4-Methyl-2-phenylmorpholine - ≥95% , CAS No.21532-10-5

CAS: 21532-10-5 Cat. No.: M970736 Formula: C₁₁H₁₅NO Molecular Weight: 177.240

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifications & Purity

≥95%

Storage

Room temperature

Purity

≥95%

Names and Identifiers

Canonical Smiles

CN1CCOC(C1)C2=CC=CC=C2

IUPAC Name

4-methyl-2-phenylmorpholine

InChIKey

FXDYCASQPGXSMZ-UHFFFAOYSA-N

INCHI

1S/C11H15NO/c1-12-7-8-13-11(9-12)10-5-3-2-4-6-10/h2-6,11H,7-9H2,1H3

Molecular Weight

177.240

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: Aralkylamines Benzene and substituted derivatives Trialkylamines Oxacyclic compounds Dialkyl ethers Azacyclic compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Phenylmorpholine - Aralkylamine - Monocyclic benzene moiety - Benzenoid - Tertiary amine - Tertiary aliphatic amine - Dialkyl ether - Ether - Oxacycle - Azacycle - Organooxygen compound - Organonitrogen compound - Organic oxygen compound - Hydrocarbon derivative - Organic nitrogen compound - Amine - 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: 177.240 g/mol
• XLogP3: 1.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 177.115 Da
• Monoisotopic Mass: 177.115 Da
• Topological Polar Surface Area: 12.500 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 154.000
• 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

No tested bioanalytical application protocols (e.g., WB, IHC, IF, FC) are provided for this item. As a small-molecule amine, it is typically used in synthetic chemistry workflows rather than direct biological assays.

• General lab use suggestions (literature-based)
  • For stock solutions in screening: prepare 10–100 mM solutions in DMSO or prepare aqueous stocks as an acid salt; sterile-filter if required for cell-free assays.
  • For amide coupling: dissolve amine and acid (1.0 equiv each) in DMF or DCM, add coupling reagent and base at 0–25 °C, monitor by LC–MS.

Refer to your lab’s SOPs and validate any protocol for your specific application.

Biological Roles

This product is intended for research and synthetic chemistry use; no biological activity testing or roles are provided in the Product Data. The compound is a small organic secondary amine/heterocycle rather than a biomolecule.

• General chemistry context (literature)

  • Morpholine rings appear in numerous research compounds as solubilizing, hydrogen-bonding motifs; incorporation can modulate pKa, permeability, and metabolic stability in structure–property studies.
  • The presence of a phenyl substituent increases hydrophobic character relative to morpholine, potentially affecting membrane partitioning in research probes.

• No claims

  • No biological targets, pathways, or activities are claimed or implied for this specific item. Any use in biochemical assays should be for exploratory research only, with appropriate controls.

• Handling in biological settings (practical notes)

  • Secondary amines may interact with assay components (e.g., bind to plastics, quench electrophiles, or interfere with enzyme assays). Validate compatibility before screening.
  • Prepare aqueous stocks as acid salts to improve solubility and pH control if needed.

For authoritative toxicological and exposure data, consult the SDS and primary literature; none are specified for this SKU.

Buffer Applications

Not typically used as a buffering agent. 4-Methyl-2-phenylmorpholine is a secondary amine building block, not a dedicated buffer system.

• Practical note (literature)
  • If dissolution in aqueous media is required for assays, prepare a defined acid salt (e.g., hydrochloride) and dissolve in standard laboratory buffers (PBS, HEPES). Titrate to the desired pH to avoid perturbing buffer capacity.

For buffer formulation needs, consider established buffers (Tris, HEPES, MOPS); see their dedicated products and datasheets.

Green Alternatives

Because 4-methyl-2-phenylmorpholine is a specific amine building block rather than a solvent or auxiliary, “greener alternatives” pertain to the reaction context in which it is used.

• Greener media choices (literature guidance)

  • Prefer bio-derived ethers/esters (2-MeTHF, CPME, EtOAc) or alcohols (EtOH, i-PrOH) over chlorinated solvents (DCM, DCE) where compatible with chemoselectivity.
  • For reductive aminations, ethanol or EtOAc/i-PrOH mixtures with solid-supported acid catalysts can reduce hazardous waste relative to MeCN/DCM.

• Greener reagents for typical transformations

  • Reductive amination: replace NaBH3CN with NaBH(OAc)3 or catalytic hydrogenation (H2, Pd/C) in EtOH when the substrate tolerates it, eliminating cyanide waste.
  • Amide coupling: use T3P (propylphosphonic anhydride) in EtOAc/2-MeTHF or CDI where feasible to minimize urea waste from uronium reagents; consider aqueous micellar conditions (e.g., TPGS-750-M) for some couplings.

• Process intensification

  • Employ inline scavengers (acidic resins) for amine salt formation and purification; consider solvent recycling and reduced E-factor through concentrated reactions.

• Trade-offs

  • Switching to greener solvents may impact solubility of this comparatively hydrophobic amine vs morpholine; heating or co-solvent systems may be needed.
  • Catalytic hydrogenation avoids stoichiometric reducers but introduces metal handling and potential aryl hydrogenation risks.

Summary table (literature, qualitative)

• DCM/DCE -> EtOAc/2-MeTHF: reduced toxicity, similar polarity; may require longer times.
• NaBH3CN -> NaBH(OAc)3/H2: lower hazard; substrate scope considerations apply.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided in the Product Data, and this material is offered strictly for research use only.

• General context (literature)

  • Morpholine-containing motifs are common in discovery chemistry to adjust physicochemical properties. 4-Methyl-2-phenylmorpholine can serve as a scaffold/intermediate in synthetic routes to research compounds.
  • It is not a formulated excipient and has no declared compendial monograph (USP/EP) to our knowledge; verify independently if required.

• Process/formulation notes (for intermediates only)

  • Intermediates are commonly handled as free bases for reactions and converted to crystalline salts (e.g., HCl, sulfate, p-toluenesulfonate) for isolation and storage.
  • If incorporated in a multi-step synthesis, assess residual amine carryover by validated methods (GC, LC–MS) per internal quality systems.

No therapeutic claims are made. Do not use for diagnostic or clinical applications.

Physical Properties

Item-specific physicochemical specifications (appearance, purity, BP/MP, density, water/peroxide content, UV cutoff, etc.) are not provided in the Product Data for this SKU.

• 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/estimated physical properties (informational; not item specifications)

  • Molecular formula (from name): C11H15NO; calculated Mr ≈ 177.24 g/mol.
  • Physical state: many arylmorpholine derivatives are liquids or low-melting solids; this compound is expected to be a low-viscosity liquid or low-melting solid at ambient conditions (literature expectation for similar structures).
  • Basicity: secondary amine typically pKaH ≈ 9–10 (literature, for morpholine derivatives; exact value will vary with aryl substitution). The ether oxygen is not protonated under neutral conditions but can hydrogen-bond.
  • Solubility profile (qualitative, literature): expected to be miscible with many organic solvents (EtOAc, alcohols, chlorinated solvents, ethers) and moderately to sparingly soluble in water due to the hydrophobic phenyl group counterbalanced by one amine and one ether heteroatom.
  • Partitioning: logP likely in the low-to-moderate range (>1) relative to morpholine (literature rationale: phenyl increases hydrophobicity).
  • Boiling/melting points, density, refractive index, and vapor pressure: Not located in standard references at the time of writing; consult the CoA/SDS or measure as needed for process design.

Always verify with the Certificate of Analysis for lot-specific data before use in regulated or quantitative applications.

Quality & Grades

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

• How to interpret common grades (general guidance)

  • Analytical Reagent (AR) or ACS grade: conforms to purities suitable for analytical work; typically low levels of trace metals and non-volatile residue.
  • ≥98–99% (neat): typical for many small-molecule building blocks; residual solvents and related impurities should be assessed by GC/HPLC and NMR.
  • HPLC grade (for solvents) is not applicable here; this product is a building block/amine, not a mobile-phase solvent.

• Considerations for amine-containing heterocycles (general, literature-based)

  • Amines can pick up CO2 or moisture; apparent assay may drift if weighed in open air. Where possible, standardize by titration or confirm purity by quantitative NMR (qNMR) before critical uses.
  • Stabilizers are generally unnecessary for secondary amines, but inhibition of nitrosation (avoid nitrite contamination) is important. If the item contains any stabilizer, it will be declared on the CoA (none specified here).
  • Trace metal content, water content, and residual solvent limits: Not specified for this item; refer to CoA/Spec Sheet.

• Recommended verification on receipt (best practice)

  • Identity confirmation by 1H/13C NMR and HRMS.
  • Purity check by GC or HPLC with UV/ELSD; verify absence of nitrosamines per internal policies if applicable.
  • Record pH of an aqueous solution/salt if relevant to your application.

Reaction & Applications

4-Methyl-2-phenylmorpholine is a versatile secondary amine and oxygen-containing heterocycle useful as a nucleophilic building block and as a ligand/basic component in organic synthesis.

• As a nucleophile/base (literature)

  • N-Acylation to form amides, carbamates, and ureas via acid chlorides, anhydrides, CDI, or coupling reagents (EDC/HATU/T3P). The ether oxygen remains inert under typical conditions, offering chemoselective N-functionalization.
  • Reductive amination with aldehydes/ketones to access N-substituted tertiary amines; common hydride sources include NaBH(OAc)3 in AcOH-buffered media or NaBH3CN in MeOH.
  • N-Alkylation with alkyl halides, sulfonates, and carbonate electrophiles to form tertiary amines or quaternary ammonium salts (phase-transfer agents), mindful of over-alkylation.
  • Salt formation with mineral/organic acids for isolation, purification, or modulation of solubility.

• As a heterocyclic motif (literature)

  • Incorporated into medicinal chemistry libraries as a polar, conformationally restricted amine scaffold combining hydrogen-bonding capacity (N–H) and lipophilicity (phenyl). No clinical claims are made; research use only.
  • Potential ancillary ligand behavior via the amine (e.g., temporary coordination in transition-metal catalysis), though it is not a privileged ligand per se.

• Practical tips

  • Drying: free bases can be dried over K2CO3 or molecular sieves; avoid strong bases that may deprotonate and cause side reactions.
  • Protecting group strategies: N-Boc protection proceeds under standard conditions (Boc2O, base); deprotection with TFA regenerates the secondary amine.
  • Analytical control: monitor reactions by LC–MS; the aryl group provides strong UV response (254 nm).

These use-cases derive from general reactivity of secondary amines and morpholine scaffolds.

Reaction Conditions

Representative conditions for common transformations of 4-methyl-2-phenylmorpholine are provided as general literature guidance. Optimize for your substrates.

• N-Acylation (to amides/carbamates)

  • Solvent: DCM, THF, or EtOAc.
  • Base: Et3N, DIPEA, or NaHCO3 (aqueous biphasic for acid chlorides).
  • Temperature: 0–25 °C typically; 1–4 h to completion by TLC/LC–MS.
  • Coupling alternatives: EDC·HCl/HOBt or HATU in DMF/DIPEA at 0–25 °C.

• Reductive amination (to tertiary amines)

  • Carbonyl partner: aldehyde/ketone (1.0–1.5 equiv).
  • Reductant: NaBH(OAc)3 (3–4 equiv) in DCE or MeCN with 1–2 equiv AcOH; 20–25 °C, 2–16 h. Alternatively, NaBH3CN in MeOH at pH 5–6.
  • Catalytic hydrogenation: H2 (1–5 bar), Pd/C (5–10 wt%), EtOH, 20–40 °C, 2–8 h; avoid aryl hydrogenation by moderating conditions.

• N-Alkylation

  • Electrophile: primary alkyl bromide/iodide or mesylate (1.0–1.5 equiv).
  • Base: K2CO3 or Na2CO3; solvent: MeCN or acetone; 50–80 °C, 4–16 h.
  • To suppress over-alkylation, use excess amine and add electrophile slowly.

• Salt formation/crystallization

  • Dissolve free base in EtOAc or IPA; add dry HCl in EtOAc or gaseous HCl to precipitate the hydrochloride; 0–25 °C. Filter, wash with cold solvent, dry under vacuum.

• Analytical monitoring

  • UV at 254 nm (aryl chromophore); LC–MS ESI+ readily detects protonated molecular ion [M+H]+.

These conditions are typical literature starting points and are not item-specific specifications. Always assess scalability, safety, and impurity profiles experimentally.

Safety & Handling

• Classification and hazard statements

  • GHS classification, signal word, H-statements, and pictograms: Not specified for this item; refer to the SDS for authoritative classification.

• General hazards for secondary amine, arylmorpholine derivatives (literature guidance)

  • May cause irritation to skin, eyes, and respiratory tract; basic amines can be corrosive to eyes/skin at higher concentrations.
  • Amines can form salts with acids; avoid exposure to strong acids and oxidizers. Combustible/flammable behavior should be assumed for organic liquids.
  • Amines may absorb CO2 from air and form carbamates; keep containers tightly closed.

• Recommended PPE and controls

  • Use chemical-resistant gloves (e.g., nitrile), lab coat, and safety glasses or face shield.
  • Handle in a fume hood to avoid inhalation of vapors and to control odors.
  • Have an eyewash and safety shower accessible.

• First-aid overview (consult SDS for full instructions)

  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin contact: remove contaminated clothing; wash skin with soap and water.
  • Eye contact: rinse cautiously with water for several minutes; remove contact lenses if present; seek medical attention.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.

• Storage incompatibilities and special risks

  • Segregate from strong oxidizers, strong acids, and acylating/alkylating agents.
  • Secondary amines can undergo nitrosation with nitrosating agents—avoid nitrite sources under acidic conditions.
  • Refer to the SDS for spill, fire-fighting media, and disposal guidance.

Solvent Selection

This product is a functionalized secondary amine/building block rather than a process solvent. Solvent selection is therefore about dissolving it and enabling its reactions.

• Polarity and miscibility (literature expectations)

  • Amphiphilic: contains one protonatable amine and one ether oxygen plus a hydrophobic phenyl group.
  • Likely high solubility in polar aprotic solvents (DMF, DMSO, NMP, MeCN), alcohols (MeOH, EtOH, i-PrOH), and many ethers (THF, MTBE). Solubility in water is expected to be moderate to low compared to morpholine; complete miscibility may be achievable as the protonated salt.

• Choosing media by application

  • N-acylation/urea formation: use inert aprotic solvents (DCM, THF, toluene, DMF) with base or coupling agents; minimize water.
  • Reductive amination: alcohols (MeOH, EtOH), DCE, THF, or AcOH-containing media with NaBH(OAc)3/NaBH3CN; DMSO/DMF as cosolvents for poorly soluble carbonyl partners.
  • Salt formation/crystallization: select ether/ester solvents (EtOAc, MTBE) mixed with alcohols to induce crystallization of amine salts (HCl, HBr, p-TsOH).
  • N-alkylation/quaternization: use polar aprotic (MeCN, DMF) to solubilize alkyl halides and amine.

• Comparison notes (literature)

  • Versus morpholine: lower water solubility, improved solubility in less polar organics; basicity slightly reduced by aryl at C-2 but still suitable for nucleophilic reactions.
  • Versus anilines: far more nucleophilic/basic; reactions proceed under milder conditions.

Always confirm actual solubility experimentally for your specific lot and process scale.

Storage & Reconstitution

• Item-specific storage/shipping

  • Storage Conditions: Room temperature (per Product Data).
  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

• General storage guidance for secondary amine free bases (literature)

  • Store tightly sealed under inert headspace if possible to minimize CO2 uptake and moisture ingress.
  • Keep away from strong acids, oxidizers, and sources of nitrosating agents. Protect from prolonged light/air exposure to limit discoloration or oxidative byproducts.
  • If long-term storage is required, consider converting to a stable crystalline salt (e.g., HCl or p-toluenesulfonate) and store in a desiccator.

• Handling and reconstitution

  • Warm gently to ambient temperature before opening if stored cold to avoid condensation.
  • If solidified or viscous, gently heat (30–40 °C) or add a small volume of a suitable dry solvent (EtOAc, MeCN, DCM) to facilitate transfer; verify dryness before moisture-sensitive reactions.
  • For aqueous use, generate the corresponding acid salt and dissolve in buffer; adjust pH carefully to avoid precipitation of the free base.

• Shelf life

  • No item-specific shelf-life is provided. Inspect periodically by NMR/LC–MS for purity if stored long term.

Always defer to the product’s SDS and lot-specific CoA for authoritative handling and storage details.

Structure & Identity

4-Methyl-2-phenylmorpholine is an N–O heterocycle (morpholine ring) bearing a phenyl substituent at C-2 and a methyl substituent at C-4. The ring contains one tertiary ether oxygen and one secondary amine nitrogen (–NH–) embedded in a six-membered ring.

• Item-specific identifiers (Product Data)

  • SKU: M970736
  • CAS: 21532-10-5
  • CID: 12761206
  • InChIKey: 94523 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identity details (informational; not item-specific specs)

  • Typical molecular formula (literature inference from name): C11H15NO
  • Approximate molecular weight (literature, calculated from formula): ~177.24 g/mol
  • Core structural features: morpholine ring (O–(CH2CH)2–NH) with sp3 carbons at C-2 and C-4; C-2 substituted by a phenyl (sp2 aromatic) and C-4 by a methyl (sp3). One stereogenic center may exist at C-2 if the ring conformation is frozen, but the compound is generally handled as racemic/achiral in practice due to rapid ring inversion.
  • Functional groups: secondary amine (basic), ether (non-basic Lewis base), aryl group (phenyl). These confer amphiphilic character and nucleophilicity at nitrogen.

• 2D description in words (literature): a six-membered heterocycle containing one O and one N positioned 1,4 relative; the carbon adjacent to O bears a phenyl substituent, and the carbon opposite O bears a methyl group; the nitrogen is secondary (–NH–).

Synthetic Utility

As a secondary amine featuring an embedded ether, 4-methyl-2-phenylmorpholine is a chemoselective nucleophile with several strategic uses in synthesis.

• Key reactivity (literature)

  • N-selective functionalization: the nitrogen is the dominant nucleophilic site; O-alkylation/acylation is disfavored under standard conditions.
  • Amide formation: acyl chlorides/activated acids react rapidly to give tertiary amide derivatives; useful for generating conformationally restricted amide motifs.
  • Reductive amination: serves as the amine component to append an additional alkyl substituent and convert to a tertiary amine scaffold.
  • Alkylation: SN2 with primary halides/mesylates; control mono- vs di-alkylation by using limiting electrophile and base scavengers.
  • Salt/cocrystal formation: protonation with Brønsted acids affords isolable salts that can aid purification or enable phase switching in process chemistry.

• Retrosynthetic value (literature)

  • Access via N–O morpholine ring construction (e.g., from 2-amino-2-phenylethanol cyclization then N–O closure), or via C–N bond formation on an aryl precursor followed by ring assembly.
  • Alternatively, install the phenyl at C-2 via addition/cyclization strategies, then methylate at C-4 using enolate/organometallic methodologies on suitable precursors.

• Selectivity/compatibility

  • The ether oxygen tolerates many conditions; avoid strong Lewis acids that may coordinate and promote side reactions.
  • The aryl group provides UV chromophore for monitoring and can engage in π–π interactions in purification.

Overall, it is a practical, polar, arylated morpholine scaffold enabling rapid exploration of tertiary amine chemical space.

Target Specificity

Not applicable. This product is a small-molecule amine building block and not a biological reagent (e.g., antibody, enzyme, or inhibitor) with defined target specificity. No target, epitope, isotype, or species reactivity information is provided or implied.

Frequently Asked Questions

What is the purity of this product?

This product is supplied at ≥95% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

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

The CAS Number is 21532-10-5, the molecular formula is C11H15NO, and the molecular weight is 177.240 g/mol. InChIKey FXDYCASQPGXSMZ-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.