3-Bromo-2-nitrobenzonitrile - ≥98% , CAS No.1261777-18-7

CAS: 1261777-18-7 Cat. No.: B932675 Formule: C₇H₃BrN₂O₂ Poids moléculaire: 227.010

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Spécifications et pureté

≥98%

Conditions de stockage de stockage

Room temperature

Pureté

≥98%

Noms et identifiants

Sourires canoniques

C1=CC(=C(C(=C1)Br)[N+](=O)[O-])C#N

IUPAC Name

3-bromo-2-nitrobenzonitrile

InChIKey

GRJNIVGBEWRZQY-UHFFFAOYSA-N

INCHI

1S/C7H3BrN2O2/c8-6-3-1-2-5(4-9)7(6)10(11)12/h1-3H

Poids moléculaire

227.010

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Nitrobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Nitrobenzenes
• Alternative Parents: Nitroaromatic compounds Benzonitriles Bromobenzenes Propargyl-type 1,3-dipolar organic compounds Nitriles Organopnictogen compounds Organobromides Organic oxoanionic compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Nitrobenzene - Nitroaromatic compound - Benzonitrile - Halobenzene - Bromobenzene - Organic nitro compound - C-nitro compound - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Allyl-type 1,3-dipolar organic compound - Nitrile - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organonitrogen compound - Organobromide - Organic hyponitrite - Organohalogen compound - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as nitrobenzenes. These are compounds containing a nitrobenzene moiety, which consists of a benzene ring with a carbon bearing a nitro group.
• 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

Propriétés chimiques et physiques

• Poids moléculaire: 227.010 g/mol
• XLogP3: 2.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 225.938 Da
• Monoisotopic Mass: 225.938 Da
• Topological Polar Surface Area: 69.600 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 229.000
• 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 biological assay protocols (WB, IHC, IF, FC, ELISA) apply to this product. For laboratory use, consider the following general synthetic handling practices (literature/general guidance):

• Weigh the solid quickly to minimize ambient moisture exposure; transfer to a dry vessel.
• Pre-dissolve in a compatible solvent (e.g., DMF, DMSO, MeCN, DCM) before charging to reactors to improve mixing.
• For air/moisture-sensitive reactions (Pd-catalyzed couplings), charge under inert atmosphere and use degassed, anhydrous solvents.
• Monitor reactions by TLC/HPLC/LC–MS; aryl bromide disappearance is a convenient handle.

Item-specific application protocols are Not specified for this item; refer to CoA/Spec Sheet.

Biological Roles

This substance is a synthetic aromatic building block and is not known to have intrinsic biological roles or metabolic functions. As such, it is typically used in chemical synthesis rather than in biochemistry or cell biology experiments.

General considerations (literature/general knowledge):

• Nitro- and nitrile-containing arenes can interact nonspecifically with biomolecules and are often cytotoxic at sufficient concentrations; they are therefore not used as biological buffers or metabolites.
• The compound may serve as a precursor to more complex molecules that could be evaluated in medicinal chemistry campaigns; however, no biological activity is implied or claimed for the material itself.

Research Use Note: For research use only. No clinical or diagnostic applications are intended.

Buffer Applications

Not typically applicable. 3-Bromo-2-nitrobenzonitrile is a hydrophobic synthetic intermediate, not a buffering agent. It lacks acid/base conjugate pairs in aqueous media and is poorly soluble in water. For practical use with this compound, refer instead to the Solvent Selection, Reaction & Applications, and Reaction Conditions sections.

Green Alternatives

Choice of solvent, base, and catalyst system has the greatest sustainability leverage for this substrate. Consider the following greener options (literature/general guidance):

• Solvents:

  • Prefer 2-MeTHF, CPME, or propylene carbonate over DMF/DMAc where feasible (e.g., Suzuki in 2-MeTHF/H2O with K3PO4).
  • Aqueous micellar catalysis (e.g., TPGS-750-M) can enable couplings in water at lower catalyst loadings.
  • Replace chlorinated solvents with ethyl acetate or 2-MeTHF for workups and recrystallizations when solubility permits.

• Catalysts and bases:

  • Use ligand-enabled, low-Pd systems (BrettPhos/XPhos) at 0.1–0.5 mol% where possible; explore Ni-catalyzed couplings for aryl–alkyl or aryl–aryl couplings to avoid Pd.
  • Choose inorganic bases with lower EHS footprint (K2CO3, K3PO4) over strong organic bases when compatible.

• Energy and process:

  • Employ continuous flow for exothermic SNAr or hydrogenations to enhance safety and heat/mass transfer.
  • Microwave assistance can shorten reaction times, reducing energy consumption.

Comparison snapshot (general):

| Aspect | Conventional | Greener alternative | |---|---|---| | Suzuki solvent | DMF or dioxane | 2-MeTHF/H2O or aqueous micelles | | Workup solvent | DCM | EtOAc or MTBE | | Catalyst | 2–3 mol% Pd | 0.1–0.5 mol% Pd or Ni | | Base | NaOtBu | K2CO3/K3PO4 |

Note: Verify solubility and reactivity for this specific substrate before switching; small test reactions are recommended.

Pharmaceutical Uses

There are no pharmacopeial monographs or excipient roles specified for this item. It is best regarded as a research chemical building block that can be incorporated into synthetic routes for candidate molecules.

• Excipient/formulation role: Not applicable.
• API manufacturing: May serve as an intermediate in multi-step syntheses due to its orthogonal handles (Ar–Br, –NO2, –CN), but no claims are made for any specific drug process.
• Regulatory status: Not specified for this item; refer to CoA/Spec Sheet for any available compliance notes.

All uses are strictly for research and development in laboratory or process development settings; no clinical or diagnostic use is intended.

Physical Properties

Item-specific physico-chemical specifications (bp, mp, density, UV cutoff, metal content, water/peroxide content) are Not specified for this item; refer to CoA/Spec Sheet.

General/literature-reasoned profile for 3-bromo-2-nitrobenzonitrile:

• Physical state/appearance: Typically a crystalline aromatic solid (literature/general knowledge); exact appearance Not specified for this item.
• Polarity: Moderately polar aromatic due to −NO2 and −CN; significantly less polar than typical salts; far less water-soluble than DMSO/DMF.
• Solubility (literature/general trends):
  • Low in water.
  • Good in polar aprotic organics (DMF, DMSO, NMP, acetonitrile) and chlorinated solvents (DCM, chloroform); moderate in ethyl acetate and acetone; variable in toluene/THF depending on temperature.
• LogP/logD: Not widely reported; expected positive logP due to aryl bromide with electron-withdrawing substituents (literature expectation), but Not specified for this item.
• pKa: Not applicable (no acidic/basic protic sites); the ring is deactivated; nitrile pKa of conjugate acid is very low (strongly basic media required), but specific values Not specified for this item.
• Refractive index, melting/boiling point, density: Not specified for this item; refer to CoA/Spec Sheet.

Always verify exact values against the CoA/SDS for the supplied lot.

Quality and Grades

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

Guidance on interpreting common grades for this compound class (general information):

• Analytical/Reagent grade: Typically controlled for assay, major impurities, and often low residual solvents/metals; suitable for most synthetic applications including Pd-catalyzed couplings.
• Low-metal or “cross-coupling grade”: Emphasizes minimized metal contaminants and halide purity that can affect catalytic reactions; useful if catalyst poisoning is observed.
• HPLC grade (solids context): Less common terminology for solids; when used, refers to low UV-absorbing impurities and high assay, facilitating purity analysis by HPLC/UPLC.

What matters for this building block:

• Halide integrity: Confirm correct aryl bromide identity and absence of debrominated or over-brominated isomers by NMR/LC-MS.
• Residual moisture: While solids are less hygroscopic, traces of moisture can affect base-sensitive steps (e.g., SNAr with alkoxides) and some cross-couplings. Drying prior to use may improve reproducibility.
• Particle size: Can influence dissolution and reaction initiation; milling or pre-dissolution in a compatible solvent may help scale-up consistency.

Always consult the batch CoA for assay, impurity profile, and any special notes from QC.

Reaction and Applications

3-Bromo-2-nitrobenzonitrile is a densely functionalized aryl electrophile useful for stepwise and orthogonal synthesis (literature/general guidance):

Key reaction families enabled by the aryl bromide:

• Pd-catalyzed cross-couplings:
  • Suzuki–Miyaura: Install (hetero)aryl or vinyl groups; the nitro and nitrile tolerate many catalytic systems.
  • Buchwald–Hartwig amination: Couple anilines or amines; care with base/ligand to avoid SNAr competition.
  • Sonogashira: Append alkynes; nitro group typically survives under mild conditions.
  • Carbonylations (Pd/Cu): Convert Ar–Br to amides/esters/acids under CO.

Reactivity of the nitro/nitrile handles:

• SNAr: The bromide is ortho to the nitro group, enabling nucleophilic aromatic substitution by amines, alkoxides, or thiolates under strong conditions (DMF/DMSO, base, heat) to give 2-nitro-3-substituted benzonitriles.
• Nitro group transformations: Reduction (e.g., H2/Pd-C, Fe/AcOH, SnCl2) to the aniline unlocks further derivatization (diazotization, coupling). Nucleophilic additions to the ring are possible post-reduction.
• Nitrile chemistry: Hydrolysis to amide/acid (acidic or basic conditions); reduction to primary amine (Raney Ni, catalytic hydrogenation, or borane). Nitrile also serves as a directing group in certain metalations.

Strategic value:

• Orthogonal functionalization: Couple at Ar–Br first, then reduce NO2 or manipulate CN; or perform SNAr to replace Br with heteroatom nucleophiles prior to cross-coupling at other positions.
• Electron-withdrawing groups enhance regioselectivity and stabilize Meisenheimer intermediates during SNAr.

Practical tips:

• Monitor for debromination in Pd-catalysis; optimize ligand/base to suppress.
• Avoid strong nucleophiles if the goal is to retain Ar–Br for cross-coupling.

Reaction Conditions

Typical literature conditions for this substrate class (adjust per substrate/catalyst; optimize experimentally):

• Suzuki–Miyaura coupling (Ar–Br → Ar–Ar):

  • Catalyst: Pd(PPh3)4 (1–2 mol%) or Pd-PEPPSI; Ligand alternatives: XPhos, SPhos.
  • Base: K2CO3 or K3PO4 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (3:1) or DMF; 80–100 °C.
  • Time/Yield: 2–12 h; often 60–90% isolated for compatible boronates (literature ranges).

• Buchwald–Hartwig amination (Ar–Br → Ar–NR2):

  • Catalyst: Pd2(dba)3 (0.5–1 mol% Pd) with XPhos/BrettPhos; Base: NaOtBu or Cs2CO3.
  • Solvent: Toluene, dioxane, or DMAc; 80–110 °C.
  • Note: Nitro group generally tolerated; avoid excessive reducing conditions.

• Sonogashira coupling (Ar–Br → Ar–C≡C–R):

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (2–5 mol%); Base: Et3N or i-Pr2NH.
  • Solvent: THF, DMF, or MeCN; rt–60 °C under inert atmosphere.

• SNAr at C–Br (ortho to NO2):

  • Nucleophile: RNH2 (2–4 equiv) or RO− (generated in situ with NaH/NaOMe).
  • Solvent: DMF/DMSO (amines) or the alcohol itself (alkoxides). 80–140 °C (or microwave 120–160 °C, 10–60 min).

• Nitro reduction (→ aniline):

  • H2 (1–5 bar), Pd/C (5–10 wt%), EtOH or EtOAc, rt–50 °C; or Fe/AcOH or SnCl2/HCl (stoichiometric) at reflux.

• Nitrile transformations:

  • Hydrolysis: Acidic (H2SO4 aq., reflux) or basic (KOH/EtOH/H2O, reflux) to amide/acid.
  • Reduction: BH3·THF or catalytic hydrogenation (Raney Ni) to primary amine.

All values are general literature guidance; verify on small scale before scale-up.

Safety and Handling

Hazard and GHS specifics for this catalog item are Not specified for this item; refer to the SDS for authoritative safety data.

General safety considerations for nitro- and nitrile-substituted aryl bromides (literature/general guidance):

• Likely hazards: May cause skin/eye irritation; harmful if swallowed or inhaled. Dust may be irritating. Nitroarenes can present methemoglobinemia risks upon significant exposure; nitriles may liberate toxic vapors under strong hydrolysis or combustion. Avoid creating dust.
• PPE: Wear lab coat, safety glasses or goggles, and appropriate chemical-resistant gloves (nitrile or equivalent). Use in a fume hood to control dust and vapors, especially during heating or coupling reactions.
• Incompatibilities: Strong bases and nucleophiles may react (intended in synthesis). Avoid strong oxidizers/reductants unless controlled. Thermal decomposition may produce HBr, NOx, and cyanide-containing species; maintain good ventilation.
• First aid (overview; follow SDS):
  • Skin: Wash with soap/water. Remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes; remove contact lenses if easy.
  • Inhalation: Move to fresh air; seek medical advice if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire-fighting: Use CO2, dry chemical, or foam. Combustion may release corrosive/toxic gases (HBr, NOx, HCN). Firefighters wear SCBA.

Research Use Note: For research use only.

Solvent Selection

This product is a solid aryl electrophile, not a solvent. The following guidance focuses on choosing solvents to dissolve and react 3-bromo-2-nitrobenzonitrile effectively (literature/general guidance):

• Polarity class: Moderately polar aromatic substrate; dissolves best in polar aprotic media and chlorinated organics.
• Good dissolution solvents: DMF, DMSO, NMP, acetonitrile, dichloromethane, chloroform; moderate in acetone/ethyl acetate; limited in toluene/THF unless heated.
• Aqueous miscibility: Insoluble to sparingly soluble in water; for biphasic couplings (e.g., Suzuki) use dioxane/H2O or DMAc/H2O with a phase-transfer base if needed.

When to choose which solvent (use-case focus):

• Pd-catalyzed cross-coupling (Suzuki/Buchwald/Sonogashira): 1,4-dioxane, DMAc, DMF, toluene (with polar cosolvent), or MeCN. Dioxane/H2O is a versatile choice for Suzuki with K2CO3.
• SNAr substitutions (amines/alkoxides): DMF/DMAc or DMSO for solubility and to stabilize anionic nucleophiles; MeOH or ROH as both solvent and nucleophile for alkoxide substitutions.
• Reductions (nitro to amine; nitrile to amine): Ethanol, isopropanol, or THF with hydrogenation catalysts; for hydride reductions, THF or EtOAc are common.

Practical tips:

• Pre-warm viscous polar aprotic solvents for rapid dissolution.
• Degas and dry solvent when performing moisture/oxygen-sensitive couplings.
• For workup, dilute with EtOAc or MTBE and wash with brine to remove polar solvents.

Storage and Reconstitution

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

General handling and reconstitution (literature/general guidance):

• Keep container tightly closed in a cool, dry, well-ventilated place. Protect from prolonged light and heat.
• If long-term storage is planned, consider desiccation over silica gel and storing in amber glass to mitigate photolysis.
• Before use, if necessary, dry under vacuum at ambient to 40 °C to remove adsorbed moisture/volatiles.
• Preparation of stock solutions: Dissolve in dry DMF, DMSO, NMP, MeCN, DCM, acetone, or EtOAc to the desired concentration. Filter if particulates remain. Store solutions in sealed vials under inert gas at 2–8 °C when compatible; assess stability prior to extended storage.
• Avoid repeated heating/cooling cycles and minimize headspace oxygen for solutions destined for Pd-catalyzed couplings.

Always consult the SDS/CoA for lot-specific stability notes and handling instructions.

Structure and Identity

A multifunctional aryl building block bearing three strong directing/activating features on a benzonitrile core: bromo (aryl halide), nitro (strong −I/−M), and nitrile.

• SKU: B932675
• Product name: 3-Bromo-2-nitrobenzonitrile
• CAS: 1261777-18-7
• PubChem CID: 118798306
• InChIKey (as provided in Product Data): 109561; standard InChIKey (literature): Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (computed/literature): C7H3BrN2O2
• Molecular weight (computed/literature): ~227.01 g/mol

Structural features (described in 2D terms):

• Benzonitrile ring (nitrile at position 1), with a nitro group at the 2-position (ortho to CN) and a bromo substituent at the 3-position (meta to CN, ortho to NO2).
• Functional groups: aryl bromide (cross-coupling handle), nitro (electron-withdrawing/activation for SNAr; reducible), nitrile (electrophilic carbon; hydrolyzable/reducible; directing group).
• Aromatic, no defined stereocenters, planar π-system with strongly deactivated ring due to −I/−M effects of NO2 and CN.

Note: Item-specific identifiers not listed above are Not specified for this item; refer to CoA/Spec Sheet.

Synthetic Utility

Strategic value (literature/general guidance):

• Three orthogonal handles on a benzonitrile core enable diverse, step-efficient elaborations:
  • Aryl bromide: Cross-coupling, carbonylation, metal–halogen exchange.
  • Nitro: SNAr activation and downstream reduction to an aniline (gateway to diazotization, Sandmeyer, acylation, sulfonylation).
  • Nitrile: Hydrolysis (amide/acid), reduction (primary amine), or used as a directing group.

Retrosynthetic considerations:

• As an intermediate toward 2-aminobenzonitrile derivatives: reduce NO2 → aniline, then leverage CN for further diversification or ring closures.
• For heteroaryl libraries: First install heteroaryl via Suzuki at Ar–Br, then convert NO2 to amine for urea/carbamate formation; CN retained as a handle for late-stage amide introduction.

Transformational highlights:

• SNAr at C–Br (ortho to NO2) with RO−/RNH− provides 2-nitro-3-heteroatom-substituted benzonitriles without metal catalysis.
• Tandem sequences: (i) Cross-couple at Ar–Br, (ii) chemoselective NO2 reduction, (iii) CN hydrolysis to amide for convergent assembly.
• Directed ortho-metalation adjacent to CN (where sterics/electronics permit) can enable further substitution patterns before or after manipulating the bromide.

Pitfalls and control:

• Competing pathways: Debromination in Pd-catalysis; over-reduction (NO2 → hydroxylamine → aniline) control via catalyst choice.
• Protecting-group logic: Consider temporary protection of the aniline formed after NO2 reduction if further cross-coupling is needed.

Target Specificity

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