N-benzyl-3-ethynylaniline - ≥95% , CAS No.864754-01-8

CAS: 864754-01-8 Cat. No.: N942911 Summenformel: C₁₅H₁₃N Molekulargewicht: 207.270

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥95%

Storage

Room temperature

Reinheit

≥95%

Namen und Kennungen

• Kanonisches Lächeln: C#CC1=CC(=CC=C1)NCC2=CC=CC=C2
• IUPAC Name: N-benzyl-3-ethynylaniline
• InChIKey: HOJRZUZHFVUTHL-UHFFFAOYSA-N
• INCHI: 1S/C15H13N/c1-2-13-9-6-10-15(11-13)16-12-14-7-4-3-5-8-14/h1,3-11,16H,12H2
• Molekulargewicht: 207.270

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Phenylmethylamines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylbenzamines
• Alternative Parents: Phenylalkylamines Benzylamines Aniline and substituted anilines Secondary alkylarylamines Acetylides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Phenylbenzamine - Phenylalkylamine - Aniline or substituted anilines - Benzylamine - Aralkylamine - Secondary aliphatic/aromatic amine - Acetylide - Secondary amine - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Amine - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as phenylbenzamines. These are aromatic compounds consisting of a benzyl group that is N-linked to a benzamine.
• 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 207.270 g/mol
• XLogP3: 3.400
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 4
• Exact Mass: 207.105 Da
• Monoisotopic Mass: 207.105 Da
• Topological Polar Surface Area: 12.000 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 243.000
• 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

No assay or bioanalytical application protocols are specified for this item. As a synthetic building block, typical procedures relate to organic synthesis (e.g., couplings, acylations, hydrogenolysis). For practical step-by-step methods, see the Reaction Conditions section and consult primary literature for substrate-specific optimizations.

Biological Roles

This product is intended strictly for research use; no biological function is claimed for this specific compound.

• General context (literature, not item-specific):

  • Aromatic amines are not biometabolites; they can interact with proteins via hydrogen bonding at nitrogen and π–π interactions via aryl rings, which is why related motifs are common in medicinal chemistry scaffolds.
  • Terminal alkynes can act as bioorthogonal handles. In chemical biology, alkynes are frequently used for copper-catalyzed azide–alkyne cycloaddition (CuAAC) after appropriate functionalization of biomolecules with azides; this compound’s alkyne could be leveraged in derivatization strategies, though the parent molecule itself is not a probe.
  • Metabolism considerations for the class: oxidative N-debenzylation (CYP-mediated) and alkyne oxidation/hydroxylation are common in vivo transformations of related structures (literature note), but such data are not established for this exact compound.

• Practical implication for researchers:

  • Use as a synthetic intermediate to assemble analog libraries prior to biological testing. Any biological evaluation should be performed on the derived targets, not inferred from this building block.

Reminder: No clinical/therapeutic claims are made. For any toxicological or ADME data, consult primary literature specific to the final compounds prepared from this intermediate.

Buffer Applications

This compound is a hydrophobic organic building block and is not typically used to prepare aqueous buffer systems. It lacks acid–base properties in the physiological pH range that would make it a practical buffering agent. For work involving this compound, refer instead to the Solvent Selection, Reaction & Applications, and Synthetic Utility sections for guidance on suitable organic media and transformations.

Green Alternatives

As a building block (not a solvent), greener choices relate to reaction media, reagents, and protection strategies rather than replacement of the substrate itself.

• Greener solvent options (literature/general guidance):

  • Replace chlorinated solvents (DCM, CHCl3) with 2-MeTHF or CPME for acylations and metal-catalyzed couplings.
  • For polar processes (Sonogashira, Cu-free), consider propylene carbonate or bio-based esters when compatible with bases and catalysts.
  • For hydrogenolysis, use EtOH or i-PrOH instead of DMF/THF when feasible.

• Reagent/catalyst considerations:

  • Cu-free Sonogashira (Pd with bulky phosphines) minimizes Glaser byproducts and copper waste.
  • Use ligand-optimized Pd catalysts that operate at low loadings in green solvents (e.g., XPhos, SPhos systems), reducing precious metal usage.
  • Explore electrochemical oxidative couplings as alternatives to stoichiometric oxidants for diyne formation.

• Workup/waste minimization:

  • Favor aqueous biphasic extractions with greener solvents (EtOAc, MTBE) and avoid halogenated waste streams when possible.
  • Implement in-line hydrogen uptake monitoring for safe, efficient debenzylations; recover Pd via filtration aids to improve metal accounting.

Comparison snapshot:

• DCM vs 2-MeTHF: similar solvating power for acylations; 2-MeTHF is renewable and has better safety/profile but can contain peroxides over time (monitor).
• DMF vs EtOH/i-PrOH: alcohols are greener and less problematic in waste streams but may affect catalyst activity/selectivity.

Pharmaceutical Uses

No pharmacopeial or excipient status is claimed for this item.

• Context (general, not item-specific):

  • Aromatic amine/alkyne scaffolds are frequently employed as intermediates in medicinal chemistry to access target candidates via diversification at nitrogen (amides, ureas) and at the alkyne (couplings, cycloadditions).
  • The benzyl group on nitrogen provides a temporary protecting group that can be removed by hydrogenolysis, facilitating stepwise synthesis en route to APIs without committing to final N-substitution early.

• Formulation relevance:

  • The parent compound is not used as an excipient. If incorporated into drug discovery workflows, it is handled as a small-molecule intermediate under research-use-only conditions.

Any claims of therapeutic action or clinical use are outside scope. For GMP or regulatory-grade materials, separate sourcing and documentation would be required.

Physical Properties

Item-specific specifications (for this SKU) are not provided; consult the CoA/Spec Sheet for authoritative values.

• 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 properties for the described structure (C15H13N; informational only):

  • Molecular weight (calc.): ~207.27 g/mol
  • Estimated boiling point: High-boiling organic liquid/low-melting solid expected; typical anilide benzyls with similar MW boil around 320–360 °C at 1 atm; lower under vacuum (literature ranges; not item-specific).
  • Melting point: Likely low-melting or liquid at RT (literature expectation for analogous N-benzyl anilines).
  • Density (20–25 °C): Approximately 1.0–1.1 g/mL for similar aromatic amines (literature, indicative only).
  • Solubility: Poorly soluble in water; soluble in common organic solvents (EtOAc, DCM, toluene, THF, MeCN, alcohols) — literature expectation.
  • pKa (anilinium conjugate acid): ~4.6–5.5 (literature range for N-aryl secondary anilines).
  • pKa (terminal alkyne): ~25 (literature, typical of arylacetylenes).
  • LogP: Likely ~2.5–3.5 for diaryl/benzyl anilines (literature estimate).

Note: Do not use literature/computed values as product specifications. Always verify with the lot-specific CoA.

Quality and Grades

• Item-specific quality information:

  • 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 grades (general, for context only):

  • Research grade materials are suitable for synthetic and analytical research where pharmacopeial compliance is not required. Impurity profiles emphasize starting-material and process-related species.
  • High-purity (≥98–99%) aromatic amines are often preferred for catalysis and cross-coupling to minimize catalyst poisoning by residual metals/sulfur- or nitrogen-rich impurities.
  • Chromatography/HPLC grade solvents should be used when preparing analytical standards or conducting kinetic/photophysical studies with this compound to minimize background UV absorbance and baseline noise.

• Implications for this compound class:

  • Secondary anilines can carry trace basic or nitroaromatic impurities that affect reactions (e.g., Pd-catalysis). Lot-specific metal content, residual solvents, and water should be checked on the CoA when reactions are moisture- or base-sensitive.
  • If used as a building block for SAR libraries, request or verify data such as NMR purity, GC/HPLC area %, and residual-metal screening when relevant to your workflows.

For definitive grade/purity specifications and acceptance criteria, consult the lot-specific CoA/Spec Sheet.

Reaction and Applications

N-benzyl-3-ethynylaniline is a bifunctional building block combining a secondary aniline and a terminal arylacetylene, enabling orthogonal diversification.

• Transformations at the terminal alkyne (literature/general):

  • Sonogashira coupling: Convert the terminal alkyne into internal aryl–alkynes with aryl/vinyl halides (Pd/Cu catalysis or Cu-free variants). Typical bases: Et3N, i-Pr2NEt, Cs2CO3.
  • Glaser–Hay oxidative coupling: Homocouple to diynes under Cu catalysis and O2; control overoxidation with ligands (TMEDA) and oxygen sparging.
  • Hydrofunctionalizations: Au-/Pt-catalyzed hydroarylation/hydroamination; radical additions (e.g., thiol–yne) for polymer conjugation.
  • Nucleophilic acetylides: Deprotonation (n-BuLi, LDA) to give lithium acetylide for addition to electrophiles (aldehydes/ketones) or for alkylation with primary halides.

• Transformations at nitrogen/aromatic ring:

  • Acylation/Carbamates/Ureas: Reaction with acid chlorides, chloroformates, isocyanates to modulate basicity and H-bonding.
  • N-Debenzylation: Hydrogenolysis (Pd/C, H2) to access 3-ethynylaniline; or oxidative methods (DDQ) when hydrogen-sensitive.
  • Electrophilic aromatic substitution: The anilide directs ortho/para; the meta-ethynyl exerts weak –I/–M; use protecting groups if competing N-acylation is problematic.

• Use cases in synthesis:

  • Scaffold for click-chemistry precursors (convert amine to azide or alkyne to azido-alkyne hybrids).
  • Intermediate for heteroaryl–alkyne linkers in materials/medchem libraries.

Practical tips: Dry, oxygen-free conditions improve Pd-catalyzed couplings; control amine basicity via transient protection (Boc) when selective alkyne functionalization is desired. Monitor with TLC/GC/MS; the UV-active diaryl core aids detection.

Reaction Conditions

The following conditions are general literature guidance for this compound class; optimize for your substrate, scale, and equipment. These are not product specifications.

• Sonogashira coupling (on the terminal alkyne):

  • Typical: Aryl bromide (1.0 eq), this alkyne (1.2–1.5 eq), Pd(PPh3)2Cl2 (1–3 mol%), CuI (1–5 mol%), Et3N or i-Pr2NEt (2–3 eq), THF/DMF/toluene, 50–80 °C, 2–12 h. Cu-free variants: Pd/XPhos or Pd/SPhos (0.5–2 mol%), Cs2CO3 in toluene or dioxane.

• Glaser–Hay oxidative homocoupling:

  • CuCl (5–10 mol%), TMEDA (10–20 mol%) in O2/air, THF or toluene, rt–50 °C, 2–24 h. Maintain controlled oxygenation to limit overoxidation.

• Formation of metal acetylides for additions:

  • n-BuLi (1.05–1.2 eq) in dry THF or ether at −78 to 0 °C, then add electrophile (aldehyde/epoxide). Quench at low temperature. Protect or transiently acylate the amine if competitive deprotonation/coordination inhibits reactivity.

• N-acylation/carbamate formation:

  • Acid chloride (1.05–1.2 eq), Et3N/DIPEA (2 eq) in DCM/2-MeTHF, 0 °C to rt, 1–3 h. Monitor to avoid overacylation or O-acylation side products.

• N-debenzylation:

  • Pd/C (5–10 wt% relative to substrate), H2 (1–3 bar) in EtOH/EtOAc, rt–40 °C, 2–16 h. Alternative: DDQ (1.5–2 eq) in DCM/MeOH at rt.

• Analytical monitoring:

  • UV-active at 254 nm; GC/MS or LC/MS suitable. The secondary amine may tail on silica; add 0.1–1% Et3N to eluent for sharper bands.

Always conduct small-scale trials to define exact reagent loadings, temperatures, and times.

Safety and Handling

• Item-specific GHS information (for this SKU):

  • Signal word / H-statements / Pictograms / GHS classification: Not specified for this item; refer to SDS.

• General hazards for aromatic secondary anilines and terminal alkynes (literature/general guidance; not item-specific):

  • Health: May be harmful if swallowed, inhaled, or upon skin contact; aromatic amines can cause skin/eye irritation and may be absorbed through skin. Avoid prolonged exposure.
  • Flammability: Organic compound; combustible. Terminal alkynes are not peroxidizable like ethers but vapors may form flammable mixtures when heated.
  • Reactivity: Deprotonation of the terminal alkyne generates metal acetylides; avoid contact with strong oxidizers. Amines react with acid chlorides/anhydrides and may corrode some metals in presence of moisture/CO2.

• Handling recommendations (best practice):

  • Work in a fume hood; avoid inhalation and contact. Use PPE: lab coat, nitrile gloves, splash goggles. For larger-scale operations, consider additional skin protection.
  • Keep away from strong oxidizers, acylating agents unless intentionally reacting, and ignition sources. Avoid acids during storage to prevent salt formation.
  • In case of contact: rinse skin/eyes with water for ≥15 min; seek medical advice. If inhaled, move to fresh air. If ingested, do not induce vomiting; seek medical attention.

• Reference: Always consult the product’s SDS and your institutional EHS procedures for definitive safety, spill response, and disposal guidance.

Solvent Selection

This compound is a moderately lipophilic aromatic secondary amine bearing a terminal alkyne. It dissolves well in many organic media and poorly in water.

• Polarity/miscibility (literature-based expectations):

  • Water: very low solubility expected.
  • Good solvents: DCM, chloroform, toluene, THF, dioxane, EtOAc, MeCN, alcohols (MeOH, EtOH), DMF, DMSO.
  • pH effects: Protonation (acidic media) forms anilinium salts that are more polar and may dissolve in water/alcohols; free base prefers organic phases.

• Selection by application (general guidance):

  • Metal-catalyzed couplings on the alkyne (Sonogashira, Glaser): Amide solvents (DMF, DMAc), polar ethers (THF, dioxane), or toluene under inert atmosphere. Add co-solvents (Et3N, i-Pr2NEt) when base serves as cosolvent.
  • Acylation/Carbamate formation at N: DCM, THF, or MeCN with non-nucleophilic base (TEA/DIPEA). For greener options, 2-MeTHF or CPME can substitute DCM/THF.
  • Hydrogenolysis (N-debenzylation): Alcoholic solvents (EtOH, i-PrOH) or EtOAc/MeOH mixtures with Pd/C under H2.

• Practical notes:

  • Avoid highly acidic aqueous systems for storage to prevent salt formation unless intended.
  • For analytical work (UV/LC), choose low-UV-cutoff solvents (MeCN, MeOH) to minimize baseline interference.
  • Dry solvents for base-sensitive operations (e.g., formation of lithium acetylides).

Comparison tip: THF and 2-MeTHF offer similar polarity; 2-MeTHF is often preferred for greener workflows and improved phase separation in workup.

Storage and Reconstitution

• Item-specific storage/shipping:

  • Storage Conditions: Room temperature (per Product Data). Keep container tightly closed in a dry, well-ventilated place.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• General handling/storage guidance (not item-specific):

  • Store under inert atmosphere (nitrogen/argon) if long-term to protect the terminal alkyne from adventitious oxidation and to limit amine discoloration.
  • Protect from strong light and oxidants. Avoid prolonged exposure to air and moisture, which can lead to gradual degradation or color change typical of anilines.
  • If solidifies or contains crystallizable impurities, warm gently to ambient and mix to homogenize before use. If supplied as an oil, consider aliquoting to minimize repeated air exposure.

• Reconstitution:

  • No reconstitution is required. If dilution is needed for handling or analysis, dissolve in a suitable organic solvent (e.g., DCM, THF, MeCN, EtOH, or DMSO) under dry conditions.

• Stability notes:

  • Prepare analytical reference solutions fresh or store short-term at 2–8 °C in amber vials. For long-term solution storage, validate stability under your conditions.

Always refer to the product’s label and CoA/SDS for definitive storage and handling instructions.

Structure and Identity

N-benzyl-3-ethynylaniline is an aniline derivative bearing a benzyl substituent on nitrogen and a meta-ethynyl (–C≡CH) group on the aniline ring.

• Item-specific identifiers (from Product Data):

  • CAS: 864754-01-8
  • CID: 28422088
  • InChIKey: 126839 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature structural data (not item-specific; for reference):

  • Molecular formula (derived from name): C15H13N (literature/computed)
  • Molecular weight (calculated): ~207.27 g/mol (literature/computed)
  • Suggested SMILES (literature): c1ccc(cc1N(Cc2ccccc2))C#C (one of several equivalent representations)

• Structural features (general description):

  • Core ring system: An aniline (phenyl–NH–) ring substituted at the 3-position with a terminal alkyne (ethynyl).
  • Amine functionality: Secondary aniline (N-benzyl aniline), nucleophilic but less basic than aliphatic amines due to anilide resonance.
  • Alkyne functionality: Terminal acetylene (sp-hybridized carbon) capable of deprotonation and coupling chemistry.
  • Aromatic content: Two phenyl rings (one aniline ring bearing –C≡CH; one benzyl phenyl attached to N).
  • Stereochemistry: None (achiral; no stereogenic centers).

• 2D depiction in words: A central aniline ring bears –C≡CH at the meta position. The aniline nitrogen is benzylated (–NH–CH2–Ph), linking to a second phenyl ring via a methylene spacer.

Synthetic Utility

N-benzyl-3-ethynylaniline provides two orthogonal handles for rapid diversification and strategic protection.

• Functional group leverage:

  • Terminal alkyne: gateway to C–C and C–X bond formation (Sonogashira to internal alkynes; Glaser to diynes; hydroboration to vinyl boronates; azide–alkyne cycloaddition after azidation of a counterpart).
  • Secondary aniline (N-benzyl): tunable nucleophile for acylation/carbamate/urea formation; the benzyl group serves as a removable N-protecting group (hydrogenolysis or DDQ), unlocking the corresponding 3-ethynylaniline.

• Retrosynthetic advantages:

  • Late-stage installation of the alkynyl unit allows modular connection to aryl/vinyl partners while preserving the N-benzyl group to temper amine basicity and coordinate less strongly to catalysts.
  • The N-benzyl group improves solubility in nonpolar media, aiding purification and handling versus the free aniline.

• Downstream derivatizations (examples, literature-based):

  • Alkyne → triazoles (CuAAC) after coupling with azides; valuable for linkers and conjugation chemistry.
  • Alkyne → ketones/alcohols via acetylide additions to carbonyls after strong-base deprotonation.
  • N-center → Boc/CBz protection, sulfonamides (e.g., tosylation) to direct electrophilic aromatic substitution or adjust electronic properties of the ring before further coupling.

Overall, this scaffold is well-suited for library synthesis, enabling divergent routes from a common intermediate.

Target Specificity

Not applicable. This product is a small-molecule organic intermediate and is not an antibody, enzyme, or affinity reagent. No target, epitope, clone, or species reactivity applies.