5-Chloro-3,4-dihydroquinolin-2(1H)-one: Properties & Applications
5-Chloro-3,4-dihydroquinolin-2(1H)-one: Properties & Applications
5-Chloro-3,4-dihydroquinolin-2(1H)-one is a chlorine-substituted bicyclic lactam belonging to the dihydroquinolinone family, widely used as a versatile heterocyclic building block in medicinal chemistry and organic synthesis.
- IUPAC Name
- 5-chloro-3,4-dihydroquinolin-2(1H)-one
- Molecular Formula
- C₉H₈ClNO
- Molecular Weight
- 181.62 g/mol
- Core Scaffold
- Dihydroquinolinone (bicyclic lactam)
- Key Substituent
- Chlorine at position 5 of the aromatic ring
- Aladdin SKU
- C729495
- Typical Use
- Heterocyclic intermediate for drug discovery and organic synthesis
Chemical Structure and Physicochemical Properties
5-Chloro-3,4-dihydroquinolin-2(1H)-one (molecular formula C₉H₈ClNO, MW 181.62 g/mol) is a bicyclic compound comprising a benzene ring fused to a six-membered lactam ring. The lactam carbonyl at position 2, together with the saturated methylene groups at positions 3 and 4, defines the dihydroquinolinone scaffold. The chlorine substituent at position 5 on the aromatic ring imparts distinctive electronic and steric properties relative to the unsubstituted parent compound, influencing reactivity and intermolecular interactions.
The electron-withdrawing nature of the ring chlorine reduces electron density on the aromatic system, making the compound amenable to nucleophilic aromatic substitution under appropriate conditions. The secondary amide (lactam) nitrogen is a potential site for N-alkylation or N-acylation, while the active methylene groups at C-3 and C-4 can participate in condensation reactions. These multiple reactive handles make this compound a versatile synthetic intermediate.
Synthesis and Preparation Methods
The dihydroquinolinone core is classically accessible via the Baeyer-Villiger oxidation of the corresponding tetralone, or through cyclization of appropriately substituted aniline derivatives with succinic or glutaric acid equivalents. For the 5-chloro derivative specifically, two general strategies are commonly employed: (1) direct chlorination of 3,4-dihydroquinolin-2(1H)-one at the 5-position using electrophilic chlorinating agents under controlled conditions, and (2) de novo ring construction starting from 2-chloro-6-aminobenzene precursors followed by intramolecular lactamization.
Researchers should consult primary literature for optimized procedures, as regioselectivity and yield are sensitive to reagent choice, temperature, and solvent. Aladdin Scientific supplies 5-Chloro-3,4-dihydroquinolin-2(1H)-one (SKU: C729495) as a ready-to-use reagent-grade material, eliminating the need for in-house synthesis in most applications.
Research Applications in Medicinal Chemistry
Dihydroquinolinone scaffolds are well-represented in bioactive natural products and pharmaceutical agents, making 5-Chloro-3,4-dihydroquinolin-2(1H)-one a valuable building block for drug discovery programs. The fused bicyclic lactam framework is recognized for its ability to mimic peptide turn structures, its favorable drug-like properties, and its compatibility with diverse pharmacophore assembly strategies.
In medicinal chemistry workflows, this compound serves primarily as an intermediate for: (1) the construction of more complex heterocyclic architectures via ring expansion, annulation, or cross-coupling reactions at the C-5 chloro position or the lactam nitrogen; (2) fragment-based drug discovery, where the dihydroquinolinone fragment provides a rigid, geometrically defined scaffold; and (3) structure–activity relationship (SAR) studies exploring the influence of halogen substitution on target binding and selectivity. The C-5 chlorine can also serve as a handle for palladium-catalyzed cross-coupling reactions (e.g., Suzuki, Buchwald-Hartwig), enabling rapid diversification of the molecular library.
Handling, Storage, and Safety Considerations
As with most fine chemical reagents, 5-Chloro-3,4-dihydroquinolin-2(1H)-one should be handled with standard laboratory precautions. Users should wear appropriate personal protective equipment (PPE) including nitrile gloves, safety glasses, and a laboratory coat. Handling in a well-ventilated fume hood is recommended to minimize inhalation exposure to dust or aerosols.
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. Compatibility with standard organic solvents (e.g., DMSO, DMF, ethanol, dichloromethane) makes it straightforward to prepare stock solutions for biological or synthetic assays. Always consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use, and dispose of waste in accordance with local institutional and governmental regulations.
Frequently asked questions
What is the molecular weight of 5-Chloro-3,4-dihydroquinolin-2(1H)-one?
The molecular weight of 5-Chloro-3,4-dihydroquinolin-2(1H)-one is 181.62 g/mol, with the molecular formula C₉H₈ClNO.
What solvents are suitable for dissolving 5-Chloro-3,4-dihydroquinolin-2(1H)-one?
5-Chloro-3,4-dihydroquinolin-2(1H)-one is generally soluble in polar aprotic solvents such as DMSO and DMF, as well as in common organic solvents including dichloromethane and ethanol. Aqueous solubility is expected to be limited due to the hydrophobic aromatic core; prepare stock solutions in an organic solvent and dilute as needed.
How can the C-5 chlorine substituent be utilized in further synthetic transformations?
The C-5 chlorine on the aromatic ring is well-suited for palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura (with arylboronic acids), Buchwald-Hartwig (amination), and Negishi couplings, enabling rapid structural diversification. It can also serve as a leaving group in nucleophilic aromatic substitution reactions under appropriate activating conditions.
What is the Aladdin Scientific SKU for 5-Chloro-3,4-dihydroquinolin-2(1H)-one?
5-Chloro-3,4-dihydroquinolin-2(1H)-one is available from Aladdin Scientific under SKU C729495.
References
- March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992.
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012.
- Manske, R. H. F. The Chemistry of Heterocyclic Compounds: Quinolines; Wiley: New York, 1977.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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