6-Chloro-1,2,3,4-tetrahydroisoquinolin-1-one: Properties & Uses
6-Chloro-1,2,3,4-tetrahydroisoquinolin-1-one: Properties & Uses
6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one is a chlorinated bicyclic lactam belonging to the tetrahydroisoquinolinone family, widely valued in medicinal chemistry and organic synthesis as a versatile heterocyclic building block.
- IUPAC Name
- 6-chloro-3,4-dihydroisoquinolin-1(2H)-one
- Molecular Formula
- C₉H₈ClNO
- Molecular Weight
- 181.62 g/mol
- Core Scaffold
- Bicyclic tetrahydroisoquinolinone (benzene fused δ-lactam)
- Key Functional Groups
- Aryl chloride, secondary lactam (NH), carbonyl (C=O)
- Typical Application
- Pharmaceutical intermediate and medicinal chemistry scaffold
- CAS Number
- Review flag: CAS not confirmed in source material
Chemical Structure and Physicochemical Properties
6-Chloro-1,2,3,4-tetrahydroisoquinolin-1-one features a bicyclic framework in which a saturated six-membered lactam ring is fused to a benzene ring bearing a chlorine substituent at the 6-position. The lactam nitrogen (position 2) carries a hydrogen atom, conferring both hydrogen-bond donor and acceptor capability on the molecule.
The aryl chloride at C-6 is a versatile handle for transition-metal-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Buchwald–Hartwig, and related transformations, making the compound an attractive starting material or intermediate in multi-step synthesis. The carbonyl group (C-1 keto) offers additional reactivity toward nucleophiles and can participate in further functionalization, such as reduction to the corresponding amine or conversion to thiolactam derivatives.
The compound is expected to be a solid at ambient temperature based on analogy with closely related tetrahydroisoquinolinones; however, precise melting point, solubility, and logP values should be confirmed from analytical certificates or validated databases, as these are not specified in the current source material.
Synthesis and Preparation Routes
Tetrahydroisoquinolinones are classically accessed via Bischler–Napieralski cyclization, Pictet–Spengler condensation, or Beckmann rearrangement strategies applied to suitably substituted phenethylamine or homophthalic anhydride precursors. For the 6-chloro variant, chlorinated aryl precursors (e.g., 4-chlorophenethylamine or the corresponding homophthalic acid derivative) serve as the starting point.
An alternative and operationally straightforward approach involves intramolecular Friedel–Crafts acylation of a chloro-substituted phenethylamine acyl chloride derivative, delivering the bicyclic lactam directly. The regioselectivity of ring closure is governed by the electronic and steric directing effects of the chloro substituent on the aromatic ring.
Because the exact published synthetic procedure for this specific compound is not detailed in the provided source material, researchers are encouraged to consult primary literature or validated protocol databases before commencing synthesis.
Research Applications in Medicinal Chemistry
The tetrahydroisoquinolinone scaffold is a privileged structure in drug discovery, appearing in compounds with diverse pharmacological profiles including activity at dopamine receptors, opioid receptors, and various enzyme targets. The introduction of a halogen at C-6 provides both a synthetic handle and the potential to modulate lipophilicity, metabolic stability, and binding affinity relative to the unsubstituted parent.
6-Chloro-1,2,3,4-tetrahydroisoquinolin-1-one is primarily employed as a building block: the aryl chloride enables direct elaboration via palladium- or nickel-catalyzed coupling to introduce aryl, heteroaryl, amino, or alkyl groups, rapidly expanding structural diversity. The lactam NH can be alkylated or acylated to tune pharmacokinetic properties.
This compound may also serve as a reference standard or synthetic intermediate in the preparation of more complex drug candidates. Researchers in CNS drug discovery, kinase inhibitor programs, and natural product total synthesis are among the end users who benefit from well-characterized, high-purity material.
Handling, Storage, and Safety Considerations
As with all aryl chloride-containing heterocyclic compounds, standard laboratory precautions should be observed when handling 6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one. Personal protective equipment including gloves, laboratory coat, and eye protection is recommended. Operations that may generate dust or aerosols should be conducted in a well-ventilated area or under a fume hood.
The compound should be stored in a tightly sealed container, away from moisture, heat, and incompatible materials such as strong oxidizers and strong bases. Cool, dry storage conditions at room temperature or below are generally appropriate for solid lactam derivatives of this class, pending confirmation from the product's certificate of analysis.
Researchers should consult the Safety Data Sheet (SDS) supplied by Aladdin Scientific for precise hazard classification, first-aid measures, and disposal requirements specific to this compound before use. Specific GHS hazard statements and precautionary statements are not confirmed in the current source material and should be reviewed in the official SDS.
Frequently asked questions
What is 6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one used for in research?
It is primarily used as a heterocyclic building block in medicinal chemistry and organic synthesis. The aryl chloride at C-6 enables palladium- or nickel-catalyzed cross-coupling reactions, while the lactam NH allows further N-functionalization, facilitating rapid assembly of structurally diverse drug candidates.
How should 6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one be stored?
The compound should be stored in a tightly sealed container under cool, dry conditions, away from moisture, heat, strong oxidizers, and strong bases. Refer to the Aladdin Scientific certificate of analysis and SDS for confirmed storage temperature and specific precautionary requirements.
What cross-coupling reactions are compatible with 6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one?
The aryl chloride moiety is compatible with palladium-catalyzed Suzuki–Miyaura (aryl boronic acid coupling), Buchwald–Hartwig (C–N bond formation), and Negishi or Kumada couplings, among others. Reaction conditions should be optimized on a case-by-case basis; specific published protocols for this exact compound should be verified in primary literature.
What is the molecular formula and weight of 6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one?
The molecular formula is C₉H₈ClNO with a molecular weight of approximately 181.62 g/mol. Researchers should verify these values against the certificate of analysis provided with the specific lot purchased from Aladdin Scientific.
Is 6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one available from Aladdin Scientific?
Yes, 6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one is available from Aladdin Scientific under SKU C175778. Contact Aladdin Scientific for current stock availability, pricing, and purity specifications.
References
- Kappe, C. O.; Stadler, A.; Dallinger, D. Microwaves in Organic and Medicinal Chemistry, 2nd ed.; Wiley-VCH: Weinheim, 2012. (General reference for heterocyclic synthesis strategies.)
- Czollner, L. et al. Synthesis of tetrahydroisoquinolinone derivatives via Bischler–Napieralski cyclization. (Illustrative general reference; exact article details not confirmed in source material.)
- Aladdin Scientific. Product Page: 6-chloro-1,2,3,4-tetrahydroisoquinolin-1-one, SKU C175778. Aladdin Scientific, Shanghai.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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