4-(4-Fluorophenyl)cyclohexan-1-amine - ≥95% , CAS No.1368942-09-9

CAS: 1368942-09-9 Cat. No.: F953173 Fórmula: C₁₂H₁₆FN Peso molecular: 193.260

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Especificaciones y pureza

≥95%

Condiciones de almacenamiento de almacenamiento

Room temperature

Pureza

≥95%

Nombres e identificadores

• Sonrisas canónicas: C1CC(CCC1C2=CC=C(C=C2)F)N
• IUPAC Name: 4-(4-fluorophenyl)cyclohexan-1-amine
• InChIKey: GHIWHKYACNCFFY-UHFFFAOYSA-N
• INCHI: 1S/C12H16FN/c13-11-5-1-9(2-6-11)10-3-7-12(14)8-4-10/h1-2,5-6,10,12H,3-4,7-8,14H2
• Peso molecular: 193.260

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Clase Benzene and substituted derivatives
      • Subclass Halobenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Clase: Benzene and substituted derivatives
• Subclass: Halobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Fluorobenzenes
• Alternative Parents: Cyclohexylamines Aralkylamines Aryl fluorides Organopnictogen compounds Organofluorides Monoalkylamines Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Aralkylamine - Fluorobenzene - Cyclohexylamine - Aryl halide - Aryl fluoride - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Primary amine - Organonitrogen compound - Organofluoride - Organohalogen compound - Primary aliphatic amine - Amine - Aromatic homomonocyclic compound
• Descripción: This compound belongs to the class of organic compounds known as fluorobenzenes. These are compounds containing one or more fluorine atoms attached to a benzene ring.
• 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

Propiedades químicas y físicas

• Peso molecular: 193.260 g/mol
• XLogP3: 2.400
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 193.127 Da
• Monoisotopic Mass: 193.127 Da
• Topological Polar Surface Area: 26.000 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 167.000
• 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

Not applicable. No validated bioassay or immunoassay protocols are provided for this small-molecule reagent. For synthetic chemistry, refer to the Reaction Conditions and Application notes above.

Biological Roles

Item-specific biological roles are not specified. The compound is offered for research use only.

General context (non-clinical)

• Chemical class: small-molecule primary amine on an arylcyclohexyl scaffold. Such structures are frequently explored in medicinal chemistry for modulating physicochemical properties (basicity, lipophilicity) and for probing structure–activity relationships, with the para-fluoro substituent often used to adjust metabolic stability and serve as a 19F NMR tracer in binding studies.
• Ionization: At physiological pH, the amine is largely protonated (ammonium), increasing aqueous compatibility; as a free base it is hydrophobic and membrane-permeant.
• Conjugation handles: The primary amine enables formation of amide/sulfonamide linkages to reporter tags, linkers, or surfaces for biochemical assays.

No endogenous biological function is implied, and no diagnostic, therapeutic, or clinical claims are made.

Buffer Applications

This product is not a buffering agent. As a primary amine, it can be converted to water-soluble ammonium salts and used in aqueous media, but it does not constitute a defined buffer system with a narrow pH range. For aqueous work, adjust pH with standard buffer systems (e.g., phosphate, acetate, HEPES) and dissolve this amine as its salt when needed.

Green Alternatives

Greener choices relate primarily to solvent and reagent selection; the substrate is a non-halogenated amine aside from the aryl-F, which is persistent but comparatively low-hazard in use.

• Prefer greener solvents when possible

  • Replace DCM with EtOAc, 2-MeTHF, or CPME for acylations and extractions.
  • Use ethanol or isopropanol as media for reductive amination instead of MeOH/CH2Cl2 when compatible.
  • Favor MeCN over DMF/DMSO to ease removal and reduce worker exposure, if solubility permits.

• Reagent choices

  • For amide couplings, employ catalytic coupling (e.g., CDI, T3P) with lower EHS footprints compared to HATU/HBTU; avoid benzotriazole additives where possible.
  • For N-alkylations, consider green alkylation strategies (carbonate electrophiles, Mitsunobu alternatives using greener reagents or flow hydrogenation for reductive amination).

• Workup/waste

  • Minimize chlorinated waste; switch to EtOAc/hexane or 2-MeTHF/brine partitions.
  • Capture amine-containing aqueous waste for appropriate neutralization to reduce nitrogen load.

Trade-offs

• 2-MeTHF/CPME can retain water; ensure adequate drying for moisture-sensitive steps.
• Greener coupling reagents may give slower reactions or require higher temperatures; optimize to balance yield and EHS considerations.

Pharmaceutical Uses

No pharmacopeial grade or excipient designation is specified for this item. In a research/manufacturing development context, primary amines like this are used as synthetic intermediates in API discovery and as link points for conjugation (e.g., amide/sulfonamide formation). Any formulation roles would be limited to intermediate use and not as an approved excipient unless otherwise documented. Refer to the CoA/Spec Sheet for any GMP or quality certifications if applicable.

Physical Properties

Item-specific values

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

Literature/computed (non-item-specific) guidance for the free base

• Phase at ambient: Primary arylcyclohexylamines of this size are often low-melting solids or viscous oils; actual form depends on purity and polymorph/solvate state.
• Basicity: Primary aliphatic amine, expected pKaH (conjugate acid) typically ~9.5–10.5 (literature range for cyclohexylamines). Free base is neutral and more hydrophobic; protonated salts are water-soluble.
• Lipophilicity: Arylcyclohexylamines commonly exhibit moderate hydrophobicity (logP often in the 2–3+ range; literature trend).
• Solubility: Free base—miscible with many organic solvents (alcohols, ethers, chlorinated, aromatics); limited solubility in water at neutral pH. Readily soluble in aqueous mineral acids as the ammonium salt.
• Volatility: Low-to-moderate; expect negligible vapor pressure compared to low MW amines.
• Spectroscopic notes: Primary amines show N–H stretches ~3300–3500 cm⁻¹ (IR), and characteristic 1H NMR signals for –NH2 (exchangeable) plus cyclohexyl multiplets; aryl-F gives 19F NMR resonance (often –110 to –115 ppm vs CFCl3, literature).

Note: Precise BP/MP/density/refractive index for this specific item are not specified; consult the CoA/Spec Sheet or measure under your laboratory conditions.

Quality and Grades

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

Interpreting typical grades (general guidance)

• Research/Technical grade: Suitable for synthetic chemistry and screening; assay and impurity profile vary by supplier. Verify by NMR/LC–MS prior to critical use.
• ≥98–99% (if specified): Indicates low-level organic impurities; does not imply metal or residual solvent limits unless explicitly stated.
• HPLC grade (for solvents) or LC–MS grade (for analytes): Not applicable unless designated. For solids, “HPLC” often refers to purity determination method rather than use as a mobile phase.

Stabilizers and salt forms

• This material is a primary amine. Suppliers sometimes offer amine salts (e.g., hydrochloride) to improve handling, stability, and aqueous solubility. If a salt form is required, confirm the exact counterion and assay on the CoA.
• UV cutoff, metal content, water/peroxide limits: Not specified for this item; refer to CoA/Spec Sheet.

Quality control recommendations (general)

• Identity: Confirm by 1H/13C NMR; 19F NMR is diagnostic for the para-F aryl group; HRMS for exact mass; IR for N–H stretches.
• Purity: Assess by HPLC/GC as appropriate; monitor for residual solvents and trace oxidation byproducts. For salts, confirm counterion by titration or ion chromatography.

Reaction and Applications

This compound is a versatile primary amine on an aryl–cyclohexyl scaffold, useful as a building block for discovery chemistry and materials.

Representative application areas (general)

• Amide/urea/sulfonamide libraries: Rapid diversification via acylation (acid chlorides, anhydrides), carbamoylation (CDI, chloroformates), and sulfonylation (sulfonyl chlorides). Suitable for parallel synthesis and SAR exploration around arylcyclohexyl cores.
• Reductive amination: Couples with aldehydes/ketones to access N-alkyl analogs. NaBH(OAc)3 in MeOH/AcOH or catalytic hydrogenation (H2/Pd/C) are common choices.
• N-alkylation: Alkyl halides or sulfates under basic conditions; consider protective strategies to avoid over-alkylation if secondary amines are the target.
• Protecting-group chemistry: Boc, Cbz, and Fmoc protection proceed under standard conditions, enabling orthogonal manipulations elsewhere on the molecule.
• Salt formation: Formation of HCl or mesylate salts for purification, crystallinity tuning, and handling in aqueous media.

Aryl fluoride handle

• The para-F on the phenyl ring is typically inert to nucleophilic aromatic substitution without strong EWGs; however, it can serve as a spectroscopic probe (19F NMR) and modulates lipophilicity and metabolic stability.

Practical tips

• Dry the amine (e.g., vac over P2O5 or molecular sieves) prior to moisture-sensitive couplings.
• For acylations, maintain base control (e.g., DIPEA or triethylamine) and temperature to suppress bis-acylation or self-condensation.
• For reductive amination, pre-form the imine/imine–hemiaminal at mild acidity, then add reductant to minimize alcohol reduction.

Manufacturer applications: Not specified; the above reflects general synthetic utility for this scaffold.

Reaction Conditions

General conditions reported for analogous primary aliphatic amines on arylcyclohexyl scaffolds (non-item-specific):

• Amide coupling

  • Reagents: HATU or T3P (1.1–1.5 equiv), DIPEA (2–3 equiv), carboxylic acid (1.0–1.2 equiv)
  • Solvent: DMF or DCM; 0–25 °C, 1–12 h
  • Notes: Pre-cool when using acid chlorides; monitor for bis-acylation and quench with aqueous base.

• Sulfonamide formation

  • Reagents: R–SO2Cl (1.05–1.2 equiv), DIPEA or NaHCO3
  • Solvent: DCM or acetonitrile; 0–25 °C, 0.5–4 h
  • Notes: Control exotherm; sequential additions improve selectivity.

• Reductive amination

  • Step 1: Mix amine with carbonyl (1.0–1.5 equiv) in MeOH or iPrOH; add AcOH (0.2–0.5 equiv) to favor imine formation.
  • Step 2: Add NaBH(OAc)3 (1.5–2.5 equiv); 20–30 °C, 2–16 h.
  • Alternative: H2 (1–3 bar) with 5–10 wt% Pd/C in EtOH; ambient–50 °C, 2–8 h.

• N-Boc protection

  • Reagents: (Boc)2O (1.1–1.3 equiv), base (Na2CO3 or DIPEA)
  • Solvent: DCM, THF, or dioxane/water; 0–25 °C, 1–3 h

• Salt formation (HCl)

  • Bubble dry HCl gas into anhydrous IPA/Et2O solution at 0–5 °C until pH <1; stir 0.5–2 h; filter and wash with cold ether; dry under vacuum.

Expected outcomes: Many of these reactions proceed in good to excellent yields (60–95%) with appropriate stoichiometry and exclusion of moisture where required. Optimize based on substrate and scale.

Note: The above are general literature conditions; adapt based on your specific reagents and process constraints.

Safety and Handling

Item-specific hazard data

• GHS classification, signal word, pictograms, and H-statements: Not specified for this item; refer to SDS.

General safety guidance for primary amines and aryl fluorides (literature/industry practice)

• Hazards: Primary amines are typically skin/eye irritants and may cause respiratory irritation; some are corrosive in concentrated form. Aryl-fluorides are generally of low acute reactivity, but the base can be harmful if ingested or absorbed. Avoid inhalation of aerosols/vapors.
• PPE: Wear lab coat, safety glasses or goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to control vapors and odors.
• Incompatibilities: Strong oxidizers; acylating and sulfonylating agents (vigorous reactions); carbonyl compounds forming imines in the presence of dehydrating agents; acid chlorides/anhydrides; CO2 can react over time to form ammonium carbamates at surfaces.
• Handling tips: Keep containers tightly closed. Minimize exposure to air and moisture if long-term purity is critical (amines can discolor on oxidation). When preparing salt forms (e.g., HCl), add acid slowly with cooling.
• First aid (overview; consult SDS): If on skin/eyes, rinse with water for at least 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth—seek medical attention. Provide SDS to healthcare professionals.
• Fire safety: Many amines are combustible; use CO2, dry chemical, or foam. Thermal decomposition can release nitrogen oxides and hydrogen fluoride from aryl-F under extreme conditions; firefighters should wear SCBA.

Always consult the product-specific SDS for authoritative safety and regulatory information.

Solvent Selection

Solubility and polarity considerations (general for arylcyclohexyl primary amines)

• Free base solubility: Readily soluble in polar aprotic organics (THF, MeCN, DMF, DMSO, CH2Cl2), alcohols (MeOH, EtOH), and aromatics (toluene). Limited solubility in water at neutral pH; forms water-soluble ammonium salts under acidic conditions.
• Salt forms: Hydrochloride, mesylate, or sulfate salts are typically highly water-soluble and convenient for bioconjugation or aqueous-phase transformations.

Selecting a medium by task

• N-acylation/sulfonylation: Use CH2Cl2, THF, or EtOAc with organic base (e.g., DIPEA). Low dielectric solvents suppress side reactions.
• Amide couplings (peptide-type): DMF, NMP, or DCM with coupling reagents (HATU, EDC/HOBt alternatives). Maintain anhydrous conditions.
• Reductive amination: MeOH, iPrOH, or EtOH with NaBH(OAc)3 or H2/Pd; buffer to mildly acidic pH to balance imine formation and reduction rate.
• Salt exchange or crystallization: IPA/Et2O or EtOAc/hexanes mixtures often tune crystallinity of salts.

Comparison notes

• DCM vs EtOAc: DCM maximizes reactivity and solubility; EtOAc is greener and less dense—prefer when feasible.
• DMF/DMSO vs MeCN/EtOH: Highly polar aprotics dissolve most reagents but are harder to remove; MeCN or EtOH can be greener and easier to purge.

Item-specific solvent specifications: Not specified for this item; refer to CoA/Spec Sheet.

Storage and Reconstitution

• Storage temperature (item-specific): Room temperature (per Product Data). Protect from moisture and air to maintain assay and color. For long-term storage, consider inert-atmosphere packaging and desiccation.
• Container: Store in tightly sealed amber glass to limit light exposure; amines can adsorb CO2 and moisture over time.
• Stability: Primary amines are generally stable, but slow oxidative discoloration can occur on air exposure. If extended storage is anticipated, converting to a crystalline salt (e.g., HCl) can improve shelf life and handling; regenerate free base as needed.
• Reconstitution/dissolution: Dissolves readily in common organic solvents (e.g., DCM, THF, MeOH, EtOH, DMF, DMSO). For aqueous applications, prepare an aqueous mineral acid solution (e.g., 0.1–1 M HCl) to form the ammonium salt.
• Freeze–thaw: Typically not required for solids; if a solution is prepared, store aliquots to minimize repeated warming/cooling cycles.

Note: For definitive stability, impurity limits, and packaging details for this lot, refer to the item’s CoA/Spec Sheet and SDS. Research use only.

Structure and Identity

Brief description: 4-(4-Fluorophenyl)cyclohexan-1-amine is an aryl–cyclohexyl primary amine bearing a para-fluorophenyl substituent at the cyclohexane 4-position.

• Item-specific identifiers (from Product Data)

  • CAS: 1368942-09-9
  • CID: 21534470
  • InChIKey: 102112 (as provided; atypical format—verify on request)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Composition and formula

  • Molecular formula (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight (item-specific): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identity (non-item-specific, for reference)

  • Typical molecular formula: C12H17FN (computed from name/structure)
  • Typical molecular weight: ~194.27 g/mol (computed)
  • Representative SMILES: NC1CCC(CC1)c2ccc(F)cc2 (literature, non-item-specific)

• Structural features (general description)

  • Functional groups: primary aliphatic amine (–CH–NH2), aryl fluoride (para-F on phenyl), cyclohexyl ring.
  • Connectivity: a cyclohexane bearing an amino group at C1 and a 4-fluorophenyl substituent at C4 (1,4-disubstituted cyclohexane). No defined stereocenter at C1 if unsubstituted by different groups; chair conformers possible.
  • 2D description: A six-membered alicyclic ring with –NH2 on one carbon; the carbon opposite (para on the ring) carries a phenyl ring bearing F at the para position.

Synthetic Utility

Key functional group: primary aliphatic amine attached to a 1,4-disubstituted cyclohexane bearing a para-fluorophenyl moiety.

Transformations enabled (general)

• Amide formation: Rapid coupling with carboxylic acids via EDCI/HOBt alternatives, HATU, T3P, or acid chlorides; delivers stable linkages for library synthesis.
• Urea/carbamate synthesis: Reaction with isocyanates/chloroformates or CDI-activated carbonates for probe and prodrug motifs.
• Sulfonamide formation: Reaction with sulfonyl chlorides under base for bioisosteric exploration.
• Reductive amination: N-alkyl derivatives from aldehydes/ketones using NaBH3CN/NaBH(OAc)3 or catalytic hydrogenation.
• N-protection: Boc/Cbz/Fmoc to orchestrate multi-step sequences; deprotection under standard acidic or hydrogenolysis conditions.
• N-oxidation/derivatization: Formation of hydroxylamines or N–O derivatives is less common but possible; monitor for over-oxidation.

Scaffold-specific notes

• The para-fluorophenyl group is synthetically robust and can withstand many conditions (hydrogenation, many bases). It is typically inert to SNAr without activating substituents, which is advantageous for chemoselective N-modifications.
• The cyclohexyl ring provides conformational bias and can influence stereochemical outcomes in downstream transformations (e.g., diastereoselective acylations in chiral environments).

Purification

• Free base often oils; convert to crystalline salts (e.g., HCl in IPA/Et2O) for isolation and storage, then regenerate the base with aqueous base when required.

Target Specificity

Not applicable. This product is a small-molecule amine, not a biological targeting reagent (e.g., antibody, aptamer). No antigen, clone, isotype, or species reactivity applies.