1-(4-Methoxyphenyl)cyclohexan-1-amine , CAS No.125802-09-7

CAS: 125802-09-7 Cat. No.: M1308906 Formula: C₁₃H₁₉NO Molecular Weight: 205.29 EC Number: 831-251-1 PubChem CID: 24273705

Storage

Room temperature

Specifications

Storage

Room temperature

Names and Identifiers

Canonical Smiles

COC1=CC=C(C=C1)C2(CCCCC2)N

IUPAC Name

1-(4-methoxyphenyl)cyclohexan-1-amine

InChIKey

CFTBUCKEQRAUOF-UHFFFAOYSA-N

INCHI

1S/C13H19NO/c1-15-12-7-5-11(6-8-12)13(14)9-3-2-4-10-13/h5-8H,2-4,9-10,14H2,1H3

Isomeric SMILES

COC1=CC=C(C=C1)C2(CCCCC2)N

PubChem CID

24273705

Molecular Weight

205.29

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Phenol ethers
      • Subclass Anisoles

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Phenol ethers
• Subclass: Anisoles
• Intermediate Tree Nodes: Not available
• Direct Parent: Anisoles
• Alternative Parents: Phenoxy compounds Methoxybenzenes Cyclohexylamines Aralkylamines Alkyl aryl ethers Monoalkylamines Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Phenoxy compound - Anisole - Methoxybenzene - Alkyl aryl ether - Cyclohexylamine - Aralkylamine - Monocyclic benzene moiety - Ether - Organooxygen compound - Organonitrogen compound - Primary aliphatic amine - Hydrocarbon derivative - Organic nitrogen compound - Organic oxygen compound - Amine - Primary amine - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.
• 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: 205.300 g/mol
• XLogP3: 2.400
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 205.147 Da
• Monoisotopic Mass: 205.147 Da
• Topological Polar Surface Area: 35.300 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 191.000
• 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 immunoassay or cell-based application protocols (e.g., WB, IHC, IF, FC) are specified for this small-molecule reagent. For synthetic uses, refer to the Reaction Conditions and Synthetic Utility sections for practical guidance.

Biological Roles

This product is supplied for research use only. No biological activity or clinical use is claimed.

General biochemical considerations for primary aliphatic amines (literature):

• Interaction motifs: Primary amines engage in ionic interactions with acidic residues and form H‑bonds as acceptors (and weak donors), making them common components of ligands in chemical biology screens.
• Protonation state: At physiological pH, aliphatic amines are largely protonated (pKaH typically ~9–10.5), impacting membrane permeability and target engagement.
• Structural role: The para‑methoxyphenyl (anisyl) group can enhance lipophilicity and π–π interactions in probe molecules; cyclohexyl groups can improve metabolic stability relative to linear alkyl chains (literature trends in medicinal chemistry).

If utilized as a fragment/scaffold in discovery:

• Consider preparing both free base and water-soluble acid salts for assays to decouple permeability/solubility effects.
• Confirm purity and residual solvent profile to avoid confounding biological readouts.

Note: The points above are general literature observations for similar amines and do not represent activity or suitability claims for this specific material.

Buffer Applications

This compound is not a dedicated buffer reagent and is not typically used to prepare defined pH buffer systems.

Practical notes (general):

• As a primary amine, it can be protonated with mineral/organic acids to form salts, improving aqueous solubility transiently; however, such solutions do not constitute standardized buffer systems with known pKa/pH ranges.
• For buffer preparation, use established buffering agents (e.g., phosphate, Tris, HEPES) and reserve this compound for synthetic or screening applications.

Green Alternatives

While the compound itself is a reagent/building block (not a solvent), greener choices can be implemented around its use.

Greener media and auxiliaries (literature/general):

• Solvents: Prefer 2‑MeTHF, CPME, EtOAc, MeOH/EtOH, or propylene carbonate over chlorinated solvents when compatible.
• Coupling reagents: Consider greener amide couplings (e.g., CDI, DMTMM) instead of HATU/HBTU to reduce hazardous byproducts.
• Workups: Employ aqueous micellar catalysis or biphasic EtOAc/brine extractions; minimize halogenated waste.

Comparison snapshot (general guidance):

• DCM vs 2‑MeTHF: 2‑MeTHF is biorenewable, higher boiling (difficult to remove at scale) but often excellent for amine chemistry; DCM is nonflammable but has higher environmental impact.
• THF vs CPME: CPME resists peroxide formation better than THF and offers wider liquid range; THF is widely compatible but forms peroxides and often requires stabilizer management.
• NaBH(OAc)3 vs H2 with Pd/C: For reductive amination, transfer hydrogenation or H2 can reduce inorganic salt waste, but requires pressure equipment and careful selectivity control.

Process hints:

• Target salt formation (e.g., p‑TsOH salt) to enable crystallization from greener alcohol/ether solvent systems.
• Recycle solvents where feasible; choose bases/acids with simpler neutralization (e.g., CO3 2−/AcOH systems).

Pharmaceutical Uses

No therapeutic claims are made for this material. Research-use only.

General roles in pharmaceutical R&D/manufacturing (literature):

• Medicinal chemistry intermediate: The hindered primary amine can be diversified into amides, ureas, carbamates, and sulfonamides, enabling SAR exploration around a cyclohexyl–anisyl scaffold.
• Salt screening: Formation of pharmaceutically acceptable salts (e.g., HCl, mesylate, tosylate) can aid in crystallinity, stability, and handling during preformulation studies.
• Impurity/reference standard: Potential use as a reference or process intermediate standard where this motif appears in synthetic routes.

Regulatory/formulary status: Not specified for this item; refer to internal program requirements. Any application in drug product manufacturing would require independent qualification, impurity profiling, and release testing according to relevant pharmacopeial and GMP standards.

Physical Properties

Item-specific quantitative specifications (bp, mp, density, refractive index, assay, residuals) are Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for this structure (for planning only):

• Physical state/appearance: Primary arylalkyl amines of comparable size can be low-melting solids or high-boiling oils (literature trend). Exact appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Basicity: Aliphatic primary amines typically have pKaH ~9–10.5 (literature). Steric hindrance at the α-carbon can slightly depress basicity versus unhindered cyclohexylamine.
• Solubility (qualitative, literature):
  • Good in common organic solvents (EtOAc, THF, DCM, toluene, alcohols).
  • Forms water-soluble salts with mineral or organic acids (e.g., HCl, H2SO4, p-TsOH). Free base has low water solubility.
• Partitioning: Aryl–cyclohexyl amines are moderately lipophilic; logP often in the 2–3 range for related scaffolds (literature trend, not a specification).
• Spectral features (literature expectations):
  • 1H NMR: –NH2 (exchangeable, broad), anisyl OCH3 singlet (~3.7–3.9 ppm), aromatic AA′BB′ pattern (~6.8–7.2 ppm), cyclohexyl multiplets (1.0–2.2 ppm).
  • IR: N–H stretches (~3300–3400 cm−1), aliphatic/aromatic C–H, aromatic C=C, aryl–O stretch (~1240–1270 cm−1).

All property values above are general literature guidance for similar compounds and are not specifications for this SKU.

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 on typical grades (general):

• Research grade: Suitable for most synthetic and discovery workflows. Trace impurity limits and assay may vary by lot; consult CoA for exact specifications.
• HPLC grade (if offered): Emphasizes low UV background and low non-volatile residues for analytical work.
• ≥98–99% purity (if specified): Useful where side-reactions from residual amines/impurities would be problematic (e.g., peptide couplings, catalytic reactions).

Quality considerations for this scaffold (general):

• Primary amines can carry residual moisture or CO2-derived carbamate; brief drying in vacuo and handling under inert atmosphere can improve consistency in moisture‑sensitive couplings (e.g., HATU/EDC-mediated amide formation).
• For biological screening, confirm residual solvent profile and assay purity by HPLC/GC as required by internal SOPs.

Documentation: Request the CoA/Spec Sheet for this specific lot to verify assay, residual solvents, and any metal/halide or peroxide limits (Not specified for this item).

Reaction and Applications

As a hindered primary aliphatic amine with an appended p‑methoxyphenyl group, 1-(4-Methoxyphenyl)cyclohexan-1-amine is a versatile nucleophile and building block in organic synthesis.

Representative application families (literature/general):

• Amide formation: Coupling with carboxylic acids (HATU/HOAt, EDCI/HOBt, CDI) to give tertiary-carbinyl amides. Steric hindrance at C1 may slow acylation; activating agents and elevated temperature improve rates.
• Ureas/carbamates/sulfonamides: Reaction with isocyanates/chloroformates/sulfonyl chlorides (e.g., TsCl) to access derivatives for SAR exploration.
• Reductive amination/N-alkylation: Condense with aldehydes/ketones to imines (or use NaBH(OAc)3/BH3•THF for one-pot reductive amination) to furnish secondary amines; control selectivity to avoid tertiary amines if undesired.
• N‑Protection: Boc (Boc2O, base), Cbz (CbzCl), Fmoc (Fmoc-Cl) to modulate reactivity and solubility; deprotection under standard conditions (TFA for Boc; hydrogenolysis for Cbz).
• Salt formation: HCl, HBr, or p‑TsOH salts improve crystallinity, handling, and purification; useful for formulation and characterization.
• Cross-coupling as nucleophile surrogate: Convert to amide/urea/carbamate and engage in further diversification; direct N‑arylation via Buchwald–Hartwig amination uses the amine as nucleophile to form anilide-type products.

Practical notes:

• Dry conditions and non-nucleophilic bases (DIPEA, Hunig’s base) reduce side reactions.
• For challenging acylations, pre-activate acids (acid chlorides via SOCl2/oxalyl chloride) and add amine last at 0–25 °C.
• Monitor by TLC/HPLC; amines often streak—use stains (ninhydrin, KMnO4) or convert aliquots to amide for cleaner analytics.

Reaction Conditions

General literature conditions for common transformations of primary aliphatic amines (guidance only; optimize per substrate):

• Amide coupling:

  • Reagents: HATU (1.1–1.5 equiv), EDCI (1.2–1.5 equiv) + HOBt/HOAt or Oxyma, CDI (1.1–1.3 equiv)
  • Base: DIPEA (2–3 equiv)
  • Solvent: DMF, DCM, or THF (anhydrous)
  • Temperature/time: 0–25 °C, 1–16 h (steric hindrance may require warming to 40–60 °C)
  • Notes: Add amine last to pre-activated acid; monitor for overacylation of unprotected functionalities if present.

• Reductive amination (to secondary amines):

  • Carbonyl: Aldehyde or ketone (1.0–1.5 equiv)
  • Reductant: NaBH(OAc)3 (1.5–2.0 equiv) in DCE/MeCN/MeOH; or BH3•THF (1.5–2.0 equiv) in THF
  • Additives: AcOH (0.5–1.0 equiv) to promote iminium formation (with NaBH(OAc)3)
  • Temperature/time: 0–25 °C, 2–18 h

• N‑Protection (Boc):

  • Reagents: Boc2O (1.1–1.5 equiv), base (NaHCO3 or DIPEA)
  • Solvent: DCM/MeCN/THF; 0–25 °C, 1–4 h
  • Deprotection: TFA/DCM, 0–25 °C, 0.5–2 h

• Sulfonamide formation:

  • Reagents: TsCl (1.1–1.3 equiv), base (pyridine or TEA)
  • Solvent: DCM/MeCN; 0–25 °C, 1–6 h

Workup/purification:

• Quench with aqueous bicarbonate or dilute acid as appropriate; extract with EtOAc or DCM.
• Convert to acid salts (e.g., HCl) for crystallization from i-PrOH/Et2O or EtOAc/hexanes.

All conditions above are literature-style guidance for similar amines; verify compatibility with your substrate and scale.

Safety and Handling

Authoritative safety information must be taken from the product SDS.

Product Data (item-specific):

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

General hazards and precautions for primary aliphatic amines (literature/typical):

• Hazards: Irritating to skin, eyes, and respiratory tract; may cause sensitization in susceptible individuals. Can be harmful if swallowed. Amines are basic and can be corrosive to some materials.
• Incompatibilities: Strong oxidizers; acylating/sulfonylating agents (vigorous reactions); carbonyl compounds (can form imines); acid chlorides/anhydrides (exothermic acylation); CO2 from air can form carbamates on prolonged exposure in some amines.
• PPE: Lab coat, nitrile gloves, safety glasses/goggles; use in a fume hood to avoid vapor/aerosol exposure.
• First aid (overview):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin: Wash with soap and water; remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; seek medical attention if irritation persists.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire safety: Organic amines are combustible; use CO2, dry chemical, or foam. Avoid water jets on neat material.

Always consult the SDS for definitive hazard classification and response procedures.

Solvent Selection

Compound type and polarity:

• A lipophilic, primary aliphatic amine bearing a para‑methoxyphenyl ring. Moderately polarizable and hydrogen-bond basic; poor hydrogen-bond donor strength in nonpolar media.

Miscibility and preferred media (general/literature):

• Excellent solubility in chlorinated solvents (DCM, CHCl3), ethers (THF, MTBE), esters (EtOAc), aromatic hydrocarbons (toluene), and alcohols (MeOH, EtOH, i-PrOH).
• Limited solubility in water as free base; readily soluble as salts in aqueous acidic media (e.g., 0.1–1 M HCl).

Selection tips by application:

• Acylation/urea/carbamate formation: Use dry DCM, THF, or DMF; base scavengers (DIPEA) as needed.
• Reductive amination/N-alkylation: Alcohol (MeOH/EtOH) or DCE/MeCN with NaBH(OAc)3 or BH3•THF; control over-alkylation with stoichiometry.
• Salt formation and isolation: IPA/Et2O or IPA/MTBE for precipitating HCl or p‑TsOH salts.

Quick comparison (general):

• DCM vs 2-MeTHF: DCM offers rapid extractions and low boiling; 2‑MeTHF is greener and often dissolves amines well while enabling biphasic workups.
• MeOH vs EtOH: MeOH dissolves amines more readily; EtOH is less toxic and often adequate for reductive amination.

Always ensure solvent dryness for moisture‑sensitive couplings, and verify compatibility with planned reagents and downstream analytics.

Storage and Reconstitution

Item-specific storage: Room temperature (Product Data). Avoid prolonged exposure to air and moisture to minimize salt/carbamate formation typical of amines.

General handling guidance (literature/best practice):

• Storage: Tightly sealed container under ambient conditions; for long-term storage, consider an inert gas blanket (N2/Ar) and desiccation. Protect from strong oxidizers and acids unless intentionally forming salts.
• Form of material: Appearance not specified; verify by CoA/Spec Sheet. If a salt form is desired for handling or solubility, generate in situ (e.g., HCl salt) and store dry.
• Reconstitution/stock solutions:
  • Organic stocks: Dissolve in dry DCM, THF, MeOH, EtOH, or DMSO to desired concentration. Filter if needed through PTFE (0.2 µm).
  • Aqueous use: Prepare acidified aqueous solutions by first forming an appropriate salt (e.g., 0.1 M HCl). Avoid prolonged storage of aqueous solutions; prepare fresh or store short-term at 2–8 °C.
• Freeze–thaw: Not typically required. If solutions are frozen (e.g., in DMSO), minimize cycles by aliquoting.

Always consult the current CoA and SDS for lot-specific stability, appearance, and safety information. Research use only.

Structure and Identity

Brief description: 1-(4-Methoxyphenyl)cyclohexan-1-amine is a primary aliphatic amine in which the amine-bearing carbon is a tertiary (quaternary center) at C1 of a cyclohexane ring, also substituted by a para‑methoxyphenyl group.

• Synonyms: p-Anisylcyclohexan-1-amine; 1-(p-Methoxyphenyl)cyclohexan-1-amine (literature)
• CAS: 125802-09-7 (Product Data)
• PubChem CID: 24273705 (Product Data)
• InChIKey: 43087 (Product Data; truncated as provided)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (literature): C13H19NO
• Molecular weight (literature): ~205.30 g/mol
• Structural features:
  • One cyclohexane ring (alicyclic, saturated)
  • One para-methoxy-substituted phenyl ring (anisyl moiety)
  • One primary amino group (–NH2) bonded to a tertiary carbon (C1 of cyclohexane), yielding a neopentyl-like, hindered primary amine
  • Ether function on the aryl ring (–OCH3 at para position)
• 2D description in words: A cyclohexane ring whose C1 carbon bears both an –NH2 group and a 4‑methoxyphenyl substituent; the phenyl ring carries a para methoxy substituent relative to the cyclohexyl linkage.

Notes: Molecular formula and mass are provided as literature/computed identifiers for recognition only; they are not item-specific specifications.

Synthetic Utility

Key functional groups and reactivity:

• Primary aliphatic amine (nucleophilic, basic)
• Para‑methoxyphenyl ether (electron-rich aryl for further electrophilic substitution or oxidative transformations)
• Tertiary-carbinyl center at C1 (steric effects influence reaction rates and selectivity)

Useful transformations (literature/general):

• Amide synthesis with carboxylic acids/acid derivatives (CDI, EDCI/HATU, acid chlorides) to generate sterically encumbered amides.
• Urea/carbamate formation (isocyanates/chloroformates) for polarity and H‑bond modulation.
• Reductive amination to access secondary amines; subsequent acylation/alkylation expands chemical space rapidly.
• N‑Protection strategies (Boc/Cbz/Fmoc) to orchestrate multi-step sequences and improve chromatographic behavior.
• Conversion to sulfonamides (e.g., TsCl, MsCl) for stable, often crystalline derivatives.
• Salt formation to enable phase switching/crystallization and streamline purification.

Retrosynthetic value:

• The motif can arise from reductive amination of 4‑methoxybenzaldehyde/acetophenone analogs with 1‑aminocyclohexane precursors, or via addition of organometallic anisyl equivalents to cyclohexanone followed by amination (literature strategies). The presence of the anisyl group allows downstream selective O‑demethylation (e.g., BBr3) to phenol derivatives if desired.

Analytical tips:

• Derivatize to amides (e.g., acetic anhydride) for sharper chromatographic spots/peaks and improved GC compatibility when needed.

Target Specificity

Not applicable. This product is a small-molecule amine, not an antibody, enzyme, or targeted biological reagent. No antigen/epitope, clone, isotype, or species reactivity data apply.