5-Bromobenzofuran-3(2H)-one: Properties, Uses & Research Guide
5-Bromobenzofuran-3(2H)-one: Properties, Uses & Research Guide
5-Bromobenzofuran-3(2H)-one is a halogenated benzofuranone heterocycle widely employed as a versatile synthetic building block in medicinal chemistry, agrochemical research, and the development of bioactive small molecules.
- CAS Number
- 7355-54-6
- Molecular Formula
- C8H5BrO2
- Molecular Weight
- 213.03 g/mol
- Core Scaffold
- Benzofuran-3(2H)-one (2,3-dihydrobenzofuran-3-one)
- Key Functional Group
- Aryl bromide at C-5 position
- Primary Research Use
- Synthetic intermediate and cross-coupling partner
- Aladdin SKU
- B193858
Chemical Structure and Physical Properties
5-Bromobenzofuran-3(2H)-one belongs to the benzofuranone family of oxygen-containing bicyclic heterocycles. Its core structure consists of a benzene ring fused to a five-membered lactone ring bearing a ketone carbonyl at the 3-position and a methylene (–CH2–) group at the 2-position. The bromine substituent at the 5-position of the aromatic ring confers both electronic and steric properties that make this compound highly reactive in transition-metal-catalyzed transformations.
The compound has a molecular formula of C8H5BrO2 and a molecular weight of approximately 213.03 g/mol. The aryl bromide moiety is an excellent handle for palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Heck, Sonogashira, and Buchwald–Hartwig protocols, enabling efficient diversification of the scaffold. The carbonyl group further opens possibilities for nucleophilic addition and condensation chemistry at the 3-position.
Synthesis and Functionalization Strategies
5-Bromobenzofuran-3(2H)-one can be accessed from commercially available 5-bromosalicylaldehyde or related bromophenol precursors through well-established cyclization protocols. Alternatively, direct bromination of benzofuran-3(2H)-one at the 5-position provides a straightforward route, though regioselectivity must be carefully controlled.
Once in hand, the compound serves as a bifunctional platform for further elaboration. The C-5 aryl bromide participates readily in palladium(0)- and nickel-catalyzed coupling reactions under mild conditions, allowing installation of aryl, vinyl, alkynyl, or amino groups. Simultaneously, the activated methylene at C-2 can undergo base-mediated alkylation or aldol-type condensations, while the C-3 carbonyl is susceptible to reduction (e.g., with NaBH4) or Wittig olefination to access diverse benzofuran derivatives. This orthogonal reactivity makes 5-Bromobenzofuran-3(2H)-one a highly efficient scaffold for parallel synthesis campaigns.
Research Applications in Medicinal and Materials Chemistry
The benzofuran-3(2H)-one scaffold is a privileged structure found in numerous natural products and pharmaceutical candidates exhibiting a broad spectrum of biological activities, including anti-inflammatory, antimicrobial, antifungal, and anticancer properties. The introduction of a bromine atom at the C-5 position modulates the electronic density of the ring system, potentially influencing binding affinity and selectivity toward biological targets.
In medicinal chemistry, 5-Bromobenzofuran-3(2H)-one is primarily exploited as an intermediate for the rapid construction of compound libraries via diversity-oriented synthesis. Researchers leverage its cross-coupling reactivity to introduce pharmacophoric elements and screen resulting analogs in biological assays. Beyond pharmaceutical research, halogenated benzofuranone derivatives have attracted interest in materials science, particularly for the development of organic semiconductors and fluorescent probes, where the tunable electronic properties of the scaffold are advantageous.
Handling, Storage, and Safety Considerations
As with all organobromine compounds and lactone-containing reagents, appropriate laboratory safety precautions should be observed when working with 5-Bromobenzofuran-3(2H)-one. Personal protective equipment including nitrile gloves, safety goggles, and a laboratory coat should be worn at all times. Operations generating dust or aerosols should be conducted in a well-ventilated fume hood.
The compound should be stored in a tightly sealed container, protected from moisture and light, at room temperature or as specified on the product label. Prolonged exposure to air or moisture may lead to degradation. Researchers should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific prior to use for detailed hazard classifications, first-aid measures, and disposal guidelines compliant with local regulations.
Frequently asked questions
What cross-coupling reactions are compatible with 5-Bromobenzofuran-3(2H)-one?
The C-5 aryl bromide in 5-Bromobenzofuran-3(2H)-one is compatible with a wide range of palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with boronic acids), Heck (with alkenes), Sonogashira (with terminal alkynes), and Buchwald–Hartwig amination (with amines). Nickel-catalyzed variants may also be applicable. Optimization of catalyst loading, base, solvent, and temperature is recommended for each specific coupling partner.
How should 5-Bromobenzofuran-3(2H)-one be stored to maintain stability?
5-Bromobenzofuran-3(2H)-one should be stored in a tightly sealed container, away from moisture, light, and heat. Room-temperature storage under an inert atmosphere (nitrogen or argon) is generally recommended to prevent hydrolysis of the lactone and degradation of the aryl bromide functionality. Always refer to the Aladdin Scientific SDS and certificate of analysis for product-specific storage guidance.
What is the significance of the bromine substituent at C-5 compared to other positions?
The C-5 position on the benzofuran-3(2H)-one scaffold is electronically and sterically accessible, making it an ideal site for regioselective functionalization. Bromination at this position activates the aryl ring toward oxidative addition in transition-metal catalysis while introducing a moderate electron-withdrawing effect that can be exploited to tune the reactivity of the carbonyl at C-3. Compared to ortho or meta substitution patterns, the para-like C-5 substitution generally offers superior coupling efficiency and reduced steric interference.
Can 5-Bromobenzofuran-3(2H)-one be used directly in biological assays?
While the benzofuranone scaffold itself is associated with various biological activities in the literature, 5-Bromobenzofuran-3(2H)-one is primarily intended as a synthetic intermediate rather than a final active compound. Researchers wishing to evaluate its direct biological activity should consult relevant cytotoxicity and solubility data and work within appropriate biosafety guidelines. Its main value lies in enabling rapid synthesis of structurally diverse analogs for biological screening.
References
- Kaur R, Chaudhary S, Kumar K, Gupta MK, Rawal RK. Recent synthetic and medicinal perspectives of dihydrobenzofurans: An overview. Eur J Med Chem. 2017;132:108-134. doi:10.1016/j.ejmech.2017.03.026
- Mérour JY, Buron F, Plé K, Bonnet P, Routier S. The azaindole framework in the design of kinase inhibitors. Molecules. 2014;19(12):19935-19979.
- Clayden J, Greeves N, Warren S. Organic Chemistry. 2nd ed. Oxford University Press; 2012.
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