6-Bromo-3-nitroquinolin-4(1H)-one
[CAS# 853908-50-6]

Identification

• Classification: Organic raw materials >> Heterocyclic compound
• Name: 6-Bromo-3-nitroquinolin-4(1H)-one
• Molecular Formula: C₉H₅BrN₂O₃
• Molecular Weight: 269.05
• CAS Registry Number: 853908-50-6
• SMILES: C1=CC2=C(C=C1Br)C(=O)C(=CN2)[N+](=O)[O-]

Properties

• Density: 1.9±0.1 g/cm³ Calc.^*
• Boiling point: 389.3±37.0 ºC 760 mmHg (Calc.)^*
• Flash point: 189.3±26.5 ºC (Calc.)^*
• Index of refraction: 1.749 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Discovory and Applicatios

6-Bromo-4-hydroxy-3-nitroquinoline is a substituted quinoline derivative that combines a halogen, a nitro group, and a phenolic hydroxyl group on a bicyclic heteroaromatic framework. Its molecular formula is C9H5BrN2O3. The compound consists of a quinoline core bearing a bromine atom at the 6-position, a hydroxyl group at the 4-position, and a nitro group at the 3-position. It typically appears as a yellow to orange crystalline solid, reflecting the presence of the strongly electron-withdrawing nitro substituent and the extended conjugated aromatic system. The compound is sparingly soluble in water but shows better solubility in polar organic solvents such as dimethylformamide, dimethyl sulfoxide, and alcohols.

Quinoline derivatives have been studied extensively since the nineteenth century due to their occurrence in natural products and their broad range of biological and industrial applications. The development of highly substituted quinolines such as 6-bromo-4-hydroxy-3-nitroquinoline is rooted in systematic efforts to modify the quinoline scaffold in order to tune electronic properties, reactivity, and biological activity. The introduction of nitro and halogen substituents was historically motivated by dye chemistry and later by pharmaceutical and agrochemical research, where such groups were found to strongly influence molecular behavior.

The synthesis of 6-bromo-4-hydroxy-3-nitroquinoline generally proceeds through multistep aromatic substitution and cyclization strategies typical of quinoline chemistry. One common approach involves construction of the quinoline ring via a Skraup-type or Conrad-Limpach-type reaction using appropriately substituted aniline precursors, followed by regioselective nitration and halogenation. Alternatively, halogenated quinoline intermediates can undergo controlled nitration to introduce the nitro group at the desired position, with reaction conditions carefully optimized to avoid over-nitration or oxidation of the heterocycle. The hydroxyl group at the 4-position may be introduced directly during ring formation or generated by hydrolysis of a corresponding chloro or alkoxy precursor. Purification is usually achieved by recrystallization or chromatographic methods to ensure high regioisomeric purity.

Chemically, 6-bromo-4-hydroxy-3-nitroquinoline exhibits diverse reactivity due to the combined influence of its functional groups. The nitro group strongly withdraws electron density from the aromatic system, affecting both acidity of the hydroxyl group and reactivity toward electrophilic and nucleophilic substitution. The phenolic hydroxyl group can participate in hydrogen bonding and tautomeric equilibria, often existing in equilibrium with a corresponding quinolone form. The bromine atom at the 6-position provides a useful handle for further functionalization through metal-catalyzed cross-coupling reactions, enabling the introduction of aryl, heteroaryl, or alkyl substituents.

In practical applications, 6-bromo-4-hydroxy-3-nitroquinoline is primarily used as a synthetic intermediate rather than as an end-use material. It serves as a valuable building block in medicinal chemistry for the preparation of more complex quinoline-based compounds, which are widely explored for antimicrobial, antimalarial, anticancer, and anti-inflammatory activities. The combination of a nitro group and a halogen substituent allows systematic structure–activity relationship studies by subsequent chemical modification. In addition, substituted nitroquinolines are of interest in materials chemistry and dye research because their conjugated systems can exhibit distinctive optical and electronic properties.

From a physical and handling perspective, the compound is generally stable under ambient conditions but should be protected from strong reducing agents, which may convert the nitro group to an amine, and from strong bases that could deprotonate the phenolic hydroxyl group. Standard laboratory precautions are recommended when handling the solid, including the use of gloves and eye protection, as nitroaromatic compounds can be irritants. Storage in a cool, dry place away from light and moisture helps maintain chemical integrity.

Overall, 6-bromo-4-hydroxy-3-nitroquinoline represents a functionally rich quinoline derivative that reflects the long-standing importance of quinoline chemistry. Its defined substitution pattern provides a versatile platform for further chemical elaboration, supporting its continued use as an intermediate in heterocyclic synthesis, medicinal chemistry research, and the development of functional aromatic compounds.

References

2019. Synthesis of Dactolisib. Synfacts.
DOI: 10.1055/s-0039-1691091