid): not commonly reported; liquid density near melt is expected >1 g/mL due to Cl content (qualitative, literature trend)
• pKa (phenolic OH): ~7.0–7.2 at 25 °C (literature)
• LogP (octanol/water): ~3.0–3.2 (literature)
• Water solubility: sparingly soluble; increased solubility in alkaline media via phenolate formation (general phenol behavior)
• Solubility (organic): good in common organic solvents such as alcohols, acetone, ethyl acetate, chlorinated solvents, and aromatics (literature)
• UV characteristics: phenols show π→π* absorbance near 270–280 nm; exact cutoff/ε not specified for this item.

Notes for practitioners:

• The phenolic OH enables formation of sodium or potassium phenolate, markedly changing solubility and reactivity; plan workup accordingly.
• Always verify exact values and acceptance criteria on the item’s CoA/specification when these parameters are critical to your method.

Quality & Grades

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

General guidance on grades relevant to 2,6-dichlorophenol (for researchers selecting material):

• Analytical/AR grade: Intended for analytical work; tighter impurity profiles. Suitable when trace impurities (e.g., other dichloro isomers or residual phenol) may interfere.
• Synthetic grade: Adequate for routine transformations (O-alkylation, acylation, Pd cross-coupling) where downstream purification is planned.
• HPLC grade (less common for solids): When available, implies low UV-absorbing and metal impurities; useful if the compound is used as a chromatography standard.
• Stabilizers: Phenolic solids are generally offered without stabilizers; if any stabilizer is used, it should be disclosed on the CoA. This item: Not specified for this item; refer to CoA/Spec Sheet.

Best practices:

• If using in metal-catalyzed cross-coupling at low catalyst loadings, consider screening lots for trace metal content and halide/isomeric purity.
• Verify water content if moisture sensitivity affects your route (e.g., base-promoted O-alkylations). If Karl Fischer data are required: Not specified for this item; refer to CoA/Spec Sheet.

Reaction & Applications

As a sterically encumbered phenol bearing ortho dichloro substituents, 2,6-dichlorophenol is a versatile intermediate with notable para selectivity.

• Key transformations (literature/general):
  • Selective para-functionalization: Electrophilic aromatic substitution (nitration, sulfonylation, Friedel–Crafts type reactions tailored to phenols) predominantly at C4 due to 2,6-blocking and OH activation.
  • O-derivatization: Formation of ethers (Williamson ether synthesis) and esters (acyl chlorides/anhydrides, Steglich) via the phenoxide; enables protecting-group strategies or ligand synthesis.
  • Cross-couplings on aryl chlorides: With optimized catalysts (Pd/XPhos, BrettPhos, SPhos systems), the 2- and 6-chloro positions can undergo Suzuki–Miyaura, Buchwald–Hartwig, or Negishi couplings at elevated temperatures.
  • Oxidation/reduction: Phenolic oxidation to quinone-like species is possible under strong oxidants; generally avoided unless synthetic target demands.
  • Directed transformations via phenolate: O-alkylation to introduce handles for further elaboration (e.g., benzyl/allyl ethers for subsequent deprotection or Claisen rearrangements).
• Practical tips:
  • Generate the phenolate in situ with K2CO3/Cs2CO3 for mild O-alkylation; employ NaH or t-BuOK for more challenging alkyl halides (avoid elimination-prone substrates).
  • For Pd-catalyzed coupling on C–Cl, rigorously exclude moisture/air, use strong electron-rich ligands, and consider micro-wave heating or high-boiling solvents (120–150 °C).
  • Para-selectivity is a strategic advantage vs. phenol; leverage this when positional isomers are problematic.
• Representative uses:
  • Intermediate for chlorinated phenyl ethers/esters; precursor to hindered phenolic ligands and specialty monomers; scaffold for materials and agrochemical research.

All uses are for research and laboratory synthesis only.

Reaction Conditions

General literature guidance (example conditions; optimize for your system):

• O-alkylation (Williamson ether synthesis):

  • Substrate: 2,6-dichlorophenol (1.0 eq), alkyl bromide/iodide (1.1–1.5 eq)
  • Base: K2CO3 (2–3 eq) or Cs2CO3 (1.5–2 eq); for hindered electrophiles, NaH (1.1–1.5 eq)
  • Solvent: DMF, MeCN, acetone, 2-MeTHF
  • Temperature/time: 25–60 °C, 2–16 h
  • Notes: Quench with NH4Cl, extract; avoid strong base with elimination-prone secondary halides.

• O-acylation (Steglich):

  • Carboxylic acid (1.1 eq), DCC or EDCI (1.1–1.2 eq), DMAP (0.05–0.1 eq), DCM/DMF (0–25 °C)
  • Clean conversions to aryl esters with minimal racemization (if chiral acid).

• para-Electrophilic substitution (e.g., sulfonation/nitration):

  • Controlled conditions to avoid overreaction; solvents like AcOH or DCE; temperature 0–25 °C for sensitive electrophiles.

• Suzuki–Miyaura coupling on aryl C–Cl (challenging but feasible):

  • Catalyst: Pd2(dba)3 (1–2 mol%) with SPhos/XPhos (2–4 mol%)
  • Base: K3PO4 or Cs2CO3 (2–3 eq)
  • Solvent: dioxane/H2O (or CPME/H2O), 90–120 °C; inert atmosphere
  • Time: 6–24 h; consider microwave heating for rate enhancement.

• Buchwald–Hartwig amination at aryl C–Cl:

  • Catalyst: Pd(OAc)2 (1–3 mol%) with BrettPhos/XPhos (3–6 mol%)
  • Base: NaOtBu or K3PO4
  • Solvent: toluene, dioxane, or DMAc; 100–130 °C

These are representative literature-style conditions meant for planning. Always run small-scale screens to identify optimal ligands, bases, and temperatures for your specific substrate set.

Safety & Handling

Item-specific hazard statements, pictograms, and GHS classes: Not specified for this item; refer to SDS.

General safety profile for chlorinated phenols (literature/general guidance; not a substitute for SDS):

• Hazards: Phenols can be corrosive/irritant to skin and eyes; ingestion or significant inhalation may be harmful. Chlorinated phenols are often hazardous to the aquatic environment and may have notable odor.
• PPE: Use chemical-resistant gloves (e.g., nitrile), lab coat, splash goggles. Handle solids in a fume hood to control dust and vapors, especially during heating/melting.
• First aid (overview):
  • Skin: Remove contaminated clothing, rinse with water for ≥15 min. Seek medical attention for persistent irritation.
  • Eyes: Rinse cautiously with water for ≥15 min; remove contact lenses if easy. Seek medical attention.
  • Inhalation: Move to fresh air; monitor breathing; seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Incompatibilities: Strong oxidizers; strong bases (forms phenolates; exotherm possible); reactive metals; acid chlorides/anhydrides without control (acylation). Avoid strong heating; do not distill to dryness.
• Environmental: Prevent release to the environment; collect/contain spills with inert absorbent and dispose per regulations.

Always consult the product’s SDS for authoritative hazard classification, exposure limits, and emergency measures.

Solvent Selection

This product is a solid reagent, not a solvent. The following guidance addresses suitable media for its use in synthesis and handling (literature/general):

• Polarity and dissolution:
  • Dissolves well in moderately polar organics (EtOAc, acetone, MeOH/EtOH) and nonpolar aromatics (toluene). Sparingly soluble in water; readily soluble as phenolate in basic aqueous/MEK/EtOH mixtures.
• Typical choices by transformation:
  • O-alkylation/O-acylation: Polar aprotic solvents (DMF, DMSO, MeCN) or acetone/MeTHF/toluene with a base (K2CO3, Cs2CO3, NaH). Alcoholic solvents for Mitsunobu alternatives may be used.
  • Electrophilic aromatic substitution at C4: Glacial acetic acid, dichloroethane, nitromethane, or solvent-free melt depending on electrophile; para-selectivity aided by 2,6-blocking.
  • Cross-coupling on aryl C–Cl: High-boiling ethers (dioxane, CPME), toluene, or DMAc/DMF with strong Pd systems.
• Workup considerations:
  • Phenolate salts partition into aqueous phase; reprotonate before extraction if needed.
  • Avoid prolonged contact with strong bases in protic media to limit side reactions (e.g., hydrolysis of acyl groups after protection).

Comparison (general):

• Toluene vs dioxane: Toluene favors higher-temp couplings and easy removal; dioxane offers better polarity for catalyst solubility but has peroxide/health concerns.

Storage & Reconstitution

• Storage conditions (item-specific from Product Data): Store at -80 °C.
• Shipping (item-specific from Product Data): Shipped on dry ice packs + cold packs.
• Reconstitution/handling (general guidance for this solid reagent):
  • The compound is typically supplied as a solid. No reconstitution is required; dissolve the desired quantity directly in a suitable anhydrous organic solvent (e.g., acetone, MeCN, EtOAc, toluene) for immediate use.
  • For stock solutions, prepare under dry, inert atmosphere if subsequent steps are base- or moisture-sensitive. Store aliquots in amber vials to minimize light exposure.
  • If forming the sodium/potassium phenolate, generate in situ immediately before use to avoid moisture uptake.
• Stability notes (general):
  • Phenolic solids are generally stable under dry, cool, and dark conditions. Avoid prolonged exposure to heat and light.
  • If long-term storage deviates from the item’s recommended -80 °C, verify integrity by NMR/LC before critical use.
• Thawing guidance:
  • Upon receipt on dry ice, allow container to equilibrate to room temperature in a desiccator before opening to prevent condensation.

For definitive stability, impurity limits, and shelf-life, consult the item’s CoA/Spec Sheet and SDS. Research use only.

Structure & Identity

2,6-Dichlorophenol is a chlorinated phenolic building block featuring a phenyl ring bearing a hydroxyl at C1 and chloro substituents at the 2- and 6-positions, creating a sterically encumbered, para-directing phenol with blocked ortho sites.

• Item-specific identifiers (from Product Data):
  • CAS: 87-65-0
  • SKU: D660567
  • Category: 化学和生化试剂 (research use)
• Structure descriptors (literature/general):
  • Molecular formula: C6H4Cl2O (literature)
  • Molecular weight: ~163.00 g/mol (literature)
  • SMILES: Clc1cccc(Cl)c1O (literature)
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• Structural features (general description):
  • Aromatic ring with one phenolic OH and two chloro substituents in a 1,2,6-arrangement (OH at C1; Cl at C2 and C6).
  • The two ortho chlorides increase steric hindrance around the phenolic OH and block further ortho electrophilic substitution; the OH remains a strong para director to C4.
  • Functional groups: phenol (acidic OH), aryl chlorides (relatively inert toward SNAr without strong activation, but competent in Pd-catalyzed cross-coupling under appropriate conditions).
  • No stereocenters; planar aromatic core predominates.

Synthetic Utility

Key functional elements and reactivity (literature/general):

• Phenolic OH (acidic, nucleophilic upon deprotonation):
  • O-alkylation (Williamson), O-acylation (acid chlorides/anhydrides, Steglich) to give ethers/esters.
  • Protection as benzyl/allyl/TBS ethers to enable subsequent C–C bond-forming steps.
• Aryl C–Cl bonds (at 2,6):
  • Engage in Pd-catalyzed couplings (Suzuki, Buchwald–Hartwig, Kumada, Negishi) with appropriate ligand/catalyst systems and elevated temperatures.
• Aromatic substitution patterning:
  • OH directs electrophiles para; ortho sites are sterically blocked by Cl. This yields high para selectivity without regioisomeric mixtures common with phenol.

Retrosynthetic value:

• Serves as a para-selective phenolic synthon. For targets requiring a para-substituted phenol with ortho deactivation/steric hindrance, 2,6-dichlorophenol reduces protecting-group and regiocontrol challenges.

Analytical and purification considerations:

• The phenol/phenolate equilibrium affects TLC/R_f; acidify samples for consistent chromatography.
• Chlorinated aromatics often show strong signals in GC–MS (m/z patterns due to 35Cl/37Cl); useful for reaction monitoring.

Use cases:

• Precursor to hindered phenolic ethers (ligands, materials), para-functionalized building blocks, and advanced intermediates for agrochemical/materials research.

Target Specificity

Not applicable. This product is a small-molecule reagent, not a biological targeting agent (e.g., antibody, ligand with defined biomolecular target). No antigen/epitope, clone, isotype, or species-reactivity information applies.