6-Methylbiphenyl-3-amine , CAS No.13480-37-0

CAS: 13480-37-0 Cat. No.: M167047 Formula: C₁₃H₁₃N Peso molecolare: 183.25 Numero EC: 808-779-6

Synonyms

DTXSID90482275 | 2-Methylbiphenyl-5-amine | EN300-1141838 | A887807 | SCHEMBL3791175 | E90651 | COYWNBKOPFAEDG-UHFFFAOYSA-N | 6-Methyl-biphenyl-3-ylamine | 6-Methyl-[1,1'-biphenyl]-3-amine | 6-Methylbiphenyl-3-amine | 4-Methyl-3-phenylaniline | AKOS012638

Storage

Room temperature

Shipped In

Normal

Specifications

Sinonimi

DTXSID90482275 | 2-Methylbiphenyl-5-amine | EN300-1141838 | A887807 | SCHEMBL3791175 | E90651 | COYWNBKOPFAEDG-UHFFFAOYSA-N | 6-Methyl-biphenyl-3-ylamine | 6-Methyl-[1,1'-biphenyl]-3-amine | 6-Methylbiphenyl-3-amine | 4-Methyl-3-phenylaniline | AKOS012638

Condizioni di conservazione di stoccaggio

Room temperature

Spedito in

Normal

Nomi e identificatori

Sorrisi canonici

CC1=C(C=C(C=C1)N)C2=CC=CC=C2

IUPAC Name

4-methyl-3-phenylaniline

InChIKey

COYWNBKOPFAEDG-UHFFFAOYSA-N

INCHI

1S/C13H13N/c1-10-7-8-12(14)9-13(10)11-5-3-2-4-6-11/h2-9H,14H2,1H3

Isomeri SMILES

CC1=C(C=C(C=C1)N)C2=CC=CC=C2

Peso molecolare

183.25

Reaxy-Rn

2803276

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=2803276&ln=

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Biphenyls and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Biphenyls and derivatives
• Alternative Parents: Aniline and substituted anilines Aminotoluenes Primary amines Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Biphenyl - Aminotoluene - Aniline or substituted anilines - Toluene - Organic nitrogen compound - Hydrocarbon derivative - Primary amine - Organonitrogen compound - Amine - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
• 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: 183.250 g/mol
• XLogP3: 3.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 1
• Exact Mass: 183.105 Da
• Monoisotopic Mass: 183.105 Da
• Topological Polar Surface Area: 26.000 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 172.000
• 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 biological assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule reagent. For synthetic use, see the Reaction Conditions and Synthetic Utility sections for generalized procedural guidance.

Biological Roles

This product is a synthetic aromatic amine building block and is not known to have endogenous biological roles.

• General context (literature; not item-specific)

  • Primary anilines can undergo metabolic N-acetylation and N-oxidation in vivo, and some aryl amines are studied in the context of mutagenicity after metabolic activation; such information is mechanistic/biochemical and not indicative of suitability for any biological application.
  • Biphenyl scaffolds occur in various synthetic ligands and materials but are not natural metabolites.

• Research-use framing

  • Suitable as a chemical intermediate for preparing ligands, probes, and materials that may later be evaluated in biological assays. Any biological assessment should be performed on the derived compounds with appropriate controls.

No medical, diagnostic, or therapeutic use is intended or implied. For research use only (per Product Data).

Buffer Applications

Not typically applicable. 6-Methylbiphenyl-3-amine is a hydrophobic aromatic amine used as a synthetic intermediate rather than as a buffering agent. If aqueous handling is required (e.g., for extractions or reactions in biphasic media), the amine may be protonated with mineral acid to form a water-soluble ammonium salt, but dedicated biological buffer systems are not relevant here.

Green Alternatives

When planning syntheses with this aromatic amine, consider greener solvents and milder reagents without compromising performance.

• Greener solvent swaps (general guidance)

  • Replace chlorinated solvents: use EtOAc or 2-MeTHF instead of DCM/CHCl3 for acylations/extractions when feasible.
  • For cross-couplings: 2-MeTHF, CPME, toluene, or water/ethanol mixtures with micellar catalysts can substitute for DMF/NMP/dioxane in many ligand systems.
  • Workup: heptane/EtOAc biphasic systems often replace hexane/DCM combinations.

• Comparison snapshot (illustrative; not product-specific)

  • DCM vs EtOAc: EtOAc has lower toxicity and better biodegradability; slightly higher bp may lengthen evaporation but reduces fugitive emissions.
  • DMF vs 2-MeTHF: DMF excels in solubilizing polar reagents and salts but is reproductive toxic and problematic in GMP waste; 2-MeTHF is bio-derived, less toxic, and supports many Pd-catalyzed couplings with appropriate ligands.
  • Toluene vs CPME: CPME offers low peroxide formation, broader liquid range, and good water tolerance; toluene remains widely available and recyclable.

• Reagent-level choices

  • Use activated carbonate reagents (CDI) or green coupling agents (DMTMM) for amide/urea formation instead of phosgene-derived reagents.
  • Employ aqueous micellar catalysis for certain substitutions and cross-couplings to minimize organic solvent usage.

• Waste and energy

  • Favor telescoped sequences to avoid isolations; crystallize from greener solvents; design robust salt formations for purification instead of chromatographic silica (solvent-intensive).

Pharmaceutical Uses

No pharmacopeial or excipient role is specified for this item; refer to CoA/Spec Sheet for any compliance statements (none provided).

• General context (non-clinical, not product-specific)
  • Aromatic amines like this one are commonly used as intermediates in the synthesis of active pharmaceutical ingredients (APIs), agrochemicals, and functional materials.
  • The aniline nitrogen enables rapid diversification via amide/urea/carbamate formation, sulfonamide synthesis, and diarylamine coupling, facilitating SAR campaigns in medicinal chemistry.

This product is supplied strictly for research and laboratory use. No therapeutic, diagnostic, or human/animal administration uses are claimed or supported.

Physical Properties

• Item-specific specifications

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

• Literature/general reference values for related structures (for planning only; not product specifications)

  • Molecular formula (literature): C13H13N; formula weight ~183.25 g/mol (calculated)
  • Physical state: typically a low-melting solid or high-boiling oil for substituted aminobiphenyls (literature, class behavior)
  • Acid–base: aniline nitrogens are weak bases; conjugate acid pKa (anilinium) typically ~4.6–5.6 depending on ring substitution (literature, general for anilines)
  • Polarity/partitioning: biphenyl core is hydrophobic (parent biphenyl logP ~4.1, literature); introduction of –NH2 and –CH3 leads to moderately lipophilic behavior with some H-bonding capacity in the free-base form (qualitative)
  • Solubility (qualitative, literature):
    • Free base: low solubility in water at neutral/basic pH; soluble in common organic solvents (EtOAc, toluene, DCM, THF, MeOH/EtOH to varying degrees)
    • Protonated salt (e.g., HCl): enhanced aqueous solubility in acidic media
  • Spectral features (general):
    • 1H NMR: aromatic multiplets across ~6.6–7.6 ppm; benzylic methyl singlet ~2.2–2.4 ppm; NH2 broad signal often ~3.5–4.5 ppm (solvent- and concentration-dependent)
    • IR: N–H stretches ~3300–3500 cm−1 (two bands often observed), aromatic C–H stretches ~3030 cm−1

For precise constants (bp/mp, density, refractive index, UV cutoff, elemental limits), consult the item’s CoA/Spec Sheet; not specified for this item.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet for assay, impurity profile, metals, residual solvents, and any stabilizers.

• Guidance on common grades (general information; not item-specific)

  • Research/technical grade: suitable for synthesis and R&D; impurity levels adequate for most transformations; verify by NMR/LC before critical steps.
  • Purified/≥98% grade: supports structure–activity or materials work where impurities could bias results or poison catalysts.
  • HPLC grade (solvents) or LC-MS grade (analytes) concepts do not directly apply to this solid building block; however, “low UV-absorbing impurities” and “volatile impurity control” can still matter if using in photophysical studies.

• Stabilizers/inhibitors: Not specified for this item; most anilines are shipped without stabilizers. If inhibitor or acid scavenger is present, verify its identity and level on the Spec Sheet as it may affect downstream reactions (e.g., acylations or cross-couplings).

• Recommended incoming QC (best practice)

  • Identity: 1H/13C NMR, HRMS, melting point/TLC vs literature.
  • Purity: HPLC/GC and NMR integration; check for aniline oxidation products (azo/quinone-imine) by LC-UV.
  • Water and residual solvents: Karl Fischer and GC as needed for moisture-sensitive coupling chemistry.

Reaction and Applications

As a 3-aminated, 6-methyl-substituted biphenyl, this reagent is a versatile aryl amine building block for advanced organic synthesis and materials chemistry.

• Representative application domains (literature/general)

  • Amide/urea/carbamate formation: rapid access to biphenyl-derived amides via acyl chlorides, activated esters (HATU/EDC), or CDI for ureas; useful in medicinal chemistry SAR libraries and polymeric materials.
  • Electrophilic aromatic substitution (EAS): the –NH2 directs ortho/para on its ring; methyl further activates benzylic C–H for oxidation or bromination; nitration/sulfonation require care to manage overreaction.
  • Diazonium chemistry: conversion to diazonium salts enables Sandmeyer-type substitutions (Cl, Br, CN), Schiemann (F, via BF4−), or azo coupling to dye-like structures.
  • C–N cross-coupling: the aniline functions as a nucleophile in Buchwald–Hartwig amination to form secondary/tertiary anilides or diarylamines.
  • Directed ortho metalation (DoM): the aniline (or its amide/urea derivatives) can direct lithiation adjacent to the amino group, enabling regioselective functionalization on the same ring; methyl at C-6 may influence site selectivity and hinder one ortho position.
  • Benzylic transformations: the 6-methyl group allows selective benzylic oxidation (to aldehyde/acid), halogenation, or radical functionalization to diversify the scaffold.

• Practical tips

  • Protecting groups: Boc, Cbz, or acyl protection of the aniline can improve chemoselectivity in EAS or metalations.
  • Base sensitivity: free aniline may bind and poison Pd/Ni catalysts; preforming ammonium salts or using tailored ligands/bases can mitigate.
  • Workup: formation of ammonium salts in acidic washes can aid purification; back-neutralize as needed for isolation.

Reaction Conditions

The following are literature-style, general conditions suitable for similar aniline substrates; optimize for your specific system. These are not product specifications.

• Amide formation (acyl chloride route)

  • Solvent: DCM or THF (anhydrous). Base: DIPEA or pyridine (2–3 equiv). Temp: 0 °C to rt. Time: 1–4 h. Typical isolated yields: 70–95% with clean acyl chlorides.

• Urea/carbamate formation (CDI route)

  • Solvent: THF or MeCN. Reagents: CDI (1.1–1.5 equiv), then amine/alcohol coupling partner. Temp: rt to 50 °C. Time: 2–6 h. Yields: 60–90%.

• Buchwald–Hartwig C–N coupling (as N-nucleophile)

  • Electrophile: aryl bromide/chloride/triflate (1.0 equiv). Catalyst: Pd2(dba)3 (1–2 mol%) + BrettPhos/XPhos (2–4 mol%). Base: NaOtBu or Cs2CO3 (2 equiv). Solvent: toluene, dioxane, or 2-MeTHF. Temp: 80–110 °C. Time: 4–16 h. Yields: frequently 70–95% for activated aryl halides.

• Diazotization/Sandmeyer

  • Conditions: NaNO2 (1.1 equiv) in 2–4 M HCl at 0–5 °C to form diazonium salt; trap with CuX (X = Cl, Br, CN) or water. Temp: 0–25 °C. Time: 0.5–2 h. Caution: manage exotherms and gaseous byproducts; diazonium salts can be energetic—avoid isolation when possible.

• Benzylic oxidation (from 6-methyl)

  • MnO2 (excess) in DCM or toluene at rt–reflux to give aldehyde; or catalytic benzylic C–H oxidation (e.g., Co/Mn with Oxone or TBHP) in acetonitrile or acetone. Monitor for overoxidation to acid.

• Directed ortho metalation (DoM)

  • Base: s-BuLi or n-BuLi with TMEDA at −78 to −40 °C in THF or Et2O; quench with electrophiles (CO2, DMF, I2). Protecting the aniline as amide enhances control. Sterics from the 6-Me influence site selectivity.

Ensure rigorously dry conditions where required, and confirm compatibility with the substrate’s aniline functionality.

Safety and Handling

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

• General safety considerations for aromatic amines (literature/guidance; not product-specific)

  • Hazards: primary aromatic amines can be harmful if swallowed, inhaled, or in contact with skin; may cause skin and eye irritation; some positional isomers in this class are suspected mutagens/carcinogens—handle with heightened caution and consult the SDS.
  • PPE: lab coat, nitrile gloves (change regularly), chemical splash goggles; handle in a certified fume hood to avoid inhalation of vapors/dust and to control odor.
  • Incompatibilities: strong oxidizers, nitrosating agents, acyl/alkyl halides (reactivity at nitrogen), and strong acids/bases (may form salts or undergo side reactions). Avoid prolonged air/heat exposure that can lead to oxidation of anilines.
  • Peroxide formation: not a typical peroxide former (unlike ethers); however, aromatic amines can slowly oxidize—store tightly closed, minimizing headspace oxygen and light exposure when possible.
  • First-aid overview (consult SDS):
    • Inhalation: move to fresh air; seek medical advice if symptoms persist.
    • Skin contact: wash with soap and water; remove contaminated clothing.
    • Eye contact: rinse cautiously with water for several minutes; remove contact lenses if present; seek medical attention if irritation continues.
    • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
  • Spill/leak: absorb with inert material (e.g., vermiculite), place in chemical waste; avoid discharge to drains; decontaminate area with appropriate solvent and detergent.
  • Waste: collect as halogen-free organic waste unless otherwise required by local regulations.

Always defer to the product’s SDS and institutional EHS policies.

Solvent Selection

This compound is a moderately lipophilic aniline. Solvent choice should balance solubility, reactivity at the aniline nitrogen, and downstream workup.

• Polarity and miscibility (general behavior)

  • High solubility: DCM/CH2Cl2, chloroform, THF, toluene, EtOAc; often soluble in alcohols (MeOH/EtOH/IPA) and polar aprotic media (DMF, DMAc, NMP, DMSO).
  • Low solubility: water at neutral/basic pH (free-base form). Aqueous solubility improves upon protonation (e.g., forming the hydrochloride salt in acidic media).

• Use-case guidance

  • N-acylation/alkylation: employ anhydrous DCM, THF, MeCN, or toluene with a base (e.g., DIPEA, pyridine) to suppress overacylation; avoid protic solvents that promote salt formation with acid chlorides.
  • Electrophilic aromatic substitution on the aniline-bearing ring: nonpolar solvents (toluene, xylene) can improve regioselectivity; consider protecting the amine if needed.
  • Metal-catalyzed couplings (if further derivatization of the second ring or benzylic position): use polar aprotic solvents (dioxane, toluene, THF, CPME, Me-THF, DMF) depending on catalyst system.

• Small comparison (general)

  • DCM vs EtOAc: DCM offers higher solubility and lower boiling point, but EtOAc is greener and easier to remove than high-boiling amide solvents.
  • DMF/NMP vs 2-MeTHF/CPME: DMF/NMP maximize solubility and rate for many couplings but raise regulatory/EHS flags; 2-MeTHF/CPME provide greener profiles with good solubility for anilines and many catalysts.

Always verify solvent compatibility with chosen reagents and catalysts.

Storage and Reconstitution

• Item-specific storage/shipping (from Product Data)

  • Storage: Room temperature
  • Shipped: Under normal conditions

• General handling guidance for aromatic amines (not item-specific)

  • Storage: keep tightly closed in a dry, inert atmosphere if possible; protect from prolonged exposure to air and light to minimize oxidative discoloration. Use amber glass for long-term storage.
  • Stability: primary anilines can slowly oxidize; if discoloration occurs, pass through a short plug of basic alumina or recrystallize as needed.
  • Inerting: for sensitive applications, store under nitrogen/argon and include a desiccant (e.g., silica gel) in the secondary container.

• Reconstitution/stock preparation (as applicable)

  • Solubility: typically soluble in common organic solvents (DCM, THF, EtOAc, toluene, MeOH/EtOH, DMF/DMSO). For aqueous workflows, prepare an acidified solution to form a water-soluble ammonium salt (e.g., HCl in water/MeOH).
  • Working solutions: prepare fresh at intended concentrations; for DMSO stocks, store aliquots at −20 °C to limit freeze–thaw and moisture pickup.
  • Freeze–thaw: avoid repeated cycles; if crystallization occurs, warm gently and sonicate to fully dissolve.

For definitive stability limits, moisture content, and solution shelf-life, consult the item’s CoA/Spec Sheet and SDS.

Structure and Identity

A bifunctional aromatic building block: an aniline on a biphenyl core bearing a methyl substituent on the same ring (6-position relative to the biaryl bond) and an amino group at the 3-position.

• Item-specific (from Product Data)

  • CAS: 13480-37-0
  • CID: 12247800
  • InChIKey (catalog record): 49885 (note: this string is not in standard InChIKey format; consult CoA/SDS for definitive identifiers)
  • Storage: Room temperature; shipped under normal conditions

• Literature/computed identity (general reference values; not item specifications)

  • Synonym: 3-Amino-6-methylbiphenyl; 6-methyl[1,1′-biphenyl]-3-amine
  • Molecular formula (literature): C13H13N
  • Molecular weight (calculated from formula): ~183.25 g/mol
  • Structural features: biphenyl scaffold (two fused via C–C bond) with one ring bearing an aniline (–NH2) meta to the biaryl bond and a methyl group ortho to the biaryl bond; no heteroatoms other than the aniline nitrogen; no stereocenters; fully aromatic π-system
  • 2D description in words: a para-disconnected aniline on a monosubstituted biphenyl ring, where the amine sits at position 3 and a methyl at position 6 of the same ring; the second phenyl ring is unsubstituted.
  • SMILES/InChI: Not specified for this item; refer to CoA/Spec Sheet.

• General functional groups and reactivity cues

  • Primary aniline (weak base, nucleophilic at N; strong ortho/para director in electrophilic substitution on its ring)
  • Methyl substituent (weakly activating; useful handle for benzylic functionalization)
  • Biaryl axis (no restricted rotation at ambient conditions)

Synthetic Utility

Key functional elements and their synthetic implications:

• Primary aniline (–NH2)

  • Nucleophilicity: engages in acylations (amides), sulfonylations (sulfonamides), carbamoylations (ureas/carbamates), and alkylations (amines). Use non-nucleophilic bases (DIPEA, Hunig’s base) to limit over-alkylation.
  • Cross-coupling nucleophile: Buchwald–Hartwig amination with aryl/vinyl halides/triflates to give diarylamines; choice of ligand (e.g., BrettPhos, XPhos, tBuBrettPhos) controls rate/selectivity.
  • Diazonium gateway: transforms into aryl halides (CuX), nitriles (CuCN), or phenols (H2O) enabling late-stage diversification of the aniline-bearing ring.

• 6-Methyl substituent

  • Benzylic chemistry: selective halogenation, oxidation (e.g., to aldehyde/acid via SeO2, MnO2, or catalytic C–H oxidation), and radical functionalization open access to homologated libraries.
  • Steric influence: moderates ortho reactivity near the aniline, affecting regioselectivity in EAS and metalation; can improve selectivity by blocking one ortho site.

• Biphenyl core

  • Robust, planar π-architecture beneficial in materials and ligand frameworks; tolerates a wide range of cross-coupling and oxidative conditions.

• Protecting-group strategy

  • Boc, Cbz, or trifluoroacetamide protection enhances chemoselectivity and crystallinity; deprotection under acidic (Boc) or hydrogenolysis (Cbz) conditions.

• Purification notes

  • Free bases often streak on silica; convert to salts (HCl) for crystallization, or add a drop of Et3N to eluent to prevent tailing; reversed-phase chromatography is effective for polar derivatives.

Target Specificity

Not applicable. This product is a small-molecule aromatic amine, not a biological targeting agent or antibody. No antigen/epitope, species reactivity, clone, or isotype data apply.