3-(Difluoromethyl)cyclohexan-1-one - ≥97% , CAS No.1355729-67-7

CAS: 1355729-67-7 Cat. No.: D954794 Formula: C₇H₁₀F₂O Peso molecolare: 148.150 Numero EC: 841-961-3

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥97%

Nomi e identificatori

• Sorrisi canonici: C1CC(CC(=O)C1)C(F)F
• IUPAC Name: 3-(difluoromethyl)cyclohexan-1-one
• InChIKey: AOXSKWSBHVVGMI-UHFFFAOYSA-N
• INCHI: 1S/C7H10F2O/c8-7(9)5-2-1-3-6(10)4-5/h5,7H,1-4H2
• Peso molecolare: 148.150

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Classe Organooxygen compounds
      • Subclass Carbonyl compounds
        • Level5 Ketones
          • Level6 Cyclic ketones

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Classe: Organooxygen compounds
• Subclass: Carbonyl compounds
• Intermediate Tree Nodes: Ketones
• Direct Parent: Cyclic ketones
• Alternative Parents: Organofluorides Organic oxides Hydrocarbon derivatives Alkyl fluorides
• Molecular Framework: Aliphatic homomonocyclic compounds
• Substituents: Cyclic ketone - Organic oxide - Hydrocarbon derivative - Organofluoride - Organohalogen compound - Alkyl halide - Alkyl fluoride - Aliphatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as cyclic ketones. These are organic compounds containing a ketone that is conjugated to a cyclic moiety.
• 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

Proprietà chimiche e fisiche

• Peso molecolare: 148.150 g/mol
• XLogP3: 1.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 148.07 Da
• Monoisotopic Mass: 148.07 Da
• Topological Polar Surface Area: 17.100 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 134.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• 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 for assay-format protocols (e.g., WB, IHC, IF, FC). This item is a synthetic organic reagent/building block. For practical laboratory use, refer to the Reaction Conditions, Synthetic Utility, and Solvent Selection sections for step-by-step chemistry guidance.

Biological Roles

This product is a small-molecule synthetic building block and does not have an intrinsic biological role. The following points summarize general, literature-based context relevant to fluorinated motifs in chemical biology (not clinical claims):

• –CF2H as a motif: Acts as a weak hydrogen-bond donor while increasing lipophilicity and metabolic stability compared to –CH3 or –CH2– groups. It can modulate pKa and conformation when placed adjacent to heteroatoms or π-systems.
• Ring-constrained presentation: The cyclohexanone ring offers conformational control, which can impact ligand–protein interactions in medicinal chemistry campaigns once the scaffold is elaborated.
• Biotransformation considerations: Ketones may undergo reductive metabolism in biological systems to secondary alcohols; fluorine substitution can slow oxidative and hydrolytic pathways (literature trend).

No biological activity, targets, or pathways are assigned to this catalog item; it is provided strictly for research and laboratory use.

Buffer Applications

This compound is a neutral organic building block and is not used as a buffering agent. It lacks acid/base conjugate pairs appropriate for maintaining pH in aqueous systems. For laboratory use, select traditional buffers (e.g., phosphate, HEPES, Tris) as suitable for your application. Refer instead to the Synthetic Utility and Reaction & Applications sections for relevant usage.

Green Alternatives

Greener considerations center on solvent choice and step economy; the molecule itself contains fluorine, which typically persists in the environment, so process greening should focus on minimizing waste and using safer media.

Greener solvent swaps (literature guidance):

• THF → 2‑MeTHF: similar enolate performance, bio-based, higher boiling point simplifies low‑temp work but may slow cooling; water immiscible aids separation.
• DCM/CHCl3 → EtOAc/MTBE/MeTHF: reduce chlorinated waste for extractions and medium-polar reactions.
• Toluene → Cyclopentyl methyl ether (CPME) or p‑cymene where heat transfer and hydrophobic media are required.

Small comparison (general):

• THF vs 2‑MeTHF: comparable yields in many enolate reactions; 2‑MeTHF has lower peroxide formation tendency and is often preferred under green metrics.
• DCM vs EtOAc: EtOAc is safer and biodegradable; may require temperature or time adjustments due to polarity differences.

Process intensification:

• Favor one‑pot sequences (e.g., enolate generation → electrophile addition → quench/workup in the same vessel) to reduce solvent usage.
• Explore flow chemistry for hazardous bases (n‑BuLi) to enhance safety and reduce over‑base consumption.

Waste handling:

• Segregate fluorinated organic waste; consider solvent recovery (distillation) for ether/ester media where feasible.

Pharmaceutical Uses

• Regulatory/excipient status: Not specified for this item; no pharmacopeial monograph indicated. This product is sold for research use only and is not intended for use in humans or for clinical applications.

Formulation/manufacturing context (general, non-clinical):

• Fluorinated ketone building blocks like this are commonly employed as intermediates in the synthesis of candidate drug molecules, enabling introduction of the –CF2H motif as a lipophilic, weak H‑bond donor bioisostere.
• The cyclohexanone core allows late-stage diversification (enolate alkylation, reductive transformations, oxime/hydrazone formation) to produce intermediates for SAR exploration.

If GMP or clinical supply is required, additional qualification (specification setting, impurity profiling, stability program, and vendor audit) would be necessary beyond this research-use listing.

Physical Properties

Item-specific specifications are limited in the provided data. Values below are either not specified for this catalog item or are general literature expectations for this structural class.

• Appearance: 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 small cyclohexanone derivatives: typically in the ~160–210 °C range, depending on substitution (guidance only).
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Density (20–25 °C): Not specified for this item; refer to CoA/Spec Sheet.
  • Fluorinated ketones often show densities slightly >1.0 g/mL (literature trend, not an item spec).
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
  • General behavior (literature): expected to be miscible with common organic solvents (EtOAc, DCM, THF, toluene) and have low water solubility.
• pKa (–CF2H): Literature values for difluoromethyl C–H in analogous systems are typically in the mid‑20s (strong base required for deprotonation). Exact pKa for this specific compound is not established here.
• logP/logD: Not specified for this item; refer to CoA/Spec Sheet.
  • Literature expectation: moderate lipophilicity due to –CF2H and cyclohexanone.

Note: Treat all numerical literature values above as contextual guidance only. For lot-specific properties, consult the item’s CoA/Spec Sheet.

Quality and Grades

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

Guidance for interpreting grade (general, literature/industry practice):

• For synthetic building blocks such as fluorinated cyclohexanones, labs typically seek ≥95% GC/LC purity for discovery work and ≥98% for route scouting or reference standards; HPLC-grade designation is uncommon unless specified.
• If a “research grade” designation is provided on the CoA, it generally implies suitability for lab R&D but not for GMP manufacturing without further qualification.
• If present, trace stabilizers (e.g., small amounts of acid or base) can influence enolization/aldol behavior; verify via CoA if sensitive transformations (e.g., enolate alkylations, chiral catalysis) are planned.

Verification & incoming QC (practical tips):

• Confirm identity via NMR (19F, 1H, 13C). The –CF2H typically shows a characteristic triplet in 1H NMR (JHF ~50–55 Hz) and a multiplet in 19F NMR.
• Check water content by KF if using moisture-sensitive bases (LDA, n‑BuLi). Any specific water or metal limits are not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

As a fluorinated cyclic ketone, 3-(difluoromethyl)cyclohexan-1-one serves as a versatile building block in discovery and process chemistry.

Key application families (literature/practice):

• Enolate chemistry: α‑Functionalization (alkylation, aldol, Mannich, Michael additions). LDA or LiHMDS in THF at −78 to −40 °C is typical. Electrophiles include alkyl halides, acyl donors, and imines.
• Carbonyl transformations: Reduction to the corresponding alcohol (NaBH4, DIBAL‑H), oxime/hydrazone formation, and Wittig/Julia–Kocienski olefinations of derived carbonyls.
• Difluoromethyl (–CF2H) handling:
  • The –CF2H proton is relatively acidic (literature mid‑20s pKa range), allowing deprotonation with strong bases (e.g., LDA, n‑BuLi) to form a carbanion that can be trapped with electrophiles (e.g., carbonyls, CO2, halides). Careful temperature control minimizes side reactions.
  • Oxidation or halogenation at the CF2 moiety can access CF2X derivatives; radical pathways (e.g., NFSI, Selectfluor on related systems) enable further diversification.
• Cross-coupling on derivatives: Installation of handles (vinyl/allyl from olefination, or aryl via enolate arylation) expands SAR space for medicinal chemistry.

Use cases:

• Medicinal chemistry: –CF2H acts as a lipophilic H‑bond donor bioisostere, tuning pKa and metabolic stability compared to –CH3, –CF3, or –CH2OH. This scaffold allows ring-constrained vectors to project –CF2H in 3D space.

Practical tips:

• Dry glassware/solvent and slow base addition are crucial for clean enolate formation.
• Monitor by 19F NMR; –CF2H signal provides a sensitive handle to track conversions and side products.

Reaction Conditions

General, literature-based conditions for this structural class (not item specifications):

• Enolate formation & α‑alkylation:

  • Base: LDA or LiHMDS (1.1–1.5 equiv)
  • Solvent: dry THF (or 2‑MeTHF)
  • Temp: −78 to −40 °C for generation; −78 to 0 °C for electrophile addition
  • Typical electrophiles: MeI/allyl bromide/benzyl halides, acyl chlorides, imines
  • Workup: quench with NH4Cl or HOAc; 0–25 °C

• Reduction to alcohol:

  • NaBH4 (1.1–2.0 equiv) in MeOH, EtOH, or THF/MeOH at 0–25 °C, 0.5–2 h; or DIBAL‑H in toluene/THF at −78 to 0 °C

• Deprotonation at –CF2H:

  • Base: n‑BuLi or LDA (≥1.1 equiv) at −100 to −78 °C in THF/Et2O; slow addition then trap with electrophile (e.g., aldehyde, CO2, MeI). Strict anhydrous conditions essential.

• Oxime/hydrazone formation:

  • Hydroxylamine or hydrazine derivatives (1.2–1.5 equiv) in EtOH or MeOH with catalytic acid, 25–60 °C.

• Wittig/Julia–Kocienski (on derived carbonyls):

  • Base: NaHMDS or KOtBu; solvent: THF/DMF; −78 to 25 °C depending on ylide/sulfone stability.

Yields and times depend on substrate/electrophile; monitor by TLC, GC, or 19F/1H NMR. All conditions above are literature guidance for analogous ketones/difluoromethyl substrates and should be optimized experimentally.

Safety and Handling

• GHS classification, pictograms, signal word, H‑statements: Not specified for this item; refer to the SDS for authoritative hazard communication.
• General hazards (ketone + difluoromethyl, literature-informed):
  • Many ketones are combustible liquids and may cause eye/skin irritation; avoid heat, sparks, and open flame until SDS confirms otherwise.
  • Fluorinated organics can exhibit enhanced lipophilicity; avoid prolonged skin contact and inhalation of vapors.
• Recommended PPE: Lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to minimize inhalation exposure.
• Handling practices:
  • Keep containers tightly closed. Use only with adequate ventilation.
  • Avoid contact with strong oxidizers and strong bases unless intentionally used under controlled reaction conditions.
• First aid overview (consult SDS for details):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin contact: Wash with soap and water; remove contaminated clothing.
  • Eye contact: Rinse cautiously with water for several minutes; remove contact lenses if present and easy; seek medical attention for irritation.
  • Ingestion: Rinse mouth; do not induce vomiting unless directed by medical personnel; seek medical attention.
• Spill/Fire response: Contain with inert absorbent; ventilate area. For fire, use CO2, dry chemical, or foam as appropriate for solvent fires. Avoid water jet.
• Peroxide formation: Not a typical risk for ketones like this; still follow standard solvent aging checks if used in peroxide-sensitive workflows.
• Always defer to the product’s SDS for definitive safety, exposure limits, and reactivity information.

Solvent Selection

This compound is a moderately polar, aprotic organic building block. While item-specific solubility is not provided, experience with analogous fluorinated cyclohexanones informs practical choices.

• Preferred solvents (literature/practice): THF, diethyl ether, MTBE, DCM, chloroform, toluene, EtOAc, MeCN. Alcohols (MeOH/EtOH) may also dissolve it but can interfere with base‑mediated reactions.
• Aqueous solubility: Expected to be low (general trend); consider biphasic extraction using moderately polar organics (EtOAc, MTBE) for workups.
• Dielectric considerations: For enolate chemistry, THF at low temperature (−78 to −40 °C) is a standard choice. For reductive chemistries (NaBH4), protic solvents or mixed MeOH/THF are common, while for catalytic hydrogenation, EtOH or EtOAc are convenient.

Quick comparison (literature-based guidance):

• THF: excellent for strong-base enolate formations; easy to cryo-cool; greener alternatives exist (2‑MeTHF).
• DCM: good for acylation/halogenation at ambient temp; volatile and chlorinated (waste concerns).
• MeCN: polar aprotic for SN1/SN2 on derived substrates; can stabilize salts; higher bp than DCM.
• Toluene: useful for higher-temp reactions and hydrophobic substrates; poor for strong base at cryo.

Tip: When planning deprotonation at –CF2H or α‑to‑C=O positions, select ether solvents (THF/2‑MeTHF) and rigorously exclude moisture.

Storage and Reconstitution

• Storage Conditions (from Product Data): Room temperature.
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.
• Form/Appearance: Not specified for this item; refer to CoA/Spec Sheet.

Practical guidance (general):

• Store tightly closed in an inert atmosphere (e.g., nitrogen) if frequent opening is expected, especially before strong-base chemistry, to minimize moisture uptake.
• Protect from strong light and heat sources. Keep away from strong oxidizers and bases unless used intentionally under controlled conditions.
• If solid, reseal promptly with desiccant present in the container or cabinet. If liquid, ensure cap integrity to limit solvent loss.

Reconstitution:

• Not applicable; this is a neat small-molecule reagent. If crystallized or viscous at lower temperatures, gentle warming to ambient and/or dissolution in a suitable dry organic solvent (THF, EtOAc, DCM, toluene) is acceptable.

Stability testing and exact shelf-life are not specified for this item; consult the CoA/Spec Sheet and perform a small‑scale assay (e.g., NMR/GC) before critical applications.

Research Use Only: As noted, this product is for research use only.

Structure and Identity

Brief description: 3-(Difluoromethyl)cyclohexan-1-one is a fluorinated cyclic ketone bearing a difluoromethyl (–CF2H) substituent at the 3-position of a cyclohexanone ring.

• Product name (SKU): 3-(Difluoromethyl)cyclohexan-1-one (D954794)
• CAS: 1355729-67-7
• PubChem CID (literature): 84716361
• 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.
  • Literature/computed for the named structure: C7H10F2O
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Literature/computed for the named structure: ~148.15 g/mol

Structural features (descriptive, literature-based):

• Core ring system: Six-membered cyclohexanone ring (one carbonyl at C1). Typically adopts chair conformations.
• Functional groups: A ketone (C=O) and a difluoromethyl group (–CF2H) at C3. The –CF2H moiety is mildly acidic at the C–H and is both lipophilic and capable of weak H-bond donation.
• 2D description in words: Starting from the carbonyl carbon as C1, the ring continues through five methylene carbons. At C3 (relative to the carbonyl carbon as C1), a –CF2H substituent replaces one ring hydrogen. No defined stereocenter is present at C3 in the parent (achiral) structure.

Synthetic Utility

Functional elements and their reactivity (literature-based):

• Ketone (C=O):
  • Enol/enolate formation enables α‑alkylation, aldol, Mannich, Michael, and Claisen-type condensations. Stereocontrol can be leveraged via chiral auxiliaries or organocatalysts.
  • Chemoselective reductions (NaBH4 → alcohol; DIBAL‑H → alcohol; Wolff–Kishner or Clemmensen → methylene) to tailor oxidation state.
  • Formation of oximes/hydrazones → access to imines, reductive amination products.
• Difluoromethyl (–CF2H):
  • Deprotonation with strong bases (LDA, n‑BuLi, t‑BuOK under cryogenic conditions) affords a carbanion that can be trapped with electrophiles (carbonyls, CO2, alkyl halides), installing new C–C/X bonds while retaining fluorines.
  • Radical functionalization strategies can transform –CF2H into CF2– linkers or introduce heteroatoms (e.g., photoredox methods on related substrates).
• Ring constraints: Cyclohexanone offers diastereotopic α‑positions; careful choice of base/temperature can bias kinetic vs thermodynamic enolate.

Retrosynthetic value:

• Serves as a masked synthon for difluoromethylene insertion on saturated carbocycles. Forward synthesis can introduce vectors for aryl/alkyl appendages around the ring with preserved –CF2H polarity effects.

Analytical handles:

• 19F NMR is highly diagnostic for –CF2H; 1H–19F couplings assist in assignment. IR: strong C=O ~1715 cm−1 (typical for cyclohexanone derivatives; literature value).

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, protein, or targeted biological reagent. No antigen, epitope, clone, isotype, or species reactivity information applies.