1-(5-Bromo-2-nitrophenyl)ethanone: Handling & Use Protocol

1-(5-Bromo-2-nitrophenyl)ethanone is a halogenated, nitro-substituted aromatic ketone widely employed as a versatile electrophilic intermediate in the synthesis of pharmaceutically relevant heterocycles and fine chemicals.

CAS Number

99194-43-1

Molecular Formula

C₈H₆BrNO₃

Molecular Weight

244.04 g/mol

Appearance

Pale yellow to yellow crystalline solid

Recommended Storage

Store in a cool, dry place away from light, in a tightly sealed container

SKU

B193343

Safety Precautions and Personal Protective Equipment

1-(5-Bromo-2-nitrophenyl)ethanone contains both a nitro group and a bromine substituent on the aromatic ring, and must be handled with appropriate caution. Before beginning any procedure, consult the Safety Data Sheet (SDS) for product B193343.

• Personal Protective Equipment (PPE): Wear nitrile gloves, a laboratory coat, and chemical splash goggles at all times when handling this compound.
• Ventilation: All weighing and dissolution steps must be performed inside a certified chemical fume hood to prevent inhalation of dust or vapors.
• Skin and Eye Contact: Avoid contact with skin and eyes. In the event of contact, flush immediately with copious amounts of water for at least 15 minutes and seek medical attention.
• Waste Disposal: Dispose of all waste materials, including contaminated solvents and gloves, in accordance with local institutional and regulatory guidelines for halogenated and nitro-aromatic waste.

Stock Solution Preparation and Solubility

Proper preparation of a stock solution is essential for reproducible experimental results. The following general procedure is recommended for 1-(5-Bromo-2-nitrophenyl)ethanone (B193343).

1. Solvent Selection: This compound is generally soluble in common organic solvents such as dichloromethane (DCM), dimethyl sulfoxide (DMSO), ethyl acetate, tetrahydrofuran (THF), and acetone. It has limited solubility in water. Select the solvent compatible with your downstream application.
2. Weighing: Tare a clean, dry glass vial. Using a calibrated analytical balance inside a fume hood, accurately weigh the required amount of solid compound.
3. Dissolution: Add the appropriate volume of dry, high-purity solvent to the vial. Cap and mix gently by vortexing or swirling until complete dissolution is achieved. If necessary, warm the solution gently (do not exceed 40 °C) to aid dissolution.
4. Concentration Verification: For critical applications, verify the actual concentration by UV-Vis spectrophotometry using an appropriate extinction coefficient, or by quantitative NMR.
5. Storage of Stock Solution: Aliquot the stock solution into amber glass vials, seal under inert gas (nitrogen or argon) if possible, and store at –20 °C or as dictated by stability data.

Note: Specific solubility values have not been independently verified; flag for experimental confirmation.

Application as a Synthetic Intermediate

1-(5-Bromo-2-nitrophenyl)ethanone (B193343) is a bifunctional building block exploited in multi-step organic synthesis. Its reactivity profile is defined by three key functional handles:

• Bromine substituent (C-5): The aryl bromide is amenable to palladium-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira), enabling introduction of diverse aryl, vinyl, alkynyl, or amino groups.
• Nitro group (C-2, ortho to carbonyl): The electron-withdrawing nitro group activates the ring toward nucleophilic aromatic substitution (SNAr) and can be selectively reduced to an aniline for further elaboration, including diazotization or cyclization to form indoles, benzimidazoles, or related heterocycles.
• Acetyl group: The methyl ketone participates in condensation reactions (aldol, Claisen, Knoevenagel) and can serve as a handle for enolate chemistry.

Typical reaction conditions should be optimized for the specific transformation. Conduct small-scale optimization reactions before scale-up. Monitor reactions by TLC or HPLC and confirm product identity by NMR and HRMS.

Quality Control and Analytical Characterization

Before use in critical experiments, verify the identity and purity of 1-(5-Bromo-2-nitrophenyl)ethanone (B193343) using the following analytical methods:

• Melting Point: Determine the melting point using a calibrated melting point apparatus and compare with literature values. Flag for review as the specific literature value was not confirmed in the source material.
• Thin-Layer Chromatography (TLC): Dissolve a small aliquot in DCM or ethyl acetate and spot on silica gel TLC plate. A single spot indicates high purity; Rf value will depend on solvent system selected.
• ¹H NMR Spectroscopy: Dissolve approximately 5–10 mg in deuterated DMSO (DMSO-d₆) or CDCl₃. Expected signals include: aromatic protons (3H, consistent with 1,2,4-trisubstituted pattern) and a methyl singlet from the acetyl group (~δ 2.6 ppm). Exact chemical shifts should be verified against authenticated reference spectra.
• HPLC Purity: Analyze by reverse-phase HPLC (C18 column, acetonitrile/water gradient) to determine purity percentage. A purity of ≥97% is typical for research-grade material.
• Mass Spectrometry: Confirm molecular ion consistent with MW 244.04 (¹⁷⁹Br/⁸¹Br isotope pattern expected for monobrominated compound).

Frequently asked questions

What solvents are suitable for dissolving 1-(5-Bromo-2-nitrophenyl)ethanone?

1-(5-Bromo-2-nitrophenyl)ethanone is generally soluble in polar aprotic and chlorinated organic solvents including DMSO, DCM, THF, acetone, and ethyl acetate. It has limited solubility in water. Always test solubility at your target concentration before use in a critical experiment.

What are the recommended storage conditions for B193343?

Store 1-(5-Bromo-2-nitrophenyl)ethanone in a tightly sealed container in a cool, dry, well-ventilated location away from direct light, heat, and incompatible materials such as strong oxidizers and bases. For long-term storage of solutions, aliquot into amber vials under inert atmosphere at –20 °C.

Can 1-(5-Bromo-2-nitrophenyl)ethanone be used directly in palladium-catalyzed cross-coupling reactions?

Yes, the aryl C–Br bond in 1-(5-Bromo-2-nitrophenyl)ethanone makes it a suitable electrophilic partner in palladium-catalyzed cross-coupling reactions such as Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig couplings. Reaction conditions, catalyst loading, ligand, base, and solvent should be optimized empirically for each specific transformation, as the electron-withdrawing nitro group may influence oxidative addition kinetics and catalyst compatibility.

How should I reduce the nitro group of this compound selectively without affecting the aryl bromide?

Selective reduction of the nitro group to an amine in the presence of an aryl bromide is feasible using mild, chemoselective reducing conditions. Commonly reported approaches include catalytic hydrogenation with carefully controlled conditions (low H₂ pressure, Pd/C), iron or zinc in acetic acid, or sodium dithionite in aqueous mixtures. The optimal conditions depend on substrate concentration and desired chemoselectivity and must be optimized experimentally; literature precedent for closely related substrates should be consulted.

References

1. Aladdin Scientific. Product Information Sheet: 1-(5-Bromo-2-nitrophenyl)ethanone, SKU B193343. Aladdin Scientific.
2. March, J.; Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. 7th ed. Wiley, 2013.
3. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.