3-Chloro-4-morpholinophenylboronic acid - ≥96% , CAS No.1426246-59-4

CAS: 1426246-59-4 Cat. No.: C181476 분자식: C₁₀H₁₃BClNO₃ 분자량: 241.5

등급 & 순도 ≥96%

Storage

Room temperature

Shipped In

Normal

사양

사양 및 순도

≥96%

보관 조건

Room temperature

배송

Normal

순수함

≥96%

이름과 식별자

정식 스마일

B(C1=CC(=C(C=C1)N2CCOCC2)Cl)(O)O

IUPAC Name

(3-chloro-4-morpholin-4-ylphenyl)boronic acid

InChIKey

MLYNSBCEZWQQEF-UHFFFAOYSA-N

INCHI

1S/C10H13BClNO3/c12-9-7-8(11(14)15)1-2-10(9)13-3-5-16-6-4-13/h1-2,7,14-15H,3-6H2

이성체 SMILES

B(C1=CC(=C(C=C1)N2CCOCC2)Cl)(O)O

분자량

241.5

Reaxy-Rn

37920903

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=37920903&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • 분류 Oxazinanes
      • Subclass Morpholines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• 분류: Oxazinanes
• Subclass: Morpholines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylmorpholines
• Alternative Parents: Dialkylarylamines Aniline and substituted anilines Chlorobenzenes Aryl chlorides Boronic acids Oxacyclic compounds Organic metalloid salts Dialkyl ethers Azacyclic compounds Organopnictogen compounds Organometalloid compounds Organochlorides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Phenylmorpholine - Tertiary aliphatic/aromatic amine - Dialkylarylamine - Aniline or substituted anilines - Chlorobenzene - Halobenzene - Benzenoid - Aryl chloride - Aryl halide - Monocyclic benzene moiety - Tertiary amine - Boronic acid derivative - Boronic acid - Organic metalloid salt - Oxacycle - Azacycle - Dialkyl ether - Ether - Hydrocarbon derivative - Organohalogen compound - Organic metalloid moeity - Amine - Organochloride - Organonitrogen compound - Organooxygen compound - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Aromatic heteromonocyclic compound
• 설명: This compound belongs to the class of organic compounds known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
• 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

화학 및 물리적 특성

• 분자량: 241.480 g/mol
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 241.068 Da
• Monoisotopic Mass: 241.068 Da
• Topological Polar Surface Area: 52.900 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 226.000
• 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

XLogP3

Application Protocols

• Not applicable as standardized bioassay protocols (WB, IHC, IF, FC) do not pertain to small-molecule reagents of this type.
• For synthetic applications, see the Reaction Conditions and Synthetic Utility sections for general procedural guidance. Always validate conditions on small scale and consult peer-reviewed literature for closely related substrates.

Biological Roles

• Item-specific (Product Data): None provided beyond “For research use only.”

• General chemistry knowledge:

  • This compound is a synthetic small molecule building block; it is not known as a natural metabolite or a component of endogenous biochemical pathways.
  • The morpholine ring is a common motif in chemical biology and medicinal chemistry tool compounds due to its basicity and hydrogen-bonding capacity; however, any biological activity would pertain to derivatives synthesized from this boronic acid rather than the reagent itself.
  • Boronic acids can engage in reversible covalent interactions with diols (e.g., sugars) forming boronate esters; this property underlies certain sensor designs and affinity materials, but the presence of the morpholinyl and chloro substituents makes this specific reagent primarily suited as a synthetic intermediate rather than a probe.
  • In enzymology, arylboronic acids can serve as precursors to phenols or as handles for bioconjugation after further functionalization; direct biological “roles” are limited without additional structural tailoring.

• Practical implication:

  • When using this reagent to generate bioactive compounds or probes, thoroughly remove palladium/copper residues and confirm identity/purity to avoid misattributing biological effects to impurities or catalysts.

Buffer Applications

• Not typically applicable.
• Rationale (general chemistry knowledge): This substance is a neutral/weakly acidic arylboronic acid building block, not a dedicated buffering agent. While boronic acids have pKa values in the 8–9 range, they are not used as primary buffer components due to poor buffering capacity and potential reactivity toward diols.
• Guidance: For aqueous work with this reagent, select an appropriate buffer for your biological system (e.g., phosphate, HEPES, MOPS) and consider pH effects on solubility (boronate formation above pH ~8 can increase aqueous solubility).

Green Alternatives

• General chemistry knowledge (sustainable choices for cross-coupling with arylboronic acids):

Comparison of solvent platforms (literature-based, not product specifications):

• Dioxane/H2O (conventional) vs. 2-MeTHF/H2O (greener):

  • EHS profile: 2-MeTHF is bio-based, lower toxicity, and higher boiling point; dioxane is a probable human carcinogen and groundwater contaminant.
  • Performance: Many modern Pd systems (e.g., XPhos/SPhos ligands) work efficiently in 2-MeTHF/H2O at 60–90 C.

• DMF/DMSO (conventional) vs. EtOH/H2O or MeOH/H2O (greener):

  • EHS: Alcohol/water blends are preferred green solvents; DMF and DMSO have higher environmental and EHS burdens (DMF is a reproductive toxin).
  • Performance: With soluble bases (K2CO3, K3PO4) and suitable ligands, EtOH/H2O often delivers high conversions at moderate temperatures.

• Emerging methodologies:

  • Aqueous micellar catalysis (e.g., TPGS-750-M, Savie) allows couplings in water at room temperature to 60 C, reducing organic solvent usage.
  • Flow chemistry reduces solvent inventory and improves heat/mass transfer, enabling lower catalyst loadings.

Trade-offs:

• Greener solvents may require longer reaction times or adjusted ligation to maintain catalyst activity.
• Workup differences (e.g., emulsions in surfactant media) should be planned for with salt breaks or solvent switches.

Item-specific note: No mandated solvent system for this SKU; select greener options where compatible with your catalyst/substrate set.

Pharmaceutical Uses

• Item-specific (Product Data): None specified.

• General chemistry knowledge (no medical/clinical claims):

  • Role: Research-grade synthetic intermediate. Arylboronic acids are widely used to assemble aryl–aryl and aryl–heteroaryl linkages found in drug candidates via Suzuki–Miyaura coupling.
  • Process considerations: The para-morpholinyl group can enhance solubility and aid crystallization or salt formation in intermediates; the meta-chloro serves as a latent handle for subsequent diversification.
  • Regulatory notes: No pharmacopeial monograph is expected for this specialized reagent. For API route development, impurity profiles (e.g., boroxines, homocoupled biaryls) and residual metals must be controlled to ICH limits.
  • Workup/purification: After coupling, boron residues are commonly removed by oxidative workups (H2O2, NaBO3) or by aqueous extraction at basic pH; metal scavengers or adsorbents (e.g., silica, activated carbon) help reduce Pd/Cu residuals.
  • Documentation: For any use in regulated environments, obtain batch-specific CoA, residual solvent data, and elemental analysis—Not specified for this item; refer to CoA/Spec Sheet.

Physical Properties

• Item-specific (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.

• Literature/computed (for reference only; not product specifications):

  • Physical state: Typically a solid arylboronic acid (literature, general for analogous compounds).
  • Solubility: Arylboronic acids are often moderately soluble in polar aprotic solvents (DMF, DMSO, MeCN) and alcohol/water mixtures; limited solubility in nonpolar solvents; variable in pure water (literature, general trends).
  • Acid–base behavior: Boronic acid pKa (B(OH)2 ⇌ B(OH)O− + H+) typically ~8–9 for arylboronic acids; the morpholinyl substituent introduces basicity (conjugate acid pKa of morpholine ~8.3; literature general values). These values influence aqueous partitioning under buffered conditions.
  • Partitioning: Substitution with morpholine increases polarity relative to simple arylboronic acids; aryl chloride increases lipophilicity (qualitative, literature trend).

• General chemistry knowledge (practical notes):

  • Hygroscopicity: Many boronic acids show limited hygroscopicity but can form cyclic boroxines upon drying/heating; exposure to moisture reverses boroxine formation.
  • Thermal behavior: Arylboronic acids can decompose by protodeboronation upon prolonged heating, especially under basic aqueous conditions.
  • Spectral characteristics: Strong B–O stretching bands in IR; 11B NMR typically broad (δ ~ 28–34 ppm for trigonal boronic acids in noncoordinating solvents). Exact values should be confirmed experimentally for this item.

Quality and Grades

• Item-specific (Product Data):

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

• General guidance for this compound class:

  • Arylboronic acids supplied for synthesis are typically offered as research grade with purity often ≥95% by HPLC/GC/NMR. Exact limits for this SKU are not specified for this item; refer to CoA/Spec Sheet.
  • Stabilizers: Boronic acids are usually shipped neat without stabilizers. Trace boroxine content may be present depending on drying history; this is generally reversible upon exposure to moisture or during reaction setup with aqueous bases.
  • What to check on the CoA:
    • Identity confirmation by 1H NMR/13C NMR and optionally 11B NMR.
    • Purity by HPLC or qNMR.
    • Water content (KF) and residual solvents if your application is moisture-sensitive—Not specified for this item; refer to CoA/Spec Sheet.
    • Inorganic impurities/metal content (relevant for cross-coupling catalysis)—Not specified for this item; refer to CoA/Spec Sheet.
  • Use-case alignment:
    • For Suzuki–Miyaura couplings or medicinal chemistry SAR campaigns, low UV background and consistent boron speciation (boronic acid vs. boroxine) improve reproducibility.
    • If your workflow is GxP-regulated or requires enhanced documentation, request extended QC data and batch-specific analytical traces.

Reaction and Applications

• Core reactivity (general chemistry knowledge for arylboronic acids):

  • Suzuki–Miyaura cross-coupling: Couples with aryl/vinyl halides or triflates under Pd catalysis and base to give biaryls or aryl–vinyl products. The morpholine at para-position often enhances electron density, potentially facilitating transmetalation; the meta-chloro on the product side can serve as a handle for orthogonal follow-up couplings.
  • Chan–Lam coupling: Oxidative coupling with amines, alcohols, or amides under Cu and O2 to form C–N or C–O bonds.
  • Oxidation to phenols: Conversion to the corresponding phenol via oxidation (e.g., with H2O2 or peracids) as a route to 3-chloro-4-morpholinophenol.
  • Protodeboronation: Under strong base/heat, loss of boron to give the arene—useful if deboronation is desired; otherwise, minimize via milder conditions.

• Strategic utility of this substitution pattern:

  • Orthogonal handles: –B(OH)2 enables C–C/C–heteroatom bond formation; –Cl (meta) allows subsequent Pd-catalyzed coupling (with more forcing conditions than Br/I) or nucleophilic aromatic substitution if activated by additional ring electronics.
  • Polarity tuning: The morpholinyl substituent confers basicity and solubility, aiding parallel synthesis and purification in medicinal chemistry workflows.

• Practical tips (general):

  • Maintain slight water content in the medium for Suzuki (facilitates boronate formation); typical bases include K2CO3, K3PO4, Na2CO3, or Cs2CO3.
  • If boroxine formation is suspected (reduced solubility), pre-stir the solid with base/water or briefly pre-hydrolyze.
  • For sensitive substrates, use precatalysts (e.g., Pd-PEPPSI, Pd(dba)3 + ligand) and air- and moisture-stable ligands to improve reliability.

Reaction Conditions

All conditions below are literature-based general guidance for arylboronic acids and should be optimized for your substrates. They are not product specifications.

• Suzuki–Miyaura cross-coupling:

  • Catalyst: Pd(PPh3)4 (1–3 mol%), Pd(dppf)Cl2·DCM (1–3 mol%), or Pd-PEPPSI-type precatalysts (0.5–2 mol%).
  • Ligands: SPhos, XPhos, RuPhos, P(tBu)3 for challenging aryl chlorides (on the coupling partner if applicable).
  • Base: K2CO3, K3PO4, Cs2CO3, or Na2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O, THF/H2O, toluene/H2O, EtOH/H2O, DMF/H2O.
  • Temperature/Time: 60–100 C, 1–16 h; many systems reach 70–95% isolated yields with optimized ligation.
  • Tips: Maintain some water to assist boronate formation; pre-activate catalyst when using stubborn aryl chlorides.

• Chan–Lam C–N/C–O coupling:

  • Catalyst/Oxidant: Cu(OAc)2 (5–20 mol%) under air or O2; base such as Et3N or pyridine.
  • Solvent: MeOH, MeOH/DCM, or MeCN.
  • Temperature/Time: rt to 40 C, 4–24 h; typical yields 40–80%.

• Oxidation to phenol:

  • Reagents: H2O2/NaOH or Oxone in aqueous alcohols.
  • Conditions: 0–25 C, 0.5–4 h; quench and extract under basic conditions.

• Cautions (general):

  • Protodeboronation increases with strong base, prolonged heating, and electron-deficient rings—monitor by GC/HPLC.
  • Boroxine content may slow initial rate; brief pre-hydrolysis with base/water can normalize performance.

Safety and Handling

• Item-specific (Product Data):

  • GHS Classification: Not specified for this item; refer to SDS.
  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements: Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.
  • Storage Conditions: Room temperature.
  • Research Use Note: For research use only.

• General chemistry knowledge (safe handling guidance; not a substitute for SDS):

  • Likely hazards: Arylboronic acids and morpholine-containing aromatics are commonly classified as irritants. Avoid inhalation of dust and contact with skin/eyes.
  • PPE: Lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to limit inhalation of dust or solvent vapors during handling/dissolution.
  • Incompatibilities: Strong oxidizers may react with organic substrates; strong bases at elevated temperatures can promote protodeboronation. Avoid moisture during long-term storage if boroxine content is a concern; however, normal lab humidity is typically acceptable when containers are tightly closed.
  • First aid overview: If inhaled—move to fresh air; if on skin—wash with soap/water; if in eyes—rinse cautiously with water for several minutes; if ingested—rinse mouth and seek medical attention. Always follow site-specific emergency procedures.
  • Spills: Avoid dust generation; collect solids with minimal agitation. For solutions, absorb with inert material and dispose per local regulations.
  • Disposal: Treat as organic laboratory chemical waste; follow institutional and regulatory guidelines.
  • SDS: Consult the product-specific SDS for authoritative hazard classifications and response measures.

Solvent Selection

• General chemistry knowledge (applicability to arylboronic acids):

  • Polarity/functional profile: Amphiphilic due to polar B(OH)2 and morpholine (basic, polar) balanced by an aryl core and aryl chloride. Works well in polar aprotic media and mixed aqueous systems used for cross-coupling.
  • Typical solvent systems:
    • Polar aprotic: DMF, DMAc, DMSO, NMP—excellent for dissolution and for copper- or palladium-catalyzed couplings.
    • Mixed aqueous-organic for Suzuki: 1,4-dioxane/H2O; THF/H2O; MeOH/H2O; toluene/H2O (with phase-transfer or surfactants); MeCN/H2O.
    • Protic: EtOH/H2O blends are common when using soluble bases (K2CO3, K3PO4).
  • Solubility notes: The morpholinyl group increases solubility in polar media vs. unsubstituted arylboronic acids; water solubility remains formulation- and pH-dependent (boronate formation above pH ~8 increases aqueous solubility).

• Comparison (literature-based, general):

  • Dioxane/H2O vs. MeOH/H2O:
    • Dioxane mixtures often enable higher temperatures and good catalyst stability; MeOH/H2O can offer greener profiles and faster dissolution but may affect catalyst/ligand stability.
  • DMF/DMSO vs. 2-MeTHF/H2O:
    • DMF/DMSO maximize solubility; 2-MeTHF/H2O is greener and can work with modern micellar/ligated Pd systems, sometimes requiring higher temperatures or longer times.

• Item-specific (Product Data):

  • No solvent specifications are provided for this item; select based on the reaction platform and catalyst system.

Storage and Reconstitution

• Item-specific (Product Data):

  • Storage Conditions: Room temperature.
  • Shipped In: Normal.

• General chemistry knowledge (handling guidance):

  • Container: Store in a tightly sealed, chemically compatible container with desiccant if possible to limit moisture uptake and reversible boroxine formation.
  • Light/heat: Protect from excessive heat. Ambient light is generally acceptable; opaque storage is optional.
  • Stability: Arylboronic acids are typically stable for months to years at room temperature when kept dry and closed. Avoid prolonged exposure to strong bases or acids in solution.

• Reconstitution/stock solutions (practical guidance; not specifications):

  • Solvents: Prepare stocks in DMSO, DMF, MeCN, or alcohol/water blends depending on downstream use. Typical screening stocks are 10–100 mM in DMSO for medicinal chemistry workflows.
  • Filtration: If particulates are present, pass solutions through a PTFE or PES syringe filter (0.2–0.45 µm).
  • Freeze–thaw: For solutions, aliquot and store at 2–8 C or −20 C as appropriate for the solvent to minimize degradation; avoid repeated freeze–thaw cycles.
  • Solid recovery: If boroxine forms upon drying, gentle exposure to moist air or stirring in aqueous base during reaction setup reconverts to the boronic acid.

• Documentation: For batch-specific stability and any recommended solution shelf-life, refer to the CoA/Spec Sheet and SDS.

Structure and Identity

Brief description: 3-Chloro-4-morpholinophenylboronic acid is a substituted arylboronic acid bearing a para-morpholinyl group and a meta-chloro substituent on the phenyl ring.

• Item-specific (Product Data):

  • SKU: C181476
  • CAS: 1426246-59-4
  • Product Name: 3-Chloro-4-morpholinophenylboronic acid
  • Storage Conditions: Room temperature
  • Shipped In: Normal
  • InChIKey: 222575 (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 (for reference only):

  • Preferred name: 3-chloro-4-(morpholin-4-yl)phenylboronic acid
  • Typical molecular formula: C10H13BClNO3 (literature)
  • Typical molecular weight: ~241.48 g/mol (literature, calculated from formula)
  • Representative SMILES: B(O)O c1cc(Cl)cc(N2CCOCC2)c1 (literature)
  • Likely InChIKey (structure-derived): Not provided here; rely on SDS/CoA.

• Structural features (general chemistry knowledge):

  • Aromatic ring bearing three substituents: boronic acid group (–B(OH)2), chlorine (–Cl) at meta (3-) position, and a para (4-) morpholin-4-yl group attached via the ring nitrogen of morpholine.
  • Functional groups: arylboronic acid (Lewis acidic boron), tertiary amine within morpholine (basic), ether oxygen in the morpholine ring, aryl chloride (C–Cl).
  • 2D description: A 1,4-disubstituted phenyl (para to morpholine, meta to chlorine) with boronic acid at the ipso carbon; morpholine is a six-membered heterocycle containing one O and one N in a 1,4-relationship.

Synthetic Utility

• Functional group handles:

  • –B(OH)2: Platform for C–C (Suzuki–Miyaura) and C–heteroatom bond formations (Chan–Lam, oxidative couplings). Amenable to conversion to halides (via Matteson-type chemistry on boron derivatives) or to phenols (oxidation).
  • –Cl (meta): Orthogonal aryl chloride for secondary cross-couplings (often requiring more active catalysts/ligands, e.g., Buchwald-type ligands), or for nucleophilic aromatic substitutions when further ring activation is present.
  • Morpholin-4-yl: Modulates electronics (para electron-donating), increases polarity, and provides a tertiary amine site for salt formation or protecting-group strategies in downstream chemistry.

• Retrosynthetic value:

  • Enables convergent assembly of trisubstituted arenes: Couple this boronic acid with aryl/vinyl electrophiles to forge the biaryl/aryl–vinyl bond while deferring manipulation of the aryl chloride.
  • Late-stage diversification: The residual C–Cl can be transformed (e.g., to C–N, C–O, C–S, or C–C) after initial bond construction.

• Named reactions (literature):

  • Suzuki–Miyaura, Chan–Lam, Miyaura borylation (on derived intermediates), and Sandmeyer-type diversifications on subsequent anilines (post-coupling).

• Practical guidance:

  • For sequential couplings, first employ the boronic acid in Suzuki coupling (milder), then address the aryl chloride with stronger catalysts/conditions.
  • If solubility limits reaction rate, consider co-solvents (MeOH/H2O, DMF) or in situ formation of the more soluble boronate with aqueous base.

Target Specificity

• Not applicable. This product is a small-molecule chemical reagent (arylboronic acid), not a biological targeting agent (e.g., antibody, ligand with defined biomolecular target specificity). No antigen/epitope, clone, isotype, or species reactivity information applies.

자주 묻는 질문

What is the purity of this product?

This product is supplied at ≥96% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

How is this product shipped?

This product ships under standard ambient conditions. No temperature-controlled packaging is required.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1426246-59-4, the molecular formula is C10H13BClNO3, and the molecular weight is 241.5 g/mol. InChIKey MLYNSBCEZWQQEF-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.