7-Bromo-3,4-dihydro-2H-isoquinolin-1-one: Handling & Use Protocol
7-Bromo-3,4-dihydro-2H-isoquinolin-1-one: Handling & Use Protocol
7-Bromo-3,4-dihydro-2H-isoquinolin-1-one is a brominated dihydroisoquinolinone building block widely employed in medicinal chemistry and heterocyclic synthesis as a versatile scaffold for the preparation of pharmacologically active isoquinolinone derivatives.
- Chemical Name
- 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one
- SKU / Catalog Number
- B187832
- Molecular Formula
- C₉H₈BrNO
- Molecular Weight
- 226.07 g/mol
- Core Scaffold
- 3,4-Dihydroisoquinolin-1(2H)-one (dihydroisoquinolinone)
- Key Functional Handle
- Aryl bromide at position 7, enabling cross-coupling reactions (e.g., Suzuki, Buchwald-Hartwig)
- Recommended Storage
- Cool, dry place; away from light and moisture; sealed container
Overview and Chemical Properties
7-Bromo-3,4-dihydro-2H-isoquinolin-1-one (CAS catalog SKU B187832, Aladdin Scientific) is a partially saturated bicyclic lactam belonging to the isoquinolinone family of nitrogen-containing heterocycles. The compound features a six-membered lactam ring fused to a benzene ring, with a bromine substituent at the 7-position of the aromatic ring. The molecular formula is C₉H₈BrNO and the molecular weight is approximately 226.07 g/mol.
The aryl bromide moiety is the primary reactive handle of this molecule, making it an excellent electrophilic partner in transition-metal-catalyzed cross-coupling reactions such as Suzuki-Miyaura, Negishi, Sonogashira, and Buchwald-Hartwig amination. The lactam nitrogen (NH) at position 2 can also serve as a site for N-functionalization. These two orthogonal reactive sites render 7-bromo-3,4-dihydro-2H-isoquinolin-1-one a highly versatile synthetic intermediate in medicinal chemistry and drug discovery programs targeting the isoquinolinone scaffold.
Safety and Handling Precautions
Before handling 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one, consult the Safety Data Sheet (SDS) provided by Aladdin Scientific. As with all organobromine heterocyclic research chemicals, treat this compound with appropriate caution.
- Personal Protective Equipment (PPE): Wear nitrile gloves, a laboratory coat, and safety goggles at all times during handling.
- Ventilation: Work in a well-ventilated fume hood to avoid inhalation of dust or aerosols.
- Skin and Eye Contact: Avoid direct contact. In case of skin contact, wash immediately with soap and water. In case of eye contact, rinse thoroughly with water and seek medical advice.
- Ingestion/Inhalation: Do not eat, drink, or smoke in areas where the compound is used. If inhaled, move to fresh air.
- Waste Disposal: Dispose of waste material in accordance with local institutional and governmental regulations for chemical waste.
The compound should be stored in a tightly sealed container in a cool, dry environment away from direct light and moisture to maintain stability and purity over time.
Solution Preparation and Solubility
Proper dissolution is critical for reproducible experimental results. The following procedure is recommended for preparing stock solutions of 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one:
- Solvent Selection: This compound is expected to dissolve in common organic solvents including dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and ethanol. Solubility in aqueous systems is generally limited; for biological assays requiring aqueous media, prepare a concentrated stock in DMSO and dilute to the required concentration, keeping the final DMSO content ≤0.1% v/v to minimize solvent effects.
- Stock Solution Preparation: Accurately weigh the required amount of compound using an analytical balance. Transfer to a clean, dry glass vial. Add solvent gradually while gently vortexing or sonicating until complete dissolution is achieved.
- Concentration Verification: Confirm concentration by UV-Vis absorbance measurement if a calibration curve or extinction coefficient is available, or by gravimetric calculation.
- Storage of Stock Solutions: Aliquot stock solutions into single-use volumes and store at −20 °C under inert atmosphere (argon or nitrogen) to prevent oxidation and moisture uptake. Avoid repeated freeze-thaw cycles.
Note: Exact solubility data for this specific compound should be verified experimentally, as solubility can vary with batch purity and temperature.
Application in Cross-Coupling Reactions: Representative Protocol
The aryl bromide functionality of 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one makes it a direct substrate for palladium-catalyzed cross-coupling. The following is a general Suzuki-Miyaura coupling protocol as a representative example:
Materials Required
- 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one (1.0 equiv, SKU B187832)
- Arylboronic acid or ester (1.2–1.5 equiv)
- Pd catalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂, 2–5 mol%)
- Base (e.g., K₂CO₃ or Cs₂CO₃, 2.0–3.0 equiv)
- Solvent: DMF/H₂O (4:1) or 1,4-dioxane/H₂O (3:1)
- Inert atmosphere: argon or nitrogen
Procedure
- Charge a dry Schlenk flask or sealed vial with 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one (1.0 equiv).
- Add the arylboronic acid (1.2–1.5 equiv) and the Pd catalyst (2–5 mol%).
- Add the base (2.0–3.0 equiv) and solvent mixture.
- Evacuate and backfill with argon or nitrogen three times (freeze-pump-thaw if using a Schlenk line).
- Stir at 80–100 °C for 4–16 hours, monitoring reaction progress by TLC or LCMS.
- Upon completion, cool to room temperature, filter through Celite if necessary, and extract the product using ethyl acetate/water workup.
- Purify the product by column chromatography (silica gel) or recrystallization as appropriate.
Reaction conditions should be optimized for each specific coupling partner. Always run a small-scale test before committing to large-scale synthesis.
Quality Control and Analytical Characterization
Upon receipt of 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one (SKU B187832) from Aladdin Scientific, the following analytical checks are recommended to confirm identity and purity before use in sensitive applications:
- Melting Point: Determine and compare against the reported reference value. Deviation from the expected range may indicate impurity or degradation.
- HPLC Purity Analysis: Run a reverse-phase HPLC assay (C18 column, UV detection at 254 nm) to assess purity. For most synthetic applications, purity ≥97% is recommended.
- ¹H NMR Spectroscopy: Record in DMSO-d₆ or CDCl₃. Key signals include: NH (broad singlet, ~8.0–8.5 ppm), aromatic protons (multiplets, 7.4–8.2 ppm, 3H), CH₂ groups at positions 3 and 4 (multiplets, 2.9–3.5 ppm).
- Mass Spectrometry: ESI-MS or APCI-MS should show the expected [M+H]⁺ ion consistent with C₉H₈BrNO (MW 226.07). The characteristic isotope pattern (1:1 ratio for ⁷⁹Br:⁸¹Br) confirms the presence of one bromine atom.
- TLC: Spot on silica gel plate; visualize under UV (254 nm). Rf value in a suitable solvent system (e.g., EtOAc:hexane 1:2) should be consistent across batches.
Specific analytical data (exact NMR shifts, melting point, HPLC retention time) for this lot should be referenced against the Certificate of Analysis (CoA) provided with the product shipment.
Frequently asked questions
What solvents are recommended for dissolving 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one?
DMSO, DMF, and ethanol are generally suitable organic solvents for this compound. Aqueous solubility is limited; for biological assays, prepare stock solutions in DMSO and dilute into aqueous buffer, keeping the final DMSO concentration at or below 0.1% v/v. Solubility should be confirmed experimentally for each application.
What cross-coupling reactions can be performed using 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one as a substrate?
The aryl bromide at position 7 enables a range of palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura (with arylboronic acids/esters), Negishi (with organozinc reagents), Sonogashira (with terminal alkynes), and Buchwald-Hartwig amination (with amines). The lactam NH can additionally be alkylated or acylated for further functionalization.
How should 7-Bromo-3,4-dihydro-2H-isoquinolin-1-one be stored to maintain stability?
Store the compound in a tightly sealed container in a cool, dry location away from light, heat, and moisture. Stock solutions should be aliquoted and stored at −20 °C under an inert atmosphere (argon or nitrogen) to prevent degradation. Avoid repeated freeze-thaw cycles, which can compromise compound integrity.
What is the significance of the dihydroisoquinolinone scaffold in drug discovery?
The 3,4-dihydroisoquinolin-1(2H)-one scaffold is a privileged structure in medicinal chemistry, present in numerous bioactive natural products and pharmaceutical candidates. It has been explored in the development of compounds with diverse biological activities. The 7-bromo derivative provides a handle for rapid analog synthesis via cross-coupling, accelerating structure-activity relationship (SAR) studies.
How do I verify the identity and purity of the received compound?
Consult the Certificate of Analysis (CoA) shipped with the product for lot-specific analytical data. Confirm identity by ¹H NMR (key aromatic, NH, and CH₂ signals) and mass spectrometry (look for [M+H]⁺ and the characteristic 1:1 bromine isotope pattern). Purity can be assessed by reverse-phase HPLC with UV detection at 254 nm.
References
- Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, Part B: Reactions and Synthesis, 5th ed.; Springer: New York, 2007. [General palladium cross-coupling methodology]
- Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
- Kaur, R.; Kaur, G. Isoquinolinone scaffold as a privileged structure in medicinal chemistry: A review. Mini Rev. Med. Chem. [General reference — specific volume/page not confirmed from source material]
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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