2',6'-Dichloro-3'-fluoroacetophenone - ≥97% , CAS No.290835-85-7

CAS: 290835-85-7 Cat. No.: D115325 Formula: C₈H₅Cl₂FO Molecular Weight: 207.03 EC Number: 627-895-6

GRADE & PURITY ≥97%

Synonyms

2`,6`-Dichloro-3`-fluoroacetophenone | Z104509154 | 1-(2,6-dichloro-3-fluorophenyl)ethan-1-one | 2',6'-Dichloro-3'-fluoroacetophenone, 98% | BP-10594 | SCHEMBL488779 | 2',6'-dichloro-5'-fluoroacetophenone | AM20061080 | PB47336 | 2,6-Dichloro-3-Fluro Acet

Storage

Room temperature

Shipped In

Normal

Overview

2′,6′-Dichloro-3′-fluoroacetophenone is an aryl fluorinated building block.

2′,6′-Dichloro-3′-fluoroacetophenone (2,6-Dichloro-3-fluoroacetophenone) may be used to synthesize the enantiomerically pure form of (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol.

Specifications

Synonyms

2`,6`-Dichloro-3`-fluoroacetophenone | Z104509154 | 1-(2,6-dichloro-3-fluorophenyl)ethan-1-one | 2',6'-Dichloro-3'-fluoroacetophenone, 98% | BP-10594 | SCHEMBL488779 | 2',6'-dichloro-5'-fluoroacetophenone | AM20061080 | PB47336 | 2,6-Dichloro-3-Fluro Acet

Specifications & Purity

≥97%

Storage

Room temperature

Shipped In

Normal

Purity

≥97%

Names and Identifiers

Pubchem Sid

488192463

Pubchem Sid Url

https://pubchem.ncbi.nlm.nih.gov/substance/488192463

Canonical Smiles

CC(=O)C1=C(C=CC(=C1Cl)F)Cl

IUPAC Name

1-(2,6-dichloro-3-fluorophenyl)ethanone

InChIKey

VJBFZHHRVCPAPZ-UHFFFAOYSA-N

INCHI

1S/C8H5Cl2FO/c1-4(12)7-5(9)2-3-6(11)8(7)10/h2-3H,1H3

Isomeric SMILES

CC(=O)C1=C(C=CC(=C1Cl)F)Cl

WGK Germany

3

UN Number

2810

Molecular Weight

207.03

Reaxy-Rn

8681499

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=8681499&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Class Organooxygen compounds
      • Subclass Carbonyl compounds
        • Level5 Ketones
          • Level6 Aryl ketones
            • Level7 Phenylketones
              • Level8 Alkyl-phenylketones

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Class: Organooxygen compounds
• Subclass: Carbonyl compounds
• Intermediate Tree Nodes: Ketones - Aryl ketones - Phenylketones
• Direct Parent: Alkyl-phenylketones
• Alternative Parents: Acetophenones Dichlorobenzenes Benzoyl derivatives Aryl alkyl ketones Fluorobenzenes Aryl fluorides Aryl chlorides Vinylogous halides Organofluorides Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Alkyl-phenylketone - Acetophenone - Benzoyl - 1,3-dichlorobenzene - Aryl alkyl ketone - Chlorobenzene - Fluorobenzene - Halobenzene - Aryl chloride - Monocyclic benzene moiety - Aryl halide - Aryl fluoride - Benzenoid - Vinylogous halide - Organohalogen compound - Organic oxide - Hydrocarbon derivative - Organochloride - Organofluoride - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
• 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

• Refractive Index: 1.529
• Flash Point(°F): 230 °F
• Flash Point(°C): 110 °C
• Boil Point(°C): 255°C
• Molecular Weight: 207.030 g/mol
• XLogP3: 3.000
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 205.97 Da
• Monoisotopic Mass: 205.97 Da
• Topological Polar Surface Area: 17.100 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 186.000
• 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 tested bioassay or immunoassay application protocols are provided for this small-molecule reagent. Typical laboratory usage involves chemical synthesis and analytical characterization (e.g., NMR, LC–MS, GC–MS). For synthetic procedures, see the Reaction Conditions and Synthetic Utility sections.

Biological Roles

This product is intended for research and laboratory synthesis. No biological role, target, or pathway associations are provided in the Product Data, and none should be inferred for laboratory use.

General considerations (literature/chemistry context):

• Aryl methyl ketones are common synthetic intermediates; they are not endogenous metabolites and have no established physiological function.
• The presence of multiple halogens typically increases lipophilicity and persistence, but biological activity, if any, would be scaffold- and substitution-specific. Any such activities are outside the scope of this catalog entry.

Research use note (Product Data): For research use only.

Buffer Applications

Not typically applicable. 2',6'-Dichloro-3'-fluoroacetophenone is a neutral, nonionizable aryl ketone and is not used as a buffering agent. For practical use, focus on the Synthetic Utility, Reaction & Applications, and Solvent Selection sections for guidance on employing it as a building block.

Green Alternatives

Greener process design focuses on solvent and catalyst choices; the substrate is a halogenated aryl ketone and inherently persistent, so improvements center on media and energy.

• Preferential solvents (relative to legacy choices):

  • Replace DCM/CHCl3 with EtOAc, MeCN, 2-MeTHF, or CPME where feasible (similar solvency, lower toxicity/photochemical risk).
  • For couplings, use 2-MeTHF or CPME instead of dioxane/DMF; they enable higher boiling points with improved safety and often comparable outcomes.
  • For SNAr, upgrade from DMAc/DMF/NMP to MeCN or sulfolane/propylene carbonate blends when nucleophile and base allow.

• Energy and workup:

  • Continuous flow heating or microwave enables shorter residence times and lower solvent volumes.
  • Aqueous workups minimizing halogenated solvent usage (salt-out extractions from EtOAc/MeCN) reduce halogenated waste.

Comparison (general guidance):

• DCM vs EtOAc: EtOAc has better environmental/safety profile and is biodegradable; it may require slightly higher volumes to dissolve highly halogenated aromatics.
• 1,4-Dioxane vs 2-MeTHF: 2-MeTHF derives from renewable resources, offers similar solvency, and is water-immiscible for easier separations; peroxide formation must still be monitored.
• DMF/NMP vs MeCN/CPME: MeCN and CPME often provide adequate polarity with lower reproductive toxicity concerns; check solubility and base compatibility.

Catalyst economy:

• Employ low-Pd loadings with modern ligands or switch to nickel catalysis when aryl chloride activation is adequate, reducing precious metal footprint.

All recommendations are general/literature-based; verify performance for your system.

Pharmaceutical Uses

No excipient or pharmacopeial role is specified in the Product Data. This compound is supplied for research use only and is typically employed as a synthetic intermediate in discovery chemistry rather than as a formulated component.

General formulation notes (literature/guidance):

• If used in medicinal chemistry campaigns, it is commonly an upstream building block; any handling in a formulation context would be limited to solution preparation for assays (organic stock solutions such as DMSO/MeCN) rather than dosage forms.
• No USP/Ph.Eur. monograph is expected for this fine chemical. Do not use in human or veterinary applications.

Always refer to internal QA policies and the CoA/SDS for handling requirements.

Physical Properties

Item-specific specifications are not provided in the Product Data. Do not use the following values as specifications; consult the CoA/Spec Sheet for release criteria.

• Appearance (Product Data): Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity (Product Data): Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not specified for this item; refer to CoA/Spec Sheet. Literature expectation for halogenated acetophenones: generally high-boiling liquids or low-melting solids; specific BP depends on substitution.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet. Aromatic haloketones typically show densities modestly above 1 g/mL (literature generalization).
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (general/literature):
  • Water: expected very low due to aryl halogenation and absence of hydrogen-bond donors.
  • Organic: typically soluble in chlorinated solvents (DCM, CHCl3), ethyl acetate, acetone, THF, acetonitrile, and aromatic solvents (toluene). Practical solubility should be verified at intended concentration and temperature.
• LogP and pKa: Not specified for this item; refer to CoA/Spec Sheet. Aryl methyl ketones are neutral (no acid/base ionization in water under physiological pH).

Notes

• If crystallinity or polymorph affects your application (e.g., solid dispensing, slurry-phase coupling), determine mp/solubility empirically under your conditions.
• For analytical work, determine UV–vis absorbance profile and GC/LC retention with your specific mobile phase; no item-specific UV cutoff is provided.

Quality & Grades

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

Guidance for interpreting grades (general):

• Research grade: Suitable for most synthesis and screening. Typical acceptance criteria include identity (1H NMR/GC/LC), assay, and limits on common impurities; actual limits are item-specific (refer to CoA).
• Purification-sensitive applications: If using as a limiting reagent in medicinal chemistry or in structure–activity studies where halide identity and positional purity are critical, request batch CoA and, if necessary, additional analytics (e.g., 13C NMR, 19F NMR, HRMS, residual solvent panel).
• Stabilizers/inhibitors: None are indicated in the Product Data. If your process is base- or nucleophile-sensitive, confirm absence of stabilizers on the CoA.
• Chromatography: For trace analysis or photochemical work, low-UV or HPLC grades of solvents are typically more relevant than reagent grade of the solid/liquid reagent.

Release documentation best practices:

• Verify substitution pattern by 1H/13C/19F NMR and MS; the 2,6-dichloro pattern reduces ortho-proton count and influences J-coupling to 19F (diagnostic multiplets).
• If halide content matters downstream (e.g., Pd coupling), check inorganic halide levels (chloride) only if specified on CoA; otherwise, treat as not controlled.
• Moisture/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

Reaction & Applications

As a 2,6-dichloro-3-fluoro-substituted acetophenone, this reagent is a versatile building block enabling orthogonal reactivity from the carbonyl and the aryl C–Cl/C–F bonds.

Representative application families (literature/general):

• Cross-coupling on aryl chloride sites: Suzuki–Miyaura, Buchwald–Hartwig, and Negishi couplings using tailored Pd(0)/Ni catalysts and bulky electron-rich ligands to activate aryl chlorides. Sequential, site-selective couplings can differentiate C–Cl positions by steric/electronic effects.
• SNAr at the 3-fluoro position: The carbonyl and vicinal chloro substituents increase ring activation toward nucleophiles; amines, alkoxides, and thiolates can displace F under polar aprotic conditions and heat.
• Carbonyl derivatization: Formation of oximes/hydrazones, imines (from the methyl ketone under dehydrating conditions), and α-functionalization (halogenation, halomethylation, or enolate alkylations) to elaborate side chains.
• Halogen–metal exchange and directed ortho metalation are generally disfavored by the deactivated ring but may be achievable with strong bases at low temperature; care is advised due to multiple leaving groups.
• Photoredox/SET strategies: The aryl ketone can participate in acyl radical generation (via NHC-catalyzed or photoredox conditions) to access benzylic acylation products.

Practical tips:

• For selective coupling, screen ligand sets (e.g., XPhos/BrettPhos/RuPhos) to bias oxidative addition into C–Cl sites; 3-F typically survives Pd coupling but can be displaced under SNAr.
• Control base strength during enolate chemistry to avoid unintended nucleophilic aromatic substitution.
• Monitor by LC–MS with 19F NMR as an orthogonal handle for positional analysis.

Reaction Conditions

General literature guidance for transformations of halogenated aryl methyl ketones; optimize for your specific substrate and catalyst system.

• Suzuki–Miyaura coupling (aryl chloride positions):

  • Catalyst: Pd2(dba)3 (0.5–1 mol% Pd) with RuPhos/XPhos/SPhos (1.5–3 mol%).
  • Base: K3PO4 or Cs2CO3 (2–3 equiv), aqueous or anhydrous.
  • Solvent: 2-MeTHF, toluene/H2O, or dioxane/H2O; 80–110 °C, 2–16 h.
  • Notes: Bulky biaryl phosphines facilitate oxidative addition into aryl C–Cl. 3-F typically survives these conditions.

• Buchwald–Hartwig amination (aryl chloride):

  • Catalyst: Pd(OAc)2 or Pd2(dba)3 with BrettPhos/XPhos; NaOtBu or Cs2CO3 as base.
  • Solvent: t-Amyl alcohol, toluene, or dioxane; 80–110 °C.
  • Notes: For hindered amines, elevate temperature and ligand loading; avoid nucleophiles that promote SNAr at C–F unless intended.

• SNAr at C–F (3-position):

  • Nucleophiles: primary/secondary amines, alkoxides, thiolates (2–4 equiv).
  • Solvent: DMF/DMSO/MeCN; 60–140 °C.
  • Additives: Inorganic base (K2CO3/Cs2CO3) or organic superbases (DBU/TBD) as appropriate.

• Enolate alkylation (α to carbonyl):

  • Base: LDA/NaHMDS/KHMDS (1.1–1.5 equiv) in THF/2-MeTHF at −78 to 0 °C; then add electrophile.
  • Quench and warm gradually to minimize competing aromatic substitution.

• Baeyer–Villiger oxidation:

  • Reagents: mCPBA or H2O2 with Lewis acid catalysts.
  • Solvent: DCM (legacy) or EtOAc/MeCN (greener); 0–40 °C.

Yields and times are substrate- and setup-dependent; the above are literature-style starting points, not specifications for this item.

Safety & Handling

Safety data are not specified in the Product Data. Always consult the product SDS for authoritative information before use.

• GHS classification and statements (Product Data): Not specified for this item; refer to SDS.
• Signal word/pictograms (Product Data): Not specified for this item; refer to SDS.

General safety considerations for halogenated aryl ketones (literature/general):

• Likely hazards: May cause skin/eye irritation and respiratory irritation; harmful if swallowed. Avoid dust/vapor formation and inhalation of aerosols.
• PPE: Lab coat, safety glasses/goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood.
• Handling: Avoid contact with strong bases (enolate formation) unless intended; avoid strong oxidizers and strong reducing agents. Prevent prolonged exposure to light/heat to limit undesired reactions.
• Incompatibilities: Strong bases/acids (can promote halogen exchange or hydrolysis under forcing conditions), reactive metals (e.g., Na, K), and powerful nucleophiles that may attack the carbonyl or undergo SNAr at activated positions.
• First aid (general): In case of skin contact, wash with soap and water; eye contact, rinse cautiously for several minutes and seek medical attention; inhalation, move to fresh air; ingestion, rinse mouth—do not induce vomiting; seek medical advice.
• Fire: Use CO2, dry chemical, or alcohol-resistant foam. Combustion may release HCl/HF and phosgene-like species; firefighters should wear SCBA.
• Spill response: Absorb with inert material, collect in chemical waste. Prevent release to drains.

Storage per Product Data

• Storage conditions: Room temperature.
• Shipping: Normal.
• Keep container tightly closed in a dry, well-ventilated place; segregate from strong bases/oxidants.

Solvent Selection

This compound is a neutral, hydrophobic halogenated aryl ketone. Solvent choice should prioritize solubility, compatibility with intended transformations (carbonyl chemistry, cross-coupling, SNAr), and heat transfer.

• Polarity/miscibility (general):

  • Poor water solubility is expected; prefer organic media.
  • Good solubility typically in DCM/CHCl3, EtOAc, acetone, acetonitrile, THF/2-MeTHF, toluene, and DMF/DMAc/DMSO.

• Selection by use case:

  • Carbonyl reactions (e.g., oxime/hydrazone formation, halogenation alpha to carbonyl): ethanol, methanol, acetonitrile, or toluene with catalytic acid/base, depending on nucleophile.
  • Enolate chemistry/alkylation: dry THF/2-MeTHF, DME, or toluene with LDA/NaHMDS/KHMDS; polar aprotics (DMPU/DMI) if stronger solvation is required.
  • Cross-coupling on aryl chloride: toluene, dioxane, CPME, or NMP/DMF mixed with t-BuOH/H2O when using base like K3PO4 or Cs2CO3; coordinate with ligand/catalyst system.
  • SNAr at the 3-fluoro (if activated by the carbonyl and ring halogens): DMF/DMSO/MeCN at elevated temperature favors nucleophilic substitution.

• Practical tips:

  • Start with 10–50 mg/mL screening solubility in MeCN, THF, and toluene; select the highest solubility solvent compatible with downstream steps.
  • For scale-up, solvents with higher boiling points (toluene, xylene, CPME) help drive equilibria and accommodate catalytic couplings.

• Green considerations: prefer 2-MeTHF, EtOAc, MeCN, or CPME over DCM/DMF where compatible (see Green Alternatives tab).

Storage & Reconstitution

• Storage (Product Data): Room temperature. Keep tightly closed in a dry, well-ventilated area. Protect from excessive heat; store away from strong bases and oxidizers.
• Shipping (Product Data): Normal.
• Reconstitution: Not applicable. Dissolve directly in a suitable organic solvent (e.g., MeCN, THF, DCM, EtOAc, toluene) at the concentration required for your process. Sonication or gentle warming may assist dissolution; avoid prolonged heating.
• Stability (general): Aryl ketones are typically stable under ambient conditions. Avoid prolonged exposure to strong light/UV and moisture if performing base-sensitive operations. Verify stability in basic media if enolate chemistry or SNAr is planned.
• Freeze–thaw: Not required. If prepared as a stock solution (e.g., in DMSO/MeCN), store aliquots in airtight vials to minimize evaporation and moisture ingress; bring to room temperature before opening to reduce condensation.
• Shelf life: Not specified for this item; refer to CoA/Spec Sheet.

Always consult the SDS for detailed handling and storage precautions. For long experiments, confirm solution stability by TLC/LC–MS over the intended time–temperature profile.

Structure & Identity

A halogenated aryl methyl ketone featuring ortho,ortho-dichloro and meta-fluoro substitution on the acetophenone ring.

• Item identifiers (Product Data)

  • SKU: D115325
  • Product name: 2',6'-Dichloro-3'-fluoroacetophenone
  • CAS: 290835-85-7
  • PubChem CID: 2733982
  • InChIKey: 380313 (as provided in Product Data; non-standard length — verify on CoA/SDS)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Structure description (general/literature)

  • Core scaffold: acetophenone (phenyl–CO–CH3) bearing three ring halogens.
  • Substitution pattern: 2- and 6-positions = Cl (ortho to the acyl group on both sides); 3-position = F (meta to the acyl group). This produces a 1,2,3,6-tetrasubstituted ring counting the carbonyl ipso carbon.
  • Functional groups: aryl methyl ketone (prototropic at the benzylic methyl under strong base), deactivating/ortho-directing halogens (Cl, F) that are synthetically useful handles (e.g., cross-coupling, SNAr at F in activated contexts).
  • Stereochemistry: none (achiral). 2D depiction would show a benzene ring with carbonyl at C1, chloros at C2 and C6, and fluoro at C3; the side chain is an acetyl (–COCH3).

• Formula and molecular weight

  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Approximate literature/computed molecular formula and mass for 2′,6′-dichloro-3′-fluoroacetophenone: C8H5Cl2FO, Mr ≈ 207.03 g/mol (literature/computed; for reference only).

Synthetic Utility

Key reactivity elements make this substrate strategically valuable in complex-molecule synthesis and SAR campaigns.

• Orthogonal handles:

  • Carbonyl (methyl ketone): amenable to oxime/hydrazone formation, Baeyer–Villiger oxidation (to aryl acetates), α-halogenation/alkylation via enolate chemistry, and reductive transformations (Clemmensen/Wolff–Kishner equivalents under protected conditions).
  • Aryl chlorides (2,6-positions): suitable for Pd/Ni-catalyzed cross-couplings (Suzuki–Miyaura, Buchwald–Hartwig, Kumada, Negishi). The 2,6-dichloro pattern allows for stepwise functionalization and steric control around the carbonyl.
  • Aryl fluoride (3-position): can be preserved as a spectroscopic tag or displaced in SNAr with nucleophiles (amines, alkoxides, thiolates) under polar aprotic conditions, leveraging ring activation by the carbonyl and flanking chlorides.

• Retrosynthetic value:

  • Serves as a convergent node: install aryl substituents via cross-coupling after securing the ketone, or elaborate the side chain first, then functionalize the ring.
  • Facilitates late-stage diversification: 19F NMR provides rapid tracking of site-selective substitutions.

• Derivatization examples (literature/general):

  • Sequential coupling to yield 2,6-diaryl or aryl-alkyl variants, followed by Baeyer–Villiger to lactones.
  • Enolate trapping (e.g., with electrophiles or Michael acceptors) to access quaternary centers adjacent to the carbonyl.

Tips:

• Use protecting strategies or chemoselective conditions to avoid competition between SNAr and cross-coupling when nucleophiles are present.

Target Specificity

Not applicable. This product is a small-molecule chemical reagent, not a biological targeting agent (e.g., antibody, enzyme inhibitor with defined biological target for this catalog entry). No target, epitope, clone, or isotype information is provided.

Frequently Asked Questions

What is the purity of this product?

This product is supplied at ≥97% 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 290835-85-7, the molecular formula is C8H5Cl2FO, and the molecular weight is 207.03 g/mol. InChIKey VJBFZHHRVCPAPZ-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.