4-(4-Iodophenyl)sulfonylmorpholine , CAS No.22950-14-7

CAS: 22950-14-7 Cat. No.: I929008 Formula: C₁₀H₁₂INO₃S Peso molecolare: 353.180

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

• Sorrisi canonici: C1COCCN1S(=O)(=O)C2=CC=C(C=C2)I
• IUPAC Name: 4-(4-iodophenyl)sulfonylmorpholine
• InChIKey: CIUYBBOXOYPJSE-UHFFFAOYSA-N
• INCHI: 1S/C10H12INO3S/c11-9-1-3-10(4-2-9)16(13,14)12-5-7-15-8-6-12/h1-4H,5-8H2
• Peso molecolare: 353.180

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Benzenesulfonamides
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzenesulfonamides
• Alternative Parents: Benzenesulfonyl compounds Iodobenzenes Organosulfonamides Morpholines Aryl iodides Sulfonyls Oxacyclic compounds Dialkyl ethers Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Organoiodides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Benzenesulfonamide - Benzenesulfonyl group - Halobenzene - Iodobenzene - Aryl halide - Aryl iodide - Morpholine - Oxazinane - Organosulfonic acid amide - Sulfonyl - Organosulfonic acid or derivatives - Organic sulfonic acid or derivatives - Dialkyl ether - Oxacycle - Azacycle - Organoheterocyclic compound - Ether - Organic oxide - Organoiodide - Organohalogen compound - Organopnictogen compound - Organic oxygen compound - Organonitrogen compound - Organooxygen compound - Organosulfur compound - Organic nitrogen compound - Hydrocarbon derivative - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
• 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: 353.180 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 352.958 Da
• Monoisotopic Mass: 352.958 Da
• Topological Polar Surface Area: 55.000 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 313.000
• 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-specific protocols are provided for this small-molecule building block.

• General handling

  • Prepare concentrated stock solutions in dry DMSO or DMF (e.g., 10–100 mM) for screening or reaction setup; store aliquots to avoid repeated freeze–thaw of solutions.
  • For synthetic reactions, charge the solid under inert atmosphere if air/moisture-sensitive reagents will be added subsequently.
  • Monitor reactions by TLC (UV 254 nm) and/or LC–MS; the iodine atom provides a strong mass handle.

• Analytical suggestions

  • NMR: DMSO‑d6 or CDCl3 typically provide well-resolved spectra.
  • LC–MS: ESI+ often shows [M+H]+; adjust gradient with MeCN/H2O + 0.1% formic acid or ammonium formate for improved ionization.

Refer to the primary literature and your lab SOPs for detailed, application-specific procedures.

Biological Roles

• Item-specific biological data: Not specified for this item; refer to CoA/Spec Sheet.

• General context (no medical/clinical claims)

  • Aryl sulfonamide motifs are prevalent in chemical biology probes and medicinal chemistry due to their metabolic stability, strong electron-withdrawing character, and capacity to act as H-bond acceptors. The morpholine ring is commonly used to modulate polarity, solubility, and pKa in small molecules intended for biochemical assays.
  • The para-iodophenyl group can serve as a synthetic handle for radiolabeling (e.g., 125I in tracer studies) or as a heavy-atom tag in biophysical methods; however, this product is provided for non-radioactive research use only.
  • In target identification workflows, aryl iodides are sometimes leveraged in photo/redox-mediated tagging strategies to attach reporter groups via cross-coupling under mild conditions.

• Practical implications for biochemical experimentation

  • The compound is best regarded as a building block to prepare target-engaging probes rather than a probe itself. Downstream derivatives may display affinity for enzymes or receptors where aryl sulfonamides are tolerated.
  • If used in biochemical assays, dissolve in DMSO to prepare concentrated stocks; perform serial dilutions into assay buffer to minimize DMSO content (commonly ≤1–2% v/v). Confirm compatibility with protein targets to avoid nonspecific aggregation.

Buffer Applications

This compound is a small-molecule synthetic building block, not a buffering agent. It does not form a defined conjugate acid/base pair suitable for pH control in aqueous media.

• Guidance
  • For work-up or biochemistry contexts, prepare DMSO or DMF stock solutions and dilute into the chosen buffer. Ensure the final organic cosolvent fraction is compatible with your system.
  • Select standard buffers (e.g., phosphate, HEPES, Tris) appropriate to your application; this compound itself does not contribute to buffering capacity.

Green Alternatives

• Greener process considerations (general guidance)

  • Solvent choice often dominates environmental footprint. Where feasible, replace DMF/NMP with greener media (e.g., 2-MeTHF, CPME, propylene carbonate, water/ethanol cosolvents) for cross-couplings.
  • Use ligand/catalyst systems active in aqueous or alcoholic media to reduce organic solvent usage and enable milder temperatures.
  • Consider micellar catalysis (e.g., TPGS-750-M in water) for Suzuki couplings of aryl iodides.

• Comparison of solvent options (literature examples; select based on reaction specifics)

  • 1,4-Dioxane (traditional) vs 2-MeTHF (greener): similar polarity; 2-MeTHF has better safety and renewability, but sometimes lower solubility for inorganic bases.
  • DMF/DMAC vs propylene carbonate or Cyrene: greener alternatives with comparable solvating power; may require temperature optimization and different bases.
  • Toluene vs CPME: CPME offers low peroxide formation tendency and broader liquid range; toluene may provide higher solubility for some catalysts.

• Waste and catalyst considerations

  • Aryl iodides typically allow lower Pd loadings than bromides/chlorides, reducing precious metal usage. Explore heterogeneous Pd/C or nickel catalysis where compatible.
  • Base selection: aqueous K2CO3/Na2CO3 minimizes corrosivity compared with stronger bases; phase-transfer or micellar approaches can further reduce solvent volumes.

• Product-specific note

  • No formulation additives or stabilizers are specified for this item; focus green optimization on solvent/base/catalyst selection and energy input (e.g., flow, microwave, or photoredox methods where appropriate).

Pharmaceutical Uses

• Item-specific status: Not specified for this item; refer to CoA/Spec Sheet. No pharmacopeial monograph is indicated.

• General formulation/manufacturing context (no therapeutic claims)

  • Role as an intermediate: 4-(4-Iodophenyl)sulfonylmorpholine is suited for the synthesis of screening libraries and API intermediates via cross-coupling at iodine, enabling late-stage diversification while maintaining a polar sulfonamide-like fragment.
  • Property modulation: the morpholine–sulfonyl unit increases polarity and may improve chromatographic behavior and crystallinity of intermediates, aiding purification and solid-form selection studies.
  • Conjugation handle: para-iodide enables installation of motifs such as heteroarenes, alkynes, and amines under Pd-catalyzed couplings, facilitating SAR exploration.

• Practical considerations

  • Control of metal residues: if used in GMP-oriented routes, incorporate appropriate Pd/Ni scavenging and ICP testing steps post-coupling.
  • Solid handling: as a non-volatile solid, it is suitable for weigh-and-charge operations; employ standard controls to limit dust and cross-contamination.
  • Documentation: define specifications (purity, residual solvents, identification) appropriate to the development stage; confirm with CoA/Spec Sheet for this specific item.

Physical Properties

• Item-specific specifications

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Exact numerical specs (mp, bp, density, UV cutoff, residuals): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general expectations for this chemical class (aryl iodide–arylsulfonamide; for planning only, not item specifications)

  • Physical state: typically a crystalline solid due to the sulfonyl and heterocyclic functionalities increasing lattice interactions.
  • Volatility: negligible; the aryl iodide is non-volatile and the sulfonylmorpholine further suppresses volatility.
  • Solubility profile: often soluble in polar aprotic organic solvents (e.g., DMF, DMSO, acetonitrile, dichloromethane, THF, dioxane); sparingly soluble in nonpolar hydrocarbons; limited aqueous solubility but can dissolve in water miscible organics (DMSO, DMF) and in mixed solvent systems.
  • Thermal behavior: aryl iodides generally have moderate-to-high melting points; decomposition can occur before boiling under ambient pressure; purification commonly done by column chromatography or recrystallization from polar organics.
  • Partitioning: presence of the iodine increases lipophilicity relative to chloro/bromo analogs; the sulfonamide-like linkage and morpholine oxygen/nitrogen impart polarity and H-bond acceptor capacity, improving solubility in polar organics.

• Practical implications

  • Prefer high-boiling polar aprotic solvents for high-concentration reactions or metal-catalyzed couplings.
  • For analytical HPLC, reversed-phase methods with acetonitrile/water and a small amount of base or acid modifier generally give good peak shape for sulfonamide-like compounds.

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.

• Interpreting common grades (general guidance)

  • Research/technical grade: Suitable for synthesis and method development where ultra-trace impurities are non-critical.
  • ≥98% purity: Typical for small-molecule building blocks used in cross-coupling and library synthesis; supports reproducible yields and analytical characterization.
  • HPLC grade (when applicable to solvents): denotes very low UV background and particulate; not applicable to this solid reagent.

• Impurity considerations for aryl iodide building blocks (general)

  • Typical impurities may include residual halogenated benzenes, sulfonylation byproducts, inorganic salts, and trace metals from synthesis. These can impact Pd-catalyzed couplings (catalyst poisoning or side reactions).
  • Recommended QC methods: 1H/13C NMR (DMSO‑d6 or CDCl3), HRMS, HPLC or UPLC purity with PDA detection, and if used in cross-couplings, optional ICP-MS for Pd/Pt/Ni traces post-reaction.

• Documentation

  • For exact specifications (purity %, residual solvents, water, inorganic residues, and any stabilizers), consult the lot-specific CoA/Spec Sheet.

Reaction and Applications

As a para-iodoaryl–sulfonylmorpholine, this molecule is a versatile electrophile and handle-bearing building block in synthesis.

• Cross-coupling platform (literature)

  • Suzuki–Miyaura: couples with boronic acids/esters to install diverse aryl/alkenyl fragments while retaining the sulfonylmorpholine functionality for subsequent diversification.
  • Sonogashira: introduces alkynes onto the aryl ring; the sulfonylmorpholine serves as a polar handle improving solubility and chromatographic behavior.
  • Buchwald–Hartwig amination: converts the aryl iodide to anilines under Pd catalysis; the sulfonylmorpholine is typically stable under amination conditions.

• Metal–halogen exchange and electrophile trapping (literature)

  • Rapid iodine–lithium exchange at low temperature generates aryllithium intermediates, enabling formylation, carboxylation, or acylation to give para-functionalized derivatives bearing the sulfonylmorpholine.

• Electrophilic/aromatic transformations (literature)

  • Directed metalation is facilitated by the strongly electron-withdrawing arylsulfonyl substituent; careful base choice (s-BuLi, TMP bases) can enable regioselective functionalization.

• Utility of the sulfonylmorpholine motif (general)

  • Acts as a robust, polar, H-bond-accepting group that can modulate physicochemical properties of library members; can be retained or modified in late-stage diversification (e.g., N-deprotection via reductive or harsh conditions is generally difficult, so it behaves as a stable protecting/auxiliary group).

• Practical notes

  • Dry, oxygen-free conditions improve catalytic performance. Use ligand/catalyst systems optimized for aryl iodides to minimize side reactions (dehalogenation). Monitor reactions by LC–MS; the iodine provides a helpful isotopic signature.

Reaction Conditions

The following are literature-style general conditions for aryl iodide couplings and metalation; adjust to your substrate set. These are not item-specific specifications.

• Suzuki–Miyaura (aryl iodide + aryl boronic acid/ester)

  • Catalyst: Pd(PPh3)4 (1–2 mol%) or Pd-PEPPSI-type; Ligands: XPhos/SPhos if needed.
  • Base: K2CO3 or Cs2CO3 (2–3 equiv); aqueous base often beneficial.
  • Solvent: 1,4-dioxane/H2O (3:1) or EtOH/H2O; 60–90 °C, 2–8 h.
  • Notes: Iodides usually react fastest, enabling lower catalyst loadings.

• Sonogashira (alkynylation)

  • Catalyst: PdCl2(PPh3)2 (1–2 mol%); Co-catalyst: CuI (5–10 mol%).
  • Base: Et3N, i-Pr2NH, or K2CO3.
  • Solvent: DMF, THF, or toluene/amine; 25–80 °C, 2–12 h.
  • Notes: Copper-free variants (Pd-only) reduce Glaser coupling.

• Buchwald–Hartwig amination

  • Catalyst: Pd2(dba)3 (1 mol% Pd) + XPhos/BrettPhos (2–3 mol% ligand).
  • Base: NaOtBu or Cs2CO3.
  • Solvent: toluene or dioxane; 70–110 °C, 6–18 h.

• Halogen–lithium exchange / electrophile trapping

  • Reagents: n-BuLi or s-BuLi (1.1–1.5 equiv) at −78 °C in anhydrous THF.
  • Electrophiles: CO2 (dry ice), DMF (formylation), B(OMe)3 (boronation), MeI (alkylation).
  • Caution: Quench carefully; avoid protic impurities.

• Workup/purification

  • Aqueous quench with NH4Cl or NaHCO3, extraction with EtOAc/MTBE, silica gel chromatography (DCM/EtOAc/MeOH). Metal scavengers or activated carbon may be used to reduce Pd/Ni residues.

Always confirm compatibility of the sulfonylmorpholine group under chosen conditions and verify on small scale first.

Safety and Handling

• Item-specific hazard information (from Product Data)

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

• General safety considerations for aryl iodide arylsulfonamide solids (informational; defer to SDS)

  • Likely hazards: May cause skin/eye irritation and respiratory tract irritation if dust is generated. Avoid inhalation of dust and contact with skin/eyes.
  • PPE: Use appropriate lab coat, safety glasses or face shield, and nitrile gloves. Handle in a fume hood to minimize exposure to dust or solvent vapors.
  • Incompatibilities: Strong bases or strong reducing agents can, under forcing conditions, affect sulfonyl groups; strong oxidizers may react exothermically with organics. Avoid contact with strong electrophiles that could undesirably functionalize the morpholine nitrogen if deprotected (not applicable here unless reacting conditions liberate amine).
  • Stability: Aryl iodides are generally stable but can undergo light-promoted homolysis; store away from strong UV/visible light sources. No known peroxide formation tendency.
  • First aid overview: If on skin/eyes, rinse with water for ≥15 min; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth with water. Seek medical attention as needed. Provide the SDS to responders.
  • Spill/cleanup: Avoid dust generation. Sweep up solids; for solutions, absorb with inert material. Dispose per local regulations.

Always consult the product’s SDS for definitive hazard classification, exposure limits, and emergency procedures.

Solvent Selection

This product is a polar, non-volatile organic solid best handled in polar aprotic solvents for synthesis and analytics.

• Polarity/miscibility (general expectations)

  • Good solubility: DMSO, DMF, NMP, MeCN, dichloromethane, THF, 1,4-dioxane, ethyl acetate.
  • Moderate/variable solubility: alcohols (MeOH, EtOH, i-PrOH) depending on temperature; acetone; toluene when warmed.
  • Poor solubility: aliphatic hydrocarbons (hexanes, heptane); water (typically low due to aryl iodide and sulfonyl balance).

• Selection by application

  • Pd-catalyzed cross-couplings (Suzuki/Sonogashira/Buchwald–Hartwig): 1,4-dioxane/H2O, toluene with polar co-solvent, DMF, or CPME/EtOH/H2O for greener variants.
  • Lithiation/metal–halogen exchange: anhydrous THF or MTBE at low temperature (−78 to −40 °C).
  • Purification: normal-phase silica gel chromatography using DCM/EtOAc/MeOH gradients; reversed-phase preparative HPLC with MeCN/H2O if needed.

• Comparison notes

  • Versus bromo/chloro analogs: iodide improves reactivity in oxidative addition and allows milder conditions or lower catalyst loadings; slightly lower solubility in very nonpolar media.
  • Versus boronic esters/acids: aryl iodide electrophiles avoid transmetalation issues but require Pd/Ni catalysts; boronates are nucleophiles for Suzuki.

• Practical tips

  • Warm and sonicate to assist dissolution in moderately polar solvents. Dry solvents thoroughly for air/moisture-sensitive transformations (e.g., metalation).

Storage and Reconstitution

• Item-specific storage/shipping

  • Storage conditions: Room temperature (from Product Data). Protect from light and moisture for best stability. Reseal promptly after use.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• Solid handling

  • Keep container tightly closed in a dry, well-ventilated place. Consider desiccant storage if ambient humidity is high.
  • If static or dusting is observed, use antistatic measures and weigh in a balance enclosure.

• Solution preparation

  • Solubility: Readily formulated in DMSO, DMF, MeCN, DCM, THF (general guidance). Start with small volumes and gentle warming/sonication if needed.
  • Stock solutions: For screening or biochemistry, prepare DMSO stocks (e.g., 10–100 mM). Filter (0.2 µm PTFE) for sterile or particle-free solutions if required by your workflow.
  • Stability of solutions: Aryl iodide solutions are generally stable for days to weeks at 2–8 °C in the dark. For prolonged storage, prepare single-use aliquots and freeze (−20 °C) to avoid repeated warming cycles.

• Disposal

  • Dispose of unused material and solutions according to institutional and local regulations for halogenated organic compounds.

For any lot-specific stability limits, re-test intervals, or packaging details, consult the CoA/Spec Sheet.

Structure and Identity

Brief overview: 4-(4-Iodophenyl)sulfonylmorpholine is an aryl iodide bearing a para-iodobenzene moiety linked through a sulfonyl group to an N-sulfonylated morpholine ring. The molecule combines a highly cross-coupling–active C–I bond with a robust, polar sulfonamide-like functionality.

• Item-specific (from Product Data)

  • CAS: 22950-14-7
  • SKU: I929008
  • Storage: Room temperature
  • Research use: For research use only
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • 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 identifiers and structural description (for reference; verify against the product CoA)

  • Typical structural motif: p-iodophenyl–SO2–N(morpholine)
  • Functional groups: aryl iodide, sulfonyl (sulfone) linkage, tertiary sulfonamide (N-sulfonylated morpholine), heterocycle (morpholine; 1-oxa-4-azacyclohexane)
  • 2D description in words: a para-iodinated benzene ring is attached at the ipso carbon to a tetrahedral sulfur(VI) center bearing two oxygens (sulfonyl) and bonded to the ring nitrogen of a morpholine; the morpholine ring contains one oxygen and one nitrogen opposite each other in a six-membered saturated ring.

• Stereochemistry

  • None (achiral; no stereogenic centers).

Synthetic Utility

• Orthogonal functionality

  • Aryl iodide: among the most reactive aryl halides for oxidative addition; enables couplings under mild conditions with broad substrate scope.
  • Aryl–SO2–N(morpholine): a robust, electron-withdrawing sulfonamide-like linkage that is generally inert to many cross-coupling conditions, allowing it to function as a persistent “handle” for polarity and binding interactions.

• Representative transformations (literature)

  • Suzuki–Miyaura coupling to diversify the aryl ring (bases: K2CO3, Cs2CO3; solvents: dioxane/H2O, EtOH/H2O, or greener CPME/H2O).
  • Sonogashira alkynylation (Pd/Cu, amine base) to access para-alkynyl derivatives suited for further click or cycloaddition chemistry.
  • Buchwald–Hartwig amination to install anilines/diarylamines; the sulfonylmorpholine remains intact.
  • Halogen–lithium exchange (n-BuLi, −78 °C, THF) followed by trapping with electrophiles (CO2, DMF, B(OMe)3, aldehydes) to generate acids, aldehydes, boronates, or alcohols.
  • Photoredox or nickel-catalyzed cross-couplings exploiting the aryl iodide under milder, base-lean conditions.

• Strategy and retrosynthesis

  • Use as a convergent node: keep the sulfonylmorpholine constant while exploring aryl diversification, or conversely, couple first then manipulate the sulfonyl fragment in late stages if compatible.
  • The polar morpholine ring assists purification by normal-phase or RP chromatography.

• Limitations/considerations

  • Iodide can undergo competitive dehalogenation; select ligands/bases to suppress this pathway. Strongly basic conditions can, in rare cases, affect sulfonyl groups—optimize conditions accordingly.

Target Specificity

Not applicable. This product is a small-molecule reagent/building block, not a biological targeting reagent (e.g., antibody, ligand standard). No antigen/epitope or species reactivity data are associated with this item.