4-[2-(4-Iodophenyl)ethyl]morpholine , CAS No.100839-46-1

CAS: 100839-46-1 Cat. No.: I971653 Formule: C₁₂H₁₆NOI Poids moléculaire: 317.17 PubChem CID: 23437833

Storage

Room temperature

Specifications

Conditions de stockage de stockage

Room temperature

Noms et identifiants

• Sourires canoniques: C1COCCN1CCC2=CC=C(C=C2)I
• IUPAC Name: 4-[2-(4-iodophenyl)ethyl]morpholine
• InChIKey: AKNWDQHNXHTDRO-UHFFFAOYSA-N
• INCHI: 1S/C12H16INO/c13-12-3-1-11(2-4-12)5-6-14-7-9-15-10-8-14/h1-4H,5-10H2
• Isomères SMILES: C1COCCN1CCC2=CC=C(C=C2)I
• PubChem CID: 23437833
• Poids moléculaire: 317.17

Propriétés chimiques et physiques

• Poids moléculaire: 317.170 g/mol
• XLogP3: 2.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 317.028 Da
• Monoisotopic Mass: 317.028 Da
• Topological Polar Surface Area: 12.500 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 174.000
• 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 item-specific, validated biological application protocols (e.g., WB, IHC, IF, FC) are provided for this small‑molecule building block. Typical usage follows standard organic synthesis procedures for cross‑couplings and amine derivatizations. See the Reaction Conditions and Synthetic Utility sections for general guidance and adapt to your laboratory’s SOPs.

Biological Roles

This product is a synthetic organic building block. No item-specific biological activity or targets are provided in the Product Data.

General context (literature; not product claims):

• Morpholine is a common polar heterocycle in medicinal chemistry, frequently used to adjust basicity, water solubility, and metabolic profile of lead compounds. The conjugate acid pKa of morpholine derivatives is typically ~8–9, allowing partial protonation at physiological pH.
• Para‑iodoaryl groups serve as versatile synthetic handles; iodine can be replaced via cross‑coupling to install diverse pharmacophores without perturbing the remainder of the molecule.
• The phenethyl linker imparts conformational flexibility and can act as a spacer between a polar headgroup (morpholine) and a hydrophobic aryl domain, a motif often explored in SAR studies.

Use limitation: For research use only (as stated in Product Data). No clinical, diagnostic, or in vivo use is intended or supported.

Buffer Applications

Not typically applicable. 4-[2-(4‑Iodophenyl)ethyl]morpholine is a synthetic building block rather than a dedicated buffering reagent. Although the morpholine ring is a weak base (conjugate acid pKa for morpholine derivatives ~8–9, literature), this compound is not used to formulate standard laboratory buffers. For pH control around neutrality to mildly basic ranges, use established buffers (e.g., HEPES, Tris, MOPS).

Green Alternatives

Greenness considerations focus on reaction media and halide choice rather than the substrate itself.

Greener choices (literature/general):

• Solvents:
  • Replace DMF/NMP with 2‑MeTHF, cyclopentyl methyl ether (CPME), or aqueous micellar media (e.g., TPGS‑750‑M) for Pd‑catalyzed couplings.
  • Use EtOAc or MeOH for N‑acylations where feasible, instead of chlorinated solvents.
• Catalysis:
  • Employ ligand-enabled, low‑loading Pd or Ni catalysis in water or aqueous ethanol; consider heterogeneous Pd/C under flow.
• Energy:
  • Microwave‑assisted couplings in greener solvents can shorten cycle times and lower energy use.

Tradeoffs:

• Aryl iodides are highly reactive in cross‑couplings, enabling milder conditions and fewer byproducts, but iodine increases mass intensity and E‑factor. Using the iodide can reduce catalyst loading/temperature compared to aryl bromides/chlorides—balance reactivity vs. sustainability.

Compact comparison (general):

• DMF vs. 2‑MeTHF: 2‑MeTHF is biorenewable and easier to remove; DMF offers superior salt solubility but is problematic in waste streams.
• DCM vs. EtOAc: EtOAc is less toxic and biodegradable; may require temperature control to manage volatility.

Recommendation: Start with 2‑MeTHF or EtOAc and aqueous base for Suzuki couplings; validate performance versus DMF/dioxane. Capture iodine-containing wastes separately for appropriate disposal or recovery.

Pharmaceutical Uses

No pharmacopeial grade or excipient designation is provided in the Product Data; this material is for research use only.

General formulation/manufacturing context (literature/good practice):

• Role: synthetic intermediate/building block to access morpholine-containing candidates. The para‑iodide allows late‑stage diversification by cross‑coupling to install aryl, heteroaryl, alkenyl, or alkynyl groups.
• Salt formation: For improved handling or crystallinity, free-base morpholine derivatives are often converted to hydrochloride or sulfate salts; this may increase aqueous solubility and enable better material control during process development.
• Impurity control: Potential impurities include deiodinated analogs, diaryl coupling byproducts, and over‑acylated N‑derivatives. Analytical control by HPLC/LC–MS and NMR is typical.

Note: No therapeutic or clinical claims are made or implied. If pursuing process development, establish internal specifications (assay, residual solvents, metals, and polymorphism if solid) and validate against intended downstream chemistry.

Physical Properties

Item-specific physical specs (this lot):

• 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.
• Other specs (bp/mp, density, RI, water/peroxide/metal limits, UV cutoff): Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed reference values (informational only; not product specifications):

• Empirical formula estimate from structure: C12H16INO
• Formula weight estimate: ~317.2 g/mol
• Ionization: secondary amine; conjugate acid pKa for morpholine systems typically ~8.2–8.6 (literature)
• Expected solubility profile: free base likely soluble in polar aprotic organics (DMF, DMSO, NMP, THF, CH2Cl2), moderately in EtOAc, limited in hydrocarbons; very low in water as free base but can be water‑soluble as a protonated salt (literature/analogy)
• Polarity: amphiphilic; aryl iodide increases lipophilicity while morpholine increases H‑bond basicity and polarity

Notes:

• No authoritative thermophysical constants are available in the provided Product Data. For process design, confirm with batch-specific CoA or measure under your conditions.

Quality and Grades

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

General guidance on quality considerations for this compound class:

• Building-block grade: For cross-couplings, impurities such as iodide salts, residual metals, or oxidative byproducts can impact catalytic performance. Review CoA for assay (%), residual solvents, and trace metals if available.
• Amine content: Free-base vs. salt form influences assay and handling. Free bases may exhibit variable microanalytical C/H/N due to adsorbed moisture/CO2; Karl Fischer moisture may be informative where relevant—check CoA.
• Stabilizers: None stated in Product Data. In general, aryl iodides do not require stabilizers, but storage under inert gas and in amber glass can improve shelf life by limiting light/air exposure.
• Chromatography use: If intended for library synthesis or automated flow, low UV background and defined purity are helpful; HPLC/LC–MS trace confirms identity and purity.

Recommendation: For sensitive Pd-catalyzed couplings, consider pre-testing a small aliquot by LC–MS and, if necessary, purifying by flash chromatography or recrystallization to remove trace colored or polar impurities that can influence catalyst turnover.

Reaction and Applications

This substrate combines a para‑iodoaryl handle with a morpholine ring—useful in medicinal chemistry and materials discovery as a late‑stage diversification node.

Representative transformations (literature/general):

• Cross‑couplings at the aryl iodide:
  • Suzuki–Miyaura with aryl/heteroaryl/alkenyl boron reagents to access para‑substituted phenethyl‑morpholines.
  • Buchwald–Hartwig N‑arylation (if iodide is on an aniline precursor; here, aryl C–N formation to introduce amine on the ring is possible from this iodide) to form diarylamines after amination.
  • Sonogashira to introduce alkynes; Heck to install alkenes at the para position.
• Hydrogen–halogen exchange or metal–halogen exchange (e.g., with iPrMgCl·LiCl or n‑BuLi at low temperature) enabling electrophile trapping to form diverse para‑substituted products.
• N‑functionalization on morpholine: acylation, sulfonylation, carbamoylation (e.g., Boc/CBz) to tune basicity and solubility; subsequent cross-coupling tolerates protected amines better.
• Reductive manipulations: hydrogenation of the ethyl spacer (not typically needed) or deiodination under Pd/H2 for control experiments.

Practical tips:

• Free amines can bind Pd catalysts. Consider N‑Boc protection prior to Pd cross‑coupling to improve turnover numbers; deprotect after coupling.
• For metallation at the aryl iodide, maintain low temperature (≤ −78 °C) and use non‑protic, dry solvents (THF/Et2O). Quench cautiously.
• The benzylic ethyl spacer reduces risk of β‑elimination during basic conditions versus benzylic ammonium analogs.

Applications: rapid SAR exploration, linker installation to morpholine, preparation of polar–lipophilic balanced scaffolds for screening libraries.

Reaction Conditions

General literature guidance for common transformations of aryl iodides bearing free amines (not product specifications):

• Suzuki–Miyaura coupling:

  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd2(dba)3 (1 mol%) with SPhos/XPhos.
  • Base: K3PO4 or Cs2CO3 (2–3 equiv).
  • Solvent: 1,4‑dioxane/H2O (3:1) or 2‑MeTHF/H2O.
  • Temperature/time: 60–90 °C, 2–12 h.
  • Note: Protect morpholine nitrogen (e.g., Boc) to minimize catalyst inhibition; deprotect with TFA later.

• Sonogashira coupling:

  • Catalyst: PdCl2(PPh3)2 (1–2 mol%), CuI (2–5 mol%).
  • Base: Et3N or iPr2NEt.
  • Solvent: THF, MeCN, or DMF.
  • Temperature: rt to 60 °C.

• Heck reaction:

  • Catalyst: Pd(OAc)2 (1–2 mol%) with PPh3 or bulky phosphines.
  • Base: Et3N, DIPEA, or inorganic carbonate.
  • Solvent: DMF, NMP, or toluene.
  • Temperature: 80–120 °C.

• Halogen–metal exchange (for electrophile trapping):

  • Reagent: iPrMgCl·LiCl (Turbo‑Grignard) or n‑BuLi.
  • Solvent: dry THF or Et2O; temperature −78 to −20 °C.
  • Quench: electrophiles (DMF → aldehyde, CO2 → acid, B(OMe)3 → boronate) then workup.

Yields: Aryl iodides often deliver high conversions/yields (70–95%) under optimized conditions; actual outcomes depend on substrate protection, catalyst/ligand, and base.

Always conduct small‑scale scouting to optimize ligands, base, and N‑protection strategy for this amine-containing substrate.

Safety and Handling

Authoritative safety information should be taken from the item’s SDS.

Item-specific hazard data from Product Data: Not specified (Signal Word, H‑Statements, GHS class, pictograms not provided). Always refer to the SDS for definitive guidance.

General laboratory precautions for aryl iodide–morpholine building blocks (literature/good practice):

• Likely hazards: may cause skin/eye irritation and respiratory irritation; amines can be sensitizers or corrosive at high concentrations. Avoid inhalation of dust/aerosols and contact with skin/eyes.
• PPE: lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Work in a fume hood.
• Handling: keep container tightly closed. Avoid prolonged exposure to air and strong light; aryl iodides can undergo photolytic reactions. Minimize contact with oxidizers and strong bases/acids unless intended.
• Incompatibilities (general): strong oxidizing agents; strong acids/bases may lead to salt formation or degradation. Transition‑metal catalysts may be poisoned by free amines—use protection or base controls during coupling.
• First aid (overview): rinse skin with water for ≥15 min upon contact; flush eyes with water and seek medical attention; move to fresh air if inhaled; if ingested, rinse mouth—do not induce vomiting; obtain medical attention. Follow SDS procedures.
• Spills/waste: absorb with inert material, collect in compatible container. Dispose of according to local regulations; halogenated organic waste stream is typical for aryl iodides.

Solvent Selection

Applicability: This product is an organic building block, not primarily used as a solvent. Selection here refers to solvents appropriate for dissolving and reacting 4-[2-(4‑iodophenyl)ethyl]morpholine.

General solubility/miscibility expectations (literature/analogy):

• Good solvents: DMSO, DMF, NMP, acetonitrile, THF, dioxane, dichloromethane, chloroform, ethyl acetate.
• Moderate: toluene, MTBE; limited in aliphatic hydrocarbons (hexanes/heptane).
• Aqueous media: poor as free base; solubility increases substantially upon protonation (e.g., HCl, H2SO4 salts).

Selection tips by application:

• Pd-catalyzed couplings: 1,4-dioxane, THF, toluene, or mixed aqueous organic (e.g., dioxane/H2O) frequently perform well. DMF/DMSO enable higher polarity substrates but can complicate workup.
• N-derivatization/protection: dichloromethane or THF with base (e.g., DIPEA) for acylations or Boc protection.
• SNAr or alkylations on the amine: polar aprotic solvents (DMF/DMSO/MeCN) support deprotonation and nucleophilicity.

Small comparison (literature/general):

• Dioxane vs. THF: dioxane is higher boiling and often preferred in Suzuki couplings; THF offers faster mass transfer but can coordinate metals.
• MeCN vs. DMF: MeCN eases workup/evaporation; DMF enhances solubility of polar salts/bases.

Storage and Reconstitution

Item-specific storage/shipping from Product Data:

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

General handling advice (good practice for aryl iodide amines; not a specification):

• Containers: Store in tightly sealed, amber glass to limit light exposure. Consider inert gas blanket (N2/Ar) after opening to reduce oxidative degradation.
• Environment: Keep dry; protect from excessive heat and strong light. Avoid prolonged exposure to air if repeated openings are expected.
• Form: If supplied as a free base oil/solid, it can be used as is. For aqueous work, generate a salt in situ (e.g., HCl) to increase water solubility, then basify for extractions as needed.
• Freeze–thaw: Not typically relevant; if stored cold to extend shelf life, allow to warm to room temperature in a sealed container to avoid moisture condensation.

Before scale‑up or extended storage, confirm integrity by NMR/LC–MS. For any reconstitution in organic solvents (e.g., DMSO for stock solutions), prepare fresh when possible and store aliquots to minimize repeated exposure to air and moisture.

Structure and Identity

Brief description: 4-[2-(4-Iodophenyl)ethyl]morpholine is a para‑iodoaryl ethyl–linked morpholine derivative. The morpholine ring is substituted at the 4‑position (the carbon opposite the ring oxygen) by a –CH2–CH2–C6H4–I (para‑iodo) fragment. The ring nitrogen remains secondary (N–H), enabling salt formation and further derivatization.

Item-specific identifiers (from Product Data):

• CAS: 100839-46-1
• SKU: I971653
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data lists a non-standard short token “7917”.)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Computed/literature structural details (for reference; not item-specific specifications):

• Functional groups: aryl iodide (para‑iodophenyl), secondary amine (morpholine), cyclic ether (morpholine oxygen), benzylic ethyl spacer
• Ring systems: 6‑membered benzene; 6‑membered morpholine (1 O, 1 N)
• Stereochemistry: none (achiral as named)
• Empirical formula (derived from name): C12H16INO (literature/computed)
• Approx. molecular weight: ~317.2 g/mol (literature/computed from formula)

2D structure in words: a morpholine ring where the carbon at position 4 bears a methylene–methylene chain terminating at a para‑iodophenyl ring (I at the para position relative to the ethyl linkage). The nitrogen is unsubstituted (N–H).

Synthetic Utility

Key functional elements and reactivity (literature/general):

• Aryl iodide: among the most reactive aryl halides for oxidative addition. Enables Pd/Ni‑catalyzed cross‑couplings (Suzuki, Sonogashira, Heck, Stille, Negishi) under mild conditions. Also amenable to lithiation or Mg‑halogen exchange to access aryl organometallics for electrophile trapping.
• Morpholine (secondary amine + ether): nucleophilic nitrogen allows N‑protection (Boc/CBz), acylation, sulfonylation, urea/carbamate formation; the ring oxygen can engage in H‑bonding, influencing solubility.
• Benzylic ethyl linker: provides spatial separation; tolerates bases typically used in couplings (K3PO4, Cs2CO3, NaOtBu) without β‑elimination issues.

Retrosynthetic value:

• Disconnect at C–I to access a family of para‑substituted phenethyl‑morpholines from a common precursor via cross‑coupling—excellent for parallel synthesis.
• Alternatively, build the morpholine substituent first, then append aryl via electrophilic aromatic substitution or coupling of a para‑functionalized arene.

Typical downstream elaborations:

• Convert aryl iodide to boronate (Miyaura borylation) to create a versatile linchpin.
• Install heterocycles (e.g., pyridyl, pyrazinyl) via Suzuki to tune polarity and coordination.
• Introduce reporter tags (alkynes/azides) via Sonogashira/click chemistry for probe development.

Target Specificity

Not applicable. This product is a small‑molecule building block, not a biological macromolecule or affinity reagent. No antigen/epitope/clone/isotype or species reactivity applies.