2-Chloroquinoxaline: Properties, Synthesis & Applications

2-chloroquinoxaline is a halogenated bicyclic heteroaromatic compound widely employed as a versatile electrophilic building block in medicinal chemistry, agrochemical research, and the synthesis of functionally diverse quinoxaline derivatives.

CAS Number

1448-87-9

Molecular Formula

C₈H₅ClN₂

Molecular Weight

164.59 g/mol

Appearance

White to off-white crystalline solid

Melting Point

Approx. 48–51 °C (literature range)

Key Reactivity

Electrophilic C-2 position; undergoes nucleophilic aromatic substitution (SNAr)

Aladdin SKU

C132475

Chemical Structure and Physical Properties

2-Chloroquinoxaline (CAS 1448-87-9) belongs to the quinoxaline family of benzopyrazine heterocycles. Its molecular formula is C₈H₅ClN₂ with a molecular weight of 164.59 g/mol. The compound features a fused benzene–pyrazine bicyclic ring system in which a chlorine atom is installed at the 2-position of the pyrazine ring.

The presence of two ring nitrogen atoms withdraws electron density from the aromatic system, rendering the carbon bearing the chloro substituent markedly electrophilic. This electronic activation is fundamental to the compound's broad synthetic utility. As a solid at room temperature (melting point approximately 48–51 °C, subject to verification), it is readily handled and weighed in standard laboratory conditions. It is soluble in common organic solvents including dichloromethane, tetrahydrofuran, and dimethylformamide.

Reactivity and Key Synthetic Transformations

The primary synthetic value of 2-chloroquinoxaline lies in the electrophilic activation of its C-2 position toward nucleophilic aromatic substitution (SNAr). Because the adjacent ring nitrogens stabilize the Meisenheimer complex intermediate, the chloride leaving group is displaced efficiently by a range of nucleophiles under mild conditions.

Common transformations include:

• Amination: Reaction with primary or secondary amines yields 2-aminoquinoxaline derivatives, a privileged scaffold in kinase inhibitor research and antimicrobial drug design.
• Etherification and thioetherification: Alkoxides and thiolates substitute the chlorine to deliver 2-alkoxy- and 2-thioether-quinoxalines useful as pharmacophore fragments.
• Transition-metal-catalyzed cross-coupling: The C–Cl bond participates in palladium-catalyzed Suzuki–Miyaura and Buchwald–Hartwig reactions, enabling C–C and C–N bond formation to produce structurally complex quinoxaline libraries.
• Condensation and cyclization: 2-Chloroquinoxaline can serve as an electrophilic component in multicomponent reactions to build polycyclic heteroaromatic frameworks.

These diverse reaction pathways make 2-chloroquinoxaline a high-throughput building block for compound library synthesis.

Applications in Medicinal and Agrochemical Research

The quinoxaline core is a biologically relevant heteroaromatic scaffold found in natural products and approved therapeutics. Derivatives bearing substituents at C-2 have demonstrated a broad spectrum of biological activities, making 2-chloroquinoxaline a strategically important intermediate.

Medicinal chemistry: 2-Aminoquinoxalines derived from 2-chloroquinoxaline have been explored as inhibitors of protein kinases, including those implicated in oncology targets. The scaffold is also investigated for antimicrobial, antiviral, anti-inflammatory, and antiparasitic properties. The chloro group's ready displacement allows rapid SAR (structure–activity relationship) exploration around the quinoxaline pharmacophore.

Agrochemical research: Quinoxaline derivatives have been studied as fungicidal and herbicidal agents. 2-Chloroquinoxaline provides a convenient entry point for synthesizing candidate agrochemical structures.

Materials science: Quinoxaline-based organic semiconductors and fluorescent dyes are an active area of research; 2-chloroquinoxaline can serve as a monomer or coupling partner in the construction of conjugated polymers and small-molecule emitters.

Handling, Storage, and Safety Considerations

As with all halogenated heteroaromatic compounds, 2-chloroquinoxaline should be handled with appropriate laboratory precautions. Users should consult the current Safety Data Sheet (SDS) supplied with product C132475 for authoritative hazard classification, GHS pictograms, first-aid measures, and disposal guidance before use.

General guidance:

• Use in a well-ventilated fume hood; avoid inhalation of dust or vapors.
• Wear appropriate personal protective equipment: chemical-resistant gloves, safety glasses, and lab coat.
• Store in a cool, dry place away from light and moisture, tightly sealed, in accordance with the SDS recommendation.
• Incompatible with strong oxidizing agents and strong bases under forcing conditions.
• Dispose of waste in compliance with local regulations for halogenated organic waste.

Aladdin Scientific supplies C132475 with a specified purity level; refer to the product page for the current certificate of analysis (CoA) to confirm purity, appearance, and batch-specific data.

Frequently asked questions

What makes 2-chloroquinoxaline a useful synthetic building block?

The electron-withdrawing ring nitrogens of the quinoxaline system activate the C-2 chloro substituent toward nucleophilic aromatic substitution. This allows efficient replacement of the chloride by amines, alkoxides, thiolates, and organometallic nucleophiles, providing rapid access to structurally diverse quinoxaline derivatives for drug discovery and materials research.

What palladium-catalyzed reactions can be performed with 2-chloroquinoxaline?

2-Chloroquinoxaline is a competent electrophilic partner in several palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura coupling with aryl or heteroaryl boronic acids to form C–C bonds, and Buchwald–Hartwig amination to form C–N bonds. Optimization of catalyst loading, ligand, base, and solvent may be required depending on the specific nucleophile employed.

How should 2-chloroquinoxaline be stored to maintain stability?

2-Chloroquinoxaline should be stored in a tightly sealed container in a cool, dry location, protected from light and moisture. Always refer to the SDS and certificate of analysis supplied with Aladdin product C132475 for batch-specific storage instructions and shelf-life information.

Is 2-chloroquinoxaline suitable for use in kinase inhibitor drug discovery programs?

Yes, the quinoxaline scaffold is well-represented in kinase inhibitor research, and 2-chloroquinoxaline serves as a direct precursor to 2-aminoquinoxaline derivatives by SNAr reaction with amines. Such derivatives have been explored in the literature as ATP-competitive inhibitors; however, researchers should conduct their own biological evaluation and consult primary literature for specific target data.

References

1. Comprehensive Heterocyclic Chemistry (multivolume reference series). Quinoxalines chapter. Elsevier. Specific edition and page numbers to be confirmed.
2. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Nucleophilic aromatic substitution. Wiley. Specific edition to be confirmed.
3. Aladdin Scientific. Product C132475: 2-Chloroquinoxaline. Certificate of Analysis and Safety Data Sheet. Retrieved from aladdin-e.com.

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