5-Bromoisoquinoline-1-carboxylic Acid: Properties & Uses
5-Bromoisoquinoline-1-carboxylic Acid: Properties & Uses
5-Bromoisoquinoline-1-carboxylic acid is a halogenated bicyclic heteroaromatic building block bearing both a bromine substituent at the 5-position and a carboxylic acid function at the 1-position of the isoquinoline ring system, making it a versatile intermediate for medicinal chemistry and cross-coupling synthesis.
- Chemical Name
- 5-Bromoisoquinoline-1-carboxylic acid
- SKU
- B189693
- Molecular Formula
- C10H6BrNO2
- Molecular Weight
- 252.07 g/mol
- Core Scaffold
- Isoquinoline (benzo[c]pyridine) heterocycle
- Key Functional Groups
- Aryl bromide (C5) and carboxylic acid (C1)
- Primary Application
- Medicinal chemistry intermediate and cross-coupling building block
Chemical Structure and Key Properties
5-Bromoisoquinoline-1-carboxylic acid belongs to the family of halogenated isoquinoline derivatives. The isoquinoline scaffold is a nitrogen-containing bicyclic aromatic system composed of a benzene ring fused to a pyridine ring, widely recognised for its prevalence in biologically active natural products and pharmaceuticals.
In this compound, the carboxylic acid group at the 1-position confers both acidity and a versatile handle for further chemical elaboration, including amide bond formation, esterification, and decarboxylation. The bromine atom at the 5-position provides an electrophilic site that is amenable to a wide range of metal-catalysed cross-coupling reactions, such as Suzuki–Miyaura, Negishi, Buchwald–Hartwig, and Sonogashira couplings, enabling facile introduction of diverse aryl, vinyl, alkyl, or amino substituents.
The combination of these two orthogonal reactive handles within a single molecule makes 5-Bromoisoquinoline-1-carboxylic acid particularly attractive for the construction of structurally complex targets in a convergent synthetic strategy.
Applications in Medicinal Chemistry and Drug Discovery
The isoquinoline nucleus is a privileged scaffold in medicinal chemistry, present in numerous clinically relevant compounds including antitumour agents, antibiotics, and central nervous system drugs. 5-Bromoisoquinoline-1-carboxylic acid serves as a key building block for the synthesis of such biologically active molecules.
The carboxylic acid moiety can be readily converted to amides, enabling the preparation of isoquinolinecarboxamide derivatives that have been explored as kinase inhibitors, ion-channel modulators, and PARP inhibitors. The aryl bromide at C5 allows palladium-catalysed functionalisation to install pharmacophoric groups that modulate potency, selectivity, and pharmacokinetic properties.
In fragment-based drug discovery (FBDD), halogenated isoquinoline carboxylic acids are frequently employed as fragment hits that can be elaborated by cross-coupling to optimise binding affinity and selectivity against macromolecular targets.
Synthetic Utility and Cross-Coupling Chemistry
5-Bromoisoquinoline-1-carboxylic acid is routinely employed in palladium- and nickel-catalysed cross-coupling reactions. The C–Br bond at C5 undergoes oxidative addition to Pd(0) species readily, owing to the electron-withdrawing influence of both the ring nitrogen and the C1 carboxylic acid, which activates the aromatic system toward such transformations.
Common synthetic transformations include: (1) Suzuki–Miyaura coupling with arylboronic acids or esters to introduce biaryl or heteroaryl moieties; (2) Sonogashira coupling with terminal alkynes to generate alkynyl-isoquinoline derivatives; (3) Buchwald–Hartwig amination to install amine substituents; (4) Carbonylative coupling to generate ketone or ester products; and (5) conversion of the carboxylic acid to an acyl chloride or active ester, followed by nucleophilic acylation.
The dual functionality also facilitates macrocyclisation strategies and the synthesis of heterocyclic libraries for high-throughput screening campaigns.
Handling, Storage, and Safety Guidelines
As with all halogenated aromatic carboxylic acids, standard laboratory precautions should be observed when handling 5-Bromoisoquinoline-1-carboxylic acid. Personal protective equipment (PPE) including nitrile gloves, safety glasses, and a laboratory coat should be worn at all times during handling.
The compound should be stored in a tightly sealed container in a cool, dry, well-ventilated area away from incompatible materials such as strong bases, strong oxidising agents, and reactive metals. Exposure to moisture should be minimised to preserve chemical integrity and purity.
In the event of skin or eye contact, the affected area should be rinsed thoroughly with copious amounts of water. Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for complete hazard information, first-aid measures, disposal guidelines, and regulatory classification before use.
Frequently asked questions
What is 5-Bromoisoquinoline-1-carboxylic acid used for in organic synthesis?
5-Bromoisoquinoline-1-carboxylic acid is primarily used as a bifunctional building block in medicinal chemistry and complex molecule synthesis. The aryl bromide at C5 participates in palladium-catalysed cross-coupling reactions (e.g., Suzuki, Sonogashira, Buchwald–Hartwig), while the carboxylic acid at C1 can be converted to amides, esters, or acyl halides, enabling rapid structural diversification around the isoquinoline core.
How should 5-Bromoisoquinoline-1-carboxylic acid be stored to maintain purity?
The compound should be stored in a tightly sealed container under cool, dry, and well-ventilated conditions, away from moisture, strong bases, and oxidising agents. It is advisable to keep the container sealed until use and to work under inert atmosphere conditions when handling quantities intended for sensitive reactions.
What is the molecular formula and molecular weight of 5-Bromoisoquinoline-1-carboxylic acid?
5-Bromoisoquinoline-1-carboxylic acid has the molecular formula C10H6BrNO2 and a molecular weight of approximately 252.07 g/mol. The compound contains a bromine atom, a carboxylic acid group, and an isoquinoline bicyclic aromatic ring system.
Is 5-Bromoisoquinoline-1-carboxylic acid suitable for fragment-based drug discovery?
Yes, halogenated isoquinoline carboxylic acids such as this compound are well-suited for fragment-based drug discovery (FBDD). The compact isoquinoline scaffold with its embedded nitrogen and dual reactive handles allows fragment hits to be readily elaborated by cross-coupling or acylation chemistry to optimise binding affinity against biological targets.
References
- Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (General reference for isoquinoline chemistry.)
- Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
- Erlanson, D. A.; Fesik, S. W.; Hubbard, R. E.; Jahnke, W.; Jhoti, H. Twenty years on: the impact of fragments on drug discovery. Nat. Rev. Drug Discov. 2016, 15, 605–619. doi:10.1038/nrd.2016.109
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