2-Bromo-4-Fluorobenzaldehyde: Properties, Handling & Lab Use

2-Bromo-4-fluorobenzaldehyde is a bifunctionally activated aromatic aldehyde bearing both a bromine and a fluorine substituent on the benzene ring, making it a versatile and widely used building block in pharmaceutical synthesis, agrochemical research, and cross-coupling chemistry.

Chemical Name

2-Bromo-4-fluorobenzaldehyde

Molecular Formula

C₇H₄BrFO

Molecular Weight

203.01 g/mol

CAS Number

57848-46-1

Appearance

Colorless to pale yellow liquid or low-melting solid

Key Functional Groups

Aldehyde (–CHO), aryl bromide (C–Br), aryl fluoride (C–F)

Primary Applications

Suzuki/Buchwald cross-coupling, reductive amination, Schiff base synthesis, pharmaceutical intermediates

Chemical Identity and Structure

2-Bromo-4-fluorobenzaldehyde (CAS 57848-46-1; SKU B120674) is an ortho-bromo, para-fluoro substituted benzaldehyde with the molecular formula C₇H₄BrFO and a molecular weight of approximately 203.01 g/mol. The compound features three distinct reactive sites: (1) an electrophilic aldehyde carbonyl at the 1-position, susceptible to nucleophilic addition, reductive amination, and condensation reactions; (2) an aryl C–Br bond at the 2-position, which is a well-established substrate for transition-metal-catalysed cross-coupling reactions such as Suzuki–Miyaura, Negishi, and Buchwald–Hartwig amination; and (3) an aryl C–F bond at the 4-position, which, although less reactive than C–Br under standard Pd-catalysis, can participate in nucleophilic aromatic substitution (SNAr) when activated by the electron-withdrawing aldehyde group.

The combined steric and electronic effects of the ortho-bromo and para-fluoro substituents create a moderately electron-deficient aromatic ring, enhancing electrophilicity at the carbonyl carbon and at the ring positions ipso to fluorine. This electronic profile is highly valued in medicinal chemistry for fine-tuning the physicochemical properties—such as lipophilicity, metabolic stability, and membrane permeability—of drug candidates derived from this scaffold.

Physicochemical Properties and Storage

At ambient temperature, 2-Bromo-4-fluorobenzaldehyde typically presents as a colorless to pale yellow liquid or low-melting solid. Key physicochemical data are summarised below; researchers should consult the specific lot certificate of analysis (CoA) supplied with product SKU B120674 for confirmed purity and specification values:

• Molecular weight: 203.01 g/mol
• Molecular formula: C₇H₄BrFO
• CAS: 57848-46-1
• Solubility: Soluble in common organic solvents including dichloromethane, tetrahydrofuran, ethyl acetate, acetonitrile, and DMSO; sparingly soluble in water.

Storage recommendations: Store in a tightly sealed container in a cool (2–8 °C recommended), dry, and well-ventilated location away from direct light, moisture, heat sources, and incompatible materials such as strong oxidising agents and strong bases. Under these conditions the compound is expected to remain stable for an extended period; verify shelf life on the product label and CoA. Avoid prolonged exposure to air, as aldehydes are susceptible to oxidation to the corresponding carboxylic acid.

Safe Handling and Personal Protective Equipment

As with all halogenated aromatic aldehydes, 2-Bromo-4-fluorobenzaldehyde should be handled with appropriate caution in a well-ventilated laboratory environment, preferably inside a chemical fume hood. The following personal protective equipment (PPE) is strongly recommended:

• Eye protection: Chemical splash goggles or safety spectacles with side shields.
• Hand protection: Chemically resistant gloves (e.g., nitrile or neoprene); verify glove compatibility with the specific solvent system in use.
• Body protection: Laboratory coat and, where appropriate, chemical-resistant apron.
• Respiratory protection: Where ventilation is insufficient, use a respirator fitted with an organic vapour cartridge.

First aid measures: In case of skin or eye contact, flush immediately with copious amounts of water for at least 15 minutes and seek medical attention. If inhaled, remove the affected individual to fresh air and seek medical advice if symptoms persist. Consult the Safety Data Sheet (SDS) for SKU B120674 for full hazard classification, first-aid measures, and disposal procedures before use. Dispose of waste in accordance with applicable local, regional, and national regulations.

Review flag: Formal GHS hazard classification and H/P statements should be confirmed from the official SDS for SKU B120674 before publication.

Synthetic Applications and Laboratory Protocols

The multifunctional nature of 2-Bromo-4-fluorobenzaldehyde makes it a high-value reagent across diverse synthetic workflows. Key application areas include:

1. Transition-Metal-Catalysed Cross-Coupling

The aryl C–Br bond at the 2-position undergoes efficient Suzuki–Miyaura coupling with arylboronic acids in the presence of a Pd(0) or Pd(II) catalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂) and an inorganic base (e.g., K₂CO₃ or Cs₂CO₃) in aqueous THF or DMF at 80–100 °C. Negishi coupling with organozinc reagents and Buchwald–Hartwig amination with primary or secondary amines are similarly accessible via the C–Br handle, enabling rapid construction of biaryl and arylamine scaffolds relevant to drug discovery.

2. Nucleophilic Aromatic Substitution (SNAr)

The para-fluoro substituent, activated by the ortho-aldehyde electron-withdrawing group, can be displaced by nitrogen, oxygen, or sulfur nucleophiles under mild heating conditions in polar aprotic solvents such as DMF or DMSO. This reactivity enables direct introduction of amine, ether, or thioether linkages into the aromatic ring without requiring a metal catalyst.

3. Reductive Amination and Schiff Base Formation

The aldehyde functionality condenses readily with primary amines to form imines (Schiff bases), which can be isolated as stable intermediates or reduced in situ to secondary amines using reducing agents such as NaBH₄, NaBH₃CN, or NaBH(OAc)₃. This protocol is widely employed in combinatorial and medicinal chemistry for rapid library synthesis.

4. General Protocol Note

All reactions should be optimised with respect to catalyst loading, base, solvent, temperature, and reaction time using small-scale (0.1–0.5 mmol) pilot experiments before scale-up. Monitor reaction progress by TLC or HPLC. Purify products by column chromatography or recrystallisation as appropriate.

Quality, Purity and Procurement Guidance

Aladdin Scientific supplies 2-Bromo-4-fluorobenzaldehyde under SKU B120674. When ordering or evaluating this reagent, consider the following quality-related points:

• Purity verification: Check the Certificate of Analysis (CoA) for GC or HPLC purity, water content (Karl Fischer), and residual metal content if the compound is intended for sensitive catalytic reactions.
• Lot-to-lot consistency: Request CoAs for each lot received, particularly for regulated research or cGMP-adjacent workflows.
• Packaging: Available in multiple pack sizes to suit both exploratory research (small scale) and scale-up needs; consult the Aladdin Scientific product page or contact customer service for current availability and pricing.
• Regulatory and documentation support: SDS, CoA, and structural confirmation data (e.g., ¹H NMR, ¹³C NMR, or MS) may be requested from Aladdin Scientific's technical support team for SKU B120674.

Procurement teams should ensure that orders are placed through authorised Aladdin Scientific channels to guarantee product authenticity and traceability. Volume pricing and institutional account options may be available; contact Aladdin Scientific sales representatives for details.

Frequently asked questions

What are the main synthetic uses of 2-Bromo-4-fluorobenzaldehyde in medicinal chemistry?

2-Bromo-4-fluorobenzaldehyde serves as a versatile bifunctional building block. The aryl bromide participates in Pd-catalysed Suzuki, Negishi, and Buchwald–Hartwig cross-coupling reactions to form biaryl and arylamine scaffolds, while the aldehyde undergoes reductive amination or Schiff base condensation with amines. The para-fluorine can also be displaced via SNAr to install heteroatom linkages, making the compound valuable for rapid synthesis of drug-like molecules.

How should 2-Bromo-4-fluorobenzaldehyde be stored to maintain its stability?

The compound should be stored in a tightly sealed container at 2–8 °C in a cool, dry, and well-ventilated area, away from light, moisture, strong oxidising agents, and strong bases. Prolonged exposure to air should be avoided, as the aldehyde group is susceptible to oxidation to the corresponding carboxylic acid. Always refer to the product label and lot-specific CoA for confirmed shelf life.

Can the C–F bond in 2-Bromo-4-fluorobenzaldehyde be selectively reacted without affecting the C–Br bond?

Yes, under appropriate conditions the para-C–F bond can be selectively displaced via nucleophilic aromatic substitution (SNAr) without consuming the aryl C–Br bond, because fluoride is a much better leaving group than bromide in SNAr reactions due to its ability to stabilise the Meisenheimer complex. Reactions are typically run with nitrogen, oxygen, or sulfur nucleophiles in a polar aprotic solvent at elevated temperature. However, selective conditions must be empirically optimised, and the ortho-aldehyde group plays a key role in activating the ring toward SNAr.

What personal protective equipment (PPE) is required when handling 2-Bromo-4-fluorobenzaldehyde?

Handlers should wear chemical splash goggles, chemically resistant gloves (nitrile or neoprene recommended), a laboratory coat, and work inside a fume hood. Where ventilation is inadequate, an organic vapour respirator should be worn. Full hazard details are provided in the Safety Data Sheet (SDS) for SKU B120674, which should be reviewed before first use.

How do I confirm the purity of the 2-Bromo-4-fluorobenzaldehyde I receive from Aladdin Scientific?

Each batch of SKU B120674 is accompanied by a Certificate of Analysis (CoA) that reports purity data, typically determined by GC or HPLC. Additional characterisation data such as ¹H NMR or mass spectrometry confirmation may be requested from Aladdin Scientific's technical support team. Always match the lot number on the container to the CoA provided.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992. (General reference for SNAr, reductive amination, and cross-coupling mechanisms.)
2. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chemical Reviews 1995, 95, 2457–2483. doi:10.1021/cr00039a007
3. Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz, U. Industrial-Scale Palladium-Catalyzed Coupling of Aryl Chlorides and Amines—A Personal Account. Advanced Synthesis & Catalysis 2006, 348, 23–39. doi:10.1002/adsc.200505325
4. Aladdin Scientific. Product Page and Certificate of Analysis for 2-Bromo-4-fluorobenzaldehyde, SKU B120674. Retrieved from https://www.aladdin-e.com

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