Cyclohexyl(4-methylphenyl)methanamine - ≥95% , CAS No.854708-88-6

CAS: 854708-88-6 Cat. No.: C971316 Formula: C₁₄H₂₁N Peso molecolare: 203.320

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

Sorrisi canonici

CC1=CC=C(C=C1)C(C2CCCCC2)N

IUPAC Name

cyclohexyl-(4-methylphenyl)methanamine

InChIKey

JPEBAKBEFZYTJO-UHFFFAOYSA-N

INCHI

1S/C14H21N/c1-11-7-9-13(10-8-11)14(15)12-5-3-2-4-6-12/h7-10,12,14H,2-6,15H2,1H3

Peso molecolare

203.320

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Toluenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Toluenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Toluenes
• Alternative Parents: Aralkylamines Monoalkylamines Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Aralkylamine - Toluene - Organic nitrogen compound - Hydrocarbon derivative - Primary amine - Organonitrogen compound - Primary aliphatic amine - Amine - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as toluenes. These are compounds containing a benzene ring which bears a methane 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

Proprietà chimiche e fisiche

• Peso molecolare: 203.320 g/mol
• XLogP3: 3.500
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 2
• Exact Mass: 203.167 Da
• Monoisotopic Mass: 203.167 Da
• Topological Polar Surface Area: 26.000 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 176.000
• 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. No biological assay protocols (e.g., WB, IHC, IF, FC) or analytical application protocols are provided for this small-molecule reagent. For synthetic use, refer to the Reaction Conditions and Synthetic Utility sections for general guidance.

Biological Roles

This product is a synthetic organic primary amine supplied for research use only (Product Data). It is not intended for biological administration.

General chemistry/biochemistry context (non-clinical, literature):

• Primary amines are protonated under physiological pH (pKaH typically ~9–10), enabling salt formation and ionic interactions with acids and biomacromolecules.
• Benzylic amines can participate in Schiff base formation with aldehydes/ketones (e.g., with pyridoxal derivatives) and are common motifs in bioactive small molecules; however, any specific biological activity depends on full molecular context and is not implied here.
• For biochemical workflows, the amine can serve as a precursor to labeled probes or conjugates after conversion to amides, ureas, or isothiocyanates.

No item-specific biological roles are provided by the manufacturer for this product.

Buffer Applications

Not typically applicable. Cyclohexyl(4-methylphenyl)methanamine is a hydrophobic primary amine used as a synthetic building block rather than a buffering agent.

General note (literature): its conjugate acid would buffer near pH ~9–10, but volatility/odor and hydrophobicity make it unsuitable as a laboratory buffer. For buffer needs, select established systems (e.g., Tris, HEPES, phosphate) appropriate to your pH range and ionic strength requirements.

Green Alternatives

While the compound itself is a reagent/intermediate (not a solvent), greener choices can be applied to reactions that use it.

• Solvent substitution:
  • Replace DCM with EtOAc, 2-MeTHF, CPME, or toluene where feasible (comparable solvency with improved environmental profile).
  • Use 2-MeTHF instead of THF for reductive aminations and amidations—derived from renewable feedstocks, higher boiling point aids processing, and better water tolerance can simplify workups.
  • Prefer ethanol or isopropanol as hydrogenation media over MeOH/chlorinated solvents when compatible with catalyst and substrate.
• Coupling reagents: Consider catalytic amidation strategies (e.g., Pd- or boronic-acid-catalyzed, or DIC + catalytic DMAP) or lower-waste reagents like T3P (propylphosphonic anhydride) that generate water-soluble byproducts.
• Reductive amination: Use transfer hydrogenation (HCO2H/Et3N, H2 with Pd/C) instead of cyanoborohydride where selectivity allows, reducing cyanide waste.
• Workup/purification: Favor crystallization via salt formation (e.g., HCl, p-TsOH) over silica chromatography to cut solvent consumption.
• Energy efficiency: Conduct reactions at ambient temperature/pressure when possible; use continuous flow for exothermic alkylations or acylations to improve heat/mass transfer and safety.

Trade-offs: Greener solvents may alter reaction rates/selectivities; pilot small-scale screens (DoE) to identify viable substitutions without compromising yield or impurity profile.

Pharmaceutical Uses

No pharmacopeial/excipient status or formulation grade is specified for this item; refer to CoA/Spec Sheet. This product is for research use only (Product Data).

General formulation context (non-clinical):

• Primary amines are frequently converted to stable crystalline salts (e.g., hydrochloride, mesylate, sulfate) to improve handling, solubility, and stability of drug-like intermediates during process development.
• The benzylic primary amine functionality enables straightforward diversification (amide, urea, carbamate formation) in medicinal chemistry SAR campaigns.
• If used in process research, ensure trace impurity profiles (residual solvents, metals, related substances) meet internal specifications before scale-up; none are specified for this product.

Physical Properties

Item-specific specifications are not provided in the Product Data. Do not treat the following as product specifications; they are general literature/computed expectations for closely related benzylic primary amines and should be verified experimentally.

Literature/general expectations (indicative):

• Physical state: typically a colorless to pale yellow liquid or low-melting solid (literature, benzylic primary amines of comparable size often are liquids at RT).
• Boiling point: benzylic primary amines with aryl/cyclohexyl substituents often boil in the 270–320 °C range at 1 atm; 130–200 °C under reduced pressure (literature, depends on apparatus and purity).
• Density: frequently 0.90–1.00 g/mL at 20–25 °C (literature for similar C14–C16 primary amines).
• Refractive index: often nD20 ≈ 1.49–1.53 for arylalkyl primary amines (literature trends).
• pKa (conjugate acid, pKaH): primary benzylic amines typically pKaH ≈ 9.3–10.5 in water at 25 °C; para-methyl substituent is weakly electron-donating, tending toward the higher end (literature).
• Solubility: sparingly soluble in water as the free base; readily soluble in common organic solvents (EtOAc, DCM, toluene, THF, alcohols). Forms water-soluble salts with mineral acids (literature).
• LogP: benzylic/cyclohexyl primary amines of this size commonly show logP ≈ 2.5–3.5 for the free base (literature, method-dependent).

Item-specific values (this lot):

• Appearance, assay, water/peroxide/metal/UV limits: Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

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

Guidance on interpreting grades (general):

• Research/technical vs. analytical grades: Higher grades typically specify tighter limits on assay, water, residual solvents, and trace metals. For amines used in synthesis, lower water and low acidic/oxidative impurities reduce side reactions (e.g., N-acylation background, oxidation to imines).
• Chromatography suitability: If HPLC/LC–MS use is intended, choose material with documented low non-volatile residue and defined UV profile. Primary benzylic amines can show tailing on silica; amine-modified columns or basic mobile phase additives often help.
• Stabilizers: Not indicated for this product. Primary amines are generally supplied neat. If a stabilizer or inhibitor is present, it will appear on the CoA/Spec Sheet; verify compatibility with planned reactions.
• Documentation: For method validation or regulated workflows, obtain the specific CoA for your lot to confirm assay, water content (Karl Fischer), and identity (NMR/IR/HRMS) before use.

Reaction and Applications

Cyclohexyl(4-methylphenyl)methanamine is a versatile benzylic primary amine useful as a building block and nucleophile.

Key application families (general/literature):

• Amide/urea/thiourea formation: Acylation with acid chlorides/anhydrides or coupling with carboxylic acids (EDC/HATU/T3P) to access amides; reaction with isocyanates/isothiocyanates affords (thio)ureas.
• Reductive amination: The amine serves as the nucleophile to form secondary amines with aldehydes/ketones using NaBH3CN, NaBH(OAc)3, or catalytic hydrogenation (Pd/C, H2). Conversely, it can be prepared from the corresponding ketone/aldehyde precursors.
• Electrophile substitution at nitrogen: Alkylation (e.g., with alkyl halides, epoxides) to form secondary amines and amino alcohols; control over mono- vs. dialkylation via stoichiometry and protecting groups.
• Formation of imines/Schiff bases: Condensation with carbonyls; useful intermediates for further transformations (e.g., Strecker, aza-Michael, transfer hydrogenation).
• Transition-metal-catalyzed C–N coupling (as N-nucleophile): Buchwald–Hartwig amination to arylate the nitrogen (from aryl halides/triflates)—sterics/electronics of the benzylic substituents can influence N-arylation rates.
• Derivatization at benzylic carbon: Oxidation to imines/ketimines under mild conditions; potential for asymmetric transformations exploiting the benzylic stereocenter (when enantioenriched).

Practical tips:

• Maintain anhydrous conditions for acylations/borane reductions; pre-base neutralize residual acids.
• For chromatographic purification on silica, add 0.1–1% Et3N to eluents or use basic alumina to suppress streaking.
• Convert to a crystalline salt for long-term storage or to facilitate purification when oils persist.

Reaction Conditions

General literature guidance for common transformations involving benzylic primary amines like Cyclohexyl(4-methylphenyl)methanamine. These are not product specifications.

• Amide coupling: HATU (1.1–1.5 equiv), DIPEA (2–3 equiv) in DMF or DCM, 0–25 °C, 1–4 h; or T3P (50% in EtOAc, 1.5–2.0 equiv) with Et3N/DIPEA in EtOAc/THF, 20–60 °C, 2–6 h. Typical isolated yields 70–95% with unhindered acids.
• Acyl chloride/anhydride acylation: base (Et3N, pyridine) in DCM/THF, 0–25 °C; add acylating agent slowly to control exotherm. Quench with aqueous NaHCO3.
• Reductive amination (as nucleophile): carbonyl (1.0 equiv), amine (1.1–1.5 equiv), NaBH(OAc)3 (1.5–2.0 equiv) in DCE/MeOH/AcOH (0.1–0.3 equiv), 20–25 °C, 2–16 h. Alternatively, Pd/C (5–10 wt%), H2 (1–5 bar) in EtOH/AcOH at RT–50 °C, 2–8 h. Typical yields 60–90% depending on sterics.
• N-alkylation: alkyl halide (1.0–1.2 equiv), K2CO3/Na2CO3 or Et3N in MeCN/acetone/DMF, 25–70 °C, 2–16 h. Monitor for dialkylation; use excess amine or phase-transfer catalysts for selectivity.
• Salt formation: dissolve amine in Et2O/MTBE, bubble dry HCl(g) or add 2M HCl in Et2O at 0–25 °C to precipitate the hydrochloride; isolate by filtration and dry under vacuum.

Notes:

• Add 0.1–1% Et3N to silica chromatography eluents to minimize tailing.
• Dry glassware/solvents improve outcomes for moisture-sensitive couplings.
• For scale-up, calorimetry is recommended for acylations and exothermic alkylations.

Safety and Handling

Hazard classification details are not provided in the Product Data. Always consult the SDS for authoritative information.

• GHS classification, signal word, H-statements, pictograms: Not specified for this item; refer to SDS.
• Likely hazards (general for primary aliphatic/benzylic amines): skin/eye irritation, respiratory irritation, harmful if swallowed; strong, characteristic amine odor. Avoid inhalation of vapors and contact with skin/eyes (literature-based generalization).
• PPE: lab coat, chemical-resistant gloves (e.g., nitrile), splash goggles; handle in a fume hood.
• Incompatibilities: strong oxidizers; acylating agents and acid halides (vigorous reactions); isocyanates and epoxides (may react to form ureas/amino alcohols); CO2 absorption can form carbamates on prolonged air exposure (general amine behavior).
• Storage: Room temperature (Product Data). Keep tightly closed under inert gas if long-term storage to minimize oxidation/discoloration and CO2 uptake (good practice for amines).
• Spill/first aid (general): absorb small spills with inert material; neutralize odor with dilute acid if appropriate. Rinse skin with soap/water on contact; flush eyes with water for ≥15 min; move exposed persons to fresh air. Seek medical attention after significant exposure. Defer to SDS for details.
• Waste: dispose as organic amine waste per institutional and local regulations.

Solvent Selection

This product is a reactive organic amine (not a solvent). Selection below concerns using Cyclohexyl(4-methylphenyl)methanamine as a reagent or intermediate.

• Polarity/handling: As a moderately nonpolar, basic primary amine, it dissolves well in ethers (THF, MTBE), chlorinated solvents (DCM, DCE), aromatics (toluene), and alcohols; limited solubility in water as free base but readily soluble as salts in polar protic media.
• Acid–base extraction: Free base partitions into organic layers; protonated salts (e.g., HCl, p-TsOH) partition into aqueous phase—useful for workups and purifications.
• Salt-switching for crystallization: Forming crystalline salts (e.g., HCl, sulfate, camphorsulfonate) can aid isolation; revert to free base with base (Na2CO3/NaOH) and back-extract into organics.
• Comparison guidance:
  • DCM/DCE: excellent solvency and workup ease; consider safety and environmental aspects.
  • THF/2-MeTHF: good for reductive aminations and metal-catalyzed couplings; 2-MeTHF offers greener profile and better water tolerance.
  • Alcohols (MeOH/EtOH/iPrOH): beneficial in reductive amination (hydrogenation or borohydride-based) and salt formation; may participate in transesterification.
  • Toluene: favorable for high-temperature transformations and azeotropic water removal with a Dean–Stark trap.

Storage and Reconstitution

• Storage temperature: Room temperature (Product Data). Store tightly sealed, preferably under inert gas for prolonged storage to minimize oxidation and CO2 uptake common to amines.
• Container: Use amber glass where possible to limit light exposure; avoid permeable plastics that can absorb amines or allow odor migration.
• Stability: Primary amines are generally stable at ambient conditions but can discolor upon exposure to air/light/acidic impurities. Convert to a crystalline acid salt (e.g., HCl) for enhanced long-term stability if needed.
• Reconstitution/stock solutions: Not applicable to solids vs. liquids is not specified. In practice, prepare stock solutions in dry solvents such as DCM, THF/2-MeTHF, EtOAc, MeOH/EtOH, or acetonitrile. Filter through PTFE if particulates are present. For aqueous work, dissolve as an acid salt to improve solubility.
• Freeze–thaw: Not typically required. If a low-melting solid or viscous oil, gentle warming (room temperature water bath) may aid handling. Avoid repeated heating/cooling cycles.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet and SDS for any special transport requirements.
• Research use only: Yes (Product Data).

Structure and Identity

Cyclohexyl(4-methylphenyl)methanamine is a benzylic primary amine in which the benzylic carbon bears a 4-methylphenyl (p-tolyl) substituent and a cyclohexyl substituent, with an –NH2 group on the same carbon (i.e., R–CH(NH2)–R′). The benzylic center is stereogenic; commercial material is typically racemic unless otherwise specified.

• CAS: 854708-88-6 (Product Data)
• PubChem CID: 20109544 (Product Data)
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data lists: 166401, which is not a standard InChIKey format.)
• 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.

Structural features (general description):

• Functional groups: primary amine (–NH2) at a benzylic stereocenter; para-methyl-substituted phenyl ring; cyclohexyl sp3 fragment.
• Ring systems: one aromatic (p-tolyl) and one saturated cyclohexyl ring.
• Stereochemistry: one tetrahedral stereocenter at the benzylic carbon (racemate expected unless noted).
• 2D description: a central CH(NH2) connects to a para-methylphenyl ring on one side and a cyclohexyl ring on the other; the aryl para position bears a methyl substituent.

Synthetic Utility

Functional group profile and reactivity (general/literature):

• Nucleophilicity/basicity: acts as a competent nucleophile toward activated carbonyls (acid chlorides/anhydrides/activated esters) and alkyl electrophiles; forms salts with acids to modulate reactivity and handling.
• Benzylic position: the α-amine/benzylic carbon can form imines/azomethines under dehydration; oxidants (e.g., MnO2) can selectively oxidize benzylic positions in related systems—conditions must be tuned to avoid over-oxidation or N-oxidation.
• Protecting groups: convert to amide (e.g., Boc via Boc2O; Cbz via Cbz-Cl; Fmoc via Fmoc-Cl) to control selectivity in multistep synthesis; deprotection by acidolysis (Boc), hydrogenolysis (Cbz), or base (Fmoc).
• Cross-coupling at nitrogen: N-arylation (Buchwald–Hartwig) expands into diarylamines; choice of ligands (BrettPhos, XPhos) and bases (NaOtBu, Cs2CO3) governs selectivity and yield.
• Secondary/tertiary amine preparation: monoalkylate via reductive amination or alkyl halides under mild conditions; carefully control stoichiometry to minimize dialkylation.

Retrosynthetic value:

• Serves as a convergence point from a 4-methylaryl carbonyl (via reductive amination) and a cyclohexanone/benzyl halide manifold. Orthogonal diversification on the aryl para-methyl (e.g., oxidation to carboxyl) or on the nitrogen (acylation/alkylation) provides rapid library access.

Target Specificity

Not applicable. This product is a small-molecule amine, not an antibody or biological that recognizes a molecular target. No target/epitope specificity is provided or relevant.