5-Fluoro-2-methylindole
[CAS# 399-72-4]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Indoles
• Name: 5-Fluoro-2-methylindole
• Synonyms: 5-Fluoro-2-methyl-1H-indole
• Molecular Formula: C₉H₈FN
• Molecular Weight: 149.16
• CAS Registry Number: 399-72-4
• EC Number: 609-764-5
• SMILES: CC1=CC2=C(N1)C=CC(=C2)F

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 98 - 101 °C (Expl.)
• Boiling point: 269.2±20.0 °C 760 mmHg (Calc.)^*
• Flash point: 116.6±21.8 °C (Calc.)^*
• Index of refraction: 1.627 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

5‑Fluoro‑2‑methylindole is a fluorinated indole derivative with the molecular formula C₉H₈FN and CAS number 399‑72‑4. The indole nucleus (a benzene ring fused to a pyrrole) is substituted at the 5‑position with a fluorine atom, and at the 2‑position with a methyl group. These substituents confer both electronic and steric effects that can influence reactivity, biological activity, and interactions in synthetic applications.

Because of the electron-withdrawing nature of the fluorine atom and the electron-donating effect of the methyl group, 5‑fluoro‑2‑methylindole can act as a useful building block in medicinal chemistry. The fluorine can enhance metabolic stability, influence lipophilicity, and potentially engage in hydrogen-bond modulation, while the methyl increases hydrophobic character and provides a site for further functionalization or modification.

In synthetic chemistry, this compound is valuable for the preparation of more complex indole derivatives. The indole NH (pyrrole) can undergo acylation, alkylation, or metal-catalyzed cross-coupling reactions. The methyl group may serve as a handle for CH-activation chemistry, enabling functionalization at nearby positions. The overall indole scaffold, with its fluorine and methyl substituents, is often leveraged to create heterocycles, pharmacophores, and molecule libraries for drug discovery.

From a practical standpoint, 5‑fluoro‑2‑methylindole is supplied as a solid and must be handled under inert atmosphere to avoid oxidation. According to available data, it has a melting point around 98–101 °C. Storage recommendations from catalog sources include protecting it from light and keeping it under an inert gas. Its solubility profile is typical for indoles of this type: it is soluble in common organic solvents such as methanol or dimethylformamide, but not highly soluble in aqueous media.

References

Using Phosphorus Pentasulfide (2019) Science of Synthesis DOI: 10.1055/s-0037-1612028

Palladium Complexes as Catalysts (2017) Science of Synthesis DOI: 10.1055/s-0037-1612028

C–N Coupling and Heck Coupling Reactions (2016) Science of Synthesis DOI: 10.1055/s-0037-1612028