3-Bromo-2-methylbenzoic Acid: Properties, Handling & Lab Use

3-Bromo-2-methylbenzoic Acid is a halogenated aromatic carboxylic acid widely used as a versatile building block in organic synthesis, medicinal chemistry, and the preparation of pharmaceutical intermediates.

CAS Number

56909-20-7

Molecular Formula

C₈H₇BrO₂

Molecular Weight

215.04 g/mol

Appearance

White to off-white crystalline solid

Recommended Storage

Store at room temperature in a cool, dry, well-ventilated area away from light

SKU

B120922

Chemical Identity and Key Properties

3-Bromo-2-methylbenzoic Acid (CAS 56909-20-7) is an ortho-methyl, meta-bromo substituted benzoic acid derivative with the molecular formula C₈H₇BrO₂ and a molecular weight of approximately 215.04 g/mol. The compound features a carboxylic acid group at position 1, a methyl group at position 2, and a bromine atom at position 3 of the benzene ring. This specific substitution pattern creates a sterically distinct environment around the carboxyl group due to the adjacent methyl substituent, influencing its reactivity in cross-coupling and condensation reactions. The compound is typically presented as a white to off-white crystalline powder. Its dual functionality—an electrophilic C–Br bond available for transition-metal-catalyzed coupling and an acidic carboxyl group amenable to further derivatization—makes it a highly attractive scaffold in synthetic chemistry.

Synthetic Applications and Reaction Protocols

3-Bromo-2-methylbenzoic Acid serves as a multifunctional building block in several categories of organic transformations:

• Palladium-Catalyzed Cross-Coupling: The aryl C–Br bond participates in Suzuki–Miyaura, Heck, Negishi, and Buchwald–Hartwig coupling reactions. Standard Suzuki conditions employ Pd(PPh₃)₄ or Pd(dppf)Cl₂ as catalyst, an arylboronic acid partner, and a base such as K₂CO₃ in aqueous DMF or toluene at 80–100 °C.
• Carboxyl Group Functionalization: The carboxylic acid can be converted to acid chlorides (using oxalyl chloride or SOCl₂), esters, amides, or reduced to the corresponding benzyl alcohol, enabling downstream library synthesis.
• Directed Metalation: The methyl and carboxyl groups can act as directed metalation groups (DMGs) in lithiation protocols under cryogenic conditions (−78 °C, n-BuLi, THF), enabling introduction of additional substituents.
• Pharmaceutical Intermediate Preparation: Substituted benzoic acid derivatives of this type are commonly used in the synthesis of non-steroidal anti-inflammatory drug (NSAID) analogues, kinase inhibitor scaffolds, and heterocyclic precursors.

Researchers should optimize catalyst loading, base, solvent system, and temperature for each specific transformation. Thin-layer chromatography (TLC) and HPLC are recommended for reaction monitoring.

Safe Handling and Storage Guidelines

Although 3-Bromo-2-methylbenzoic Acid is a solid reagent with relatively low acute toxicity compared to reactive organohalogens, standard laboratory safety precautions must be observed:

• Personal Protective Equipment (PPE): Wear nitrile gloves, safety glasses, and a laboratory coat when weighing and handling. Use a dust mask or work in a fume hood if powder generation is possible.
• Inhalation and Skin Contact: Avoid prolonged inhalation of dust. In case of skin or eye contact, rinse thoroughly with copious amounts of water for at least 15 minutes and seek medical attention if irritation persists.
• Storage Conditions: Store in a tightly sealed container at room temperature in a cool, dry, dark location. Protect from moisture and oxidizing agents. Keep away from incompatible materials such as strong bases and oxidizers.
• Disposal: Dispose of in accordance with local, regional, and national regulations for halogenated organic waste. Do not pour down the drain.
• Spill Management: Collect solid spills with a non-sparking tool and transfer to a labeled waste container. Avoid generating airborne dust during cleanup.

Always consult the Safety Data Sheet (SDS) for the most current hazard information before use.

Quality, Purity and Analytical Verification

For research applications, the purity and identity of 3-Bromo-2-methylbenzoic Acid should be confirmed before use, especially in sensitive synthetic sequences or biological assays. Recommended analytical methods include:

• ¹H NMR Spectroscopy: Confirms the substitution pattern. Key signals include the aromatic protons (typically 3H in the 7–8 ppm region with specific coupling patterns), the methyl singlet (3H, approximately 2.3–2.5 ppm), and the broad carboxylic acid proton (1H, 10–12 ppm).
• HPLC Purity Analysis: Reverse-phase HPLC (C18 column, UV detection at 220–254 nm) provides quantitative purity assessment. High-purity grades (≥97–98%) are recommended for pharmaceutical intermediate applications.
• Melting Point Determination: Comparison of observed melting point with literature values is a useful identity and purity check.
• Mass Spectrometry: ESI-MS or GC-MS can confirm molecular weight and detect the characteristic bromine isotope pattern (M and M+2 in approximately 1:1 ratio).

Aladdin Scientific supplies 3-Bromo-2-methylbenzoic Acid (SKU: B120922) with a certificate of analysis (CoA) providing lot-specific purity and analytical data. Contact technical support for additional specifications.

Frequently asked questions

What is 3-Bromo-2-methylbenzoic Acid used for in organic synthesis?

3-Bromo-2-methylbenzoic Acid is primarily used as a bifunctional building block. The aryl bromide moiety undergoes palladium-catalyzed cross-coupling reactions (e.g., Suzuki, Heck), while the carboxylic acid group enables conversion to esters, amides, and acid chlorides. It is also a valuable precursor in the synthesis of pharmaceutical intermediates and fine chemicals.

How should 3-Bromo-2-methylbenzoic Acid be stored to maintain stability?

The compound should be stored in a tightly sealed container at room temperature in a cool, dry, and dark location, protected from moisture and incompatible materials such as strong oxidizers and strong bases. Under these conditions, the solid reagent is expected to remain stable for an extended period. Always refer to the product's Certificate of Analysis (CoA) and SDS for specific storage recommendations.

How can I confirm the identity and purity of 3-Bromo-2-methylbenzoic Acid received from Aladdin Scientific?

Identity and purity can be confirmed using ¹H NMR spectroscopy, reverse-phase HPLC, melting point determination, and mass spectrometry (looking for the characteristic M and M+2 bromine isotope pattern). Aladdin Scientific provides a Certificate of Analysis (CoA) with each lot, detailing purity data and analytical results. For further technical inquiries, contact Aladdin Scientific's technical support team.

Is 3-Bromo-2-methylbenzoic Acid compatible with Suzuki–Miyaura coupling conditions?

Yes, the aryl C–Br bond in 3-Bromo-2-methylbenzoic Acid is reactive under standard Suzuki–Miyaura conditions. However, the adjacent methyl group introduces steric hindrance near the reaction site, which may require optimization of catalyst, base, and reaction temperature to achieve high yields. Bulkier phosphine ligands or more active palladium precatalysts may be beneficial in sterically demanding cases.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992.
2. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
3. Snieckus, V. Directed ortho metalation. Tertiary amide and O-carbamate directors in synthetic strategies for polysubstituted aromatics. Chem. Rev. 1990, 90, 879–933. doi:10.1021/cr00104a001

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