6-Chloro-5-nitro-1H-indole: Properties, Synthesis & Applications
6-Chloro-5-nitro-1H-indole: Properties, Synthesis & Applications
6‐chloro‐5‐nitro‐1H‐indole is a halogenated, electron-deficient indole building block widely used in medicinal chemistry and heterocyclic synthesis as a versatile intermediate for the preparation of biologically active compounds.
- Chemical Name
- 6-Chloro-5-nitro-1H-indole
- SKU
- C174952
- Molecular Formula
- C₈H₅ClN₂O₂
- Molecular Weight
- 196.59 g/mol
- Core Scaffold
- Bicyclic indole with electron-withdrawing nitro and chloro substituents at C-5 and C-6
- Primary Use
- Pharmaceutical intermediate and heterocyclic building block
- Supplier
- Aladdin Scientific
Chemical Structure and Properties
6-Chloro-5-nitro-1H-indole belongs to the indole family of bicyclic aromatic heterocycles, consisting of a benzene ring fused to a pyrrole ring. The compound bears two electron-withdrawing substituents: a nitro group (–NO₂) at the C-5 position and a chloro group (–Cl) at the C-6 position. This combination renders the aromatic system significantly electron-deficient compared to the parent indole scaffold.
The electron-withdrawing nature of both substituents lowers the electron density across the ring system, particularly at positions adjacent to C-5 and C-6. This electronic profile modifies the compound's reactivity in electrophilic and nucleophilic aromatic substitution reactions relative to unsubstituted indole. The chloro substituent also serves as a handle for transition-metal-catalyzed cross-coupling reactions, making this compound particularly valuable as a versatile synthetic intermediate.
The nitro group at C-5 can be selectively reduced to an amine under standard conditions (e.g., catalytic hydrogenation or iron/acetic acid), providing access to the corresponding 5-amino-6-chloro-1H-indole, a further elaborated building block used in drug discovery programs.
Synthesis and Preparation
6-Chloro-5-nitro-1H-indole can be accessed through several synthetic strategies commonly employed in heterocyclic chemistry. One classical approach involves the controlled nitration of 6-chloro-1H-indole using a mild nitrating agent, with careful control of temperature and stoichiometry to achieve regioselective introduction of the nitro group at the C-5 position. Regioselectivity in such reactions is governed by the directing effects of existing ring substituents and the inherent electronic bias of the indole nucleus.
Alternatively, the compound may be synthesized via classical indole-forming reactions such as the Fischer indole synthesis or the Leimgruber–Batcho synthesis, starting from appropriately substituted aniline or nitrobenzene precursors that already bear the chloro and nitro functionalities. These routes allow the target substitution pattern to be established prior to ring closure, avoiding potentially problematic post-cyclization functionalization steps.
Researchers sourcing this compound for use as a starting material or intermediate are advised to confirm the purity specification by HPLC and to verify the identity by ¹H NMR and mass spectrometry prior to use in sensitive synthetic transformations.
Research and Pharmaceutical Applications
Halogenated and nitrated indoles represent an important class of building blocks in medicinal chemistry and drug discovery. 6-Chloro-5-nitro-1H-indole is valued primarily for the orthogonal reactivity offered by its two substituents: the chloro group enables palladium-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Buchwald–Hartwig amination), while the nitro group can be reduced to an amine for subsequent condensation, acylation, or cyclization reactions.
This dual functionality allows medicinal chemists to perform sequential, chemoselective transformations on the same scaffold, rapidly generating structurally diverse analogue libraries for structure–activity relationship (SAR) studies. Electron-deficient indoles are also of interest as potential pharmacophores in their own right, as the indole nucleus is present in numerous biologically active natural products and approved drugs.
Beyond pharmaceutical discovery, 6-chloro-5-nitro-1H-indole may find use in materials science research, particularly in the design of functional organic molecules where the electron-deficient indole unit contributes to charge-transfer or optical properties.
Handling, Storage, and Safety Considerations
As with all aromatic nitro compounds, 6-chloro-5-nitro-1H-indole should be handled with appropriate precautions in a well-ventilated laboratory environment. Standard laboratory personal protective equipment (PPE) — including nitrile gloves, safety glasses, and a laboratory coat — should be worn at all times during handling. Avoid generating dust, and use a fume hood when weighing or transferring the compound.
The compound should be stored in a tightly sealed container, protected from light, heat, and moisture, at room temperature or as specified on the product certificate of analysis (CoA). Users are strongly advised to consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific (SKU C174952) before use, as it contains authoritative hazard classification, first-aid measures, and disposal guidance specific to this material.
Waste containing this compound should be disposed of in accordance with applicable local, national, and institutional regulations governing chemical waste. Do not pour into drains or the environment.
Frequently asked questions
What is 6-chloro-5-nitro-1H-indole used for in research?
6-Chloro-5-nitro-1H-indole is primarily used as a synthetic building block in medicinal chemistry and heterocyclic synthesis. Its chloro substituent enables palladium-catalyzed cross-coupling reactions, while the nitro group can be reduced to an amine for further functionalization, making it a versatile intermediate for generating pharmacologically relevant compound libraries.
How should 6-chloro-5-nitro-1H-indole (C174952) be stored?
The compound should be stored in a tightly sealed container away from light, heat, and moisture. Refer to the product Certificate of Analysis (CoA) and Safety Data Sheet (SDS) from Aladdin Scientific for precise storage temperature recommendations and any specific handling requirements.
Can the nitro group in 6-chloro-5-nitro-1H-indole be selectively reduced?
Yes, the nitro group at C-5 can generally be reduced to the corresponding amine using standard conditions such as catalytic hydrogenation or chemical reductants like iron in acetic acid. The resulting 5-amino-6-chloro-1H-indole provides a further functionalized building block for drug discovery. Researchers should optimize conditions to preserve the chloro substituent and indole ring integrity during reduction.
What cross-coupling reactions are compatible with 6-chloro-5-nitro-1H-indole?
The C-6 chloro substituent makes this compound a suitable electrophilic partner in palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with boronic acids), Buchwald–Hartwig amination (with amines), and potentially Negishi or Sonogashira couplings. Reaction conditions should be optimized empirically, as the electron-deficient indole ring may influence catalyst performance and selectivity.
References
- Aladdin Scientific. 6-Chloro-5-nitro-1H-indole, SKU C174952, Product Information and Certificate of Analysis. Aladdin Scientific.
- Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010.
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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