4-Methoxy-7-nitro-1H-indole: Properties & Research Uses

4-Methoxy-7-nitro-1H-indole is a nitro- and methoxy-substituted indole heterocycle that serves as a versatile building block in organic synthesis, medicinal chemistry, and the preparation of biologically active compounds.

IUPAC Name

4-methoxy-7-nitro-1H-indole

Molecular Formula

C₉H₈N₂O₃

Molecular Weight

192.17 g/mol

Core Scaffold

1H-Indole with 4-methoxy and 7-nitro substituents

Primary Use

Synthetic building block in medicinal and heterocyclic chemistry

Storage

Store in a cool, dry place away from light and moisture

Chemical Identity and Structure

4-Methoxy-7-nitro-1H-indole belongs to the indole family of bicyclic heterocycles, consisting of a benzene ring fused to a pyrrole ring. The compound carries two key functional groups: a methoxy (–OCH₃) group at the 4-position and a nitro (–NO₂) group at the 7-position. These substituents are positioned on the benzene portion of the indole scaffold, conferring distinct electronic and steric properties relative to unsubstituted indole.

The molecular formula is C₉H₈N₂O₃, with a molecular weight of approximately 192.17 g/mol. The electron-withdrawing nitro group at C-7 and the electron-donating methoxy group at C-4 create an electronically differentiated aromatic system, which is of practical value in regioselective synthetic transformations.

Physicochemical Properties

The dual substitution pattern of 4-Methoxy-7-nitro-1H-indole significantly influences its physicochemical behavior. The nitro group is a strong electron-withdrawing substituent that reduces electron density across the indole π-system, lowering the nucleophilicity of the C-3 position compared to electron-rich indoles. Conversely, the 4-methoxy group partially offsets this effect through resonance donation.

The compound is expected to be a solid at room temperature, as is typical for substituted nitroindoles with comparable molecular weights. Solubility is anticipated in polar aprotic solvents such as DMSO, DMF, and acetonitrile, with limited solubility in water. Researchers should handle the material with standard laboratory precautions appropriate for nitroaromatic compounds, including avoidance of strong reducing agents and open flames.

Synthetic Applications and Research Utility

Nitroindoles are well-established intermediates in the synthesis of biologically active molecules, including natural products and pharmaceutical candidates. The 7-nitro group in 4-Methoxy-7-nitro-1H-indole can serve as a precursor to the corresponding 7-amino indole via reduction, enabling access to 7-aminoindole scaffolds that appear in numerous pharmacologically relevant structures.

The methoxy group at C-4 provides a handle for further functionalization, including demethylation to reveal a free phenol, or participation in cross-coupling reactions when combined with appropriate catalytic systems. The compound may be used in Friedel–Crafts-type alkylations, Pictet–Spengler cyclizations, and transition-metal-catalyzed C–H functionalization reactions as a substrate or coupling partner. Its differentiated substitution pattern makes it particularly attractive for the synthesis of asymmetrically substituted indole libraries used in medicinal chemistry screening.

Handling, Safety, and Storage Guidelines

As a nitroaromatic compound, 4-Methoxy-7-nitro-1H-indole should be handled in accordance with standard laboratory safety practices. Personnel should wear appropriate personal protective equipment (PPE), including gloves, safety glasses, and a lab coat. Work should be conducted in a well-ventilated fume hood to minimize inhalation exposure to dust or vapors.

The compound should be stored in a tightly sealed container in a cool, dry location, away from direct light, heat sources, and incompatible materials such as strong oxidizers or reducing agents. Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before first use. Disposal must comply with applicable local, regional, and national regulations for chemical waste.

Frequently asked questions

What is 4-Methoxy-7-nitro-1H-indole used for in research?

4-Methoxy-7-nitro-1H-indole is primarily used as a synthetic building block in medicinal and heterocyclic chemistry. The nitro group can be reduced to an amine for further derivatization, while the methoxy group enables additional functionalization, making it valuable for constructing complex indole-based molecular scaffolds.

What solvents are suitable for dissolving 4-Methoxy-7-nitro-1H-indole?

Based on the properties of comparable nitroindole compounds, polar aprotic solvents such as DMSO, DMF, and acetonitrile are expected to provide adequate solubility. Solubility in water is anticipated to be limited. Researchers should perform a preliminary solubility test before use in sensitive assays.

How should 4-Methoxy-7-nitro-1H-indole be stored to maintain stability?

The compound should be stored in a tightly closed container in a cool, dry environment, protected from light and moisture. Avoid contact with strong reducing or oxidizing agents. Always refer to the product's Safety Data Sheet (SDS) for specific storage and stability guidance.

Can the nitro group of 4-Methoxy-7-nitro-1H-indole be selectively reduced?

Yes, the nitro group on indole derivatives can typically be reduced to the corresponding amine using standard reduction protocols, such as catalytic hydrogenation or chemical reductants like iron in acetic acid or tin(II) chloride. However, specific conditions for this substrate should be optimized experimentally, as the presence of the methoxy group and the indole NH may influence chemoselectivity.

References

1. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010.
2. Sundberg, R. J. Indoles; Academic Press: London, 1996.
3. Aladdin Scientific Product Page: 4-Methoxy-7-nitro-1H-indole, SKU M734786.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.