5-Fluoroindole

Chemical Properties

off-white crystalline powder

Uses

5-Fluoroindole is a reactant used in various syntheses. It was used in the synthesis of Spirotetrahydro β-Carbolines (Spiroindolones), which is a new class of potent and orally efficacious compounds for the treatment of malaria. 5-Fluoroindole was also a reactant in direct indole and pyrrole couplings to carbonyl compound in total synthesis of Acremoauxin A and Oxazinin 3.

Application

5-fluoroindole is an organofluorine compound that is the 5-fluoro derivative of indole. It is a reagent involved in a variety of biochemical preparation procedures including:

• Reactant for preparation of 5-HT6 receptor ligands
• Reactant for preparation of tryptophan dioxygenase inhibitors pyridyl-ethenyl-indoles as potential anticancer immunomodulators
• Reactant for preparation of antitumor agents
• Reactant for preparation of antibacterial agents
• Reactant for preparation of immunosuppressive agents
• Reactant for preparation of Sodium-Dependent Glucose Co-transporter 2 (SGLT2) Inhibitors for the Management of Hyperglycemia in Diabetes
• Reactant for preparation of Myeloperoxidase Inhibitors
• Reactant for preparation of Potent Selective Serotonin Reuptake Inhibitors

Preparation

5-Fluoroindole is prepared from 2-(5-fluoro-2-nitrophenyl)-5-acetonitrile.

10% Pd/C (110 mg) was transferred into a round-bottom flask under a nitrogen atmosphere, followed by the addition of 2-(5-fluoro-2-nitrophenyl)-5-acetonitrile (564 mg, 3.13 mmol) in anhydrous ethanol (25 mL). The mixture was degassed and backfilled with hydrogen gas for a total of three cycles, then stirred overnight. After replacing the hydrogen with nitrogen, a second portion of 10% Pd/C (110 mg) was added to the reaction mixture, and hydrogen gas was reintroduced. The completion of the reaction was monitored by ¹⁹F NMR. Subsequently, the hydrogen gas was replaced with nitrogen, and chloroform (CHCl₃) was added to quench the unreacted Pd/C. The reaction mixture was concentrated under reduced pressure, then partitioned between dichloromethane (DCM) and water. After separation, the aqueous phase was back-extracted, and the combined organic layers were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. Column chromatography (mobile phase: DCM) afforded 5-fluoroindole as a white solid.
Yield: 342 mg, 2.53 mmol (81% yield based on 2-(5-fluoro-2-nitrophenyl)-5-acetonitrile).
¹H NMR (400 MHz, CDCl₃) δ: 7.27 (m, 3H), 6.96 (t, 1H), 6.53 (t, 1H).
¹⁹F NMR (376 MHz, CDCl₃) δ: –100.22.

Definition

ChEBI: 5-fluoroindole is an organofluorine compound that is the 5-fluoro derivative of indole.

References

[1] Low-potential electrochemical polymerization of 5-fluoroindole and characterization of its polymers, G. Nie et al., J. Electroanal. Chem., 604(2), 125−132(2007); DOI: 10.1016/j.jelechem.2007.03.010.
[2] http://www.diva-portal.org/smash/get/diva2:1892692/FULLTEXT01.pdf
[3] THANIGAIMALAI PILLAIYAR. A rapid, efficient and versatile green synthesis of 3,3’-diindolylmethanes[J]. Arkivoc, 2017, 2018 1: 1-19. DOI:10.24820/ARK.5550190.P010.259.