2,3-Dimethoxy-5-iodobenzaldehyde , CAS No.7396-66-9

CAS: 7396-66-9 Cat. No.: D1262067 PubChem CID: 885386

Storage

Room temperature

Shipped In

Normal

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Spedito in

Normal

Nomi e identificatori

• Sorrisi canonici: COC1=CC(=CC(=C1OC)C=O)I
• IUPAC Name: 5-iodo-2,3-dimethoxybenzaldehyde
• InChIKey: UURAEBUTDJEOBA-UHFFFAOYSA-N
• INCHI: 1S/C9H9IO3/c1-12-8-4-7(10)3-6(5-11)9(8)13-2/h3-5H,1-2H3
• Isomeri SMILES: COC1=CC(=CC(=C1OC)C=O)I
• PubChem CID: 885386

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Methoxybenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Dimethoxybenzenes
• Alternative Parents: Phenoxy compounds Benzoyl derivatives Benzaldehydes Anisoles Iodobenzenes Alkyl aryl ethers Aryl iodides Organoiodides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: O-dimethoxybenzene - Dimethoxybenzene - Phenoxy compound - Anisole - Benzaldehyde - Phenol ether - Benzoyl - Alkyl aryl ether - Aryl-aldehyde - Halobenzene - Iodobenzene - Aryl halide - Aryl iodide - Ether - Organooxygen compound - Hydrocarbon derivative - Organic oxygen compound - Aldehyde - Organic oxide - Organoiodide - Organohalogen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as dimethoxybenzenes. These are organic aromatic compounds containing a monocyclic benzene moiety carrying exactly two methoxy groups.
• 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: 292.070 g/mol
• XLogP3: 2.000
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 291.96 Da
• Monoisotopic Mass: 291.96 Da
• Topological Polar Surface Area: 35.500 Ų
• Heavy Atom Count: 13
• 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 biological assay protocols (WB, IHC, IF, FC) or analytical methods are specified for this item. As a synthetic intermediate, application protocols are reaction-dependent.

General lab-use protocols (guidance only):

• Stock solution preparation: Dissolve the solid in dry CH2Cl2, THF, 2-MeTHF, DMF, DMSO, or EtOAc to a convenient concentration (e.g., 0.1–1.0 M for coupling screens). Filter if particulates are present.
• Inert handling for reactions: Dry the solid under vacuum if needed; charge under nitrogen/argon. Use oven-dried glassware for moisture-sensitive steps (e.g., metalation, Wittig).
• TLC/HPLC monitoring: Use hexanes/EtOAc or toluene/EtOAc for TLC; visualize under UV 254 nm. For HPLC, develop a gradient in MeCN/H2O with 0.1% formic acid or buffer; monitor 254–280 nm.
• Protection strategy: If employing strong bases or nucleophiles, protect the aldehyde as an acetal; remove protection under mild acidic conditions after the transformation.

For detailed, step-specific procedures (catalyst loadings, temperatures, workups), refer to the Reaction Conditions and Synthetic Utility sections and consult primary literature.

Biological Roles

This product is a synthetic small-molecule building block and is not known to have intrinsic biological roles. The following notes are general, literature-based context and not product claims:

• Functional motif: Aromatic aldehydes and methoxy-substituted arenes are common motifs in natural products and ligands; however, 2,3-dimethoxy-5-iodobenzaldehyde is an artificial, halogenated derivative used primarily for chemical synthesis.
• Use in probe/ligand development: The aryl iodide allows modular late-stage introduction of pharmacophores via Suzuki/Sonogashira/amination, enabling SAR studies; the aldehyde can be elaborated to imines, oximes, hydrazones, or reduced derivatives for bioconjugation models.
• Reactivity considerations: Aldehydes can react with nucleophilic biomolecules (amines, thiols) under forcing conditions; in typical lab handling, this compound is used in organic synthesis, not in biological systems directly.
• ADME relevance (general): Electron-rich anisaldehyde analogs tend to be lipophilic and aromatic, but the presence of iodine significantly increases polarizability and mass; any biological data would be context- and derivative-specific.

Research Use Note: For research use only. No medical, diagnostic, or therapeutic uses are implied or permitted. If biological testing is intended on derivatives synthesized from this building block, ensure appropriate safety and ethical approvals.

Buffer Applications

Not typically applicable. 2,3-Dimethoxy-5-iodobenzaldehyde is a hydrophobic organic building block, not a buffering agent or bioreagent for aqueous systems.

Practical guidance:

• If used in biochemical assays as a synthetic intermediate or small-molecule control, stock solutions are usually prepared in organic cosolvents (e.g., DMSO, DMF, ethanol) and then diluted into buffered media immediately before use, keeping final organic content low to avoid denaturation effects.
• Buffer selection (if relevant to downstream testing of derivatives) should be driven by the biology (e.g., phosphate, HEPES, Tris), not by this compound’s properties.

Green Alternatives

While the compound itself is a specialty building block, greener choices can be considered in its use and in route design.

Greener strategy options (literature/practice):

• Replace solvent systems with greener media:
  • Swap 1,4-dioxane or DMF with 2-MeTHF, CPME, toluene, EtOAc, or water–organic biphasic systems for Suzuki couplings when compatible with catalyst/base.
  • For Sonogashira/Heck, consider propylene carbonate or bio-derived ethers as alternatives to amide solvents.
• Catalyst economy:
  • Employ ligand-efficient Pd systems (e.g., XPhos/SPhos) at ppm–low mol% loadings, or Ni catalysis for certain couplings to reduce reliance on palladium.
  • Use aqueous micellar catalysis (e.g., surfactant media) to minimize organic solvent volumes.
• Halide choice/trade-offs:
  • Aryl iodides enable mild, high-yield couplings but carry higher halogen mass and supply impacts. Where feasible, design routes from aryl bromides/chlorides and employ enhanced catalysts—balanced against energy/solvent costs from harsher conditions.
• Protection minimization:
  • Run aldehyde-tolerant couplings to avoid acetalization/deprotection cycles, cutting steps, reagents, and waste.

Comparison snapshot (general):

• Aryl iodide + Pd in dioxane (benchmark): fast, mild, high yield; less green solvent.
• Aryl iodide + Pd in 2-MeTHF/water: comparable yield; improved solvent profile.
• Aryl bromide/chloride + advanced ligands in green solvents: greener halide but may need higher temperature/time.

Always assess solvent/catalyst changes with LCA thinking: energy input, E-factor, recyclability, and safety.

Pharmaceutical Uses

No excipient or pharmacopeial role is specified for this item. It is generally employed as a synthetic intermediate in medicinal chemistry and process development.

Context (general, non-clinical):

• Intermediate for API candidate synthesis: The aryl iodide enables rapid diversification via cross-coupling to generate analog libraries. The aldehyde provides a chemoselective handle for formation of oximes, hydrazones, imines, or reduction to benzyl alcohols prior to further derivatization.
• Radiolabeling pathways: Although this is a stable iodine (127I) compound, the aryl iodide motif is structurally analogous to handles used in radioiodination chemistry; however, this specific product is not a radiochemical and is for standard laboratory synthesis.
• Impurity standards: Methoxy-substituted benzaldehydes and their halogenated congeners can serve as reference compounds for method development (HPLC/GC) in stability-indicating assays of related chemotypes.

Regulatory note:

• No pharmacopeial monograph is implied. For GMP or toxicology-enabling studies, source lot-specific CoA data (assay, residual metals/solvents, identity) and qualify according to internal quality systems.

Research Use Note: For research use only. Not for human or veterinary drug, diagnostic, or household use.

Physical Properties

Item-specific physicochemical specifications (bp, mp, density, UV cutoff, metals, residual solvents) are Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed information (for general reference only; not product specs):

• Aggregate state: Typically a crystalline solid at ambient temperature (literature observation for analogs in this class)
• Molecular weight: ~292.07 g/mol (computed from C9H9IO3)
• Polarity/functional groups: Aromatic aldehyde; aryl iodide; two methoxy donors (increases electron density and organic solvent solubility)
• Solubility profile (qualitative, literature):
  • Good solubility in chlorinated solvents (e.g., CH2Cl2, CHCl3), ethers (THF, 2-MeTHF), esters (EtOAc), and polar aprotic media (DMF, DMSO)
  • Low solubility in water
• Partitioning: Expected to be lipophilic due to aryl iodide and methoxy groups (logP > 2 qualitatively; consult experimental data for exact values)
• Spectral characteristics (general):
  • 1H NMR: aldehydic proton typically ~9.7–10.2 ppm; aromatic protons 6.5–8.0 ppm; methoxy singlets ~3.6–3.9 ppm (solvent- and substitution-dependent; literature)
  • IR: strong C=O stretch ~1690–1725 cm−1; C–O stretches ~1240–1280 cm−1; aryl C–I ~500–650 cm−1 (literature ranges)

Practical notes:

• The aldehyde functionality can slowly oxidize to the corresponding acid; minimize prolonged exposure to air and light during analytical measurements.
• For method development (HPLC/GC), determine sample solubility and UV response empirically; no UV cutoff is specified for this item.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet for assay, impurity profile, and analytical methods.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

Context and guidance (general):

• For cross-coupling and olefination chemistry, trace metal content, halide purity (iodide vs. dehalogenated byproducts), and carbonyl integrity (acid/over-oxidation content) can influence yields and selectivity.
• If using in catalytic reactions (Pd, Ni, Cu), consider grades that minimize metal contaminants and halide impurities which may poison catalysts or alter kinetics.
• Typical characterization set for this class of building blocks includes: 1H/13C NMR, HRMS or accurate-mass LC–MS, HPLC purity, and residual solvent analysis. For aldehydes, monitoring acid content by titration or LC is useful.
• Stabilizers: None specified for this item. Aldehydes are sometimes stabilized by minimal inhibitor or by storage under inert atmosphere; verify on the CoA if any stabilizer is present.
• UV/fluorescence background: If planning photochemical or fluorescence studies, request UV-Vis trace or HPLC DAD data from the CoA to ensure compatibility.

Recommendation:

• Match grade to application: synthetic transformations generally tolerate standard research-grade materials, while materials used for method validation or impurity standards may require higher assay and tighter controls (e.g., ≥98–99% by HPLC). Always verify lot-specific data on the CoA.

Reaction and Applications

2,3-Dimethoxy-5-iodobenzaldehyde integrates two powerful handles—an activated aryl iodide and an aldehyde—enabling sequential or orthogonal transformations.

Key application families (literature/general):

• Cross-coupling at C–I:
  • Suzuki–Miyaura arylation/alkenylation to access 5-substituted 2,3-dimethoxybenzaldehydes. Aldehyde typically tolerated; protect as acetal if base-sensitive downstream.
  • Sonogashira coupling with terminal alkynes to give aryl–alkynes; enables subsequent hydroarylation or cyclizations.
  • Buchwald–Hartwig amination to form anilines at the 5-position.
  • Heck alkenylation for styryl aldehydes; subsequent aldehyde chemistry expands diversity.
• Aldehyde transformations:
  • Wittig/Horner–Wadsworth–Emmons olefinations to styryl iodides (useful convergence point for further cross-coupling via C–I).
  • Knoevenagel condensations with active methylenes to yield arylidene derivatives; electron-rich ring can modulate reactivity.
  • Reductions (NaBH4/CuCl2 variants to alcohols; or chemoselective reductions while retaining C–I).
  • Acetalization for protection during aggressive cross-coupling or lithiation conditions.
• Halogen–metal exchange (I/Li) to 5-lithio intermediate at −78 °C followed by electrophile trapping (requires protection of the aldehyde to avoid addition).
• Electrophilic aromatic substitutions (limited by substitution pattern): methoxy groups are activating and ortho/para-directing; however, the ring is densely substituted, steering chemistry to prefunctionalized positions.

Use cases:

• Assembly of substituted benzaldehydes as fragrance precursors, ligand scaffolds, or advanced intermediates.
• Late-stage diversification: C–I handle enables rapid SAR exploration while preserving/derivatizing the aldehyde.

Reaction Conditions

General literature guidance (illustrative ranges; optimize per substrate and setup):

• Suzuki–Miyaura coupling (Ar–I):
  • Catalyst: Pd(PPh3)4 (0.5–2 mol%) or Pd-precatalyst with dialkylbiarylphosphine (XPhos/SPhos, 0.1–1 mol%)
  • Base: K2CO3, K3PO4, Cs2CO3 (2–3 equiv)
  • Solvent: 1,4-dioxane/H2O, THF/H2O, toluene/H2O, or 2-MeTHF/H2O
  • Temp/time: 25–80 °C, 1–12 h; aryl iodides often react at the low end
• Sonogashira coupling:
  • Catalyst/co-catalyst: Pd(PPh3)2Cl2 (1–2 mol%), CuI (5–10 mol%) or copper-free systems with bulky ligands
  • Base/solvent: Et3N, iPr2NH, or amine in THF, DMF, or MeCN
  • Temp: rt–60 °C; protect aldehyde if enamine formation is problematic
• Heck reaction:
  • Catalyst: Pd(OAc)2 + PPh3 or modern ligands
  • Base: Et3N, DIPEA, or carbonate
  • Solvent: DMF, NMP, toluene
  • Temp: 80–120 °C
• Buchwald–Hartwig amination:
  • Catalyst: Pd2(dba)3 or Pd-precatalysts with BrettPhos/XPhos; NaOtBu or Cs2CO3 as base; toluene/dioxane
  • Temp: 60–100 °C
• Wittig/Horner olefination (aldehyde handle):
  • Base: NaH, KH, t-BuOK or DBU for stabilized systems
  • Solvent: THF, toluene, CH2Cl2
  • Temp: −78 °C to rt; E/Z selectivity depends on ylide/phosphonate type
• I/Li exchange and electrophile trapping:
  • Base: n-BuLi or s-BuLi (1.0–1.2 equiv)
  • Solvent: anhydrous THF or Et2O; Temp: −78 to −40 °C; protect aldehyde as acetal to avoid addition

Workup considerations:

• Quench metal-catalyzed reactions with aqueous NH4Cl or phosphate buffers.
• Scrub residual metals with scavengers; keep pH near neutral to preserve the aldehyde.

These are literature norms; verify on small scale and adjust to your catalyst system and equipment.

Safety and Handling

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

General laboratory safety considerations for iodinated aromatic aldehydes (literature/practice guidance):

• Hazards (general):
  • Aldehydes may be irritating to skin, eyes, and respiratory tract; can cause sensitization in susceptible individuals.
  • Iodinated aromatics may be harmful if swallowed and may pose aquatic toxicity; avoid uncontrolled releases.
• PPE: Wear lab coat, safety glasses or splash goggles, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of dust or vapors.
• Handling: Avoid breathing dust; prevent contact with skin/eyes. Keep containers tightly closed. Use clean, dry tools to dispense.
• Incompatibilities (general): Strong oxidizers (risk of exothermic reaction); strong bases (aldol/self-condensation/polymerization of aldehydes); strong reducing agents; halogen–metal exchange reagents without appropriate controls. Aldehydes can form acetals with alcohols under acidic conditions.
• Peroxide formation: Not typically a concern for this solid; however, ethers used as solvents may form peroxides—verify solvent quality.
• First aid overview (brief; defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; obtain medical advice.
  • Ingestion: Rinse mouth; do not induce vomiting; get medical attention.
• Fire response: Use CO2, dry chemical, or foam. Combustion may produce CO/CO2 and hydrogen iodide/iodine vapors.

Solvent Selection

This product is a solid building block, not a solvent. Selection here refers to choosing solvents for its dissolution, reactions, and purification.

• Polarity/behavior: Aromatic aldehyde with aryl iodide and two methoxy groups—moderately lipophilic yet polarizable. Dissolves well in common organic solvents.
• Recommended dissolution solvents (literature/practice):
  • Chlorinated: dichloromethane (DCM), chloroform
  • Ethers: THF, 2-MeTHF, MTBE (moderate), CPME
  • Esters/ketones: ethyl acetate, acetone, MEK
  • Polar aprotic: acetonitrile, DMF, DMAc, DMSO (for high solubility needs)
  • Alcohols: methanol, ethanol (variable; aldehyde may acetalize under acidic conditions)
• Poor solvents: Water; aliphatic hydrocarbons (hexanes/heptane) typically dissolve only sparingly—use for trituration/crystallization.

Comparison/selection tips:

• For Pd-catalyzed couplings: 1,4-dioxane/water, toluene, THF, or DMF are common; aryl iodides generally react at lower temperatures than bromides/chlorides.
• For Wittig/Horner olefinations: THF, toluene, or CH2Cl2 under anhydrous conditions; base choice governs E/Z outcome.
• For chromatographic purification: Start with hexanes/EtOAc or toluene/EtOAc gradients; the iodide increases retention on silica.
• For recrystallization (if applicable): EtOAc/hexanes or toluene/hexanes mixtures are typical starting points—optimize empirically.

Practical cautions:

• Avoid prolonged exposure to acidic alcoholic media to limit acetal formation.
• Ensure solvents are dry and oxygen-lean for reactions sensitive to aldehyde oxidation or metal-catalyzed processes.

Storage and Reconstitution

• Storage Conditions: Room temperature (as provided in Product Data). Store tightly closed in a dry place.
• Shipped In: Normal (ambient) conditions (as provided in Product Data).
• Reconstitution: Not applicable for a solid. Prepare solutions fresh in suitable dry organic solvents (e.g., CH2Cl2, THF, 2-MeTHF, DMF, DMSO) as required for your application.

Best practices (general):

• Protect from moisture and prolonged light exposure to limit aldehyde oxidation (to carboxylic acid) and potential iodide-related discoloration.
• For long-term storage after opening, consider secondary containment with desiccant and, if feasible, blanket headspace with inert gas (N2/Ar) to minimize oxidative degradation.
• If preparing stock solutions, store in amber vials at 2–8 °C or room temperature depending on solvent stability, and use within days to weeks; check by TLC/HPLC prior to use. Do not freeze glass containers filled with high–freezing point solvents.

Research Use Note: For research use only. Not for human or veterinary use.

Item-specific stability (peroxide levels, acid content, assay over time) is Not specified for this item; refer to CoA/Spec Sheet and SDS for authoritative guidance.

Structure and Identity

A halogenated aromatic aldehyde bearing two methoxy substituents, useful as a bifunctional building block (aryl iodide + aldehyde) for cross-coupling and olefination chemistry.

• SKU: D1262067
• Product Name: 2,3-Dimethoxy-5-iodobenzaldehyde
• CAS: 7396-66-9
• PubChem CID: 885386 (literature)
• InChIKey: 369689 (as provided in Product Data)
• Molecular formula: C9H9IO3 (literature, computed by atom balance)
• Molecular weight: ~292.07 g/mol (literature, calculated from formula)
• Structural features:
  • Aryl iodide at ring position 5 (highly reactive in Pd-catalyzed cross-couplings)
  • Aldehyde (–CHO) ring substituent (electrophilic carbonyl; acetalizable/protectable)
  • Two methoxy (–OCH3) ortho and meta to the aldehyde (electron-donating, ortho/para directing)
• Stereochemistry: None (achiral, planar aromatic core)
• 2D description in words: A benzaldehyde core with methoxy groups at the 2- and 3-positions and an iodine at the 5-position; the ring is electron-rich due to the methoxy groups while the iodine provides a superb leaving group for cross-coupling.
• SMILES: COc1c(OC)cc(I)cc1C=O (literature, one of several equivalent representations)

Notes:

• Identity fields explicitly listed under “literature/computed” are not item-specific specifications; confirm against the CoA/Spec Sheet if critical for regulated work.

Synthetic Utility

Functional group synergy makes 2,3-dimethoxy-5-iodobenzaldehyde an efficient hub for divergent synthesis.

• Cross-coupling platform:
  • Aryl iodide is the most reactive aryl halide class for Suzuki, Sonogashira, Heck, and Buchwald–Hartwig couplings, allowing mild conditions and broad scope. The electron-rich ring from two methoxy groups often accelerates oxidative addition.
• Carbonyl chemistry:
  • Wittig/HWE reactions furnish styrenyl iodides or conjugated alkenes while retaining C–I for subsequent diversification.
  • Condensations (Knoevenagel with malonates, cyanoacetates) give push–pull chromophore precursors.
  • Reductive transformations deliver benzyl alcohols/ethers with orthogonal retention of the iodide.
• Directed metalation/lithiation:
  • Halogen–lithium exchange at low temperature provides a lithiated aryl species for trapping with electrophiles (e.g., CO2, DMF, borates). Protect aldehyde as an acetal to prevent nucleophilic addition.
• Protecting-group logic:
  • Aldehyde → acetal (ethylene glycol, p-TsOH, Dean–Stark) to withstand strong base or metalation; facile deprotection restores the carbonyl.
• Retrosynthetic value:
  • Serves as an advanced intermediate in routes to 2,3-dimethoxy-substituted biaryls, alkynes, stilbenes, and anilines, with the aldehyde enabling late-stage polarity tuning or linker installation.

Purification/analysis tips:

• Iodinated arenes exhibit strong UV absorbance; DAD monitoring at 254–280 nm is effective.
• Residual Pd/Cu from cross-couplings can be reduced by scavengers (silica–thiol, metal scavenging resins). Maintain aldehyde integrity by minimizing basic exposure during workup.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological targeting reagent (e.g., antibody, enzyme inhibitor standard with defined target binding). There is no antigen/epitope, species reactivity, clone, or isotype associated with this item.

For target-specific applications, consider downstream derivatives prepared from this aryl iodide/aldehyde scaffold and characterize their binding or activity empirically.