4-Bromo-2-isopropoxybenzonitrile - ≥95% , CAS No.1369898-82-7

CAS: 1369898-82-7 Cat. No.: B954902 Formula: C₁₀H₁₀BrNO Peso molecolare: 240.100

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

CC(C)OC1=C(C=CC(=C1)Br)C#N

IUPAC Name

4-bromo-2-propan-2-yloxybenzonitrile

InChIKey

UVNQIMNRAKEMJH-UHFFFAOYSA-N

INCHI

1S/C10H10BrNO/c1-7(2)13-10-5-9(11)4-3-8(10)6-12/h3-5,7H,1-2H3

Peso molecolare

240.100

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Phenol ethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Phenol ethers
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenol ethers
• Alternative Parents: Phenoxy compounds Benzonitriles Bromobenzenes Alkyl aryl ethers Aryl bromides Nitriles Organopnictogen compounds Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Phenoxy compound - Benzonitrile - Phenol ether - Alkyl aryl ether - Bromobenzene - Halobenzene - Aryl bromide - Aryl halide - Monocyclic benzene moiety - Ether - Carbonitrile - Nitrile - Organic nitrogen compound - Organohalogen compound - Organobromide - Organonitrogen compound - Organooxygen compound - Hydrocarbon derivative - Cyanide - Organopnictogen compound - Organic oxygen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with 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: 240.100 g/mol
• XLogP3: 3.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 238.995 Da
• Monoisotopic Mass: 238.995 Da
• Topological Polar Surface Area: 33.000 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 208.000
• 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 as an assay reagent. No validated biological assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic use, refer to the Reaction Conditions and Synthetic Utility sections for general laboratory guidance.

Biological Roles

This product is a synthetic aromatic building block without an inherent biological role.

• Endogenous function: None; not a metabolite or biomolecule.
• Biochemical interactions (general considerations): Aromatic nitriles can bind hydrophobic pockets and occasionally act as weak electrophiles or polar acceptors in medicinal chemistry SAR contexts; however, any biological activity is highly scaffold- and target-dependent and is not implied for this specific compound.
• Stability in biological media: The nitrile group is generally metabolically robust; ether O–alkyl substituents may undergo oxidative O-dealkylation in vivo (literature, general). These comments are non-specific and for conceptual planning in research only.
• Use context: Suitable as a research building block for synthesis of small molecules that may later be screened in biological assays. No claims are made regarding activity, safety, or suitability for clinical applications.

Item-specific bioactivity data, ADME, or toxicology are not provided for this SKU; consult your institutional screening and safety protocols when incorporating derived compounds into biological testing.

Buffer Applications

Not typically applicable. 4-Bromo-2-isopropoxybenzonitrile is a neutral, hydrophobic organic building block and is not used as a buffering agent or pH stabilizer. For aqueous work, dissolve or disperse in suitable cosolvents (e.g., DMSO, DMF) before dilution into assay buffers if required by your protocol.

Green Alternatives

Greener choices usually pertain to solvent/catalyst selection and protecting-group strategy rather than the aryl scaffold itself.

• Solvent alternatives (general guidance):

  • Replace DMF/DMAc/dioxane with 2-MeTHF or CPME when compatible with your catalyst system; these offer improved safety profiles and facilitate phase separations.
  • Favor toluene/EtOAc mixtures over chlorinated solvents for work-up/chromatography when resolution allows.
  • Use water or water/ethanol cosolvent couplings (aqueous Suzuki protocols) where feasible to reduce organic solvent load.

• Catalyst and base choices:

  • Employ modern, highly active Pd–NHC or biaryl phosphine systems that operate at lower loadings and temperatures, minimizing energy use and metal residues.
  • Explore nickel-catalyzed couplings for cost and sustainability benefits where substrate tolerance permits.

• Protecting-group strategy:

  • If a phenol is ultimately required, consider synthesizing or sourcing the phenolic analog directly to avoid O-dealkylation steps with BBr3 (corrosive, waste-intensive). Alternatively, use milder oxidative or catalytic dealkylations when compatible.

Comparison snapshot (general):

• Dioxane vs 2-MeTHF: Similar coupling performance; 2-MeTHF is bio-derived, lower toxicity, but can change solubility/phase behavior.
• DCM vs EtOAc: EtOAc is less toxic and biodegradable; may require different chromatographic conditions.

Item-specific environmental metrics (e.g., PMI, E-factor, residual metals) are not specified for this SKU.

Pharmaceutical Uses

• Regulatory/compendial status: Not specified for this item; not offered as a pharmacopeial-grade substance.
• Formulation role: Not used as an excipient. This compound is a research-only synthetic intermediate/building block.
• Medicinal chemistry context (general): Aryl bromides with nitriles and alkoxy substituents are frequently incorporated into screening libraries to modulate lipophilicity, electronics, and vector geometry. The aryl bromide enables diversification by cross-coupling; the nitrile can serve as a polar handle or be transformed (reduction/hydrolysis) in late-stage routes.
• Manufacturing considerations: If transitioning a route to scale, consider removal of residual palladium/copper from coupling steps and verification of halogen content, nitrile integrity, and O-dealkylation byproducts by validated analytical methods.

No therapeutic or clinical claims are made. This product is provided strictly for research use only.

Physical Properties

Item-specific specifications are not provided in the Product Data; consult the CoA/Spec Sheet for authoritative values. The notes below reflect literature/general expectations for this structural class and should be used only as guidance.

• Physical state/appearance (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• Melting/boiling point (literature/general): Aryl bromonitriles with an additional alkoxy substituent are typically crystalline solids or low-melting solids with relatively high boiling points due to polarity and molar mass. Exact MP/BP for this compound is not widely tabulated; check primary literature or experimental records.
• Density (literature/general): Expected >1.2 g/mL for liquids containing bromine; solids may exhibit typical aromatic crystal densities. Not specified for this item.
• Solubility (literature/general):
  • Water: Expected very low due to hydrophobic aromatic core and limited H-bonding donors.
  • Organic solvents: Typically soluble in chlorinated solvents (DCM, CHCl3), moderately to well soluble in THF, EtOAc, acetone, toluene; highly soluble in polar aprotics (DMF, DMSO).
• Partitioning (literature/computed expectation): Moderately lipophilic (aromatic ring + isopropoxy + halogen); cLogP commonly in the ~3–4 range for similar scaffolds. Exact value not specified for this item.
• Refractive index, UV cutoff, residuals, trace metals (item-specific): Not specified for this item; refer to CoA/Spec Sheet.

Always verify critical property targets (e.g., solubility for assay prep, thermal behavior for purification) with a small-scale test under your exact conditions.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet for actual assay, impurity profile, and residual solvent limits.
• What grade implies (general guidance):
  • For synthetic building blocks, vendors often report HPLC area% assay and LC–MS purity. If designated “research grade,” materials are suitable for R&D synthesis and screening but are not qualified for GMP manufacturing without further controls.
  • If “99%” or similar is stated on the CoA, it typically refers to chromatographic purity under a specific method. Verify suitability for your analytical method (UV vs ELSD, gradient, detection wavelength).
• Stabilizers/antioxidants: Not specified for this item. Alkoxyaryl bromides/nitriles are generally stable without stabilizers under ambient storage when protected from moisture and strong light. If stabilizers are present, check compatibility with downstream reactions (e.g., coupling catalyst poisons).
• UV/fluorescence background: Not specified for this item. Aromatic materials can show UV absorbance; if using in trace analytics, verify baseline cleanliness with your gradient and detector settings.
• Batch-to-batch considerations (practical): Confirm halogen content by HRMS/ICP if critical, check water content by KF before moisture-sensitive steps, and screen for trace palladium/copper if sourced from cross-coupling-heavy routes (only if relevant to your process).
• Always rely on the CoA/Spec Sheet for definitive specifications on this specific SKU.

Reaction and Applications

4-Bromo-2-isopropoxybenzonitrile is a versatile bifunctional aryl building block combining a cross-coupling handle (Ar–Br), an electron-modulating isopropoxy group, and a nitrile as a robust, orthogonally reactive function.

Key application families (literature/general):

• Cross-coupling chemistry:
  • Suzuki–Miyaura: Formation of biaryls/heterobiaryls from the aryl bromide. The nitrile is generally well-tolerated; isopropoxy can direct subtle electronic effects on oxidative addition rate.
  • Buchwald–Hartwig amination: Installation of anilines/anilides using Pd, bulky phosphines; nitrile typically survives.
  • Sonogashira: Coupling to terminal alkynes (Pd/Cu or Pd-only protocols) to access aryl alkynes; nitrile remains intact under standard conditions.
• Directed metalation/functionalization: The nitrile can act as a weak ortho-directing group for lithiation adjacent to CN under strong base/low temperature (literature), though the present ortho isopropoxy changes directing patterns; care is required to avoid halogen–lithium exchange at bromide.
• O-Dealkylation to phenol: The isopropoxy can be cleaved (e.g., BBr3, AlCl3, or iodocyclohexane systems, literature) to reveal the phenol, enabling subsequent etherification, acylation, or sulfonylation.
• Nitrile elaboration (orthogonal): Hydrolysis (amide/acid), reduction (to aldehyde via DIBAL-H or to amine via LiAlH4/catalytic hydrogenation), and cyclizations to heterocycles. These transformations can be staged after cross-coupling to build complexity.

Practical tips:

• Use dry, degassed solvents for Pd-catalyzed couplings; control base strength to avoid unintended nitrile hydrolysis at elevated temperatures.
• If competing debromination is observed, consider more active ligands, lower temperature, or change solvent/base combination.

Reaction Conditions

General, literature-style guidance for typical transformations of aryl bromides bearing nitriles/alkoxy groups. Optimize for your substrates and scale.

• Suzuki–Miyaura coupling (biaryl formation):
  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd-PEPPSI/IPr-type NHCs (0.5–1 mol%).
  • Base: K2CO3, Cs2CO3, or K3PO4 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O, toluene/H2O, or 2-MeTHF/H2O.
  • Temperature: 70–100 °C; 2–8 h typically. Nitrile tolerated.
• Buchwald–Hartwig amination:
  • Catalyst/ligand: Pd2(dba)3 (1 mol% Pd) with XPhos/BrettPhos or Pd-precatalysts (e.g., XPhos Pd G2).
  • Base: NaOtBu or K3PO4.
  • Solvent: Toluene, dioxane, or CPME.
  • Temperature: 80–110 °C; 4–16 h.
• Sonogashira coupling (alkynylation):
  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) with CuI (2–5 mol%) or copper-free protocols with Buchwald-type ligands.
  • Base: Et3N, DIPEA, or K2CO3.
  • Solvent: THF, toluene, or DMAc; 40–80 °C.
• O-Deisopropylation to phenol (if desired):
  • Reagent: BBr3 (1–3 equiv) in DCM at −78 to 0 °C, then warm to rt; or AlCl3 in toluene (literature). Protect coupling-sensitive functions before Lewis acid exposure.
• Nitrile manipulations:
  • Reduction to aldehyde: DIBAL-H, −78 to −40 °C, toluene/THF.
  • Reduction to amine: LAH or catalytic hydrogenation (Raney Ni/Pd-C) where compatible.
  • Hydrolysis: Aqueous acid/base at reflux to amide/acid (longer times).

Notes:

• Degas solvents (freeze–pump–thaw or sparge) for Pd catalysis.
• If debromination or low conversion occurs, increase ligand bite angle, switch to more polar solvent, or raise temperature carefully.
• These are literature-style ranges; item-specific optimized conditions are not provided.

Safety and Handling

Item-specific GHS details are not provided in the Product Data. Always consult the product SDS for definitive hazard classification and first-aid measures.

• GHS/SDS: Not specified for this item; refer to SDS. As a general note, aromatic nitriles and aryl bromides are often classified as irritants; some may cause skin/eye irritation or respiratory discomfort on dust/vapor exposure.
• Primary hazards (general):
  • Irritation to skin/eyes/respiratory tract if contacted or inhaled as dust or vapors.
  • Combustible organic compound; avoid ignition sources.
  • Nitriles can hydrolyze under harsh acidic/basic conditions to amides/acids, generating heat and potentially releasing irritant vapors.
• PPE (good laboratory practice): Lab coat, safety glasses or goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Work in a fume hood to control vapors/particulates.
• Handling guidance:
  • Avoid breathing dust; minimize aerosol formation when weighing or transferring.
  • Use dry glassware if employing in moisture-sensitive reactions (e.g., metalation, cross-couplings).
• Incompatibilities (general): Strong bases/acids at elevated temperatures (nitrile hydrolysis), strong Lewis acids for extended times (may promote O-dealkylation), powerful nucleophiles, and reducing metals that may debrominate.
• First aid (overview; defer to SDS):
  • Skin/eye: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical evaluation.
  • Inhalation: Move to fresh air; monitor for symptoms; seek medical advice if persistent.
  • Ingestion: Rinse mouth; do not induce vomiting; obtain medical attention.
• Waste: Dispose according to local regulations for halogenated organic waste.

Solvent Selection

This compound is an apolar-to-moderately polar aromatic with one nitrile and one isopropoxy group; it is expected to be hydrophobic and to dissolve in common organic solvents.

• Polarity class (general): Weakly polar, non-protic aromatic. No H-bond donors; limited H-bond acceptors (nitrile N and ether O).
• Miscibility/solubility (general expectations):
  • Good: DCM, CHCl3, THF, EtOAc, acetone, toluene, acetonitrile, DMF, DMSO.
  • Poor: Water, brine, very nonpolar alkanes may require warming.
• When to choose which solvent (practical):
  • Cross-couplings: 1,4-dioxane/H2O, toluene, THF, or DMAc/DMF depending on base and catalyst.
  • Nucleophilic substitutions/metalations: THF, MTBE, or toluene under dry, inert atmosphere.
  • Chromatography: Elutes in mid-polarity regimes; hexanes/EtOAc or hexanes/MTBE gradients are often effective.
• Small comparison (general):
  • THF: Excellent for metal-mediated steps; peroxide formation risk upon storage (solvent, not substrate).
  • Toluene: Thermal robustness; good for high-temperature couplings.
  • DMF/DMAc: Strong solvating power; higher boiling points; ensure thorough work-up.
  • DCM: Fast evaporation; good for extractions and TLC.

Note: No item-specific solubility data are provided for this SKU; verify empirically at your working concentrations.

Storage and Reconstitution

• Storage condition (per Product Data): Room temperature. Store tightly closed in a dry place away from strong acids/bases and oxidizers. Protect from prolonged exposure to strong light.
• Shipped in: Not specified for this item.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Stability (general): Aryl bromide/nitrile ethers are typically stable under ambient conditions. Avoid extended exposure to moisture if subsequent moisture-sensitive reactions are planned.
• Reconstitution/solution preparation (general guidance):
  • Prepare stock solutions in dry organic solvents such as DMSO, DMF, THF, toluene, acetone, or DCM depending on downstream use.
  • For biological assays, dissolve in DMSO to make a concentrated stock, then dilute into aqueous buffers with vigorous mixing to minimize precipitation. Verify compatibility with assay components.
  • Filter solutions (0.2 µm PTFE) if particles are present.
• Freeze–thaw: If solutions are stored cold, minimize freeze–thaw cycles by aliquoting. Inspect for precipitation or decomposition before use.
• Shelf life: Not specified for this item; refer to CoA/Spec Sheet. Periodically confirm identity/purity by LC–MS/HPLC if long-term storage is expected.
• Research use note: For research use only.

Structure and Identity

A benzonitrile derivative bearing a para-bromide and an ortho isopropoxy substituent, useful as a bifunctional aryl building block.

• Product name (SKU): 4-Bromo-2-isopropoxybenzonitrile (B954902)
• CAS: 1369898-82-7; PubChem CID (literature): 114902333
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet. (General/literature expectation for this structure: C10H10BrNO)
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (General/literature calculation for C10H10BrNO ≈ 240.10 g/mol)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general description):

• Core ring: Monosubstituted benzonitrile (C6 aromatic) bearing a nitrile (–C≡N) at the benzylic ipso carbon.
• Halogen handle: A para-bromide (Ar–Br) provides a cross-coupling site (Suzuki, Sonogashira, Buchwald–Hartwig), with the nitrile generally tolerated under these catalyses.
• Alkoxy substituent: An ortho isopropoxy (–O–CH(CH3)2) group is a weakly electron-donating substituent that modulates ring electronics and can be dealkylated to the phenol if needed (e.g., BBr3, literature).
• 2D arrangement (words): Starting from the nitrile-bearing carbon as position 1, position 2 holds the isopropoxy group, and position 4 holds bromine. The substituents are arranged ortho (OR) and para (Br) to the nitrile, giving one halogen site and one masked phenol site on the same ring.
• Stereochemistry: None (all substituents achiral as drawn; isopropoxy introduces no stereocenter at oxygen).

Synthetic Utility

Functional handles and their typical reactivity (literature/general):

• Aryl bromide (Ar–Br):
  • Oxidative addition competent under Pd(0)/Ni(0) catalysis, enabling Suzuki, Kumada, Negishi, Stille, Buchwald–Hartwig, and Sonogashira couplings.
  • Halogen–lithium exchange possible at low temperature; exercise caution with adjacent directing groups and potential competitive ortho-lithiation.
• Nitrile (–C≡N):
  • Robust to many coupling conditions; transforms orthogonally via reduction (to aldehyde or amine), hydrolysis (amide/acid), and cycloadditions/annulations to form heterocycles (e.g., imidates, amidines).
  • Can act as a weakly coordinating group, sometimes influencing regioselectivity in metalation/functionalization.
• Isopropoxy (–OiPr):
  • Electron-donating, modulating ring reactivity; removable to phenol (BBr3/AlCl3 or catalytic systems), unlocking further substitution (e.g., sulfonylation, etherification) after coupling.

Strategic roles in synthesis:

• Diversity-oriented synthesis: Rapid access to analog series by varying the coupling partner while retaining nitrile for later-stage toggling.
• Retrosynthetic handle: Aryl–Br enables late-stage diversification on a pre-installed nitrile vector; OiPr serves as a temporary protecting group for the phenol.

Purification/analysis tips:

• Monitor by TLC/UPLC with UV detection (nitrile/aryl chromophores); confirm identity by HRMS (expected isotopic pattern due to Br). If streaking occurs on silica, add a small percentage of Et3N to the eluent or use neutral alumina.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or biological affinity reagent. No antigen/epitope or species reactivity information applies.