4-(2,6-Dimethylphenyl)morpholine , CAS No.255835-91-7

CAS: 255835-91-7 Cat. No.: D1326309 Formula: C₁₂H₁₇NO Molecular Weight: 191.27

Storage

Room temperature

Shipped In

Normal

Specifications

Storage

Room temperature

Shipped In

Normal

Names and Identifiers

Canonical Smiles

CC1=C(C(=CC=C1)C)N2CCOCC2

IUPAC Name

4-(2,6-dimethylphenyl)morpholine

InChIKey

GLHNEBLMLDMUSI-UHFFFAOYSA-N

INCHI

1S/C12H17NO/c1-10-4-3-5-11(2)12(10)13-6-8-14-9-7-13/h3-5H,6-9H2,1-2H3

Molecular Weight

191.27

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Oxazinanes
      • Subclass Morpholines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Oxazinanes
• Subclass: Morpholines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylmorpholines
• Alternative Parents: m-Xylenes Dialkylarylamines Aniline and substituted anilines Oxacyclic compounds Dialkyl ethers Azacyclic compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Phenylmorpholine - M-xylene - Xylene - Aniline or substituted anilines - Dialkylarylamine - Tertiary aliphatic/aromatic amine - Monocyclic benzene moiety - Benzenoid - Tertiary amine - Dialkyl ether - Ether - Oxacycle - Azacycle - Amine - Organooxygen compound - Organonitrogen compound - Hydrocarbon derivative - Organic oxygen compound - Organic nitrogen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN 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

Chemical and Physical Properties

• Molecular Weight: 191.270 g/mol
• XLogP3: 2.400
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 191.131 Da
• Monoisotopic Mass: 191.131 Da
• Topological Polar Surface Area: 12.500 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 167.000
• 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 application protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule reagent. For chemical use, refer to the Reaction & Applications and Reaction Conditions sections for practical guidance.

If preparing assay solutions:

• Prepare stock solutions in DMSO, MeOH, or acetonitrile (typical 10–100 mM), filter (0.2 µm PTFE) if required, and dilute into assay buffers with attention to final cosolvent percentage (<1–2% v/v commonly used in biochemical assays).
• For aqueous work, consider forming a defined salt (e.g., HCl) to improve solubility and batch‑to‑batch consistency.

Biological Roles

No intrinsic biological role is assigned to 4-(2,6-dimethylphenyl)morpholine. It is a synthetic small molecule used in chemical research.

General context (literature/general):

• Morpholine motifs occur frequently in medicinal chemistry as polarity‑modulating, H‑bond–accepting fragments that can influence solubility, permeability, and basicity of candidate molecules.
• The tertiary amine (no N–H) in morpholine typically forms protonated salts under physiological pH, affecting distribution coefficients and binding modes in target screening campaigns.
• The 2,6-dimethylphenyl (xylyl) substituent increases hydrophobic surface area and can leverage steric bulk to probe binding site topology when this scaffold is incorporated into larger ligands.

Use limitations:

• This product is supplied strictly for research use only; it is not intended for diagnostic, clinical, or in vivo applications.
• No data are provided on metabolism, transporter interaction, or biomolecular target binding for this specific compound. Any such studies should be conducted under appropriate institutional approvals and biosafety practices.

Buffer Applications

Not typically applicable. 4-(2,6-Dimethylphenyl)morpholine is an organic reagent/building block and is not used as a buffer component.

Practical note:

• If dissolution in aqueous media is required for screening, prepare defined salts (e.g., HCl or sulfate) to increase water solubility, and use standard laboratory buffers (phosphate, HEPES, MOPS) appropriate to the biological assay. Verify compound stability across the working pH range.

Green Alternatives

This product is a research reagent/building block rather than a process solvent; “green” considerations revolve around how you use it rather than substituting it outright.

Greener choices in surrounding operations (general guidance):

• Solvent substitution:
  • Replace DCM/CHCl3 with EtOAc, MeTHF/2‑MeTHF, or CPME when compatible with reactivity and workup.
  • Prefer MeCN over DMF/DMAc/NMP for polar aprotic needs when feasible; for strongly basic metalations, 2‑MeTHF can substitute for THF with improved EHS profile.
• Oxidations: Use H2O2 (with catalytic acids) or Oxone in water/MeCN blends instead of peracids for N‑oxidation when compatible with selectivity.
• Benzylic functionalization:
  • Electrochemical or photoredox C–H activation may reduce reliance on stoichiometric halogenating agents (NBS) and minimize waste.
• Workup and purification: Minimize silica use via crystallization of amine salts (HCl, p‑TsOH) or apply catch‑and‑release solid‑phase scavengers to reduce solvent consumption.

Illustrative comparison (use-context, general):

• THF vs 2‑MeTHF: 2‑MeTHF derives from renewable feedstocks, has lower peroxide hazard tendency, and enables higher operating temperatures, though it can introduce isomeric impurities and has a distinct odor.
• DCM vs EtOAc: EtOAc is biodegradable with lower toxicity but may require larger volumes due to solubility limits and can hydrolyze under strong base.

Note: No greener “substitute” exists for the molecular scaffold itself in target synthesis; instead, implement greener reaction media, catalytic methods, and streamlined purifications.

Pharmaceutical Uses

This material is provided for research use only and is not approved as an excipient or active ingredient.

Research/formulation context (general):

• Scaffold/intermediate: Aryl‑morpholine fragments are common in medicinal chemistry workflows. This compound may serve as a starting point for analog generation via benzylic functionalization, N‑oxidation/reduction cycles, or quaternization to explore SAR around cationic centers.
• Salt forms for screening: Converting the free base to pharmaceutically acceptable salts (e.g., HCl, mesylate, fumarate) can facilitate handling, crystallinity, and aqueous formulation during discovery-phase ADME assays.
• Analytical standards: With appropriate qualification and assigned purity (CoA), it may be used as an internal standard or reference compound in method development for related chemotypes.

Regulatory note:

• No pharmacopeial monograph is indicated. Any use in cGMP settings would require independent qualification, impurity profiling, and stability studies per ICH guidelines.
• No medical or therapeutic claims are made or implied for this product.

Physical Properties

Item-specific physico-chemical specifications are not provided in the Product Data.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• Melting/boiling point (literature/general): Not located in the provided data. Aryl‑substituted morpholines are often low‑melting solids or oils with moderate to high boiling points; consult literature or CoA for exact values for this specific compound.
• Density, refractive index, logP, pKa: Not specified for this item; refer to CoA/Spec Sheet. In general, tertiary amine–containing morpholines are basic (conjugate acid pKa typically ~5–7, literature range for related morpholines), and exhibit moderate polarity from the ether and amine.
• Solubility (general guidance): Expected good solubility in common organic solvents (e.g., dichloromethane, ethyl acetate, THF, acetonitrile, alcohols). Water solubility may be limited in the free base but can increase markedly as a protonated salt; verify experimentally.

Notes:

• The 2,6-dimethyl substituents increase hydrophobicity and steric bulk, which can elevate boiling point relative to unsubstituted 4-phenylmorpholine and decrease water solubility.
• For method development, measure refractive index and density under your lab conditions; do not assume values from analogs.

Quality and Grades

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet for exact assay, impurity profile, and any stabilizers.
• What to expect on the CoA (typical for small-molecule reagents):
  • Identity confirmation by NMR/IR/HRMS/GC–MS or LC–MS
  • Purity by GC or HPLC (area %), and residual solvent content
  • Water content (Karl Fischer) if applicable; Not specified for this item; refer to CoA/Spec Sheet.
  • Inorganic residue or metal content if relevant to the synthesis route; Not specified for this item; refer to CoA/Spec Sheet.
• Grade guidance (general):
  • Research grade reagents are suitable for synthetic chemistry, screening, and method development. For trace analysis or sensitive catalysis, request low‑metal specs or additional purification as needed.
  • HPLC/LC–MS suitability depends on UV background and volatility; if this item is to be used as an analytical standard, confirm assigned purity and correction factors on the CoA.
• Stabilizers: None indicated in the Product Data. If present in a specific lot, the CoA will list type and approximate amount.
• Batch-to-batch consistency: For amine-containing reagents, monitor color formation over time (amines may slowly discolor upon air exposure); minor color change typically does not affect assay but verify by chromatography.

Documentation available on request: Certificate of Analysis (CoA), Specification Sheet, and SDS.

Reaction and Applications

As a sterically shielded aryl‑morpholine, 4-(2,6-dimethylphenyl)morpholine is a versatile building block and ligand candidate in discovery chemistry. The tertiary amine and benzylic methyl groups enable several families of transformations.

Representative application domains (literature/general):

• Quaternization and salt formation: Alkyl halides (MeI, BnBr) or methyl triflate give quaternary ammonium salts; simple acidification affords crystalline mineral‑acid salts useful for purification and handling.
• N‑oxidation: mCPBA or H2O2/acetic acid forms the amine N‑oxide, enabling subsequent Polonovski‑type or deoxygenation manipulations.
• Benzylic C–H functionalization: The two ortho methyl groups are amenable to radical bromination (NBS/AIBN) or metalation (sBuLi or LDA at low temperature) followed by electrophile trapping; useful for preparing diversified analog libraries.
• Cross-coupling strategies via C–H activation: Though the substrate is not prehalogenated, directed C–H activation on the aryl ring (using the morpholine moiety as a weak directing group) has precedent in related systems; alternatively, pre‑functionalize benzylic positions then elaborate.
• Electrophilic aromatic substitution: The 2,6‑dimethyl pattern resists further substitution on the ring; reactions preferentially occur at benzylic positions.
• Ligand/organocatalyst exploration: Tertiary amine/ether motifs act as weak Lewis bases or H‑bond acceptors; derivatives can be screened as phase‑transfer or organocatalyst scaffolds (general observation for arylmorpholines).

Practical notes:

• Dry, oxygen‑free conditions improve outcomes in metalation steps. Use rigorously anhydrous solvents (THF/2‑MeTHF) and inert atmosphere.
• During quaternization, control exotherm and monitor by TLC/LC–MS; quats often precipitate in Et2O/hexanes facilitating isolation.
• For benzylic bromination, maintain subdued light and remove HBr to limit side reactions.

Reaction Conditions

General, literature-style conditions for common transformations of aryl morpholine scaffolds (optimize for your substrate and scale):

• Quaternization (tertiary amine → ammonium salt):
  • Reagents: MeI, MeOTf, BnBr, or alkyl tosylates.
  • Solvent: MeCN, acetone, or CH2Cl2; 0–25 °C initially, then to RT.
  • Typical time: 1–12 h. Monitor by TLC/LC–MS. Isolate by precipitation with Et2O/hexanes.
• N‑Oxidation (amine → N‑oxide):
  • Reagents: mCPBA (1.1–1.5 equiv) in CH2Cl2 at 0–25 °C; or H2O2 (30%, 2–3 equiv) in AcOH/MeCN.
  • Time: 0.5–6 h. Quench peracid residues with sulfite; wash basifies to free base.
• Benzylic bromination (ortho‑methyl groups):
  • Reagents: NBS (1.0–2.2 equiv), AIBN or benzoyl peroxide.
  • Solvent: CCl4, CHCl3, or PhH; reflux or photochemical (hv 365 nm) at RT.
  • Notes: Control equivalents to minimize overbromination; scavenge HBr (carbonate or base wash).
• Benzylic oxidation:
  • Reagents: KMnO4 (phase-transfer), or catalytic TEMPO/NaOCl; or Mn/Co catalysis with O2/air.
  • Solvents: AcOH/H2O, MeCN/H2O, or toluene under biphasic conditions. Temperatures 0–80 °C depending on system.
• Directed metalation/alkylation:
  • Base: sBuLi or LDA (1.1–1.5 equiv) at −78 to −40 °C in anhydrous THF or 2‑MeTHF under N2/Ar.
  • Electrophiles: CO2, aldehydes, Me3SiCl, I2, or carbonyl insertion partners.

Purification:

• Amines often streak on silica; add 0.5–2% Et3N to eluents or use alumina/basic silica. Salt switching (HCl salt ↔ free base) provides orthogonal purification.

All parameters above are general literature guidance for related substrates; confirm and optimize for this specific compound.

Safety and Handling

Hazard classification data are not supplied in the Product Data for this item. Always consult the SDS for authoritative guidance.

• GHS classification, pictograms, H‑statements: Not specified for this item; refer to SDS.
• Likely hazards (general for tertiary amines/aryl morpholines): May cause skin/eye irritation and respiratory tract irritation; harmful if swallowed. Tertiary amines can be corrosive to some plastics and may have strong odors.
• PPE: Use lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Work in a fume hood to avoid inhalation of vapors or aerosols.
• Handling: Avoid contact with strong acids (forms ammonium salts and exotherm upon neutralization), strong oxidizers (risk of exothermic reactions and N‑oxide formation), and acylating/alkylating agents (may quaternize the amine). Keep away from ignition sources; although not an ether solvent, standard flammability precautions apply.
• Incompatibilities: Strong oxidants, strong mineral acids, acid chlorides/anhydrides, and potent electrophiles. Adsorbs CO2/acids from air to form salts—keep containers well sealed.
• First aid (summary; refer to SDS):
  • 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; continue rinsing and get medical advice.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spills: Absorb with inert material (e.g., vermiculite), collect for disposal. Prevent entry into drains.
• Waste: Dispose according to local regulations; neutralize amine residues before aqueous disposal where permitted.
• Research use only: For research use only (not for diagnostic or therapeutic use).

Solvent Selection

This compound is a polar, tertiary-amine–containing aryl heterocycle. While not used as a solvent, selecting appropriate media for its use or transformation improves performance.

• Polarity class (general): Moderately polar organic base; compatible with a wide range of aprotic and protic organic solvents.
• Miscibility/solubility (general expectations; verify experimentally):
  • Likely soluble in dichloromethane, chloroform, THF, acetonitrile, ethyl acetate, toluene, and alcohols (MeOH, EtOH, i‑PrOH).
  • Limited solubility in water as a free base; solubility increases upon protonation (e.g., as HCl salt) in aqueous media.
• Choosing reaction media:
  • N‑oxidation or quaternization: Acetonitrile, dichloromethane, or methanol often provide good balance of solubility and control of exotherm.
  • Benzylic functionalization/oxidation: Chlorinated solvents (DCM) or acetonitrile for radical oxidations; toluene or xylene for high‑temperature aerobic oxidations.
  • Directed metalation/benzylic deprotonation: Ethers (THF, 2‑MeTHF) or hydrocarbon/ether mixtures at low temperature.
  • Salt formation/purification: Use anhydrous ether/hexanes for precipitating amine salts (HCl, HBr, TsOH) from alcoholic or ethereal solutions.
• Practical tips:
  • Tertiary amines can retain on silica; add 0.5–2% Et3N to eluents during chromatography to sharpen bands.
  • Avoid highly acidic mobile phases unless converting to a defined salt for LC.

Small comparison (general):

• THF vs 2‑MeTHF: Similar solvation; 2‑MeTHF offers greener profile and higher boiling point useful for lithiation steps.
• DCM vs EtOAc: DCM provides superior solubility for bases; EtOAc is greener but may require larger volumes.

Storage and Reconstitution

• Storage conditions (provided): Room temperature.
• Shipping (provided): Shipped under normal conditions.
• Container: Store tightly closed in amber glass or compatible HDPE to limit air/moisture ingress and light exposure.
• Atmosphere: Keep dry and under inert gas if long-term storage is anticipated; tertiary amines can absorb acidic vapors/CO2, forming salts that may affect measured free‑base assay.
• Segregation: Separate from strong acids and oxidizers. Avoid prolonged contact with reactive plastics.
• Stability: Not specified for this item; refer to CoA/Spec Sheet. In general, tertiary amine/ether scaffolds are stable at ambient conditions; minor discoloration over time is typically cosmetic but verify by HPLC/GC.
• Reconstitution/solution preparation:
  • Solubility: Dissolve in dry organic solvents such as DCM, MeCN, THF, or alcohols. For aqueous systems, prepare a salt (e.g., HCl) to enhance solubility.
  • Stock solutions: Prepare concentrated stocks (e.g., 0.1–1.0 M) in dry solvent, aliquot, and store in sealed vials. For sensitive transformations, use freshly prepared solutions.
• Freeze–thaw: Not generally required. If refrigerated or frozen for extended stability, allow to reach room temperature before opening to prevent moisture condensation.
• Research Use Note: For research use only.

Structure and Identity

A sterically encumbered aryl–morpholine scaffold combining a 2,6-dimethylphenyl (2,6-xylyl) ring with a 4-substituted morpholine ring (oxygen and tertiary amine opposite each other in a six‑membered heterocycle). The aryl group is bonded to the C-4 position of morpholine, giving a neutral, tertiary-amine–containing heteroaromatic–heterocycle hybrid.

• SKU: D1326309
• Product name: 4-(2,6-Dimethylphenyl)morpholine
• CAS: 255835-91-7 (provided)
• PubChem CID: 10559627 (provided)
• InChIKey: 105037 (provided in Product Data)
• 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 (descriptive, general chemistry):

• Aromatic ring: 1,3,5-trisubstituted benzene core with two ortho methyl groups (2,6-dimethyl), introducing notable steric hindrance near the aryl–morpholine bond.
• Heterocycle: Morpholine (1,4-oxazinane) bearing a tertiary amine (no N–H) and an ether oxygen; substituted at the 4‑carbon by the aryl group (para to N, para to O in the ring framework).
• Functional groups: Tertiary amine (basic), cyclic ether (polar), benzylic methyl groups (potential handles for oxidation or metalation under strong base).
• Stereochemistry: None (achiral, no stereocenters expected).

2D depiction in words: a benzene ring carrying methyl groups at the 2- and 6-positions, with the 4-position attached through a C–C bond to the carbon opposite nitrogen in a morpholine ring (the ring also contains an ether oxygen opposite the nitrogen).

Synthetic Utility

Key reactive elements of 4-(2,6-dimethylphenyl)morpholine confer practical routes to diversification and late‑stage functionalization.

• Tertiary amine (morpholine N):
  • Protonation/salt formation enables purification by crystallization.
  • Alkylation (MeI, BnBr) yields quaternary ammonium salts for phase‑transfer catalysis studies or further derivatization.
  • N‑oxidation (mCPBA, H2O2/acetic acid) generates N‑oxides, which can undergo Meinwald/Polonovski‑type rearrangements or serve as polarity‑enhanced intermediates.
• Benzylic positions (2,6‑dimethyl):
  • Radical halogenation (NBS/AIBN or photochemical conditions) affords benzyl halides amenable to SN2, metal–halogen exchange, or cross‑coupling after conversion to organometallics.
  • Directed deprotonation with strong bases (sBuLi, LDA) at low temperature allows trapping with electrophiles (CO2, aldehydes, electrophilic fluorinating agents), enabling rapid library synthesis.
• Aromatic core:
  • Though sterically protected, oxidative C–H functionalization (e.g., benzylic oxidation to benzylic alcohols/acids) can proceed under catalytic conditions (e.g., Mn, Cu, or photoredox systems).
• Ring nitrogen as ligand site:
  • The tertiary amine/ether motif can coordinate weakly to metals; derivatives sometimes serve as ancillary ligands in Cu/Ni catalysis (general observation for arylmorpholines).

Practical synthesis uses:

• Intermediate toward bulkier, cationic ligands by double alkylation.
• Probe in SAR campaigns to interrogate steric effects near an aryl junction.
• Handle as free base for organic reactions; convert to salts for isolation/crystallization.

Target Specificity

Not applicable. This product is a small-molecule research reagent and not a biological affinity reagent (e.g., antibody, enzyme, ligand with validated biomolecular target specificity). No target, epitope, species reactivity, clone, or isotype information is provided or relevant.

Frequently Asked Questions

How should this product be stored?

Store at room temperature.

How is this product shipped?

This product ships under standard ambient conditions. No temperature-controlled packaging is required.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 255835-91-7, the molecular formula is C12H17NO, and the molecular weight is 191.27 g/mol. InChIKey GLHNEBLMLDMUSI-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.