7-Bromo-5-chloro-1H-indole-2-carboxylic Acid: Properties & Uses
7-Bromo-5-chloro-1H-indole-2-carboxylic Acid: Properties & Uses
7-Bromo-5-chloro-1H-indole-2-carboxylic acid is a di-halogenated indole carboxylic acid building block valued in medicinal chemistry and pharmaceutical synthesis for its reactive halogen substituents and versatile carboxylic acid handle that enable diverse downstream transformations.
- IUPAC Name
- 7-bromo-5-chloro-1H-indole-2-carboxylic acid
- Molecular Formula
- C₉H₅BrClNO₂
- Molecular Weight
- 274.50 g/mol
- Core Scaffold
- 1H-Indole with carboxylic acid at C-2, bromine at C-7, and chlorine at C-5
- Key Functional Groups
- Carboxylic acid (–COOH), C–Br bond, C–Cl bond, indole N–H
- Primary Application
- Synthetic intermediate in medicinal chemistry and drug discovery
- Aladdin SKU
- B728936
Chemical Structure and Physical Properties
7-Bromo-5-chloro-1H-indole-2-carboxylic acid belongs to the halogenated indole carboxylic acid family. Its bicyclic indole scaffold consists of a benzene ring fused to a pyrrole ring, with a carboxylic acid group at the C-2 position of the pyrrole ring. The compound bears two halogen substituents: bromine at C-7 (on the benzene ring, adjacent to the nitrogen-bearing junction) and chlorine at C-5 (on the benzene ring). This specific substitution pattern introduces significant electronic and steric effects that modulate the reactivity of both the heterocyclic core and the peripheral functional groups.
The molecular formula is C₉H₅BrClNO₂ with a molecular weight of approximately 274.50 g/mol. The compound is expected to be a solid at room temperature, consistent with other halogenated indole-2-carboxylic acids. The carboxylic acid group confers moderate acidity and enables salt formation, esterification, amide coupling, and other standard carboxylic acid transformations. The indole N–H proton may participate in hydrogen bonding, influencing solubility and crystal packing.
Note: Specific melting point, exact solubility values, and spectroscopic data (NMR, IR) should be verified against the certificate of analysis supplied with Aladdin Scientific product SKU B728936.
Synthetic Utility and Reactivity
The two halogen atoms on 7-bromo-5-chloro-1H-indole-2-carboxylic acid provide orthogonal handles for selective cross-coupling and nucleophilic aromatic substitution reactions. The C–Br bond at C-7 is generally more reactive than the C–Cl bond at C-5 under standard palladium-catalyzed cross-coupling conditions (e.g., Suzuki–Miyaura, Negishi, Buchwald–Hartwig), allowing stepwise functionalization. The C–Cl bond may be selectively engaged under more forcing conditions or with appropriate catalyst systems, enabling sequential diversification of the aromatic ring.
The carboxylic acid at C-2 serves as a versatile synthetic handle. It can be converted to acyl chlorides, active esters, or mixed anhydrides for amide bond formation with amines, which is particularly valuable in the preparation of carboxamide-containing drug candidates. Esterification with alcohols provides ester derivatives useful for prodrug strategies or further elaboration. Decarboxylation under specific conditions can yield 7-bromo-5-chloro-1H-indole if required.
The indole nitrogen (N-1) can be protected or alkylated to modulate reactivity and improve handling. Overall, the combination of a C-2 carboxylic acid, a C-7 bromo group, and a C-5 chloro group makes this compound an exceptionally versatile three-point diversifiable building block for library synthesis and lead optimization campaigns.
Applications in Medicinal Chemistry and Drug Discovery
The indole scaffold is one of the most prevalent heterocyclic frameworks in approved pharmaceuticals and natural products, owing to its favorable drug-like properties, ability to mimic tryptophan, and broad target engagement profile. Halogenated indole-2-carboxylic acid derivatives have found utility as intermediates in the synthesis of kinase inhibitors, GPCR modulators, antiviral agents, and antimicrobial compounds.
The strategic placement of bromine at C-7 and chlorine at C-5 in this compound can be exploited to tune the electron density of the indole ring, affecting binding interactions with biological targets. Halogens contribute to halogen bonding, lipophilicity, and metabolic stability of the final drug molecule. The C-2 carboxylic acid or its amide derivatives may engage in hydrogen-bond donor/acceptor interactions critical for target affinity.
Researchers engaged in fragment-based drug discovery (FBDD) or diversity-oriented synthesis (DOS) will find this compound particularly useful as a starting point for generating structurally diverse indole-based compound libraries. Its use as a coupling partner in multi-step total synthesis of indole natural product analogs has also been reported in the broader literature on halogenated indole chemistry.
Handling, Storage, and Safety Considerations
As with most halogenated organic compounds, 7-bromo-5-chloro-1H-indole-2-carboxylic acid should be handled with appropriate personal protective equipment, including nitrile gloves, safety glasses, and a laboratory coat. Work should be conducted in a well-ventilated fume hood to minimize inhalation exposure to fine particulates.
The compound should be stored in a tightly sealed container, away from moisture and light, at cool temperatures as recommended on the product label and safety data sheet (SDS). Exposure to strong bases or reducing agents should be avoided to prevent unintended reactions. Compatibility with storage containers and solvents should be confirmed prior to use.
Researchers should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for SKU B728936 for complete hazard information, GHS classifications, first-aid measures, and disposal guidelines. All local regulations regarding the handling and disposal of halogenated organic compounds must be followed.
Frequently asked questions
What makes 7-bromo-5-chloro-1H-indole-2-carboxylic acid a useful building block in synthesis?
This compound offers three independent functional handles: the C-7 bromo group for selective palladium-catalyzed cross-coupling, the C-5 chloro group for secondary functionalization, and the C-2 carboxylic acid for amide coupling, esterification, or decarboxylation. This orthogonal reactivity allows chemists to systematically diversify the scaffold in multiple directions, making it highly efficient for library synthesis and drug candidate elaboration.
How should I select reaction conditions to differentiate the C-7 bromo and C-5 chloro groups?
Under standard palladium-catalyzed cross-coupling conditions (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂, mild temperatures), the C–Br bond at C-7 is selectively activated over the C–Cl bond at C-5 due to the higher oxidative addition rate of aryl bromides relative to aryl chlorides. To engage the C–Cl bond selectively after bromide functionalization, more active catalysts such as Pd-NHC complexes or Buchwald-type bulky phosphine ligand systems at elevated temperatures are typically required. Conditions should be optimized empirically for each specific coupling partner.
What solvents are suitable for dissolving 7-bromo-5-chloro-1H-indole-2-carboxylic acid?
Polar aprotic solvents such as DMSO and DMF are generally good choices for dissolving halogenated indole carboxylic acids due to the carboxylic acid and indole N–H groups. Methanol and ethanol may also provide adequate solubility. Aqueous solubility is expected to be low at neutral pH but improves significantly upon deprotonation with dilute base. Specific solubility data should be confirmed from the Aladdin Scientific certificate of analysis for SKU B728936.
Is this compound available from Aladdin Scientific, and what is the product SKU?
Yes, 7-bromo-5-chloro-1H-indole-2-carboxylic acid is available from Aladdin Scientific under SKU B728936. Please contact Aladdin Scientific or visit the product page for current pricing, available quantities, purity specifications, and lead times.
References
- Sundberg, R. J. Indoles. Academic Press, 1996. (General reference on indole chemistry and reactivity.)
- Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed. Wiley-Blackwell, 2010. (Textbook coverage of halogenated heterocycle reactivity and cross-coupling.)
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed. Oxford University Press, 2012. (General reference for carboxylic acid and halide functional group transformations.)
- Aladdin Scientific. Product page for 7-Bromo-5-chloro-1H-indole-2-carboxylic acid, SKU B728936. (For current specifications, SDS, and CoA.)
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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