3-Bromo-4-Hydroxybenzoic Acid: Handling & Use Protocol

3-Bromo-4-hydroxybenzoic acid is a halogenated phenolic benzoic acid derivative widely used as a versatile building block in organic synthesis, medicinal chemistry, and the preparation of pharmaceutical intermediates.

CAS Number

14348-38-0

Molecular Formula

C₇H₅BrO₃

Molecular Weight

217.02 g/mol

Appearance

White to off-white crystalline powder

Key Functional Groups

Carboxylic acid (–COOH), phenol (–OH), aryl bromide (Ar–Br)

Recommended Storage

Sealed, away from light, at room temperature (15–25 °C)

SKU

B152311

Reagent Overview and Chemical Properties

3-Bromo-4-hydroxybenzoic acid (CAS 14348-38-0, MW 217.02 g/mol, molecular formula C₇H₅BrO₃) is an aromatic compound bearing three distinct reactive sites: a carboxylic acid group at the 1-position, a bromine substituent at the 3-position, and a phenolic hydroxyl group at the 4-position. This combination of functional groups makes it a highly versatile intermediate in organic and medicinal chemistry.

The aryl bromide moiety is amenable to transition-metal-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Buchwald–Hartwig), while the free carboxylic acid and phenol groups can be independently protected, esterified, etherified, or coupled to form amide bonds. The compound typically appears as a white to off-white crystalline powder and is sparingly soluble in water but soluble in polar organic solvents such as methanol, ethanol, dimethyl sulfoxide (DMSO), and acetone.

Safety and Handling Precautions

Before working with 3-Bromo-4-hydroxybenzoic acid, consult the Safety Data Sheet (SDS) provided by Aladdin Scientific. The compound is classified as an irritant; avoid inhalation of dust, contact with skin, and contact with eyes.

• Personal Protective Equipment (PPE): Wear chemical-resistant gloves (nitrile recommended), a laboratory coat, and safety goggles. Use a dust mask or work in a ventilated fume hood when handling powders.
• Inhalation Risk: Fine crystalline particles may cause respiratory irritation. All weighing and transfer operations should be conducted in a fume hood.
• Skin/Eye Contact: In case of skin contact, wash thoroughly with soap and water. In case of eye contact, flush immediately with copious water for at least 15 minutes and seek medical attention.
• Waste Disposal: Dispose of waste in accordance with local and institutional regulations for halogenated organic compounds.

Stock Solution Preparation Protocol

The following protocol describes preparation of a 100 mM stock solution for use in organic synthesis or biological assay applications.

1. Calculate required mass: For a 10 mL stock at 100 mM, calculate: mass (g) = 0.100 mol/L × 0.010 L × 217.02 g/mol = 0.217 g.
2. Weigh accurately: Tare a clean, dry glass vial. Weigh the calculated amount of 3-Bromo-4-hydroxybenzoic acid on an analytical balance inside a fume hood.
3. Select solvent: For most synthetic applications, dissolve in anhydrous DMSO or ethanol. For aqueous buffer systems, dissolve in a small volume of DMSO first, then dilute with buffer to the desired concentration (keep DMSO ≤ 1% v/v in biological assays).
4. Dissolve: Add approximately 80% of the target solvent volume and mix by vortexing or gentle stirring until fully dissolved. Gentle warming (40–50 °C) may aid dissolution. Bring to final volume.
5. Filter if necessary: Pass through a 0.22 µm PTFE syringe filter if a particle-free solution is required.
6. Label and store: Label the vial with compound name, CAS, concentration, solvent, date, and preparer. Store sealed at 2–8 °C protected from light. Use within 3 months or re-verify purity before use.

Typical Synthetic Applications

3-Bromo-4-hydroxybenzoic acid serves as a multifunctional building block in several key synthetic contexts:

• Suzuki–Miyaura Cross-Coupling: The aryl bromide can be coupled with arylboronic acids or esters in the presence of a palladium catalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂) and a base (e.g., K₂CO₃) to introduce diverse aryl groups at the 3-position. The carboxylic acid and phenol may be protected prior to coupling if needed.
• Esterification and Amide Formation: The carboxylic acid group undergoes standard esterification (Fischer, DCC-mediated, or acid chloride routes) or amide coupling (using EDC/HOBt or HATU activators) to produce esters or amide derivatives useful as pharmaceutical scaffolds.
• O-Alkylation (Phenol Etherification): The phenolic –OH can be selectively alkylated using alkyl halides under basic conditions (K₂CO₃/DMF) to produce aryl ethers while leaving the carboxylic acid intact or pre-protected.
• Pharmaceutical Intermediate Synthesis: The compound's structural features, combining a bromo handle with an acidic and a phenolic functionality, are valued in the synthesis of kinase inhibitors, antibacterial agents, and other bioactive molecules.

Note: Specific reaction conditions (catalyst loading, temperature, solvent, equivalents) should be optimized empirically for each application.

Quality Control and Analytical Verification

Upon receipt of 3-Bromo-4-hydroxybenzoic acid (SKU B152311), the following checks are recommended before use in critical applications:

• Visual Inspection: Confirm the material is a white to off-white powder with no signs of discoloration, clumping, or moisture ingress. Discoloration may indicate oxidative degradation of the phenol group.
• Melting Point: Verify identity by melting point determination. The expected melting point for 3-Bromo-4-hydroxybenzoic acid should be confirmed against literature values; flag and verify this value from a primary reference.
• TLC: Spot a dilute solution in ethyl acetate/hexane (3:7 or other appropriate system) alongside a reference standard. Visualize under UV (254 nm) and with KMnO₄ or FeCl₃ stain (to detect the phenol).
• NMR (¹H, ¹³C): Confirm structural identity. The ¹H NMR spectrum (in DMSO-d₆) is expected to show signals for three aromatic protons (characteristic ABX or AMX pattern), a broad carboxylic acid proton, and a phenolic OH proton.
• HPLC Purity: Run reverse-phase HPLC (C18 column, acetonitrile/water with 0.1% TFA gradient) to confirm purity ≥ 98% (as stated in product specification).

Record all QC data in a laboratory notebook and retain with the batch record.

Frequently asked questions

What solvents are recommended for dissolving 3-Bromo-4-hydroxybenzoic acid?

3-Bromo-4-hydroxybenzoic acid is sparingly soluble in water but dissolves readily in polar organic solvents such as DMSO, ethanol, methanol, and acetone. For aqueous biological assays, prepare a concentrated stock in DMSO and dilute with aqueous buffer, keeping the final DMSO concentration at or below 1% v/v to minimize solvent effects.

How should 3-Bromo-4-hydroxybenzoic acid be stored to ensure long-term stability?

Store the compound in a tightly sealed container away from light and moisture at room temperature (15–25 °C). Phenolic compounds can undergo oxidative discoloration upon prolonged exposure to air and light. For long-term archival storage, refrigeration at 2–8 °C in a desiccated, sealed vial is advisable. Re-verify purity by HPLC or TLC if the material has been stored for an extended period before use in critical experiments.

Can the phenolic OH and carboxylic acid groups of 3-Bromo-4-hydroxybenzoic acid be selectively functionalized?

Yes. The carboxylic acid (pKa ~4) and phenolic hydroxyl (pKa ~9) have substantially different acidities, allowing selective reactivity under appropriate conditions. For example, esterification or amide coupling at the carboxylic acid can often be conducted under mild acidic or neutral conditions without affecting the phenol. Conversely, O-alkylation of the phenol is favored under mildly basic conditions (e.g., K₂CO₃) that do not affect an unactivated carboxylic acid. Protecting group strategies (e.g., methyl ester for the acid, MOM or benzyl for the phenol) are also well established for orthogonal functionalization.

Is 3-Bromo-4-hydroxybenzoic acid suitable for Suzuki–Miyaura cross-coupling without protecting the acid or phenol groups?

Suzuki–Miyaura coupling can in principle be performed directly on unprotected 3-Bromo-4-hydroxybenzoic acid, as palladium catalysts are generally tolerant of free carboxylic acids and phenols. However, the free acid and phenol may coordinate to or partially poison the palladium catalyst under some conditions, potentially reducing yields. It is advisable to test the reaction with and without protection, or to use aqueous base conditions (e.g., Na₂CO₃ in dioxane/water) where the carboxylate anion is less problematic. Optimization of catalyst, ligand, and base is recommended.

What is the product SKU for 3-Bromo-4-hydroxybenzoic acid at Aladdin Scientific?

3-Bromo-4-hydroxybenzoic acid is available from Aladdin Scientific under SKU B152311. Please refer to the product page for current pricing, available pack sizes, purity specifications, and certificate of analysis information.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992. (General reference for carboxylic acid and phenol reactivity.)
2. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
3. Aladdin Scientific. Product Data Sheet: 3-Bromo-4-hydroxybenzoic acid, SKU B152311. (Consult current certificate of analysis for purity and spectral data.)

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