4-Hydroxy-2-iodobenzonitrile - ≥95% , CAS No.1243386-89-1

CAS: 1243386-89-1 Cat. No.: H942568 Formula: C₇H₄INO Peso molecolare: 245.020

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

• Sorrisi canonici: C1=CC(=C(C=C1O)I)C#N
• IUPAC Name: 4-hydroxy-2-iodobenzonitrile
• InChIKey: AUUHDUIJYZLFHO-UHFFFAOYSA-N
• INCHI: 1S/C7H4INO/c8-7-3-6(10)2-1-5(7)4-9/h1-3,10H
• Peso molecolare: 245.020

Proprietà chimiche e fisiche

• Peso molecolare: 245.020 g/mol
• XLogP3: 1.900
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 244.934 Da
• Monoisotopic Mass: 244.934 Da
• Topological Polar Surface Area: 44.000 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 162.000
• 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 (e.g., WB, IHC, IF, FC) are applicable to this small-molecule building block.

General synthetic handling protocol (guidance; not item-specific):

• Dissolve the compound in a suitable dry solvent (e.g., DMF, dioxane, 2-MeTHF) under inert atmosphere for cross-coupling.
• If O-alkylation is intended, pre-dissolve base (K2CO3/Cs2CO3) and add alkylating agent at controlled temperature.
• Monitor reactions by TLC or LC–MS; quench with aqueous workup and extract with EtOAc or MTBE.

Item-specific recommended dilutions, positive controls, or assay conditions: Not specified for this item; refer to CoA/Spec Sheet.

Biological Roles

This compound is a synthetic aromatic building block and is not known as a natural metabolite or biomacromolecule component.

General considerations (not item-specific):

• The phenol and nitrile functionalities can modulate binding interactions in small-molecule probe design (hydrogen bonding via –OH, dipolar interactions via –C≡N). However, this product is provided strictly for research and chemical synthesis.
• Aryl iodides may serve as precursors to radioiodinated analogs for tracer development; such applications require specialized isotopic labeling and are beyond the scope of this catalog item.

Research Use Note: For research use only.

Buffer Applications

Not typically applicable. 4-Hydroxy-2-iodobenzonitrile is a neutral organic synthetic intermediate rather than a buffering agent. It does not constitute a conventional acid/base pair with a defined buffering range in aqueous systems.

For aqueous handling needs (general):

• Limited water solubility is expected; if an aqueous medium is required (e.g., bioconjugation workflow), use co-solvents such as DMSO or MeCN and maintain final organic content within assay tolerance.
• Adjust pH only insofar as it affects the ionization of the phenolic –OH (deprotonation increases aqueous solubility, but may compromise stability of the aryl iodide under harsh basic, oxygenated, or hot conditions).

Green Alternatives

Green chemistry considerations (general guidance, not item-specific):

• Solvent choices: Substitute DMF/NMP with 2-MeTHF, CPME, propylene carbonate, or water/ethanol mixtures when compatible with the catalyst and base.
• Halogen choice: While aryl iodides provide superior reactivity, aryl bromides or even chlorides (with modern ligands) may be used to reduce the use of iodine where feasible. This is a tradeoff between reactivity (I > Br > Cl) and sustainability/cost.

Illustrative comparison (literature-based, qualitative):

| Aspect | Conventional option | Greener alternative | Tradeoffs | |---|---|---|---| | Coupling solvent | DMF, dioxane, toluene | 2-MeTHF, CPME, MeCN/H2O | Solubility vs EHS profile | | Base for O-alkylation | K2CO3 in DMF | K2CO3 in acetone/MeCN or aqueous biphasic | May need phase-transfer catalyst | | Aryl halide | Iodide | Bromide/Chloride | Requires more active ligands/catalysts |

Operational tips:

• Screen greener solvents early with ligand/catalyst suites known to operate in them (e.g., XPhos/BippyPhos for aryl chlorides in 2-MeTHF).
• Employ solvent minimization and recovery strategies; 2-MeTHF and MeCN are readily recoverable and lower-boiling than DMF/NMP.
• Favor micellar catalysis (water with surfactants) for certain couplings when substrate solubility allows.

Pharmaceutical Uses

No excipient or pharmacopeial status is specified for this item; it is offered as a research chemical/building block.

General context (not item-specific, no therapeutic claims):

• Aryl iodide/phenol/nitrile scaffolds are frequently used as intermediates in medicinal chemistry campaigns. The iodide enables rapid SAR diversification via cross-coupling, while the phenol provides a point for prodrug or solubilizing group installation; the nitrile modulates polarity and metabolic stability.
• In process development, replacing aryl iodides with bromides/chlorides may be explored for cost and availability; however, iodides are valuable in early discovery for low-temperature couplings and minimized catalyst loads.
• Quality considerations for API intermediate work: control of halogen exchange byproducts, iodide/iodine residues, and regioisomeric impurities; ensure trace metals meet project-specific limits when material is used downstream of metal-catalyzed steps.

Item-specific note:

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Research Use Note: For research use only.

Physical Properties

Item-specific properties from 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.
• Storage Conditions: Room temperature (as provided).

Not specified for this item; refer to CoA/Spec Sheet for: melting point, boiling point, density, refractive index, water/peroxide content, metal limits, UV cutoff, residual solvents.

Literature/General (for reference; not item specifications):

• Physical state: typically a crystalline solid for hydroxy-iodobenzonitriles.
• Polarity/solubility trends: poor water solubility; soluble in polar aprotic organics (DMSO, DMF, NMP, acetonitrile) and moderately in ethyl acetate/THF; variable in chlorinated solvents and aromatics depending on temperature and base.
• Acid–base: phenol pKa in substituted systems commonly ~7–10 (literature); nitrile is weakly basic and not appreciably protonated under neutral conditions.
• Lipophilicity: aryl iodides/nitriles often display moderate–high logP; exact value depends on substitution pattern (literature context only).

Practical notes (general):

• Phenolic –OH can engage in hydrogen bonding; solubility improves upon deprotonation (e.g., with carbonate) or upon formation of O-protected derivatives.
• Aryl iodides are light-sensitive in some cases; minimize prolonged UV exposure to reduce risk of homolysis or adventitious iodide release.

Quality and Grades

Item-specific quality information:

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

Interpretation and guidance (general):

• For cross-coupling and metal-catalyzed reactions, low levels of inorganic halide, residual metal catalysts, and protic impurities (water/alcohols) are often critical. When grade is specified (e.g., ≥98% or higher), review the CoA for identity confirmation (NMR/HRMS/IR), chromatographic purity, and residual solvent profile.
• Phenolic aryl iodides seldom require stabilizers; however, trace acid/base can influence phenol reactivity and coupling performance. If sensitive downstream chemistry is planned (e.g., Buchwald–Hartwig amination), consider verifying water content and using rigorous drying of solvents and bases.
• For preparative chromatography or photoredox applications, UV background and trace colored impurities may matter; an HPLC-grade or high-purity material can reduce baseline artifacts.

Documentation:

• Request the batch-specific CoA for: assay (% area), identity spectra, residual solvents (ICH), and impurity profiles. Where applicable, ask about heavy metal screening if material will be used in catalyst-sensitive transformations.

Reaction and Applications

Key application domains (literature/general):

• Cross-coupling via aryl iodide: The Ar–I bond undergoes fast oxidative addition, enabling Suzuki–Miyaura (to form biaryls), Sonogashira (alkynylation), Heck (alkenylation), Negishi, and Stille reactions. The phenol and nitrile substituents can modulate electronic properties, often facilitating oxidative addition.
• Phenol derivatization: O-alkylation or O-acylation to form aryl ethers, carbonates, or esters. Temporary protection as silyl (TBS/TIPS), benzyl (Bn), or carbonate groups helps orthogonal manipulation of the iodine handle.
• Directed metalation/functionalization: The nitrile can act as a directing group for ortho C–H activation (e.g., Pd, Rh) or serve as a handle for nucleophilic additions (e.g., conversion to amides, aldehydes, or amines via hydration/reduction).
• Nucleophilic aromatic substitution (SNAr): Although less activated than nitroarenes, the combined –CN and –OH can enable selective substitution under strongly basic or transition-metal-catalyzed conditions.
• Late-stage diversification: The scaffold allows rapid library generation by varying coupling partners (boronic acids, amines, alkynes) while retaining or transforming the nitrile to fine-tune polarity and H-bonding.

Practical tips:

• Use dry, oxygen-free conditions for Pd-catalyzed couplings; aryl iodides are typically milder than bromides/chlorides, allowing lower catalyst loadings.
• Manage phenol acidity: pre-form the phenoxide with K2CO3/Cs2CO3 when targeting O-alkylation; for C–C couplings, buffer bases to avoid undesired O-arylation.
• Protect if needed: phenol protection can suppress side reactions in Buchwald–Hartwig or Suzuki couplings.
• Work-up: iodide-containing residues can darken; include sodium thiosulfate or bisulfite washes if iodine release is suspected.

Reaction Conditions

General literature conditions (guidance only; optimize per substrate):

• Suzuki–Miyaura biaryl formation:

  • Catalyst/ligand: Pd(PPh3)4 (1–3 mol%) or Pd2(dba)3 (1 mol%) + SPhos/XPhos (2–4 mol%).
  • Base: K2CO3 or K3PO4 (2–3 equiv), often with H2O as co-solvent.
  • Solvent: dioxane/H2O, toluene/H2O, or 2-MeTHF/H2O.
  • Temperature/time: 50–90 °C, 2–16 h. Aryl iodides typically couple at the lower end of the range.

• Buchwald–Hartwig amination:

  • Catalyst/ligand: Pd2(dba)3 (1 mol%) + BrettPhos/RuPhos/BippyPhos (2–4 mol%) or Pd(OAc)2 precatalysts.
  • Base: NaOtBu or K3PO4 (2–3 equiv).
  • Solvent: toluene, dioxane, or 2-MeTHF.
  • 60–100 °C, 4–18 h; protect phenol if O-arylation is an issue.

• Sonogashira alkynylation (copper-free variant preferred):

  • Catalyst/ligand: Pd(PPh3)2Cl2 (1–2 mol%) or XPhos-type systems.
  • Base: Et3N/DIPEA or K2CO3.
  • Solvent: THF, MeCN, or DMF; 25–60 °C.

• O-alkylation of phenol:

  • Base: K2CO3 or Cs2CO3 (1.5–2.5 equiv).
  • Electrophile: primary alkyl halide or sulfate.
  • Solvent: acetone, MeCN, or DMF; 25–60 °C.

• Nitrile transformations:

  • Reduction to amine: catalytic hydrogenation (Raney Ni/Pd) or borohydride-hydride systems; protect iodide or transform prior to reduction if needed.
  • Hydrolysis: acidic or basic aqueous conditions (reflux) to amide/acid; consider sequence to avoid dehalogenation.

Notes:

• Degas solvents and employ inert atmosphere for Pd-catalyzed steps.
• Aryl iodides often allow reduced catalyst loadings; start low and titrate upward as needed.
• Monitor for iodide/iodine release; sodium thiosulfate washes can quench adventitious iodine during workup.

Safety and Handling

Hazard classification (item-specific):

• Signal Word: Not specified for this item; refer to SDS.
• H-Statements: Not specified for this item; refer to SDS.
• GHS Classification/Pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance (not item-specific; consult the SDS for authoritative information):

• PPE: lab coat, safety glasses or splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Handle in a fume hood to avoid inhalation of dust or vapors from heated solutions.
• Incompatibilities: strong bases will deprotonate the phenol; strong nucleophiles and reducing agents may displace or reduce the aryl iodide under forcing conditions; strong oxidants may over-oxidize the phenol.
• Thermal/light sensitivity: aryl iodides can be photosensitive; store away from intense light. Avoid excessive heating without appropriate controls.
• First aid (general): if inhaled, move to fresh air; in case of skin/eye contact, rinse with copious water for at least 15 minutes; if ingested, seek medical attention. Remove contaminated clothing and wash before reuse.
• Spill/cleanup: avoid dust formation; collect solids by damp wiping or HEPA vacuum; absorb solutions with inert material and dispose per institutional and regulatory requirements.
• Waste: halogenated aromatic waste; segregate as halogenated organics for disposal.

Always defer to the product SDS and institutional EHS guidance for specific hazard data and response procedures.

Solvent Selection

Applicability: 4-Hydroxy-2-iodobenzonitrile is a multifunctional aryl iodide/phenol/nitrile. Solvent choice is typically driven by the intended transformation (e.g., cross-coupling, O-derivatization) and solubility of bases and reaction partners.

General solvent compatibility (literature guidance):

• Polar aprotic (excellent): DMSO, DMF, NMP, DMAc — enhance solubility of aryl iodides and bases for C–C/C–N couplings.
• Medium polarity ethers/esters: THF, 2-MeTHF, dioxane, ethyl acetate — suitable for base-promoted O-alkylation or carbonate formation; often used with inorganic bases (K2CO3, Cs2CO3).
• Nitriles/aromatics: acetonitrile, toluene — useful for palladium-catalyzed couplings and SNAr variants; toluene favors higher-temperature protocols.
• Alcohols/water: limited solubility as a neutral phenol; solubility increases upon deprotonation (aqueous base) though aryl iodides can be less stable under strongly basic, hot aqueous conditions.

Selection tips:

• Cross-coupling on Ar–I: dioxane/H2O or toluene, DMF, or MeCN commonly balance catalyst stability and solubility; water co-solvent can accelerate oxidative addition and base turnover.
• O-alkylation/acylation: acetone/MeCN/DMF with carbonate or tertiary amine base minimize competing elimination of alkylating agents.
• Purification: chlorinated solvents (DCM) typically dissolve product/intermediates well; for greener practices, use EtOAc/hexanes gradients.

Small comparison (general):

• DMF/NMP: high solvating power; thermal stability; consider work-up challenges.
• 2-MeTHF/dioxane: facilitate coupling with better environmental profile; sometimes lower solubility requires higher temperature.
• MeCN: low viscosity, easy removal; may require stronger bases for phenol deprotonation.

Storage and Reconstitution

Item-specific storage:

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

General guidance (not item-specific):

• Store tightly closed in a dry, inert atmosphere to protect the aryl iodide from moisture and prolonged light exposure. Use amber glass where feasible.
• For long-term storage, desiccation (e.g., in a desiccator with silica gel or molecular sieves) is recommended. Avoid repeated heating/cooling cycles.
• Reconstitution: For stock solutions, dissolve in anhydrous DMSO, DMF, MeCN, or acetone to the desired concentration. Filter through a PTFE membrane if particulates are present.
• Solution stability: Aryl iodides can be less stable in strongly basic solutions or under UV light. Prepare fresh solutions as needed, or aliquot and store stocks at 2–8 °C protected from light if solution storage is necessary.
• Freeze–thaw: For solid, not applicable; for solutions, avoid multiple freeze–thaw cycles by aliquoting.

Always consult the batch-specific CoA/SDS for definitive storage and handling instructions.

Structure and Identity

A multifunctional aryl iodide bearing both phenolic and nitrile groups, useful as a densely functionalized coupling handle and directing group scaffold.

• SKU: H942568
• Product Name: 4-Hydroxy-2-iodobenzonitrile
• CAS: 1243386-89-1
• CID: 21613620
• InChIKey (as provided): 15495
• SMILES (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.
• Molecular Weight (item-specific): Not specified for this item; refer to CoA/Spec Sheet.

Literature/Computed (for reference only; not item specifications):

• Representative SMILES (literature): N#Cc1cc(I)cc(O)c1
• Typical elemental formula (literature): C7H4INO
• Typical formula weight (literature): ~244.9 g/mol

Structural features (general description):

• Aromatic ring (benzene) bearing three key substituents: a nitrile (–C≡N) para to a phenol (–OH) and ortho to an iodine atom (Ar–I).
• Functional groups: aryl iodide (excellent oxidative addition partner), phenol (weakly acidic, can be protected/derivatized), and nitrile (polar, Lewis-basic nitrogen; directing group potential).
• 2D topology in words: a benzonitrile core with iodine adjacent to the nitrile carbon (ortho) and a hydroxyl group para to the nitrile.

Notes:

• Stereochemistry: none (planar aromatic).

Synthetic Utility

Functional group manifold:

• Aryl iodide (Ar–I): premier handle for Pd-catalyzed cross-couplings (Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira, Heck, Negishi), and for radical-mediated transformations (e.g., photoredox-mediated arylations/deiodinations).
• Phenol (Ar–OH): platform for O-alkylation, O-acylation, carbonate/carbamate formation; easy protection/deprotection to manage chemoselectivity during couplings.
• Nitrile (–C≡N): convertible to amide, acid, aldehyde, amine via hydration, hydrolysis, reduction, or Pinner chemistry; serves as a directing group for ortho C–H activation.

Strategic value in synthesis (literature/general):

• Orthogonal reactivity: perform rapid C–C/C–N bond formation on Ar–I under mild conditions, leaving the nitrile intact; subsequently manipulate the phenol or transform the nitrile for polarity tuning.
• Regioselective diversification: the 2-iodo substituent adjacent to the nitrile can participate in directed metalation or chelation-assisted couplings, enabling selective functionalization patterns.
• Late-stage editing: iodide allows low-temperature metalation/cross-coupling on sensitive frameworks; phenol enables pro-moiety installation (e.g., carbonate-linked solubilizing groups).

Tactics and protections:

• Protect the phenol (e.g., TBS, MOM, benzyl, or carbonate) to suppress competitive O-arylation during C–N couplings.
• Use milder bases (K3PO4, K2CO3) for Pd-catalyzed couplings to maintain nitrile integrity; avoid strong nucleophiles that may attack the nitrile in polar, hot media.
• For radical chemistry, exploit the weak C–I bond for selective aryl radical generation under photoredox or AIBN/initiator conditions.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, or biological targeting reagent.

Item-specific data such as antigen, epitope, species reactivity, clone, or isotype: Not specified for this item; refer to CoA/Spec Sheet.