5-Bromo-6-methoxy-1,3-dioxaindane - ≥98% , CAS No.10022-35-2

CAS: 10022-35-2 Cat. No.: B970472 Formula: C₈H₇BrO₃ Peso molecolare: 231.040 Numero EC: 999-069-6

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Specifiche e purezza

≥98%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥98%

Nomi e identificatori

• Sorrisi canonici: COC1=C(C=C2C(=C1)OCO2)Br
• IUPAC Name: 5-bromo-6-methoxy-1,3-benzodioxole
• InChIKey: NYSXBFLEQUHZNB-UHFFFAOYSA-N
• INCHI: 1S/C8H7BrO3/c1-10-6-3-8-7(2-5(6)9)11-4-12-8/h2-3H,4H2,1H3
• Peso molecolare: 231.040

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Benzodioxoles

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Benzodioxoles
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzodioxoles
• Alternative Parents: Anisoles Alkyl aryl ethers Aryl bromides Oxacyclic compounds Acetals Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Benzodioxole - Anisole - Alkyl aryl ether - Benzenoid - Aryl halide - Aryl bromide - Oxacycle - Ether - Acetal - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Organobromide - Organohalogen compound - Aromatic heteropolycyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as benzodioxoles. These are organic compounds containing a benzene ring fused to either isomers of dioxole. Dioxole is a five-membered unsaturated ring of two oxygen atoms and three carbon atoms.
• 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: 231.040 g/mol
• XLogP3: 2.400
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 229.958 Da
• Monoisotopic Mass: 229.958 Da
• Topological Polar Surface Area: 27.700 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 164.000
• 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

Not applicable.

• No validated bioassay or immunoassay protocols apply to this small-molecule building block. For practical usage, refer to Reaction & Applications and Reaction Conditions for synthetic protocols. If you require analytical methods, consider:
  • Identity: 1H/13C NMR, HRMS (observe Br isotope pattern), IR (aromatic C–H, C–O stretches).
  • Purity: HPLC or GC (if volatile enough); TLC on silica with hexanes/EtOAc.
  • Stability studies: Monitor by NMR after exposure to acid/base to confirm acetal robustness under planned conditions.

Biological Roles

Applicability

• This product is a synthetic organic intermediate, not a biomolecule. No intrinsic biological role is assigned.

General context (literature)

• Benzodioxole motifs occur in natural products and are used in medicinal chemistry to modulate lipophilicity, metabolic stability, and π–π stacking. The methoxy substituent increases electron density and can influence CYP-mediated oxidation pathways in derived compounds.
• Halogenation (bromine) on aromatic rings often enhances binding through halogen bonding in drug discovery analogs; however, such effects are context-dependent and pertain to final molecules rather than this starting material.

Practical note

• Any biological evaluation should be performed only on final target molecules synthesized from this building block. This catalog item is for research use only, and no biological activity should be inferred without empirical testing.

Buffer Applications

Not typically applicable.

• 5-Bromo-6-methoxy-1,3-dioxaindane is a hydrophobic aromatic building block, not a buffering agent. It does not constitute a conjugate acid–base pair suitable for maintaining pH.
• For practical guidance, refer instead to the Reaction & Applications, Synthetic Utility, and Reaction Conditions sections, which are most relevant to this compound’s use.

Green Alternatives

Context

• This item is a halogenated aromatic building block. Greenness considerations focus on choice of solvents, catalysts, and coupling partners rather than substituting the substrate itself.

Greener process choices (literature)

• Solvents: Prefer 2-MeTHF, CPME, bio-based ethyl acetate, or toluene over DMF/NMP/dioxane where feasible. Water–ethanol biphasic Suzuki protocols with micellar catalysis (e.g., TPGS-750-M) can be effective.
• Catalysts: Employ ligand-enabled low-Pd loadings (≤0.1–0.5 mol%) or Ni catalysis; consider recyclable heterogeneous catalysts (Pd/C under flow) when compatible.
• Bases: K3PO4 or K2CO3 in green solvents vs strong inorganic bases in polar aprotics; avoid inorganic halogenated waste where possible.
• Reagents: For cross-coupling, pinacol boronate esters are typically less toxic than stannanes (Stille). Copper-free Sonogashira reduces heavy-metal burden.

Illustrative comparison (general)

• Conventional vs greener conditions for Suzuki coupling:
  • Conventional: DMF or dioxane/H2O, Pd(PPh3)4 (1–2 mol%), Cs2CO3, 80–100 °C.
  • Greener: 2-MeTHF/H2O or EtOAc/H2O (micellar), Pd-precatalyst with biaryl phosphine (0.1–0.5 mol%), K3PO4, 50–80 °C.

Trade-offs

• Greener solvents may lower substrate solubility; slight temperature increases or co-solvents can compensate.
• Ni catalysis reduces Pd usage but can introduce different impurity profiles; robust workup and metal scavenging may be needed.

Pharmaceutical Uses

Scope

• This item is not an approved excipient or active ingredient. It is supplied strictly for research and development.

Formulation/manufacturing context (general)

• As a halogenated aromatic intermediate, it may be used in the synthesis of medicinal chemistry leads or intermediates featuring benzodioxole cores. Any role is upstream in API route scouting rather than in finished dosage forms.
• If incorporated into process chemistry, attention should be paid to removal of residual Pd/Ni/Cu catalysts and brominated byproducts to meet ICH Q3D/Q3A impurity expectations in downstream materials (general guidance).

Regulatory note

• No pharmacopeial monograph is expected for this fine chemical. Quality control should follow internal specifications supported by CoA data for each lot (assay, identity by NMR/HRMS, residual solvents, and, if relevant, metal residues).

Physical Properties

Item-specific (from Product Data)

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Other specifications (bp, mp, density, refractive index, purity): Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed (non-authoritative, for context only)

• Physical state: Typically an aromatic organic solid or low-melting solid for this class of benzodioxole derivatives; exact form depends on substitution pattern (literature).
• Solubility: Expected to be soluble in common organic solvents (e.g., dichloromethane, THF, toluene, ethyl acetate, acetonitrile) and poorly soluble in water (literature trends for aryl bromides/benzodioxoles).
• Volatility: Low volatility relative to low-boiling ethers; handle as a standard aromatic building block (literature).

General notes

• Without item-specific CoA values, users should determine melting range and chromatographic behavior (Rf in chosen eluent) on receipt to benchmark quality for their workflow.
• For cross-coupling, solvent choice and temperature window typically dominate handling rather than intrinsic volatility. If required, differential scanning calorimetry (DSC) or thermogravimetric analysis (TGA) can be performed in-house to establish safe processing temperatures.

Quality and Grades

Item-specific (from Product Data)

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

How to interpret and use grade information (general guidance)

• Research grade aromatic building blocks are typically supplied at assay ≥95% unless otherwise noted. When exact purity, residual solvent, or metal content is critical (e.g., for SAR studies or flow chemistry), consult the CoA for this exact lot.
• HPLC vs GC purity: For nonvolatile solids, HPLC area% is common; GC may be provided for more volatile analogs. UV cutoff and baseline behavior can matter if used in photochemistry or analytics; defer to CoA when applicable.
• Trace metals: Catalysis-sensitive applications may require low Pd/Ni/Cu background; if specifications are not provided, consider a prewash through metal-scavenging resin before use in ppm-sensitive transformations.
• Stabilizer implications: Acetal-containing aromatics typically do not require inhibitors. If your downstream chemistry involves strong acids (e.g., BBr3 demethylation), verify stability of the starting material by small-scale trials first.
• Recommended incoming QC: Quick 1H NMR in CDCl3 or DMSO-d6, check for expected aryl pattern, methoxy singlet (~3.7–3.9 ppm, literature) and acetal –CH2– singlet (~5.9–6.1 ppm, literature), plus HRMS to verify isotopic pattern for bromine (M and M+2).

Reaction and Applications

Core use (literature/general)

• A versatile aryl bromide on a benzodioxole (1,3-dioxaindane) scaffold for convergent assembly of functionalized aromatics.

Representative transformations

• Cross-couplings (Pd/Ni catalysis):
  • Suzuki–Miyaura: Coupling with aryl/alkenyl/alkyl boron reagents to diversify the 5-position. Typical systems: Pd(PPh3)4 or Pd-PEPPSI-type catalysts; bases K2CO3/Cs2CO3; solvents toluene/dioxane/2-MeTHF; 60–110 °C (literature).
  • Buchwald–Hartwig amination: Arylation of amines using biaryl phosphine ligands (e.g., XPhos, BrettPhos) and Pd2(dba)3; strong bases (NaOtBu) in toluene/dioxane (literature).
  • Sonogashira: Coupling with terminal alkynes under Pd/Cu or copper-free conditions in amine or amide solvents (literature).
  • Kumada/Negishi/Stille: Formation of C–C bonds via Grignard, organozinc, or stannane partners (literature).
• Metal–halogen exchange: i-PrMgCl·LiCl ("Turbo Grignard") or n-BuLi at low temperature to access aryllithium/magnesium intermediates followed by electrophile trapping (literature). The acetal and methoxy groups can modulate directing effects and stability.
• Electrophilic substitution on the ring is deactivated by bromine but enhanced ortho/para to methoxy; regioselectivity must consider the fused acetal.

Protecting-group behavior

• The 1,3-dioxa (acetal) ring is generally stable to base and mild nucleophiles, but cleaves under strong Brønsted or Lewis acids, unveiling dihydroxy functionality (literature). The methoxy can be demethylated with BBr3/AlCl3 to phenol if desired.

Applications

• Intermediate for agrochemical and medicinal chemistry scaffolds where benzodioxole motifs modulate electronics and metabolic stability (literature).

Reaction Conditions

General literature guidance (adjust to your system; verify experimentally)

• Suzuki–Miyaura coupling: 0.5–2 mol% Pd (e.g., Pd-PEPPSI, Pd2(dba)3/XPhos), 2–3 equiv base (K3PO4, K2CO3, Cs2CO3), solvents 2-MeTHF/H2O, dioxane/H2O, or toluene/H2O, 60–110 °C, 2–16 h. Typical isolated yields for comparable aryl bromides: 70–95% when optimized.
• Buchwald–Hartwig amination: 1–3 mol% Pd2(dba)3 with BrettPhos or RuPhos, NaOtBu or K3PO4, toluene or dioxane, 80–110 °C, 6–20 h. Electron-rich rings may require elevated temperature.
• Sonogashira coupling: 0.5–1 mol% Pd(PPh3)2Cl2, 2–5 mol% CuI (or copper-free), Et3N or i-Pr2NH, THF/amine or toluene, 25–80 °C, 2–12 h. Protect the acetal from adventitious acid.
• Halogen–metal exchange: n-BuLi (−78 to −40 °C) or i-PrMgCl·LiCl (−20 to 25 °C) in THF/2-MeTHF, 0.9–1.2 equiv, followed by electrophile quench (CO2, DMF, aldehydes). Quench carefully to avoid acetal cleavage.
• Demethylation (if needed): BBr3 (1–3 equiv) in DCM, −78 to 0 °C to rt, 1–6 h; note that strong Lewis acids may also open the acetal—pilot studies recommended.

Workup and purification

• Aqueous workup with saturated NH4Cl or NaHCO3 is generally compatible. Avoid acidic washes if acetal integrity is desired.
• Silica chromatography using hexanes/EtOAc (or toluene/EtOAc) with 0.5–1% Et3N can preserve the acetal and minimize tailing.

Safety and Handling

Item-specific (from Product Data)

• GHS classification, pictograms, signal word, H-statements: Not specified for this item; refer to SDS.
• Storage conditions: Room temperature (as provided).

General safety guidance (consult the SDS for authoritative information)

• Likely hazards for aryl bromide/benzodioxole derivatives include skin/eye irritation and aquatic toxicity; avoid inhalation of dust and contact with skin and eyes.
• Recommended PPE: Laboratory coat, nitrile gloves, safety glasses or splash goggles. Handle powders in a fume hood to minimize exposure.
• Incompatibilities: Strong acids/Lewis acids may cleave the acetal (1,3-dioxa) ring; strong bases and nucleophiles may cause undesired substitutions or demethylation under forcing conditions. Avoid strong oxidizers.
• Special risks: While not an ether solvent, the acetal motif is acid-labile; prevent exposure to mineral acids during storage. No general propensity for peroxide formation is expected for this class.
• First aid (overview):
  • Inhalation: Move to fresh air, seek medical attention if symptoms persist.
  • Skin contact: Wash with soap and water; remove contaminated clothing.
  • Eye contact: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; seek medical advice.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill and disposal: Collect solids by gentle sweeping/vacuum with HEPA capture; dispose of according to institutional and local regulations for halogenated organics.

Solvent Selection

Applicability

• This product is an aromatic building block rather than a solvent. Solvent selection here refers to choosing media for reactions, workups, and purification involving this compound.

General solvent compatibility (literature-based)

• Polar aprotic: THF, 2-MeTHF, dioxane, DMF, DMAc, NMP — useful for Pd/Ni-catalyzed cross-couplings and metal–halogen exchange. Acetal ring generally stable in neutral/basic aprotic media.
• Nonpolar/aromatic: Toluene, xylenes — suitable for high-temperature couplings (Suzuki, Buchwald–Hartwig) and for minimizing solvolysis.
• Halogenated: DCM, DCE — good solubility and workup performance; avoid strong acid contaminants that could cleave the acetal.
• Alcohols: MeOH, EtOH, i-PrOH — typically fine for purification; avoid strong acid catalysis in alcohols that could transacetalize.

Purification considerations

• Normal-phase silica gel with hexanes/EtOAc or toluene/EtOAc systems often separates aryl bromides cleanly; monitor for minor acid sensitivity on highly acidic silica. Neutralized silica (1–2% triethylamine) can protect the acetal if needed.
• Reverse-phase (C18, MeCN/H2O or MeOH/H2O) is feasible but the compound’s low aqueous solubility may limit loading.

Small comparison (literature guidance)

• THF vs 2-MeTHF: 2-MeTHF offers greener credentials and broader temperature range for organometallics; both dissolve aryl bromides well.
• DMF/DMAc vs toluene: Polar amides enhance catalyst solubility at moderate temps; toluene allows higher reflux for challenging couplings.

Storage and Reconstitution

Item-specific (from Product Data)

• Storage conditions: Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

General guidance

• Keep container tightly closed in a dry, well-ventilated area. Protect from strong acids and acid vapors to avoid acetal cleavage. Store away from oxidizing agents and strong bases.
• Moisture considerations: While acetals are generally stable to neutral moisture, prolonged exposure to acidic moisture can lead to hydrolysis; include a desiccant if local humidity is high.
• Light/air: No special light sensitivity is typical for aryl bromides, but storing in amber glass under air is standard. For long-term storage, an inert headspace (N2/Ar) is prudent but not required.
• Reconstitution/solution preparation: Dissolve in dry organic solvents (e.g., DCM, THF, toluene, EtOAc, MeCN). Filter through a PTFE syringe filter if particulates are present. Prepare reaction solutions immediately prior to use to minimize any adventitious acid exposure.
• Stability on bench: Expect good stability at room temperature in closed containers. Always refer to the product’s CoA/SDS for any lot-specific stability notes.

Research use

• For research use only. Not for human or veterinary use.

Structure and Identity

Item-specific (from Product Data)

• Product name: 5-Bromo-6-methoxy-1,3-dioxaindane (SKU: B970472)
• CAS: 10022-35-2
• InChIKey: 251451 (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 (non-authoritative, for context only)

• Structural class: Substituted 1,3-dioxaindane (benzodioxole-type acetal) bearing an aryl bromide (5-position) and a methoxy substituent (6-position) on the aromatic ring.
• Key functional groups:
  • Aryl bromide (cross-coupling handle)
  • Methoxy (electron-donating, ortho/para-directing)
  • 1,3-dioxa acetal ring (benzodioxole-like motif; acetal functionality)
• 2D description: A benzene ring fused to a 1,3-dioxole-type ring (two adjacent oxygens forming a five-membered acetal ring with a –CH2– bridge), with bromine at the 5-position and a methoxy group at the 6-position relative to the acetal bridgehead.

General notes

• The 1,3-dioxaindane scaffold is commonly used as a protected form of catechol-like motifs; the acetal ring can be unmasked under strong acidic or Lewis acidic conditions. The aryl bromide enables a wide range of Pd/Ni-catalyzed cross-couplings for late-stage diversification.

Synthetic Utility

Functional handles and reactivity (literature)

• Aryl bromide: Facilitates C–C and C–N bond formation via Pd/Ni-catalyzed cross-couplings (Suzuki, Sonogashira, Buchwald–Hartwig, Negishi, Kumada, Stille).
• Methoxy group: Electron-donating, ortho/para-directing; can serve as a temporary protecting group for phenol, removable by BBr3 or strong Lewis acids.
• 1,3-Dioxa (acetal) ring: Acid-labile protecting/embedding of a vicinal diol motif; resilient under basic and neutral conditions, enabling divergent sequences.

Strategic value

• Rapid library diversification at the 5-position via coupling, while preserving the benzodioxole core. Subsequent selective manipulations (e.g., demethylation, acetal opening) allow orthogonal access to catecholic phenols or further functionalization.
• Halogen–lithium or –magnesium exchange unlocks electrophile introduction (formylation, carboxylation, acylation) not always accessible by direct coupling.

Practical tips

• Use ligand sets tolerant of oxygenated aromatics (e.g., SPhos/XPhos/BrettPhos) to maintain high turnover on electron-rich rings.
• If acid-sensitive steps follow, protect the acetal by avoiding silica with residual acidity or neutralize with Et3N during chromatography.
• Monitor bromine isotopic pattern (M/M+2 ≈ 1:1) in MS as a rapid identity check.

Target Specificity

Not applicable.

• This product is a small-molecule building block and is not an antibody, enzyme, or biological targeting reagent. No target, epitope, species reactivity, clone, or isotype information applies.