4-Bromo-2,5-dichlorotoluene - ≥95% , CAS No.1807208-46-3

CAS: 1807208-46-3 Cat. No.: B954909 Formula: C₇H₅BrCl₂ Peso molecolare: 239.920

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

CC1=CC(=C(C=C1Cl)Br)Cl

IUPAC Name

1-bromo-2,5-dichloro-4-methylbenzene

InChIKey

XOARIGZDFQSITM-UHFFFAOYSA-N

INCHI

1S/C7H5BrCl2/c1-4-2-7(10)5(8)3-6(4)9/h2-3H,1H3

Peso molecolare

239.920

Proprietà chimiche e fisiche

• Peso molecolare: 239.920 g/mol
• XLogP3: 4.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 0
• Rotatable Bond Count: 0
• Exact Mass: 237.895 Da
• Monoisotopic Mass: 237.895 Da
• Topological Polar Surface Area: 0.000 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 118.000
• 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 immunoassay or bioanalytical application protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For practical use, see the Reaction Conditions section for chemistry workflows and typical coupling parameters.

Biological Roles

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

• General context

  • 4-Bromo-2,5-dichlorotoluene is a synthetic halogenated aromatic used as a chemical building block. It is not known as a natural metabolite or cofactor and has no established physiological role.
  • Hydrophobic, halogenated arenes typically partition into nonpolar phases and membranes; in biological systems they may display persistence and potential bioaccumulation—handle with care to prevent environmental release.

• Research use only

  • Any use in biochemical assays or probe development should be confined to in vitro or ex vivo research settings. Do not infer biological activity, safety, or efficacy from its chemical properties alone.

For toxicology, biodegradation, or ecotoxicity profiles, consult dedicated databases and the SDS; such endpoints are not specified for this catalog item.

Buffer Applications

This compound is a hydrophobic aromatic building block and is not used to formulate aqueous buffers. It has no conventional buffering capacity or defined pKa in the physiological range. For experimental work, focus instead on the Reaction & Applications and Synthetic Utility sections. If dissolution in aqueous media is required for assays, use cosolvents (e.g., DMSO) and appropriate dilution protocols.

Green Alternatives

As a halogenated aromatic building block, the compound itself is not readily replaceable; however, greener choices can be made in the processes that use it.

• Greener solvent choices (for couplings)

  • 2-MeTHF or CPME in place of THF/MTBE for organometallic steps (renewable origin, higher boiling, easier phase separation).
  • Toluene or anisole preferred over chlorinated solvents when compatible with catalyst and base.
  • Water-containing biphasic systems for Suzuki–Miyaura using aqueous carbonate/boronate salts when solubility permits.

• Catalyst/base optimization

  • Use highly active Pd–NHC or biaryl phosphine ligands to reduce catalyst loading (ppm levels) and lower energy input.
  • Nickel catalysis for aryl chloride activation can avoid rare/precious metals in later diversification steps.

• Comparative considerations (process-focused) | Aspect | Conventional choice | Greener alternative | Trade-offs | |---|---|---|---| | Ether solvent | THF | 2-MeTHF | Slightly different solubility; peroxide control still needed | | Halide activation | High Pd loading | Ni catalysis | Scope may narrow; air sensitivity | | Workup | DCM extraction | EtOAc or Me-THF | Partition changes; evaporation energy |

• Waste minimization

  • Favor boronate couplings with recyclable bases; implement solvent recovery; design telescoped sequences to use the aryl bromide first, deferring aryl chloride activation until needed to reduce protecting-group-like steps.

Pharmaceutical Uses

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

• General notes (formulation/excipient context)

  • 4-Bromo-2,5-dichlorotoluene is a synthetic intermediate and is not an approved excipient. Its primary role is as a building block en route to drug-like molecules during discovery and process development (research use only).
  • The orthogonal halides (Br vs Cl) on the ring enable convergent introduction of diverse substituents, facilitating SAR exploration in medicinal chemistry workflows.

• Process considerations

  • Downstream intermediates derived from this material must meet ICH and pharmacopeial impurity limits; early control of halogenated residuals, solvents, and metal catalysts is recommended.
  • Purification strategies (e.g., crystallization of advanced intermediates) can be designed to purge this starting material effectively due to its distinct hydrophobicity and UV absorbance.

No therapeutic claims are made or implied. This product is offered strictly for research and laboratory synthesis.

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.
  • Molecular weight (Product Data field): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed values (informational; not product specifications)

  • Empirical formula: C7H5BrCl2 (derived from substituent pattern)
  • Calculated formula mass: ~239.93 g/mol
  • Physical state at ambient conditions: many tri-halogenated toluenes are low-melting solids or high-boiling liquids; the exact MP/BP for this specific isomer is not provided here—consult primary literature or CoA for definitive values.
  • Polarity/solubility (general): nonpolar to weakly polar aromatic; expected to be sparingly soluble in water, and soluble in nonpolar and moderately polar organic solvents (e.g., hexanes, toluene, dichloromethane, THF, ethyl acetate).

• Not specified for this item; refer to CoA/Spec Sheet

  • Melting point, boiling point, density, refractive index, UV cut-off, water content, residual metals, or other analytical specs.

Note: Use the CoA/Spec Sheet for definitive, lot-specific properties when planning purification, storage, or scale-up.

Quality and Grades

• Item-specific status

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

• Guidance on interpreting grade (general)

  • Research-grade aryl halides are typically specified by GC/HPLC purity and residual solvent content; for coupling chemistry, low halide impurities and minimal protodehalogenated byproducts are advantageous.
  • If HPLC/GC grade is indicated on the CoA, it often implies low UV background impurities—useful for chromatographic monitoring and LC analytics.
  • Trace metals: For Pd-catalyzed couplings, adventitious metals rarely interfere, but if downstream catalysis is metal-sensitive, consult the metals panel on the CoA or purify further.

• Practical quality notes for this scaffold (general)

  • The aryl bromide position is typically the most reactive site under Pd-catalysis; ensure purity to avoid competitive reactions from unintended isomers.
  • Drying: If moisture-sensitive steps follow (e.g., lithium–halogen exchange), dry the substrate over molecular sieves and verify by Karl Fischer if needed (value not specified for this item).

For procurement control, rely on the Aladdin CoA/Spec Sheet for the definitive purity assay, analytical methods, and any stabilizers used for this catalog item.

Reaction and Applications

4-Bromo-2,5-dichlorotoluene is a versatile, differentially halogenated arene useful for modular assembly of polyfunctional targets.

• Cross-coupling platform (literature)

  • Aryl bromide site (C–Br) is the most reactive locus under Pd-catalysis, enabling selective first-step Suzuki–Miyaura, Sonogashira, Heck, or Buchwald–Hartwig reactions while preserving aryl chlorides.
  • Subsequent activation of the C–Cl bonds can proceed under more forcing conditions (e.g., Pd/XPhos, BrettPhos, or Ni catalysis) to allow orthogonal diversification.

• Benzylic functionalization

  • Oxidation of the methyl to benzaldehyde or benzoic acid derivatives (e.g., KMnO4, RuCl3/NaIO4, or Co/Mn/Br-catalyzed aerobic systems) retains the aryl halides for further cross-coupling.
  • Radical bromination (NBS/AIBN) affords benzyl bromide derivatives amenable to SN1/SN2 or transition-metal catalysis.

• Lithiation/metalation (handle with care)

  • Directed lithium–halogen exchange at the aryl bromide with n-BuLi at −78 °C in THF can generate aryl lithium for electrophile trapping; presence of aryl chlorides offers additional handles post-quench.

• Electrophilic aromatic substitution

  • The methyl group is ortho/para-directing and weakly activating; however, the two halogens are deactivating/ortho-para directing—overall, further EAS is diminished and regioselectivity is complex; cross-coupling routes are generally preferred.

• Applications

  • Assembly of drug-like scaffolds, agrochemical intermediates, materials monomers, and ligands where stepwise aryl functionalization is required (research use only).

Reaction Conditions

General literature guidance for reactions featuring aryl bromides and aryl chlorides; adjust to your substrate/catalyst system and consult primary sources.

• Suzuki–Miyaura coupling (C–Br first)

  • Catalyst: Pd(PPh3)4 (1–2 mol%) or Pd-PEPPSI/NHC (0.1–1 mol%)
  • Base: K2CO3, K3PO4, or Cs2CO3 (2–3 equiv)
  • Solvent: Toluene, 1,4-dioxane, or THF; often with H2O or EtOH/H2O (1:1) co-solvent
  • Temperature/time: 60–100 °C, 2–12 h

• Buchwald–Hartwig amination (C–Br first; C–Cl later with stronger ligands)

  • Catalyst/ligand: Pd2(dba)3 (0.5–1 mol%) with XPhos/SPhos/BrettPhos (2–4 mol%)
  • Base: NaOtBu or Cs2CO3 (2–3 equiv)
  • Solvent: Toluene or dioxane
  • Temperature: 80–110 °C

• Sonogashira coupling (terminal alkyne)

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (2–5 mol%)
  • Base: Et3N or i-Pr2NH
  • Solvent: THF, toluene, or DMF; 25–80 °C

• Aryl chloride activation (second-stage diversification)

  • Catalyst/ligand: Pd or Ni with bulky biaryl phosphines (BrettPhos, t-BuBrettPhos) or NHCs
  • Conditions: Often higher temperature (100–130 °C), polar aprotic solvents (dioxane, toluene, DMAc)

• Benzylic oxidation (to acid)

  • Oxidant: KMnO4 (aq. basic) or RuCl3/NaIO4 (biphasic)
  • Solvent: t-BuOH/H2O or CCl4/CH3CN/H2O (for Ru/NaIO4 systems)
  • Temperature: 0–80 °C depending on the system

• Metal–halogen exchange

  • Reagent: n-BuLi (1.0–1.2 equiv)
  • Solvent: Dry THF or 2-MeTHF
  • Temperature: −78 °C; quench with electrophile

These ranges are representative literature conditions and not product specifications. Optimize for your specific transformation and scale.

Safety and Handling

• Item-specific hazard data

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

• General safety guidance for halogenated aromatic compounds (informational)

  • Likely hazards: May cause skin/eye irritation and respiratory tract irritation on inhalation of vapors or dust. Halogenated aromatics can be harmful if swallowed and may present aquatic toxicity—avoid release to the environment.
  • PPE: Use chemical-resistant gloves (e.g., nitrile), lab coat, eye protection (splash goggles). Handle in a fume hood to minimize inhalation exposure.
  • Storage incompatibilities: Keep away from strong oxidizers (e.g., nitric acid, peroxides) and strong bases that could promote benzylic deprotonation under forcing conditions. Avoid prolonged exposure to light/heat.
  • Fire safety: As an organic aromatic, it is combustible. In fire, may release HCl/HBr and other corrosive/irritant fumes; use CO2, dry chemical, or foam for small fires.
  • Spill/first aid (overview): Absorb small spills with inert material; avoid environmental release. In case of skin contact, wash with soap and water. If in eyes, rinse cautiously with water for several minutes and seek medical attention if irritation persists. If inhaled, move to fresh air.

Always consult the product’s SDS for authoritative hazard classifications, exposure limits, and first-aid measures.

Solvent Selection

This product is a halogenated aromatic building block, not a solvent. However, solvent choice is critical for its handling, dissolution, and reactions.

• Polarity/miscibility profile (general)

  • Hydrophobic, weakly polar aromatic; expected to be insoluble in water but soluble in organic solvents such as toluene, xylene, dichloromethane (DCM), chloroform, ethyl acetate, THF, dioxane, and DMF/DMSO.

• Typical solvent choices by application (literature guidance)

  • Pd-catalyzed cross-coupling (Suzuki, Sonogashira): Toluene, dioxane, THF, or mixtures with water/alcohol; DMF or DMAc for more challenging couplings at elevated temperature.
  • Buchwald–Hartwig amination: Toluene or dioxane for aryl bromides; polar aprotics (DMF/DMSO) may enhance rates but complicate workup.
  • Metal–halogen exchange: Anhydrous ether solvents (THF, diethyl ether, or 2-MeTHF) at low temperatures.
  • Benzylic oxidations: Acetonitrile, t-BuOH/H2O, or glacial acetic acid depending on oxidant system.

• Practical tips

  • Solubilize at ambient or mild warming (30–40 °C) in toluene or DCM for solution-phase dispensing.
  • For biphasic couplings (e.g., toluene/H2O with K2CO3), add a phase-transfer agent if needed.
  • Avoid strong protic solvents when planning organometallic steps (e.g., lithiation).

When selecting the solvent system, balance substrate solubility, catalyst stability, green metrics, and downstream isolation needs.

Storage and Reconstitution

• Item-specific storage

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

• General handling guidance

  • Keep container tightly closed in a dry, well-ventilated place. Protect from excessive heat and direct sunlight.
  • If performing moisture- or air-sensitive transformations (e.g., lithiation), consider transferring to a dry glovebox-compatible vial or add a desiccant (e.g., 3 Å molecular sieves) after opening.
  • Minimize headspace and consider inert gas blanket for long-term storage to reduce potential oxidative discoloration.

• Reconstitution/solubilization

  • No reconstitution required. For stock solutions, dissolve in a suitable organic solvent (e.g., toluene, DCM, THF, DMF, or DMSO) at the desired concentration. Filter through PTFE (0.2 µm) if particulate is present.
  • For biological assays requiring aqueous media, prepare a DMSO concentrate and dilute into buffer with vigorous mixing; maintain final DMSO at ≤1–2% v/v when possible.

Always consult the product label and CoA/Spec Sheet for any lot-specific storage notes or stabilizers.

Structure and Identity

Brief overview: 4-Bromo-2,5-dichlorotoluene is a halogenated aromatic building block (aryl bromide with two aryl chlorides and a benzylic methyl). The substitution pattern offers orthogonal reactivity for stepwise cross-couplings and benzylic transformations.

• Item-specific facts (from Product Data)

  • SKU: B954909
  • Product name: 4-Bromo-2,5-dichlorotoluene
  • CAS: 1807208-46-3
  • CID: 117789394
  • InChIKey: 422886 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature identifiers (informational)

  • Molecular formula (derived from name): C7H5BrCl2
  • Calculated molecular weight: ~239.93 g/mol (literature/computed)
  • One plausible SMILES (literature/computed): CC1=CC(=C(C(=C1)Cl)Cl)Br

• Structural features (general description)

  • Core: monosubstituted toluene ring (benzene with a benzylic CH3)
  • Substituents: Br para to the methyl (4-position); Cl at 2- and 5-positions on the ring
  • Functional groups: aryl bromide, aryl chlorides, benzylic methyl (weakly activated C–H)
  • 2D description: six-membered aromatic ring bearing CH3 at C1; Cl at C2 (ortho to CH3); Br at C4 (para to CH3); Cl at C5 (meta to CH3). No stereocenters; planar aromatic system.

• Category context

  • Halogenated aromatic building block useful in Pd-catalyzed cross-coupling (Br site most reactive), with residual aryl chlorides enabling sequential diversification.

Synthetic Utility

• Orthogonal halide reactivity

  • C–Br position: Highly competent in Pd-catalyzed couplings under mild conditions; ideal for first-installation of aryl/vinyl/alkynyl/nucleophilic partners.
  • C–Cl positions: Less reactive; address in subsequent steps using stronger ligands (BrettPhos/XPhos/SPhos), Ni catalysis, or higher temperature for selective late-stage diversification.

• Benzylic handle

  • CH3 group enables oxidation (→ CHO/CO2H), halogenation (→ CH2X), or radical-mediated functionalization while maintaining aryl halides for later cross-couplings.

• Named reactions and strategies (literature)

  • Suzuki–Miyaura, Sonogashira, Heck, Negishi, Kumada–Tamao–Corriu at the aryl bromide; later, Buchwald–Hartwig or C–O/C–S couplings at the aryl chlorides.
  • Lithium–halogen exchange (−78 °C, THF) followed by electrophile trapping affords ortho/para elaborations inaccessible by EAS.
  • Directed metalation may be feasible adjacent to halogens under strong base with careful temperature control.

• Retrosynthetic value

  • Serves as a nodal intermediate for densely substituted anisoles, phenyl ethers, anilides, and biaryls with precise substitution patterns.

• Practical advantages

  • Step economy via selective activation: install at C–Br, then differentiate the two C–Cl sites based on sterics/electronics.
  • Stability: Generally stable to air and moisture; compatible with routine handling and storage (see Storage tab for conditions).

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, protein, or biological reagent with defined antigen/epitope specificity. Refer instead to the Reaction & Applications and Synthetic Utility sections for relevant use cases.