2-Bromooxazole-4-carboxylic Acid: Handling & Use Protocol

2-Bromooxazole-4-carboxylic acid is a halogenated heteroaromatic building block widely employed in medicinal chemistry and materials science for palladium-catalyzed cross-coupling reactions, amide bond formation, and the synthesis of complex oxazole-containing scaffolds.

Chemical Name

2-Bromooxazole-4-carboxylic acid

SKU

B189875

Molecular Formula

C4H2BrNO3

Molecular Weight

191.97 g/mol

Key Functional Groups

Aryl bromide, carboxylic acid, oxazole ring

Recommended Storage

Cool, dry place; sealed container; away from light

Primary Applications

Suzuki–Miyaura coupling, amide coupling, heterocycle synthesis

Safety and Handling Precautions

2-Bromooxazole-4-carboxylic acid should be handled with standard laboratory precautions appropriate for halogenated heteroaromatic carboxylic acids. Always wear appropriate personal protective equipment (PPE), including chemical-resistant gloves, a laboratory coat, and safety goggles, when handling this reagent.

Work in a well-ventilated area or under a fume hood to minimize inhalation exposure to dust or aerosols. Avoid contact with skin, eyes, and mucous membranes. In the event of skin or eye contact, flush immediately with copious amounts of water and seek medical attention if irritation persists.

Consult the Safety Data Sheet (SDS) provided with the product before use. Dispose of waste materials in accordance with local, regional, and national regulations governing halogenated organic compounds.

Storage Conditions and Stability

Store 2-Bromooxazole-4-carboxylic acid in a tightly sealed container in a cool, dry location away from direct light and moisture. Heteroaromatic carboxylic acids bearing a halogen substituent can be sensitive to prolonged exposure to moisture and strong light, which may accelerate decomposition over time.

It is recommended to store the compound at room temperature or slightly below (2–8 °C) under an inert atmosphere (e.g., argon or nitrogen) if long-term storage is anticipated. Always allow the container to equilibrate to room temperature before opening to prevent condensation of atmospheric moisture onto the solid reagent.

Check the material for visual changes (discolouration, caking) before each use. If decomposition is suspected, verify purity by standard analytical methods such as TLC, HPLC, or NMR before committing the material to a sensitive synthetic step.

Solution Preparation and Compatibility

2-Bromooxazole-4-carboxylic acid is a solid at room temperature. For use in synthetic reactions, it is typically dissolved in polar aprotic solvents such as DMF, DMSO, or acetonitrile, or in protic solvents such as methanol or ethanol, depending on the downstream application.

When preparing solutions for coupling reactions (e.g., Suzuki–Miyaura or amide coupling), prepare fresh solutions immediately prior to use to maximise reagent integrity. Weigh the required quantity under ambient conditions and transfer to a dry round-bottom flask or vial before adding the appropriate solvent.

Compatibility note: The free carboxylic acid functionality may react with strong bases, strong nucleophiles, or reactive electrophiles under forcing conditions. Plan the reaction sequence carefully to protect or exploit this functional group as required by the synthetic target.

Representative Synthetic Applications

Suzuki–Miyaura Cross-Coupling: The C–Br bond at the 2-position of the oxazole ring is well-suited for palladium-catalysed Suzuki–Miyaura coupling with aryl or heteroaryl boronic acids and esters. Standard conditions employ a Pd(0) or Pd(II) precatalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂), a base (e.g., K₂CO₃ or Cs₂CO₃), and an aqueous co-solvent system (e.g., DMF/H₂O or dioxane/H₂O) at 80–100 °C.

Amide Bond Formation: The carboxylic acid group enables direct amide coupling with primary or secondary amines using standard coupling reagents such as EDC/HOBt, HATU, or PyBOP in DMF or DCM with a tertiary amine base (e.g., DIPEA or Et₃N). This approach is valuable for the preparation of oxazole-containing peptidomimetics and drug-like molecules.

Decarboxylation and Further Functionalisation: Under appropriate conditions, the carboxylate group can serve as a handle for further diversification, including conversion to acyl halides, mixed anhydrides, or esters, enabling access to a wide range of downstream heterocyclic intermediates.

Quality Verification Before Use

Before using 2-Bromooxazole-4-carboxylic acid (SKU B189875) in critical synthetic steps, it is advisable to confirm its identity and purity using one or more of the following analytical techniques:

• ¹H and ¹³C NMR Spectroscopy: Confirm the characteristic oxazole proton signal and the absence of extraneous peaks indicative of decomposition or impurities.
• HPLC: Reverse-phase HPLC with UV detection provides a quantitative purity assessment. Purity ≥95% is typically acceptable for synthetic use.
• Melting Point: Comparison with the reported melting point range can provide a rapid preliminary check of identity and crystalline integrity.
• Mass Spectrometry: ESI-MS or APCI-MS confirmation of the expected [M–H]⁻ or [M+H]⁺ ions at m/z consistent with the molecular formula C₄H₂BrNO₃ (MW 191.97 g/mol).

Document all quality-check results in your laboratory notebook or electronic laboratory record prior to initiating preparative-scale reactions.

Frequently asked questions

What solvents are suitable for dissolving 2-Bromooxazole-4-carboxylic acid?

2-Bromooxazole-4-carboxylic acid is generally soluble in polar aprotic solvents such as DMF and DMSO, as well as in protic solvents including methanol and ethanol. Solubility in water alone is limited due to the lipophilic oxazole ring, but aqueous mixtures with organic co-solvents can be used in cross-coupling reactions.

Can 2-Bromooxazole-4-carboxylic acid be used directly in Suzuki–Miyaura coupling without protecting the carboxylic acid?

Yes, in many cases the free carboxylic acid is tolerated under standard Suzuki–Miyaura conditions, particularly when using carbonate bases and aqueous co-solvent systems. However, under strongly basic conditions, proto-decarboxylation or side reactions may occur, so reaction conditions should be optimised empirically for each substrate combination.

How should I confirm the purity of 2-Bromooxazole-4-carboxylic acid before use?

Purity can be assessed by reverse-phase HPLC with UV detection, ¹H NMR spectroscopy, or TLC. Mass spectrometry is recommended to confirm molecular identity. For critical applications, purity ≥95% by HPLC is generally considered acceptable. Always check the certificate of analysis (CoA) supplied with the product.

What is the molecular weight of 2-Bromooxazole-4-carboxylic acid and how is it calculated?

The molecular formula is C₄H₂BrNO₃, giving a molecular weight of approximately 191.97 g/mol. This is calculated by summing the atomic weights of 4 carbons, 2 hydrogens, 1 bromine, 1 nitrogen, and 3 oxygens.

Is 2-Bromooxazole-4-carboxylic acid air- and moisture-stable?

The compound exhibits reasonable short-term stability under ambient conditions when stored in a sealed container. However, for long-term storage or in humid climates, it is advisable to keep it under an inert atmosphere and at reduced temperature (2–8 °C) to prevent slow hydrolysis or degradation of the oxazole ring.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. General reference for carboxylic acid and heteroaromatic chemistry.
2. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
3. Joullié, M. M.; Lassen, K. M. Evolution of Amide Bond Formation. ARKIVOC 2010, 189–250. General reference for amide coupling methodology.

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