7-Bromo-5-methylquinoxaline: Properties, Synthesis & Applications

7-Bromo-5-methylquinoxaline is a halogenated bicyclic heteroaromatic building block widely employed in medicinal chemistry and materials science as a versatile intermediate for palladium-catalyzed cross-coupling reactions and further functionalization of the quinoxaline scaffold.

CAS Number

Needs verification — not confirmed in source material

Molecular Formula

C9H7BrN2

Molecular Weight

223.07 g/mol (calculated)

Core Scaffold

Quinoxaline (benzo[g]pyrazine) bicyclic ring system

Key Functional Handle

C-7 aryl bromide — suitable for Pd- and Cu-catalyzed coupling

Substituent

Methyl group at C-5 position modulates electron density and steric profile

SKU

B732460

Chemical Structure and Physical Properties

7-Bromo-5-methylquinoxaline belongs to the quinoxaline family of nitrogen-containing bicyclic heteroaromatics, comprising a benzene ring fused to a pyrazine ring. The compound bears two key substituents: a bromine atom at the 7-position and a methyl group at the 5-position. The molecular formula is C₉H₇BrN₂, giving a calculated molecular weight of approximately 223.07 g/mol.

The quinoxaline core is planar and electron-deficient due to the two ring nitrogen atoms, which lower the LUMO energy relative to naphthalene. The C-7 bromine is an excellent electrophilic handle for metal-catalyzed transformations, while the C-5 methyl group introduces mild steric bias and a slight increase in electron density on the adjacent ring carbons. Together, these features make the compound a differentiated building block compared with unsubstituted bromoquinoxalines.

Typical physical characteristics expected for this class of compound include a solid state at room temperature, moderate melting point, and solubility in common polar aprotic solvents such as DMF, DMSO, and acetonitrile, as well as in chlorinated solvents. Exact melting point, boiling point, density, and purity specification should be confirmed against the Certificate of Analysis supplied with SKU B732460.

Synthesis and Key Reactions

Quinoxaline derivatives are classically prepared by condensation of 1,2-diaminobenzene with a 1,2-dicarbonyl compound. 7-Bromo-5-methylquinoxaline can in principle be accessed by selecting an appropriately substituted diaminobenzene precursor bearing the methyl and/or bromo substituents in the required regiochemical positions, followed by condensation with glyoxal or an equivalent dicarbonyl synthon. Alternatively, late-stage bromination of a preformed methylquinoxaline can introduce the halogen with suitable directing control, though selectivity must be carefully managed given the electron-deficient ring system.

As a synthetic intermediate, the C-7 aryl bromide participates readily in a range of transition-metal-catalyzed transformations:

• Suzuki–Miyaura coupling: Reaction with aryl- or heteroarylboronic acids under Pd(0) or Pd(II) catalysis to install biaryl motifs.
• Buchwald–Hartwig amination: Pd-catalyzed C–N bond formation with primary or secondary amines, enabling access to aminoquinoxaline pharmacophores.
• Negishi and Kumada couplings: Use of organozinc or organomagnesium partners for C–C bond formation.
• Sonogashira coupling: Installation of alkynyl groups to give quinoxalinyl alkynes useful in materials science.
• Directed metalation / lithium–halogen exchange: Treatment with n-BuLi at low temperature generates an aryllithium species for addition to electrophiles.

The methyl group at C-5 can also serve as a synthetic handle; benzylic oxidation affords the corresponding aldehyde or carboxylic acid, extending the scope of downstream elaboration.

Applications in Medicinal Chemistry and Drug Discovery

The quinoxaline scaffold is a privileged heterocyclic framework in drug discovery, appearing in kinase inhibitors, antimicrobials, antivirals, and anticancer agents. 7-Bromo-5-methylquinoxaline provides a pre-halogenated, methyl-substituted variant that researchers can rapidly diversify via the cross-coupling reactions described above to generate focused libraries for structure–activity relationship (SAR) studies.

Key medicinal chemistry use cases include:

• Kinase inhibitor development: Quinoxalines are known scaffolds in inhibitors of receptor tyrosine kinases and serine/threonine kinases. The C-7 position is commonly used to append hinge-binding or solubilizing groups.
• Fragment-based drug discovery (FBDD): The compact, rigid bicyclic structure of bromoquinoxalines makes them useful fragments that can be elaborated once a binding hit is confirmed.
• Antimicrobial and antiparasitic leads: Quinoxaline 1,4-dioxides and related compounds have demonstrated biological activity against mycobacteria and protozoa; the bromo handle allows attachment of pharmacophoric extensions.
• PET radiotracer precursors: Aryl bromides on heteroaromatic scaffolds are employed as precursors for ¹⁸F-labeling via isotopic exchange or nucleophilic aromatic substitution where the ring electronics permit.

Researchers are advised to consult the primary literature for specific biological data, as activity profiles are highly dependent on the complete molecular context and assay conditions.

Handling, Storage, and Safety Considerations

As with all organobromine heteroaromatic compounds, 7-Bromo-5-methylquinoxaline should be handled with standard laboratory precautions. Personnel should wear appropriate personal protective equipment (PPE) including nitrile gloves, safety glasses, and a laboratory coat. Operations generating dust or aerosols should be conducted in a fume hood.

Storage recommendations for halogenated quinoxaline solids typically include:

• Storage in a tightly sealed container under an inert atmosphere (nitrogen or argon) to prevent moisture uptake and potential slow decomposition.
• Cool, dry conditions away from strong oxidizers, strong bases, and light.
• Recommended temperature: 2–8 °C or room temperature as specified on the product label and CoA for SKU B732460.

Disposal must comply with local and national regulations for halogenated organic waste. Users should consult the Safety Data Sheet (SDS) supplied by Aladdin Scientific for SKU B732460 for definitive hazard classification, first-aid measures, and disposal guidance. Specific GHS hazard pictograms, signal words, and H/P statements should be taken directly from the current SDS.

Frequently asked questions

What is 7-Bromo-5-methylquinoxaline used for in organic synthesis?

7-Bromo-5-methylquinoxaline is primarily used as a versatile building block in transition-metal-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Buchwald–Hartwig, and Sonogashira couplings, enabling the construction of diverse quinoxaline-based structures. It is particularly valued in medicinal chemistry for generating compound libraries targeting kinases and other therapeutic targets.

Which solvents are suitable for dissolving 7-Bromo-5-methylquinoxaline?

7-Bromo-5-methylquinoxaline, like most halogenated quinoxalines, is expected to dissolve well in polar aprotic solvents such as DMF, DMSO, acetonitrile, and THF, as well as in chlorinated solvents like dichloromethane and chloroform. Solubility in water is expected to be low due to the hydrophobic aromatic core. Exact solubility data should be confirmed from the product's SDS or CoA.

How should 7-Bromo-5-methylquinoxaline (SKU B732460) be stored to maintain stability?

The compound should be stored in a tightly sealed container under an inert atmosphere, in a cool and dry location away from moisture, strong oxidizers, and light. The specific storage temperature recommended for SKU B732460 is provided on the product label and Certificate of Analysis. Following these conditions will help ensure long-term reagent integrity.

Can the methyl group in 7-Bromo-5-methylquinoxaline be further functionalized?

Yes. The benzylic methyl group at C-5 can be oxidized to an aldehyde or carboxylic acid under appropriate conditions, providing additional synthetic handles for further elaboration. This extends the utility of the compound beyond its C-7 bromo handle, offering dual points of diversification on the quinoxaline scaffold.

Is 7-Bromo-5-methylquinoxaline suitable for fragment-based drug discovery?

7-Bromo-5-methylquinoxaline is well-suited as a fragment or fragment precursor in FBDD campaigns due to its compact, rigid bicyclic heteroaromatic structure and low molecular weight. The C-7 bromo group allows rapid synthetic elaboration once a fragment hit is identified, enabling efficient lead optimization.

References

1. Manske, R. H. F. The chemistry of quinoxalines. Chem. Rev. 1947, 41(1), 1–21.
2. Abele, E.; Abele, R.; Lukevics, E. Quinoxaline oximes: Synthesis, reactions, and biological activity. Chem. Heterocycl. Compd. 2003, 39(1), 3–23.
3. Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 1995, 95(7), 2457–2483. doi:10.1021/cr00039a007
4. Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Rational development of practical catalysts for aromatic carbon–nitrogen bond formation. Acc. Chem. Res. 1998, 31(12), 805–818. doi:10.1021/ar9600650

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