N-[(2-chlorophenyl)methyl]cyclohexanamine - ≥98% , CAS No.46425-73-4

CAS: 46425-73-4 Cat. No.: N1038970 分子式: C₁₃H₁₈ClN 分子量: 223.75 EC番号: 973-700-5 PubChem CID: 4722373

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

仕様と純度

≥98%

保管条件

Room temperature

純度

≥98%

名前と識別子

• カノニカル・スマイル: C1CCC(CC1)NCC2=CC=CC=C2Cl
• IUPAC Name: N-[(2-chlorophenyl)methyl]cyclohexanamine
• InChIKey: LMTAAEZJLLIHMH-UHFFFAOYSA-N
• INCHI: 1S/C13H18ClN/c14-13-9-5-4-6-11(13)10-15-12-7-2-1-3-8-12/h4-6,9,12,15H,1-3,7-8,10H2
• 異性体SMILES: C1CCC(CC1)NCC2=CC=CC=C2Cl
• PubChem CID: 4722373
• 分子量: 223.75

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • 分類 Benzene and substituted derivatives
      • Subclass Phenylmethylamines

• Kingdom: Organic compounds
• Superclass: Benzenoids
• 分類: Benzene and substituted derivatives
• Subclass: Phenylmethylamines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylmethylamines
• Alternative Parents: Benzylamines Cyclohexylamines Chlorobenzenes Aralkylamines Aryl chlorides Dialkylamines Organochlorides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzylamine - Phenylmethylamine - Aralkylamine - Halobenzene - Cyclohexylamine - Chlorobenzene - Aryl halide - Aryl chloride - Secondary amine - Secondary aliphatic amine - Organonitrogen compound - Organochloride - Organohalogen compound - Amine - Hydrocarbon derivative - Organic nitrogen compound - Aromatic homomonocyclic compound
• 説明: This compound belongs to the class of organic compounds known as phenylmethylamines. These are compounds containing a phenylmethtylamine moiety, which consists of a phenyl group substituted by an methanamine.
• 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

化学的性質と物理的性質

• 分子量: 223.740 g/mol
• XLogP3: 3.700
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 3
• Exact Mass: 223.113 Da
• Monoisotopic Mass: 223.113 Da
• Topological Polar Surface Area: 12.000 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 177.000
• 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 bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule reagent. For synthetic procedures using this compound, see Reaction Conditions and Synthetic Utility.

Biological Roles

• Item-specific biological role: Not applicable; this is a synthetic organic building block supplied for research use only.

• General context (informational):

  • Secondary aliphatic/benzylic amines are common motifs in bioactive small molecules and ligands due to their basicity and ability to form hydrogen bonds as donors/acceptors. However, N-[(2-chlorophenyl)methyl]cyclohexanamine itself is not a known metabolite or endogenous compound.
  • The benzylic position adjacent to the aromatic ring is susceptible to oxidative metabolism in biological systems (literature), and protonated amines partition differently across membranes compared with free bases.
  • Aryl chlorides are generally metabolically stable substituents but may participate in oxidative dechlorination under certain conditions. These statements are broad chemical-biological trends and not specific to safety or efficacy.

Research Use Note: For research use only (per Product Data). No clinical, diagnostic, or therapeutic use is intended or implied.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare laboratory buffers. As a basic amine, it will be protonated under acidic conditions, but it is not part of standard buffer systems. For aqueous handling, consider converting to a defined salt (e.g., HCl) for improved solubility and pH control. For buffer selection in reactions involving this amine, see Solvent Selection and Reaction Conditions.

Green Alternatives

While the product itself is a target building block rather than a process solvent, greener choices can be made in its use and in analogous chemistries.

• Solvent choices (preferential options per solvent selection guides):

  • Replace chlorinated solvents (e.g., CH2Cl2) with ethyl acetate or 2-MeTHF where feasible for acylations/sulfonylations.
  • Favor green ethers like CPME or 2-MeTHF over THF (peroxide formation still a concern; monitor peroxides) and over toluene/xylene when polarity is needed.
  • For polar media, consider propylene carbonate or Cyrene in place of DMF/DMA where compatible with reactivity.

• Workup/neutralization:

  • Use aqueous bicarbonate/citrate buffers instead of strong mineral acids/bases to minimize salt waste when possible.
  • Isolate as an HCl salt to improve crystallinity and reduce solvent-intensive chromatography.

• Energy and catalysis:

  • Employ flow hydrogenolysis or catalytic transfer hydrogenation (e.g., formate donors) as alternatives to high-pressure H2 where appropriate.
  • For cross-couplings on the aryl chloride, use ligand/catalyst systems active at lower temperatures and in greener solvents (e.g., aqueous micellar systems) when compatible with amines.

Trade-offs: Greener solvents may change rates/selectivity; amine basicity can be diminished in CO2-rich green solvents (e.g., carbonates). Conduct small-scale trials to verify performance.

Pharmaceutical Uses

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

• General formulation/manufacturing context (no therapeutic claims):

  • Secondary amines like N-[(2-chlorophenyl)methyl]cyclohexanamine may serve as intermediates in the synthesis of API candidates or fine chemicals. The ortho-chloro aryl group can be leveraged for late-stage diversification (e.g., cross-coupling) while the amine provides a handle for salt formation or further derivatization (amides, ureas, carbamates).
  • When used in GMP settings as an intermediate, typical expectations include well-characterized impurity profiles, control of residual solvents, and, for salts, defined counterion content. None of these are specified here and must be verified per batch documentation.
  • If isolated as a free base for process steps, selection of a pharmaceutically acceptable salt (e.g., HCl, sulfate, maleate) may be considered downstream for improved processability; selection depends on the target API and is case-specific.

Physical Properties

• Item-specific (from Product Data):

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Density, melting point, boiling point, refractive index, UV cutoff, water/peroxide/metal content: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general expectations (for secondary benzylic amines; informational only):

  • Physical state: typically a colorless to pale yellow liquid or low-melting solid, with an amine-like odor.
  • Basicity: secondary aliphatic/benzylic amines have basic nitrogen (conjugate acid pKa typically around 10–11, literature), forming stable ammonium salts with mineral acids.
  • Solubility: free base is miscible with many organic solvents (alcohols, ethers, chlorinated solvents, aromatics). Aqueous solubility of the free base is limited; solubility increases markedly as the protonated salt (e.g., HCl salt) in water or alcohol/water mixtures.
  • Partitioning: benzylic/aromatic substitution and a cyclohexyl group confer moderate hydrophobicity (logP often in the 2–3+ range for comparable structures; literature, compound-specific values not established here).

Notes: Do not treat literature values as product specifications. For definitive physical constants and acceptance criteria for SKU N1038970, consult the product’s CoA/Specification Sheet.

Quality and Grades

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

• Interpreting grades (general guidance for researchers):

  • “Analytical/AR” grade emphasizes low inorganic/organic impurities suitable for most synthetic applications.
  • “HPLC” or “LC-MS” grade (for solvents/reagents) emphasizes extremely low non-volatile residue and low UV background—typically not applicable to amine building blocks unless explicitly stated.
  • “Reagent” or “Technical” grade may be appropriate for routine synthesis; high-purity material is recommended for sensitive catalysis (e.g., Pd-catalyzed cross-coupling on the aryl chloride) to minimize amine-derived catalyst poisoning by impurities.

• Stabilizers/additives: Not specified for this item; refer to CoA/Spec Sheet. If supplied as a free base, no stabilizer is typical. If supplied as an acid salt (e.g., HCl), this can enhance stability and ease of handling; confirm with documentation.

• What to check on receipt:

  • CoA-confirmed identity (CAS, structural confirmation), assay, and limits for key impurities (residual solvents, related amines).
  • Intended counterion (if salt), water content (Karl Fischer) if relevant to process needs, and assay method. Always rely on the batch CoA/specification for acceptance criteria.

Reaction and Applications

As a benzylic secondary amine bearing an ortho-chloro substituent on the aryl ring, this molecule is a versatile intermediate and nucleophile.

• Representative transformations (general, literature-informed):

  • N-Acylation to secondary amides using acid chlorides/anhydrides (Schotten–Baumann conditions in biphasic media or in CH2Cl2/THF with base).
  • N-Sulfonylation with sulfonyl chlorides to give sulfonamides (use DIPEA or NaHCO3; 0–25 C).
  • Carbamate/urea formation with chloroformates or isocyanates.
  • Reductive alkylation to tertiary amines (aldehyde/ketone + NaBH3CN or H2/Pd under mild acid catalysis), or direct alkylation (SN2) with primary alkyl halides.
  • Quaternization to benzylammonium salts with alkyl halides (phase-transfer applications).
  • Catalytic hydrogenolysis of the N-benzyl bond (Pd/C, H2) can deprotect to cyclohexylamine while converting the 2-chlorobenzyl fragment to the corresponding toluene derivative (literature precedent for N-benzyl cleavage).
  • Aryl chloride handle enables cross-coupling (Suzuki–Miyaura, Buchwald–Hartwig, Negishi) after appropriate protection of the amine or via catalyst systems tolerant of amines; ortho substitution may influence oxidative addition and sterics.

• Practical tips:

  • Dry the amine (e.g., over K2CO3 or molecular sieves) before moisture-sensitive couplings.
  • For acylations, pre-cool and add electrophile slowly to control exotherm.
  • For Pd-catalyzed couplings on the aryl chloride, consider converting the amine to its salt or carbamate to reduce catalyst binding; use bulky electron-rich phosphines and elevated temperatures.

Reaction Conditions

The following are general literature-style conditions for reactions typical of secondary benzylic amines and aryl chlorides; they are not product specifications.

• N-Acylation (to amides):

  • Solvent: CH2Cl2, THF, or EtOAc.
  • Base: Et3N, DIPEA, or NaHCO3 (biphasic Schotten–Baumann).
  • Temperature: 0–25 C. Time: 0.5–4 h. Typical outcomes: high conversions with controlled addition of acyl chloride.

• N-Sulfonylation:

  • Reagents: RSO2Cl, base (DIPEA or NaHCO3).
  • Solvent: CH2Cl2 or MeCN. 0–25 C, 1–6 h.

• Reductive alkylation (to tertiary amine):

  • Reagents: Aldehyde/ketone (1.0–1.2 eq), NaBH3CN or NaBH(OAc)3 (1.2–2.0 eq), HOAc or TFA catalytic.
  • Solvent: MeOH, EtOH, DCE, or MeCN. 0–25 C, 2–16 h.

• Direct alkylation (SN2):

  • Reagents: Primary alkyl halide (1.0–1.2 eq), base (K2CO3, Cs2CO3).
  • Solvent: DMF or MeCN. 20–50 C, 2–24 h. Monitor to avoid overalkylation.

• Hydrogenolysis of N-benzyl (deprotection option):

  • Catalyst: 5–10% Pd/C (5–20 wt% vs substrate), H2 (1–5 bar).
  • Solvent: EtOH, iPrOH, or AcOH/EtOH.
  • 20–50 C, 2–16 h (monitor for aryl chloride stability under conditions).

• Aryl chloride cross-coupling (on 2-chlorophenyl):

  • Suzuki–Miyaura: Pd2(dba)3 or Pd(OAc)2 with SPhos/XPhos; base K3PO4 or Cs2CO3; solvent toluene/dioxane with H2O or CPME; 80–110 C.
  • Buchwald–Hartwig amination: Pd2(dba)3, BrettPhos or RuPhos, NaOtBu or Cs2CO3; 90–120 C.
  • Protect or salt the amine to reduce catalyst inhibition.

Safety and Handling

• Item-specific GHS (from Product Data):

  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements: Not specified for this item; refer to SDS.
  • GHS Classification: Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.

• General safety information for secondary aliphatic/benzylic amines (informational; defer to SDS):

  • Hazards: May cause skin and eye irritation; vapors can be irritating to the respiratory tract. Amines are basic and can be corrosive to some materials and coatings. Many are harmful if swallowed.
  • Reactivity/incompatibilities: Avoid strong oxidizers, acylating agents, and nitrosating agents (secondary amines can form nitrosamines in the presence of nitrite under acidic conditions). Can react with acid chlorides/anhydrides, isocyanates, and sulfonyl chlorides.
  • Flammability: Organic amines are often combustible; keep away from ignition sources and use in a fume hood.
  • PPE: Lab coat, safety glasses or chemical splash goggles, and suitable gloves (e.g., nitrile). Use in a well-ventilated hood. Have eyewash and safety shower accessible.
  • First aid (overview): Inhalation—move to fresh air. Skin—wash with soap/water. Eyes—rinse cautiously with water for several minutes; remove contact lenses if present. Ingestion—rinse mouth; seek medical advice. Always follow the site-specific SDS for authoritative guidance.

Storage note: Store tightly closed at room temperature (per Product Data). Protect from acids/acidic nitrite, oxidizers, and moisture/CO2 ingress.

Solvent Selection

This product is a non-volatile amine building block, not a laboratory solvent. Solvent considerations below are for dissolving/using the compound in reactions or sample prep.

• Polarity/miscibility (general):

  • Free-base secondary amines dissolve well in polar aprotic solvents (DMF, DMA, DMSO, MeCN), moderately in ethers (THF, MTBE) and aromatics (toluene), and variably in alcohols (MeOH, EtOH). Water solubility is limited for the free base but high for ammonium salts (e.g., HCl, sulfate).

• Selecting a solvent by operation:

  • N-acylation/sulfonylation: CH2Cl2, THF, or EtOAc with a non-nucleophilic base (Et3N, DIPEA). Low temperatures (0–5 C) help control exotherm.
  • Carbamate/urea/isocyanate reactions: Anhydrous THF, toluene, or CH2Cl2.
  • Alkylation to tertiary amine: Polar aprotic (DMF, MeCN) to enhance SN2; minimize overalkylation by controlled stoichiometry.
  • Catalytic hydrogenolysis of N-benzyl (if desired): Alcohols (EtOH, iPrOH) or AcOH/EtOH mixtures under H2 with Pd/C.
  • Cross-coupling on the aryl chloride (literature): Toluene, dioxane, or CPME with polar co-solvent (DMF) under Pd catalysis; amine may require temporary protection to avoid catalyst inhibition.

• Practical notes:

  • Forming the HCl salt can aid handling and water compatibility.
  • Avoid strongly acidic aqueous media for the free base to prevent aerosolized amine exposure; handle salts if aqueous work is needed.

Storage and Reconstitution

• Storage conditions (item-specific): Room temperature (per Product Data). Store in a tightly closed container.

• General handling and stability for amines:

  • Protect from strong acids/oxidizers and from nitrosating agents. Limit exposure to air/CO2 and moisture to avoid salt/carbamate formation on the surface of the free base.
  • If long-term storage is required, consider storing under inert gas in amber glass to minimize oxidative discoloration.

• Reconstitution/Preparation:

  • Not supplied as a lyophilized solid requiring reconstitution. If solidified or viscous, gently warm to ambient temperature to ensure homogeneity before dispensing.
  • For aqueous applications, prepare a defined salt (e.g., dissolve in anhydrous ether and gas with dry HCl to form the hydrochloride), then dissolve the salt in water or alcohol/water as needed. Verify stoichiometry by titration or NMR.

• Shipping: Not specified for this item; refer to CoA/Spec Sheet.

Always consult the SDS for stability and handling specifics. Research use only (per Product Data).

Structure and Identity

N-[(2-chlorophenyl)methyl]cyclohexanamine is a benzylic secondary amine: a cyclohexylamine whose nitrogen bears a 2-chlorobenzyl substituent.

• Item-specific (from Product Data):

  • CAS: 46425-73-4
  • InChIKey: 203693 (as provided)
  • SMILES: 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 (informational, not item-specific specifications):

  • Expected molecular formula for this structure: C13H18ClN (secondary amine with cyclohexyl and 2-chlorobenzyl substituents).
  • Approximate formula weight: ~223.75 g/mol (literature calculation from C13H18ClN).
  • Representative SMILES (literature): Clc1ccccc1CN(C2CCCCC2)H.

• Structural features (general description):

  • Functional groups: secondary aliphatic amine (N–H), benzylic methylene (–CH2– attached to aromatic ring), aryl chloride (ortho-chloro phenyl).
  • Ring systems: one monocyclic cyclohexane ring; one monosubstituted benzene ring (2-chloro substituent).
  • Stereochemistry: none (no stereocenters in the parent structure).
  • 2D description: a cyclohexyl group attached to the amine nitrogen; the nitrogen also bears a hydrogen and a –CH2– linker to a 2-chlorophenyl ring (chloro at the ortho position relative to the benzylic carbon).

Synthetic Utility

Key functional handles and their retrosynthetic value:

• Secondary amine (N–H):

  • N-acylation → secondary amides; further N-alkylation → tertiary amides (or tertiary amines via alkylation/reductive amination).
  • Protection strategies: carbamates (Boc, Cbz) or salts (HCl) to attenuate basicity/coordination in metal-catalyzed steps.

• Benzylic methylene (–CH2–Ar):

  • Susceptible to oxidation or hydrogenolysis; catalytic hydrogenolysis (Pd/C) can deprotect the N-benzyl to yield cyclohexylamine and an aryl hydrocarbon byproduct (literature precedent for N-benzyl scission).

• Aryl chloride (ortho):

  • Cross-coupling platform (Suzuki–Miyaura, Stille, Negishi, Buchwald–Hartwig). Ortho substitution modulates oxidative addition kinetics and sterics; appropriate ligands (e.g., bulky electron-rich phosphines or biaryl phosphines) and elevated temperature often required for Ar–Cl activation.
  • Metal–halogen exchange or lithium–halogen exchange strategies are possible in principle, but basic nitrogen must be protected or sequestered to avoid quenching and to control chemoselectivity.

• Tertiary amine synthesis:

  • One-step alkylation (SN2) with primary alkyl halides in polar aprotic media or two-step reductive amination with carbonyls provides rapid library diversification around the N-center.

These convergent handles enable orthogonal diversification at nitrogen and on the aryl ring, advantageous for SAR exploration and late-stage functionalization.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or biologic. No target, epitope, species reactivity, clone, or isotype information applies.