4-[(2-Ethoxy-4-formyl-6-iodophenoxy)methyl]benzoic acid , CAS No.428492-89-1

CAS: 428492-89-1 Cat. No.: E949045 Formula: C₁₇H₁₅IO₅ Peso molecolare: 426.200

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

Sorrisi canonici

CCOC1=C(C(=CC(=C1)C=O)I)OCC2=CC=C(C=C2)C(=O)O

IUPAC Name

4-[(2-ethoxy-4-formyl-6-iodophenoxy)methyl]benzoic acid

InChIKey

KUDQZDUAWTWSQI-UHFFFAOYSA-N

INCHI

1S/C17H15IO5/c1-2-22-15-8-12(9-19)7-14(18)16(15)23-10-11-3-5-13(6-4-11)17(20)21/h3-9H,2,10H2,1H3,(H,20,21)

Peso molecolare

426.200

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzoic acids
• Alternative Parents: Phenoxy compounds Phenol ethers Benzoyl derivatives Benzaldehydes Iodobenzenes Alkyl aryl ethers Aryl iodides Monocarboxylic acids and derivatives Carboxylic acids Organoiodides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzoic acid - Phenoxy compound - Benzaldehyde - Benzoyl - Phenol ether - Alkyl aryl ether - Halobenzene - Iodobenzene - Aryl-aldehyde - Aryl iodide - Aryl halide - Monocarboxylic acid or derivatives - Ether - Carboxylic acid - Carboxylic acid derivative - Aldehyde - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organohalogen compound - Organoiodide - Organooxygen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as benzoic acids. These are organic Compounds containing a benzene ring which bears at least one carboxyl group.
• 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: 426.200 g/mol
• XLogP3: 3.400
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 425.996 Da
• Monoisotopic Mass: 425.996 Da
• Topological Polar Surface Area: 72.800 Ų
• Heavy Atom Count: 23
• Formal Charge: 0
• Complexity: 394.000
• 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 standardized bioassay or immunoassay protocols apply to this small-molecule building block. For synthetic applications, refer to the Reaction Conditions and Synthetic Utility sections for general literature guidance and optimize parameters for your specific transformation.

Biological Roles

This compound is a synthetic small-molecule building block with no established endogenous biological role.

• General considerations (informational)
  • Functional motifs (aryl iodide, aldehyde, carboxylic acid) are common in probes and ligands but this specific structure is not known as a natural metabolite.
  • The benzoic acid can be converted to salts for formulation in biochemical assays; the aldehyde may react with biomolecules containing primary amines (Schiff base formation), typically requiring control via protection or reductive amination in designed bioconjugation workflows.
  • Any use in biological experiments should consider aldehyde reactivity toward nucleophiles and potential iodine-related photoreactivity; appropriate controls and quenching steps are recommended.

Note: For research use only. No medical or clinical claims are made or implied.

Buffer Applications

Not a conventional buffering reagent. As a benzoic acid derivative, it can form salts, but it is not typically used to prepare laboratory buffer systems. For aqueous work, dissolve in organic co-solvent or convert to its carboxylate salt transiently for extractions; otherwise refer to sections on Solvent Selection and Synthetic Utility.

Green Alternatives

• Solvent and reagent considerations (general guidance)

  • Replace chlorinated solvents (CH2Cl2, CHCl3) with greener options where possible: ethyl acetate, 2-MeTHF, cyclopentyl methyl ether (CPME), or toluene, considering solubility.
  • For Suzuki couplings, use aqueous ethanol or 2-MeTHF/water with base (K2CO3/K3PO4) and Pd catalysts supported on benign ligands; microwaves can shorten reaction times.
  • For amide couplings, consider greener coupling technologies (e.g., CDI or DMTMM) and minimize use of uronium salts; perform solvent swaps to EtOAc/MeCN when feasible.
  • Oxidations: Prefer TEMPO/bleach (Pinnick) over chromium(VI); for alcohol reductions, employ catalytic hydrogenation or transfer hydrogenation (HCO2H/Et3N) when compatible.

• Trade-offs

  • 2-MeTHF/CPME offer improved safety and lower environmental impact but may reduce solubility versus DMF/DMSO; reaction rates/catalyst solubility may need optimization.
  • Aqueous systems can hydrolyze sensitive aldehydes; protect as acetals before extended aqueous processing.

• Quick comparison (illustrative)

  • DMF → 2-MeTHF or EtOAc (workup-friendly) for coupling steps if solubility allows.
  • CH2Cl2 → EtOAc or toluene in acylations/oxidations with careful temperature control.

Pharmaceutical Uses

This product is intended for research use only and is not an excipient or drug substance.

• Formulation context (general)
  • As a synthetic intermediate, it may be employed in discovery-scale library synthesis and conjugation strategies (e.g., amide formation via the benzoic acid, or derivatization of the aldehyde) to generate candidate molecules for screening.
  • No pharmacopeial monograph is known for this specific structure.
  • If handling on process scale, typical considerations include polymorph/solvate screening, salt selection via the benzoic acid, and photostability of aryl iodides—all project-specific and beyond this listing.

No therapeutic, diagnostic, or clinical claims are made or implied.

Physical Properties

• Item-specific (from Product Data)

  • 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/computed (informational; not product specifications)

  • Formula and FW rationale (non-spec): Using the name-based composition, an inferred formula is C17H15IO5 with an estimated FW ~426.21 g/mol.
  • Physical state: Typically an organic solid for molecules of this size and functionality (literature expectation for analogous aryl-iodo benzoic acid ethers).
  • Solubility profile (qualitative):
    • Low solubility in water at neutral pH; improved solubility in basic aqueous media via carboxylate salt formation (general carboxylic acid behavior).
    • Expected good solubility in polar aprotic organic solvents (DMSO, DMF, NMP, acetone, acetonitrile) and moderate solubility in chlorinated solvents and esters; variable in alcohols depending on temperature.
  • Acid–base: One carboxylic acid (pKa typically ~4–5 for benzoic acids; literature generality, not specific to this compound).
  • Partitioning: Presence of aryl iodide and multiple aromatics suggests moderate-to-high lipophilicity, partially offset by two ether oxygens and a carboxyl group (qualitative).

Note: Exact MP/BP/density/refractive index/logP are not available here; consult primary literature or the CoA/SDS for definitive values.

Quality and Grades

• Item-specific

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

• Guidance on interpreting grade (general)

  • For complex building blocks bearing multiple reactive handles (aryl iodide, aldehyde, carboxylic acid), typical research grades emphasize assay purity (HPLC/GC/NMR) and control of related impurities (e.g., deiodinated byproducts, oxidized aldehydes to acids, hydrolysis of ether).
  • If an HPLC grade is offered for similar aromatic compounds, that often entails low UV background and tight impurity profiles suitable for photochemical or analytical work.
  • Stabilizers: None specified for this item; if included for aldehyde stability (e.g., trace acid), this would be disclosed on the CoA. Absence of disclosure implies none added, but verify the CoA for certainty.
  • Batch documentation: Request CoA for assay, residual solvents, and spectral identity (1H/13C NMR, IR showing aldehyde C=O ~1700–1740 cm−1 and acid C=O ~1680–1720 cm−1; general ranges, not item-specific specifications).

Reaction and Applications

This multifunctional aryl building block integrates three orthogonal handles—aryl iodide, aldehyde, and carboxylic acid—enabling convergent synthesis.

• Aryl iodide chemistry

  • Cross-coupling: Highly reactive in Pd- or Ni-catalyzed Suzuki–Miyaura (to install aryl/alkenyl), Sonogashira (alkynyl), Buchwald–Hartwig (C–N), Heck (vinyl) couplings. The iodide generally couples under milder conditions than Br/Cl.
  • Metal–halogen exchange: i-PrMgCl·LiCl (Turbo Grignard) or n-BuLi at low temperature to access arylmagnesium/aryllithium, enabling formylation, borylation, or homologations; protect aldehyde when incompatible.

• Aldehyde transformations

  • Reductive amination (NaBH3CN, BH3·THF, or transfer hydrogenation catalysts) to introduce benzylic amines on ring B.
  • Olefination: Wittig/HWE to install alkenes; stereocontrol via stabilized ylides.
  • Oxidation/reduction: Oxidize to the corresponding acid (e.g., Pinnick, TEMPO) or reduce to alcohol (NaBH4, DIBAL-H) as needed.

• Carboxylic acid elaboration

  • Amide formation (EDC/HATU/HBTU with DIPEA or collidine) to access peptide-like conjugates.
  • Esterification (DCC/DMAP or Fischer) to tune solubility/handling; can be used as a protecting/activation handle.

• Orthogonal strategy

  • Sequence planning: Couple at C–I first (fastest), then manipulate the aldehyde (sensitive), and finally derivatize the acid. Alternatively, protect the aldehyde (acetal) when performing strong-base operations or metalations.

• Applications (research)

  • Scaffold for SAR libraries in medicinal chemistry, late-stage diversification via C–I coupling, and preparation of conjugates through the benzoic acid terminus. For research use only.

Reaction Conditions

• Cross-coupling at aryl iodide (general literature guidance)

  • Suzuki–Miyaura: Pd(PPh3)4 (1–3 mol%), K2CO3 or K3PO4 (2–3 equiv), dioxane/H2O or DMF/H2O, 40–80 °C, 2–12 h. Aryl/alkenyl boronic acids/esters as partners.
  • Sonogashira: PdCl2(PPh3)2 (1–3 mol%) + CuI (5–10 mol%), Et3N or i-Pr2NH, THF/MeCN/DMF, 25–60 °C, 1–8 h; use copper-free conditions to minimize Glaser coupling if needed.
  • Buchwald–Hartwig amination: Pd2(dba)3 (1–2 mol%) + dialkylbiaryl phosphine ligand, NaOtBu or Cs2CO3, toluene/DME/1,4-dioxane, 60–100 °C, 6–16 h.

• Aldehyde transformations

  • Reductive amination: Amine (1.1–1.5 equiv), AcOH (catalytic), NaBH3CN or NaBH(OAc)3, MeOH/THF/DMF, 0–25 °C, 2–16 h; maintain pH ~5–6.
  • Wittig/HWE: Dry THF/CH2Cl2, 0–25 °C, 1–6 h; use stabilized ylides for E-selectivity.
  • Reduction to alcohol: NaBH4 (1.5–2 equiv), MeOH/EtOH, 0–25 °C; or DIBAL-H in toluene at −78 to 0 °C.

• Carboxyl activation/coupling

  • Amide formation: HATU (1.1 equiv), DIPEA (2–3 equiv), DMF/MeCN, 0–25 °C, 1–4 h; or EDCI/HOBt variants. Monitor for aldehyde participation—protect as needed.

• Protection strategies

  • Aldehyde → acetal (ethylene glycol, p-TsOH, Dean–Stark in toluene) prior to strong-base or metalation chemistry.

All conditions are literature-general and must be optimized for scale, concentration, and substrate; they are not product specifications.

Safety and Handling

• Item-specific Hazard Information

  • Signal word: Not specified for this item; refer to SDS.
  • H-statements: Not specified for this item; refer to SDS.
  • GHS classification: Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.

• General laboratory safety guidance (informational; defer to SDS)

  • Handle in a chemical fume hood; avoid inhalation of dust and contact with skin/eyes.
  • Recommended PPE: lab coat, nitrile gloves, splash goggles; consider double-gloving for extended handling in polar aprotic solvents.
  • Incompatibilities (general): Strong oxidizers, strong bases/acids (can cause decomposition or salt formation), and strong nucleophiles under forcing conditions that may attack the aldehyde or aryl iodide. Avoid prolonged exposure to moisture if purity of the aldehyde function is critical.
  • First aid (overview):
    • Skin/eye contact: Rinse with plenty of water for ≥15 min; remove contaminated clothing; seek medical attention.
    • Ingestion/inhalation: Move to fresh air; rinse mouth; seek medical advice.
  • Fire response: Use CO2, dry chemical, or foam; combustion may produce CO/CO2 and hydrogen iodide/iodine vapors.
  • Stability notes: Aldehydes can undergo oxidation; protect from prolonged air exposure and store tightly closed. The aryl iodide is photosensitive in some cases; store in amber container if possible.

Always consult the product’s SDS for authoritative hazard classification and emergency procedures.

Solvent Selection

• Polarity and solubility considerations (general guidance)

  • The molecule contains both polar (carboxyl, aldehyde, ethers) and hydrophobic (diaryl, iodoaryl) features.
  • Good choices for dissolution and reactions: DMSO, DMF, NMP, acetone, acetonitrile, ethyl acetate, dichloromethane, chloroform; solubility in alcohols may be moderate and temperature dependent.
  • Water: Poorly soluble at neutral pH; forms soluble salts in basic aqueous media (e.g., NaHCO3/Na2CO3) if the carboxyl group is deprotonated.

• Selection tips by use case

  • Cross-coupling at C–I: Polar aprotics (DMF/DMAc/NMP) or dioxane mixtures with water or alcohols support catalyst solubility and base dissolution.
  • Aldehyde transformations (e.g., reductive amination, Wittig, aldol): Choose dry, aprotic media (THF, toluene, CH2Cl2, MeCN) per reagent compatibility; exclude water.
  • Carboxylate couplings (amide/ester formation): DMF/MeCN/CH2Cl2 with standard coupling reagents (EDC/HATU/DIC) and bases (DIPEA).

• Brief comparison (general)

  • DMF vs DMSO: DMF typically easier to remove and less nucleophilic; DMSO offers broader solubility but can complicate workup.
  • CH2Cl2 vs EtOAc: CH2Cl2 enhances solubility and reaction rate for many electrophilic steps; EtOAc is greener and preferable for extractions and crystallizations when feasible.

Storage and Reconstitution

• Item-specific storage

  • Storage conditions: Room temperature (from Product Data). Store in a tightly closed container in a dry, well-ventilated place.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• General guidance (informational)

  • Protect from prolonged exposure to air and light to minimize aldehyde oxidation and potential iodine-related photodegradation; amber glass is recommended for long-term storage.
  • If long-term storage is planned, consider inert atmosphere (argon/nitrogen) and desiccation.

• Reconstitution/solubility tips

  • Dissolve in dry organic solvents such as DMSO, DMF, acetonitrile, THF, CH2Cl2, or ethyl acetate. Warm gently (≤40 °C) and sonicate if needed.
  • For aqueous work, prepare stock in DMSO or convert to a carboxylate salt transiently for compatibility; avoid basic aqueous media if the aldehyde must remain intact.
  • Prepare working solutions fresh when possible to limit aldehyde oxidation; store solutions at 2–8 °C under inert gas and use within a few days.

• Freeze–thaw

  • Not typically necessary for solids. If storing solutions, minimize freeze–thaw cycles and aliquot as appropriate.

Refer to the product CoA/SDS for any additional, batch-specific instructions.

Structure and Identity

An iodine-containing, bifunctional aryl ether–benzoic acid bearing an aldehyde and an ethoxy substituent; a versatile building block for cross-coupling and aldehyde chemistry.

• Item-specific (from Product Data)

  • Product name: 4-[(2-Ethoxy-4-formyl-6-iodophenoxy)methyl]benzoic acid
  • CAS: 428492-89-1
  • CID: 1339299
  • InChIKey: 189730 (as provided)
  • 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.

• Literature/computed (informational; not product specifications)

  • Likely molecular formula: C17H15IO5 (rationalized from the IUPAC name)
  • Approx. formula weight: ~426.21 g/mol (calculated from C17H15IO5)

• Structural features (descriptive)

  • Two aromatic rings connected via a benzylic –CH2–O– (phenoxy) ether linkage.
  • Ring B substituents: ortho ethoxy (–OCH2CH3), para formyl (–CHO), and ortho iodine (–I) relative to the phenoxy oxygen.
  • Ring A: para-substituted benzoic acid (–CO2H) with the –CH2–O– linkage at the para position.
  • Functional group array: aryl iodide (strong C–I activation handle), aldehyde (electrophilic carbonyl), ether, benzylic methylene, and carboxylic acid (acidic handle for salt formation/coupling).
  • 2D description: A p-substituted benzoic acid ring tethered through –CH2–O– to a second anisole-like ring carrying I (o-), CHO (p-), and –OEt (o-) substituents.

Synthetic Utility

Strategic value arises from three orthogonal functional handles:

• Aryl iodide (C–I)

  • Most reactive aryl halide in oxidative addition: enables mild Pd/Ni-catalyzed couplings (Suzuki, Sonogashira, Heck, Buchwald–Hartwig). Facilitates late-stage diversification and radioiodination (methodology perspective; not a product claim).
  • Halogen–metal exchange allows rapid access to arylmetals for formylation, borylation, and homologation; protect the aldehyde as an acetal for strongly basic steps.

• Aldehyde (–CHO)

  • Entry to alcohols (NaBH4/DIBAL-H), imines/reductive amines (NaBH3CN/BH3), and olefins (Wittig/HWE). Serves as a convergence point for fragment assembly.

• Carboxylic acid (–CO2H)

  • Robust coupling to amides/esters via EDCI/HATU/DIC and catalytic DMAP; enables attachment to linkers, polymers, or surfaces.

• Ether/methylene spacer

  • The –CH2–O– linkage provides conformational separation between rings, useful for tuning electronics and 3D shape in SAR campaigns. The o-ethoxy group adjusts electron density, assisting in regioselective metalation adjacent to iodine in some protocols (directed ortho-metalation concepts, literature-dependent).

• Retrosynthetic utility

  • Disconnection at C–I enables modular aryl install; aldehyde traced back to Vilsmeier or formylation steps; benzoic acid accessible via oxidation or coupling from corresponding esters. This makes the scaffold a practical node for branching synthetic routes.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, or biological with defined target specificity. No antigen/epitope or species reactivity information applies.