Ethyl (2-ethoxy-4-formyl-6-iodophenoxy)acetate , CAS No.428837-88-1

CAS: 428837-88-1 Cat. No.: E1018917 Formula: C₁₃H₁₅IO₅ Peso molecolare: 378.160

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

• Sorrisi canonici: CCOC1=C(C(=CC(=C1)C=O)I)OCC(=O)OCC
• IUPAC Name: ethyl 2-(2-ethoxy-4-formyl-6-iodophenoxy)acetate
• InChIKey: DPJZYJLUEMRONG-UHFFFAOYSA-N
• INCHI: 1S/C13H15IO5/c1-3-17-11-6-9(7-15)5-10(14)13(11)19-8-12(16)18-4-2/h5-7H,3-4,8H2,1-2H3
• Peso molecolare: 378.160

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Phenoxyacetic acid derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenoxyacetic acid derivatives
• Alternative Parents: Phenoxy compounds Phenol ethers Benzoyl derivatives Benzaldehydes Iodobenzenes Alkyl aryl ethers Aryl iodides Carboxylic acid esters Monocarboxylic acids and derivatives Organoiodides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Phenoxyacetate - Benzaldehyde - Benzoyl - Phenol ether - Phenoxy compound - Aryl-aldehyde - Alkyl aryl ether - Halobenzene - Iodobenzene - Aryl halide - Aryl iodide - Carboxylic acid ester - Ether - Carboxylic acid derivative - Monocarboxylic acid or derivatives - Organohalogen compound - Organic oxygen compound - Carbonyl group - Organoiodide - Aldehyde - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as phenoxyacetic acid derivatives. These are compounds containing an anisole where the methane group is linked to an acetic acid or a derivative.
• 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: 378.160 g/mol
• XLogP3: 2.600
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 8
• Exact Mass: 377.996 Da
• Monoisotopic Mass: 377.996 Da
• Topological Polar Surface Area: 61.800 Ų
• Heavy Atom Count: 19
• Formal Charge: 0
• Complexity: 297.000
• 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 assay or immunoapplication protocols are specified for this item. Typical laboratory use involves chemical synthesis workflows.

General usage notes for small-molecule handling:

• Prepare concentrated stock solutions in dry, oxygen-free organic solvents (e.g., DCM, THF, MeCN, or anhydrous DMSO) as compatible with the planned transformation.
• For biological assays, prepare DMSO stocks (e.g., 10–50 mM), filter through 0.22 µm PTFE, and dilute into assay media maintaining low final DMSO content.
• Monitor reactions by TLC/LC–MS. Iodinated aromatics often give strong UV response at 254 nm aiding detection.

No validated dilutions, positive controls, or kit-style procedures are provided for this product.

Biological Roles

This product is a synthetic organic building block intended for research and development. It is not a biological reagent and has no established endogenous biological role.

General context (for chemists designing bioactive molecules):

• Aryl iodides serve as versatile handles for late-stage diversification, enabling rapid SAR exploration via cross-coupling. The presence of –CHO allows incorporation of fragments through imine formation/reductive amination or oxime ligation, common in probe and linker synthesis.
• The phenoxyacetate motif can modulate lipophilicity and hydrogen-bond acceptor count, potentially improving membrane permeability in small-molecule design; hydrolysis can yield a phenoxyacetic acid derivative for further conjugation.
• Electron-donating alkoxy groups (–OEt, phenoxy) can increase electron density on the ring, which may influence π–π interactions and photophysical properties in dye/linker development.

No clinical or therapeutic claims are made. For any biological testing, ensure compound purity and residual-metal levels are appropriate for the intended assay, and confirm DMSO/solvent vehicle compatibility to avoid assay artifacts.

Buffer Applications

Not typically applicable. This is a hydrophobic organic synthesis building block, not a buffering agent. It lacks acid/base conjugate pairs in the relevant physiological pH range suitable for buffer formulation.

Practical guidance:

• If used in biochemical assays, dissolve first in a compatible organic co-solvent (e.g., DMSO, DMF, or ethanol) and then dilute into the assay buffer, keeping final organic content low (typically ≤1–2%).
• Validate solubility and stability of any imine/oxime derivatives in your chosen buffer system, as aldehyde-derived linkages can be pH-sensitive.

Green Alternatives

While the compound itself is a specialized building block (no direct greener “replacement”), greener choices can be made in its use—primarily solvent and catalyst systems.

Greener solvent choices (literature guidance):

• Replace THF/dioxane with 2‑MeTHF or CPME for many Pd-catalyzed couplings; both offer better safety/EHS profiles and enable water co-solvent use.
• Employ EtOH/H2O or iPrOH/H2O for Suzuki couplings when substrate solubility allows.
• Consider Cyrene or propylene carbonate for polar-aprotic needs instead of DMF/DMAc; verify stability with aldehydes.

Comparison (general):

• THF vs 2‑MeTHF: similar polarity; 2‑MeTHF has higher boiling point, reduced peroxide tendency, and bio-based sourcing.
• Dioxane vs CPME: CPME is less hazardous and more hydrophobic, aiding biphasic catalysis; dioxane is a classified substance in some regions.
• DMF/DMAc vs Cyrene/PC: greener replacements reduce reproductive toxicity concerns but may alter catalyst solubility/kinetics.

Catalyst and process considerations:

• Use ligand-efficient, low-Pd loading systems or heterogeneous Pd/C with careful control to minimize metal residuals.
• Aqueous micellar catalysis (e.g., TPGS-750-M) has enabled many cross-couplings at room temperature with low organic solvent usage—test aldehyde compatibility.
• Flow chemistry can reduce solvent inventory and improve heat/mass transfer for exothermic couplings.

Note: Always confirm substrate stability (especially the aldehyde and ester) in alternative media and under greener conditions before scale-up.

Pharmaceutical Uses

This product is offered for research use only. It is not an excipient or a drug substance.

R&D/formulation context (general, non-clinical):

• As a late-stage intermediate, the aryl iodide handle enables rapid analog generation en route to candidate APIs using Suzuki, Sonogashira, or Buchwald couplings.
• The aldehyde can be leveraged for linker installation (e.g., formation of reversible imines or stable oximes/hydrazones) in prodrug or conjugate synthesis research.
• The phenoxyacetate ester can be hydrolyzed or transesterified to adjust polarity/solubility of advanced intermediates.

Quality considerations for pharmaceutical process development:

• Control of residual palladium/copper after coupling steps per relevant guidelines (e.g., ICH Q3D) is essential—plan scavenging/purification strategies.
• Impurity profiling should include potential over-oxidation of the aldehyde, ester hydrolysis products, and homocoupling byproducts.

No therapeutic, diagnostic, or clinical claims are made for this product.

Physical Properties

Item-specific specifications are not provided in the Product Data for this SKU. Do not treat the following as specifications; consult the CoA/SDS for purchasing decisions.

• Appearance (item-specific): 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.

Literature/computed context (non-specification):

• Approximate formula/mass from structure inference: ~C13H15IO5; ~378 g/mol.
• Expected physical state: crystalline solid or viscous oil typical for multi-functional aryl iodides/esters; color may range colorless to pale yellow due to the aldehyde chromophore (literature expectation).
• Solubility profile (typical): high solubility in chlorinated solvents (DCM, CHCl3), ethyl acetate, acetone, THF; moderate in toluene; very low in water, owing to hydrophobic aryl/iodo core (literature expectation).
• UV absorption: aromatic/aldehyde chromophores absorb in UV; precise λmax and cutoff Not specified for this item; refer to CoA/Spec Sheet.
• Boiling/melting point, density, refractive index, logP, pKa: Not specified for this item; refer to CoA/Spec Sheet. For planning purposes, treat as a thermally sensitive aromatic aldehyde/ester—avoid prolonged high heat.

Practical notes (general): minimize exposure to strong base/acid and heat to limit ester hydrolysis and aldehyde degradation; handle under dry conditions to avoid hydrate formation/oxidation of the aldehyde.

Quality and 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. Aromatic aldehydes are generally supplied without stabilizers; store properly to limit oxidation/polymerization.

General guidance on grade considerations for this compound class:

• Research/Biochemical grade typically targets high assay and low residual solvents/metals—important if the aryl iodide is used in Pd-catalyzed cross-couplings where trace sulfur/halide impurities can poison catalysts.
• For chromatographic or photochemical applications, low UV background and tight control of aromatic impurities are desirable. If HPLC grade solvent compatibility is expected in downstream steps, ensure low non-volatile residue.
• Water/peroxide/metal limits, UV cutoffs: Not specified for this item; refer to CoA/Spec Sheet. Do not assume values; verify on the item’s CoA.

What to request/verify when qualifying this reagent for synthesis:

• Identity confirmation (NMR, HRMS) and halogen content consistent with an aryl iodide.
• Aldehyde integrity (e.g., absence of over-oxidized acid or acetalization products).
• Residual Pd/Cu (if prepared via halogen exchange) and residual solvents—request CoA values if critical.
• Assay and impurity profile aligned with your coupling strategy (Suzuki/Sonogashira/Buchwald).

Reaction and Applications

Ethyl (2-ethoxy-4-formyl-6-iodophenoxy)acetate is designed as a convergence point for cross-coupling and carbonyl chemistry.

Aryl iodide manifold:

• Suzuki–Miyaura coupling with boronic acids/esters to introduce diverse aryl/alkenyl motifs. Iodides generally exhibit high reactivity and work under milder conditions than bromides.
• Sonogashira coupling to install terminal/internal alkynes; copper-free variants reduce side reactions.
• Buchwald–Hartwig amination for C–N bond formation; proper ligand choice (e.g., biaryl phosphines) is crucial with hindered/alkoxy-substituted rings.
• Carbonylative couplings leveraging the iodide under CO to yield benzoyl derivatives, compatible with the pre-existing aldehyde if protected.

Aldehyde manifold:

• Condensation (oximes, hydrazones, imines) enabling traceless ligations or further reductions (NaBH3CN/BH(OAc)3) to benzylamines.
• Olefination (Wittig/HWE) to access styrenes or conjugated systems orthogonal to the iodide handle.
• Nucleophilic additions (cyanide, organometallics) when ester compatibility is managed (e.g., use of cuprates or protecting groups).

Phenoxyacetate/ether manifold:

• Hydrolysis or transesterification to tune polarity or to release phenoxyacetic acid derivatives.
• O-alkyl stability generally robust, providing an electron-donating environment that can accelerate oxidative addition in Pd catalysis.

Practical tips:

• The electron-rich ring and iodide aid oxidative addition; mild bases (K2CO3, Cs2CO3) and 50–90 °C are often sufficient (literature precedent for similar substrates).
• Protect the aldehyde (acetal) if harsh coupling conditions are needed.
• Maintain anhydrous, oxygen-minimized conditions to preserve –CHO and reduce side-products.

Reaction Conditions

General literature guidance for similar aryl iodide/aldehyde/ester substrates (non-specification; optimize per your system):

• Suzuki–Miyaura coupling:
  • Catalyst: Pd(PPh3)4 (1–2 mol%) or Pd2(dba)3 (0.5–1 mol%) with SPhos/XPhos (1–2 mol%).
  • Base: K2CO3, K3PO4, or Cs2CO3 (2–3 equiv).
  • Solvent: 1,4‑dioxane/H2O, 2‑MeTHF/H2O, or toluene/H2O (3:1 to 10:1 v/v).
  • Temperature/time: 50–90 °C, 2–8 h. Aldehyde protection may be unnecessary under mild conditions.
• Sonogashira coupling:
  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) with or without CuI (1–5 mol%).
  • Base/solvent: Et3N or iPr2NH in THF/MeCN/2‑MeTHF.
  • Temperature/time: rt–60 °C, 2–16 h; copper-free to reduce Glaser byproducts.
• Buchwald–Hartwig amination:
  • Catalyst/ligand: Pd2(dba)3 (1 mol%) with BrettPhos or RuPhos (2–3 mol%).
  • Base: NaOtBu or K3PO4.
  • Solvent: toluene, dioxane, or CPME. 60–100 °C, 4–16 h. Consider acetal protection of –CHO if using strong base.
• Wittig/HWE on the aldehyde:
  • Base: NaH/KOtBu (for stabilized ylides use weaker base).
  • Solvent: THF or DCM; 0 °C to rt, 1–6 h.
• Reductive amination:
  • Reagents: NaBH3CN or BH(OAc)3; solvent AcOH/MeCN or DCE; rt, 2–6 h.

Expected isolated yields for couplings on aryl iodides are commonly 70–95% in literature, subject to substrate/catalyst choice. Always perform small-scale scouting experiments and monitor aldehyde integrity.

Safety and Handling

Authoritative safety information must be taken from the product SDS. The following highlights are general considerations for aryl iodide/aldehyde/ester building blocks and are NOT item-specific classifications.

• GHS classification, signal word, pictograms, H‑statements: Not specified for this item; refer to SDS.
• Likely hazards (general):
  • Irritation to skin/eyes/respiratory tract is possible with aldehydes and organic iodides.
  • Combustible organic; avoid ignition sources.
  • Aldehydes may undergo autoxidation; trace peroxides are not typical for this class but monitor for degradation byproducts over time.
• Incompatibilities (general): Strong bases and acids (risk of ester hydrolysis/aldol-like side reactions), strong oxidants (oxidation of –CHO to acid), strong nucleophiles (addition to carbonyl), and halogenophiles that could displace iodide under coupling conditions.
• PPE: lab coat, nitrile gloves, splash goggles; use in a fume hood. For weigh-outs, minimize dust/aerosol formation.
• First aid (general guidance; defer to SDS):
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: rinse with water for ≥15 minutes; remove contaminated clothing; obtain medical advice as needed.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
• Fire-fighting (general): Use CO2, dry chemical, or foam. Combustion may produce CO/CO2, hydrogen iodide, and irritating vapors.
• Spill response: Absorb with inert material, avoid environmental release, collect for disposal per local regulations.

Always consult the SDS for definitive hazard and handling instructions.

Solvent Selection

This material is a multifunctional aromatic building block (aryl iodide, aldehyde, ether, and ester). While not itself a solvent, its solubility and stability in chosen media are key to successful use.

General solubility/miscibility expectations (literature context; not item specs):

• Good: DCM, CHCl3, EtOAc, acetone, THF, 2‑MeTHF, acetonitrile, DMF/DMAc, dioxane, toluene (warming may help).
• Poor: water and very protic media; prolonged exposure to strong base/acid risks ester hydrolysis and aldehyde degradation.

Selecting solvents by application:

• Suzuki–Miyaura cross-coupling: dioxane/H2O, 2‑MeTHF/H2O, toluene/H2O, or EtOH/H2O with a suitable base (K2CO3, K3PO4, Cs2CO3). A co-solvent system can aid inorganic base solubility.
• Sonogashira: THF, Et3N, iPr2NH, or acetonitrile; copper-free protocols in polar aprotic solvents mitigate Glaser coupling.
• Buchwald–Hartwig amination: toluene, dioxane, CPME, or tert-amyl alcohol depending on ligand/base.
• Aldehyde derivatizations (Wittig, oxime formation, reductive amination): non-protic, moderately polar media (THF, DCM, MeCN) to balance carbonyl reactivity and solubility.

Comparison notes:

• 2‑MeTHF and CPME can replace THF/Et2O for greener profiles and improved phase behavior.
• For aqueous co-solvent systems, maintain pH near neutral to minimize ester hydrolysis.

Always test small-scale solubility and stability before scale-up; dry, oxygen-lean conditions help preserve the aldehyde.

Storage and Reconstitution

• Storage conditions (item-specific): Room temperature (per Product Data). Store tightly capped in a dry place.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

General handling and stability guidance for this class of compound:

• Protect from moisture and prolonged air exposure to limit aldehyde oxidation (to the corresponding acid) and ester hydrolysis. Where possible, store under inert atmosphere (argon/nitrogen) and in amber containers to reduce photodegradation.
• If long-term storage is anticipated, consider refrigeration (2–8 °C) as a precaution—ensure this does not contradict your institution’s interpretation of the item-specific guidance. Allow container to equilibrate to room temperature before opening to prevent condensation.
• Avoid repeated freeze–thaw. If solution stocks are prepared (e.g., in dry DCM, THF, or MeCN), store at low temperature, under inert gas, and use within a few days; check for precipitation or discoloration before use.
• Reconstitution: Not applicable for solids/liquids supplied neat. For preparing working solutions, dissolve in an anhydrous, oxygen-lean solvent compatible with the intended reaction. Filter if particulate is observed.

Always refer to the product’s CoA and SDS for definitive storage, stability, and handling instructions.

Research Use Note: For research use only.

Structure and Identity

Ethyl (2-ethoxy-4-formyl-6-iodophenoxy)acetate is an aryl iodide/aryl ether building block bearing an aldehyde and an ethyl phenoxyacetate moiety—useful for cross-coupling and carbonyl elaborations.

• Item-specific identifiers (Product Data):
  • CAS: 428837-88-1
  • CID: 1341534
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data lists: "69404", which is not a standard InChIKey format.)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Computed/structure-inferred (non-specification; for literature context):
  • Structural features: 1,3,5-trisubstituted phenyl core with substituents at C1 (phenoxy-CH2CO2Et), C2 (ethoxy), C4 (formyl), and C6 (iodo). The ring is phenoxy-linked to an acetate ethyl ester via –O–CH2–CO2Et; an –OEt at the ortho position; –CHO para to the phenoxy junction; and iodine ortho to the phenoxy junction on the opposite side.
  • Functional groups: aryl iodide (C–I), aromatic ether (Ar–O–), aliphatic ether (–OEt), aldehyde (–CHO), and ethyl ester (–CO2Et).
  • Stereochemistry: none (achiral, no stereocenters).
  • Tentative 2D description: a substituted phenyl ring bearing (i) an oxygen linking to –CH2–CO2–CH2CH3, (ii) –O–CH2CH3 adjacent to that linkage, (iii) –CHO para to the linkage, and (iv) –I at the remaining ortho position.
• Molecular formula and MW: Not specified for this item; refer to CoA/Spec Sheet. (For literature context only, a formula of approximately C13H15IO5 is consistent with the name; corresponding formula mass ~378 g/mol, computed from the inferred structure.)

Note: Computed identifiers are provided for general context only and are not item specifications.

Synthetic Utility

Key reactivity vectors:

• C–I bond: highly reactive in oxidative addition; ideal for Pd-catalyzed cross-couplings (Suzuki, Sonogashira, Heck, Buchwald–Hartwig) and Ni-catalyzed transformations. Carbonylative couplings can introduce acyl groups under CO.
• Aldehyde (–CHO): platform for imine/oxime/hydrazone formation, reductive amination, nucleophilic additions, and Wittig/Horner–Wadsworth–Emmons olefinations. Protect as an acetal if coupling conditions are forcing.
• Phenoxyacetate: ester handle for hydrolysis (to acid), transesterification, or further derivatization; the benzylic –CH2– adjacent to oxygen can participate in alkylation under phase-transfer conditions (after deprotection to phenoxyacetic acid derivatives).
• Alkoxy activation: ortho ethoxy and phenoxy substituents increase ring electron density, often accelerating oxidative addition and enabling milder coupling conditions.

Retrosynthetic value:

• Serves as a linchpin intermediate where diversification at the aryl iodide precedes chemoselective elaboration of the aldehyde and ester.
• Orthogonal chemistries allow sequence planning: (1) Cross-coupling at C–I; (2) Carbonyl transformation; (3) Ester manipulation.

Practical considerations:

• Choose bases that spare the ester (K2CO3, Cs2CO3) and avoid strong nucleophiles that attack –CHO.
• If using organometallic additions to the aldehyde, protect the ester or employ milder reagents (e.g., organozincs, cuprates).
• Monitor reactions by LC–MS/UPLC with UV at 254–280 nm; iodinated aromatics show characteristic isotopic/fragment patterns aiding tracking.

Target Specificity

Not applicable. This product is a small-molecule building block and does not possess biological target specificity, antigen binding, clone information, or isotype characteristics. No antibody or biomolecular targeting attributes are associated with this item.