4-Chloro-8-nitroquinoline: Properties, Handling & Lab Use Guide

4-Chloro-8-nitroquinoline is a halogenated nitroquinoline heterocyclic building block widely employed in medicinal chemistry and pharmaceutical research as a versatile electrophilic intermediate for the synthesis of bioactive quinoline derivatives.

CAS Number

Confirm with Aladdin product page (C678524); flag for review

Molecular Formula

C₉H₅ClN₂O₂

Molecular Weight

208.60 g/mol (calculated)

Functional Groups

Chloro (C-4), Nitro (C-8), Quinoline ring system

Appearance

Typically a pale yellow to yellow solid (verify with CoA)

Primary Application

Pharmaceutical intermediate, heterocyclic synthesis building block

SKU

C678524

Chemical Identity and Structure

4-Chloro-8-nitroquinoline (SKU: C678524) is a bicyclic aromatic heterocycle belonging to the quinoline family. Its structure features a quinoline scaffold bearing a chloro substituent at the 4-position and a nitro group at the 8-position. These two electron-withdrawing groups act synergistically to render the ring system highly electron-deficient, making the 4-position particularly susceptible to nucleophilic aromatic substitution (SNAr) reactions.

The molecular formula is C₉H₅ClN₂O₂ with a calculated molecular weight of approximately 208.60 g/mol. The compound is related to the broader family of nitroquinolines, which are well-established scaffolds in medicinal chemistry due to their ability to interact with diverse biological targets.

Note: Researchers should verify the exact melting point, purity (≥95% or as stated on the Certificate of Analysis), and spectroscopic data (¹H NMR, HPLC) against the Aladdin product documentation for lot-specific quality confirmation.

Synthetic Applications and Reactivity

The dual electrophilic activation of 4-Chloro-8-nitroquinoline makes it an exceptionally useful intermediate in multi-step synthetic sequences. Key reaction pathways include:

• Nucleophilic Aromatic Substitution (SNAr): The 4-chloro group is an excellent leaving group under SNAr conditions due to the combined inductive and resonance withdrawal of the ring nitrogen and the 8-nitro group. Amines, alcohols, and thiol nucleophiles can displace chloride to yield 4-substituted-8-nitroquinolines under mild to moderate conditions.
• Nitro Group Reduction: The 8-nitro group can be selectively reduced to an amine (e.g., using catalytic hydrogenation, iron/acetic acid, or SnCl₂ in ethanol) to provide 4-substituted-8-aminoquinolines, which are important pharmacophores.
• Palladium-Catalyzed Cross-Coupling: The C–Cl bond at the 4-position may participate in Suzuki, Buchwald–Hartwig, or related Pd-catalysed reactions, enabling C–C or C–N bond formation for library synthesis.
• Sequential Functionalization: The orthogonal reactivity of the chloro and nitro groups allows stepwise, sequential functionalization, giving access to 4,8-disubstituted quinoline derivatives of high structural diversity.

These properties establish 4-Chloro-8-nitroquinoline as a privileged building block for the construction of drug candidates and probe molecules targeting kinases, antibacterial pathways, and other therapeutic areas.

Safe Handling, Storage, and Disposal

As with all nitro-aromatic and halogenated organic compounds, appropriate safety precautions must be observed when working with 4-Chloro-8-nitroquinoline:

• Personal Protective Equipment (PPE): Wear chemical-resistant gloves (nitrile recommended), a laboratory coat, and safety glasses or goggles. Work under adequate ventilation or in a fume hood, particularly when handling powders to minimise inhalation risk.
• Storage: Store in a tightly sealed container in a cool, dry, well-ventilated area away from heat sources, oxidisers, and incompatible materials. Typical storage temperature is 2–8 °C or room temperature as specified on the product label and CoA. Protect from light.
• Stability: The compound is expected to be stable under recommended storage conditions; however, verify shelf-life and specific stability data on the Aladdin product page or CoA for lot C678524.
• Waste Disposal: Dispose of all waste materials containing this compound in accordance with local, regional, and national hazardous chemical waste regulations. Do not pour down the drain. Consult your institution's Environmental Health and Safety (EHS) office for guidance.
• First Aid: In case of skin or eye contact, rinse immediately with copious water. Seek medical advice if irritation persists. Refer to the Safety Data Sheet (SDS) for comprehensive hazard and first-aid information.

Important: Always consult the product-specific SDS available on the Aladdin Scientific website before first use.

Quality, Purity, and Ordering Information

Aladdin Scientific supplies 4-Chloro-8-nitroquinoline under SKU C678524. The following quality considerations apply:

• Purity: Research-grade purity is typically ≥95% as determined by HPLC or NMR analysis. Lot-specific purity data are provided on the Certificate of Analysis (CoA), which is available upon request or on the Aladdin product portal.
• Identity Confirmation: Structural identity is confirmed by ¹H NMR, ¹³C NMR, and/or high-resolution mass spectrometry (HRMS). Researchers requiring additional characterisation data should contact Aladdin Scientific technical support.
• Available Pack Sizes: Multiple quantities are typically available to suit discovery-scale screening through to preparative synthesis. Check the current Aladdin catalogue or contact your regional sales representative for pricing and availability.
• Lead Time: Stock availability varies; confirm current stock and estimated delivery times on the Aladdin Scientific website or with your procurement contact.
• Regulatory Compliance: Products are manufactured and supplied in accordance with applicable quality management standards. Contact Aladdin for documentation requirements specific to your jurisdiction.

Frequently asked questions

What nucleophiles react most efficiently with 4-Chloro-8-nitroquinoline at the 4-position?

Primary and secondary amines are among the most effective nucleophiles for SNAr displacement of the 4-chloro group, typically reacting under mild heating in polar aprotic solvents such as DMF or DMSO. Alkoxides and thiols are also viable under appropriate base conditions. Reaction efficiency depends on nucleophile pKa, steric bulk, and solvent choice.

How should I selectively reduce the nitro group without affecting the C–Cl bond?

Selective reduction of the 8-nitro group to the corresponding amine can be achieved using reagents such as iron powder in acetic acid, SnCl₂ in ethanol, or transfer hydrogenation conditions (e.g., ammonium formate with Pd/C). Catalytic hydrogenation with H₂/Pd-C under controlled pressure may also reduce the C–Cl bond and should be used cautiously. The optimal method should be determined empirically for your specific substrate and scale.

What are the recommended storage conditions for 4-Chloro-8-nitroquinoline (C678524)?

Store the compound in a tightly sealed container in a cool, dry, well-ventilated location away from heat, light, and incompatible materials. The specific recommended temperature (e.g., 2–8 °C or room temperature) is stated on the product label and CoA for each lot. Always consult the current SDS available on the Aladdin Scientific website for authoritative storage guidance.

Can 4-Chloro-8-nitroquinoline be used in palladium-catalysed cross-coupling reactions?

Yes, the C4–Cl bond is a viable electrophilic partner in Pd-catalysed reactions such as Suzuki–Miyaura, Buchwald–Hartwig amination, and Negishi coupling, given appropriate ligand and base selection. The electron-poor quinoline ring can facilitate oxidative addition. Conditions should be optimised for each specific coupling partner, and the presence of the nitro group should be considered for catalyst and ligand compatibility.

References

1. PharmaBlock Sciences (Nanjing), Inc. Product page: PBKR2216, 4-Chloro-8-nitroquinoline. Available at: https://product.pharmablock.com/us/product/PBKR2216?from=sci
2. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley: New York, 1992. (General reference for SNAr reactivity of electron-deficient haloarenes.)
3. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (Reference for nitro group reduction strategies.)

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