2-(Phenoxymethyl)morpholine - ≥98% , CAS No.167273-56-5

CAS: 167273-56-5 Cat. No.: P1072670 EC Number: 861-871-8 PubChem CID: 22011795

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Specifications & Purity

≥98%

Storage

Room temperature

Purity

≥98%

Names and Identifiers

• Canonical Smiles: C1COC(CN1)COC2=CC=CC=C2
• IUPAC Name: 2-(phenoxymethyl)morpholine
• InChIKey: OFBLNBCFCXAZGW-UHFFFAOYSA-N
• INCHI: 1S/C11H15NO2/c1-2-4-10(5-3-1)14-9-11-8-12-6-7-13-11/h1-5,11-12H,6-9H2
• Isomeric SMILES: C1COC(CN1)COC2=CC=CC=C2
• Alternate CAS: 167273-56-5
• PubChem CID: 22011795

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Phenol ethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Phenol ethers
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenol ethers
• Alternative Parents: Phenoxy compounds Alkyl aryl ethers Morpholines Oxacyclic compounds Dialkylamines Dialkyl ethers Azacyclic compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Phenoxy compound - Phenol ether - Alkyl aryl ether - Monocyclic benzene moiety - Morpholine - Oxazinane - Dialkyl ether - Secondary aliphatic amine - Ether - Oxacycle - Azacycle - Secondary amine - Organoheterocyclic compound - Hydrocarbon derivative - Organonitrogen compound - Organooxygen compound - Organic oxygen compound - Organic nitrogen compound - Amine - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
• 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: 193.240 g/mol
• XLogP3: 1.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 193.11 Da
• Monoisotopic Mass: 193.11 Da
• Topological Polar Surface Area: 30.500 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 157.000
• 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 bioassay or immunoassay protocols are specified for this item. As a small-molecule reagent, usage protocols will be context-specific (e.g., synthetic transformations as outlined in Reaction Conditions). For any bioassay incorporation, determine stock solvent compatibility (e.g., DMSO) and final assay concentrations empirically.

Biological Roles

Item-specific biological data were not provided. No medical or clinical claims are made. For research use only.

General context (biochemistry/medicinal chemistry, literature):

• Morpholine is a common medicinal chemistry motif, acting as a basic, polar, H-bond-accepting group to improve solubility and modulate pKa. It appears in numerous research ligands and tool compounds.
• Aryl ethers such as phenoxy substituents can modulate lipophilicity and metabolic stability; benzylic ether linkages may be susceptible to oxidative metabolism in biological systems (general observation).
• Protonation state near physiological pH will depend on the amine pKa and environment; amine salts increase aqueous solubility for in vitro assays.
• Potential uses in chemical biology include as a building block for probe design, linker to conjugate to dyes/affinity tags via the secondary amine, or as a solubilizing appendage in fragment-like scaffolds.

Buffer Applications

This compound is not a dedicated buffering agent and is not typically used to prepare defined buffer systems. If used in biochemical assays, it would be as a small-molecule reagent or building block rather than as a buffer component. For buffering needs, select established systems (e.g., phosphate, HEPES, Tris) appropriate to the pH range of interest.

Green Alternatives

This product is a reagent/building block, not a process solvent. Greener choices relate to the media and reagents used with it.

Greener media and conditions (general guidance):

• Replace dipolar aprotics (DMF, DMAc, NMP) with greener alternatives when feasible:
  • Acetonitrile or 2-MeTHF for many N-acylations/alkylations.
  • Propylene carbonate or Cyrene for coupling reactions where high polarity is required.
• Employ aqueous micellar catalysis (e.g., TPGS-750-M in water) for amide couplings or SN2 N-alkylations to reduce organic solvent volumes.
• Choose coupling reagents with improved EHS profiles (e.g., CDI, EDC.HCl, or DMTMM) over benzotriazole-based systems when compatible.
• For deprotections or ether modifications, favor catalytic hydrogenolysis or enzymatic routes over stoichiometric halogenated reagents when possible.

Trade-offs:

• Greener solvents may change solubility of amine salts; base selection and counterion control become more critical.
• High-boiling green solvents (propylene carbonate, Cyrene) can complicate workup; plan for antisolvent crystallization or extractive quench.

Pharmaceutical Uses

No pharmacopeial monograph or excipient role is provided in the Product Data.

General formulation/manufacturing context (no therapeutic claims):

• As a basic secondary amine, it can form crystalline salts (e.g., HCl, mesylate, fumarate) that may be leveraged during process development for intermediates.
• The morpholine unit is frequently used in discovery chemistry to improve solubility and adjust basicity; this compound may serve as an intermediate for synthesizing candidate molecules or as a handle for prodrug or conjugate strategies (general).
• If used in GMP settings, impurity profiles, residual solvents, and counterion content must be controlled per ICH Q3A/B and Q3C; request lot-specific CoA and regulatory support as needed.

Physical Properties

Item-specific specifications were not provided in the Product Data.

• Appearance: 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.
• Boiling point, melting point, density, refractive index, solubility, logP, pKa: Not specified for this item; refer to CoA/Spec Sheet.

General chemistry context (literature/estimated, non-spec):

• Compounds bearing morpholine typically show moderate basicity (conjugate acid pKa around 8–9 for morpholine itself, literature) and good solubility in polar organic solvents; water solubility can be appreciable due to the ring N and O.
• The phenoxymethyl group adds hydrophobicity and an aryl ether motif; overall polarity remains intermediate compared to simple hydrocarbons (general).

Quality & Grades

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

Interpretive guidance (general):

• If provided as “research grade,” expect suitability for synthetic and discovery applications. For chromatography-sensitive uses, lots labeled “HPLC grade solvent” or “LC-MS grade” are relevant for solvents only; this product is a reagent/building block rather than a solvent.
• If an assay purity is reported on the CoA, it typically reflects GC or HPLC area percent and may exclude residual solvent and moisture. For amine-containing compounds, residual water can affect titration-based purity—verify analytical method on the CoA.
• If salt form versus free base is relevant, the CoA will state it explicitly. The Product Data do not indicate a salt; treat as free base unless the CoA specifies otherwise.

Reaction & Applications

As a morpholine-bearing benzylic ether, 2-(Phenoxymethyl)morpholine is a versatile building block in discovery chemistry and materials motif installation.

• Representative synthetic uses (general literature):
  • N-functionalization: The secondary ring nitrogen undergoes acylation (to amides/carbamates), sulfonylation (sulfonamides), and alkylation to give tertiary amines. Choice of base and solvent controls chemoselectivity versus benzylic or O-ether moieties.
  • Quaternization/salt formation: Protonation provides stable ammonium salts useful for isolation or for phase-transfer applications.
  • Cross-coupling handles via derivatization: The phenyl ring can be further elaborated if transformed to a halide or boronate (via ether cleavage/functional group interconversion first, as the phenoxy group itself is not a typical coupling handle).
  • Benzylic manipulations: The –CH2–O–Ph linkage can sometimes participate in benzylic oxidation or cleavage under strong conditions (e.g., BBr3-mediated aryl ether cleavage), enabling phenol or alcohol unveiling downstream.
  • Urea/thiourea formation: Reacts with carbonyl diimidazole, phosgene equivalents, or isothiocyanates at the secondary amine to introduce urea/thiourea motifs.
• Applications:
  • Scaffold insertion to tune solubility/basicity in lead optimization (morpholine is a common solubilizing, H-bond-accepting motif in medicinal chemistry; general context).
  • Ionizable handle for conjugation to polymers or surfaces via amide/sulfonamide linkages.
• Practical tips:
  • For selective N-acylation, use a weak base (e.g., DIPEA) in DCM/MeCN at 0–25 °C; monitor for over-alkylation.
  • Protecting strategies: Convert the amine to Boc or Cbz if orthogonality is needed during transformations on the aryl ether portion.

Reaction Conditions

Typical conditions (general literature guidance; adjust per substrate and consult primary sources):

• N-Acylation: DIPEA (2–3 equiv) in DCM or MeCN, 0–25 °C, 0.5–4 h with acid chlorides; or EDC.HCl/HOBt-free alternatives (e.g., DMTMM) in MeCN/DMF, rt to 40 °C, 1–6 h.
• N-Alkylation (SN2): K2CO3 or Cs2CO3 (2–3 equiv) in MeCN/acetone/DMF, 20–60 °C, 2–16 h; minimize over-alkylation by slow addition of electrophile and limiting equivalents.
• Reductive amination: Carbonyl (1.0 equiv), AcOH (0.2 equiv), NaBH(OAc)3 (1.5–2.0 equiv) in DCE/MeOH/MeCN, rt, 2–8 h; or H2 (1–3 bar) with Pd/C in EtOH/AcOH at rt–40 °C.
• Sulfonylation: Et3N or pyridine in DCM at 0–25 °C, 1–3 h with R–SO2Cl.
• Aryl ether cleavage (if desired): BBr3 (1–3 equiv) in DCM at −78 to 0 °C, then warm to rt; workup cautiously. Note: protect the amine (e.g., Boc) to prevent side reactions.
• Salt formation: Bubbling dry HCl in ether/IPA at 0–5 °C, then isolate the crystalline hydrochloride; optimize solvent pair for crystallinity.

Yields: Dependent on electrophile and conditions; amide/sulfonamide formations commonly 70–95% (literature, general); SN2 alkylations 50–85% with careful control of dialkylation.

Safety & Handling

Hazard classification for this specific item was not provided.

• GHS signal word / hazard statements / pictograms: Not specified for this item; refer to SDS.

General laboratory guidance (professional best practice; not a substitute for SDS):

• Likely hazards for morpholine-containing organics: irritant to skin, eyes, and respiratory tract; amines can be harmful if swallowed or inhaled (general). Avoid inhalation of vapors/aerosols and contact with skin/eyes.
• PPE: lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood.
• Incompatibilities: strong acids (forms salts/exotherm), strong oxidizers (risk of exotherm/oxidation), acylating/alkylating agents (reactivity at the secondary amine) (general).
• Spill/first aid (overview): For small spills, absorb with inert material, ventilate area. Skin/eye contact—rinse with water for 15 minutes and seek medical advice. If inhaled—move to fresh air; if ingested—rinse mouth, do not induce vomiting; seek medical attention. Defer to SDS for authoritative instructions.
• Fire fighting: Use CO2, dry chemical, or foam. Combustion may produce NOx and COx (general).
• Storage note: Keep tightly closed at room temperature as indicated in Product Data; segregate from incompatible reagents. Refer to SDS for detailed conditions.

Solvent Selection

This product is a polar, heteroatom-rich organic base/building block rather than a solvent. Selection of medium for reactions or handling should consider both the basic secondary amine and the aryl ether.

General guidance (literature/practice):

• Polarity/miscibility: Morpholine-containing molecules are typically soluble in polar aprotic solvents (DMAc, DMF, DMSO, acetonitrile) and moderately soluble in alcohols and chlorinated solvents; solubility in water can be moderate due to the basic N and ring O (verify experimentally or see CoA notes).
• Acid–base: Forms salts in protic acids (e.g., HCl, H2SO4). Salt formation can enhance aqueous solubility and aid crystallization/purification.
• When to choose solvents:
  • N-alkylation/acylation: acetonitrile, DMF, DCM, or THF with suitable base; avoid strong protic media that protonate the amine.
  • Reductive amination or coupling: alcohols (MeOH/EtOH/iPrOH) or MeCN under hydrogenation/borohydride conditions.
  • Aryl-ether-stable conditions: It tolerates many bases and nucleophiles; avoid strong Lewis acids/Brønsted acids at elevated temperature that can cleave benzylic ethers.
• Drying/handling: If water-sensitive transformations are planned, pre-dry by co-evaporation with toluene or by brief storage over molecular sieves (compatibility permitting).

Storage & Reconstitution

• Storage conditions (Product Data): Room temperature. Keep container tightly closed in a dry, well-ventilated place. Minimize exposure to air and moisture to preserve assay and handling characteristics.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Form supplied / appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: If solid, dissolve in a suitable dry solvent (e.g., DMSO, MeCN, MeOH, or DCM) appropriate to the intended use; if liquid, it may be used neat or as a stock solution. Filter if particulates are observed.
• Stock solutions: Prepare under dry, inert atmosphere when required by downstream chemistry; store aliquots in tightly sealed vials to limit moisture uptake and amine oxidation. For biological screening, DMSO stocks (10–100 mM) are typical; verify solubility empirically.
• Freeze–thaw: Not generally required at room temperature storage; if low-temperature storage is chosen for long-term stability, avoid repeated freeze–thaw by aliquoting.
• Shelf life: Refer to CoA/SDS for lot-specific guidance; inspect periodically for discoloration or precipitation before use.

Structure & Identity

Research-use small molecule combining a morpholine ring (heterocycle containing both O and secondary amine N) with a benzylic phenoxy substituent.

• Item name: 2-(Phenoxymethyl)morpholine (research grade)
• CAS: 167273-56-5 (Product Data)
• PubChem CID: 22011795 (Product Data)
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data lists “256279,” which is not a standard InChIKey format.)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Structural features (general chemistry description):
  • Contains a six-membered morpholine ring (one ring oxygen, one ring nitrogen; the nitrogen is secondary and basic).
  • Substituent at the 2-position of morpholine is a phenoxymethyl group (–CH2–O–Ph), i.e., a benzylic ether linking to a phenyl ring.
  • Functional groups: tertiary ether (aryl–O–), secondary amine (in-ring), aliphatic C–O (ring), aromatic phenyl ring.
  • 2D structure in words: a morpholine chair-like ring with O and N opposite each other; on the carbon adjacent to the ring oxygen, a –CH2–O–(phenyl) side chain extends, creating an aryl ether terminus.
• Stereochemistry: No stereocenters implied by the name; expected to be achiral (literature/general).

Synthetic Utility

Key reactivity arises from the secondary amine and the benzylic aryl ether:

• Secondary amine transformations:
  • Acylation (acid chlorides/anhydrides, EDCI/HATU/CDI couplings) to amides/carbamates.
  • Alkylation (SN2 with primary halides/sulfates under base; reductive amination with aldehydes/ketones using NaBH3CN/NaBH(OAc)3 or catalytic hydrogenation).
  • Sulfonylation (sulfonyl chlorides) to access sulfonamides.
• Salt and quaternary ammonium formation for separation or phase-transfer catalysis.
• Ether/aryl segment:
  • Under strong Lewis/Brønsted acids (e.g., BBr3, BCl3), aryl–O cleavage can yield phenol derivatives; benzylic oxidation may be feasible under Mn/Cr-based or catalytic aerobic conditions (general).
• Retrosynthetic value:
  • Can serve as a masked phenol handle while enabling parallel diversification at nitrogen.
  • The –CH2– linker provides spacing for SAR exploration, allowing independent modulation of the aryl and amine domains.

Orthogonality tips:

• Protect the amine (Boc, Cbz) prior to electrophilic aromatic substitutions or harsh Lewis acid conditions to avoid N-coordination/deactivation.
• For selective mono-alkylation, use non-nucleophilic bases (DIPEA, K2CO3) and controlled equivalents of alkyl electrophile.

Target Specificity

Not applicable. This product is a small-molecule building block, not a biological macromolecule or affinity reagent. No antigen/epitope or species reactivity information is relevant to this item.

Frequently Asked Questions

What is the purity of this product?

This product is supplied at ≥98% 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 167273-56-5. InChIKey OFBLNBCFCXAZGW-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.