387-43-9 | 4-Fluoroindole

CAS:387-43-9 | 4-Fluoroindole,Description

4-Fluoroindole is a fluorinated analog of the heterocyclic compound indole, which is a structural element found in many natural products and pharmaceuticals. The introduction of a fluorine atom into the indole ring can significantly alter the compound's physical, chemical, and biological properties, making it a valuable target for research in medicinal chemistry and materials science.

Synthesis Analysis

The synthesis of fluorinated indoles, such as 4-fluoroindole, often involves the use of fluorinating agents or the direct fluorination of indole precursors. For instance, the synthesis of (L)-4-fluorotryptophan from 4-fluoroindole is described as a seven-step process with a key diastereoselective alkylation step. Additionally, the use of 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead) has been reported for the synthesis of 4-fluoropyrrolidine derivatives, which are valuable in medicinal chemistry.

Molecular Structure Analysis

The molecular structure of fluorinated indoles is characterized by the presence of a fluorine atom on the indole ring, which can influence the electronic distribution and reactivity of the molecule. For example, the single crystal structure determination of a 3-fluorinated stilbazole provides insights into the planarity and conformation of the molecule, which can be extrapolated to understand the structural aspects of 4-fluoroindole derivatives.

Chemical Reactions Analysis

Fluorinated indoles participate in a variety of chemical reactions, leveraging the unique reactivity of the fluorine atom. The fluorine atom can act as an electrophilic site, influencing the regioselectivity and outcome of reactions such as Diels-Alder reactions, as demonstrated by the synthesis of 3-chloro-4-fluorothiophene-1,1-dioxide. Additionally, the introduction of fluorine into indole derivatives can enable further functionalization, as seen in the synthesis of 3-amino-4-fluoropyrazoles.

Physical and Chemical Properties Analysis

The physical and chemical properties of 4-fluoroindole derivatives are significantly impacted by the presence of the fluorine atom. For instance, the high thermal stability and resistance to aqueous hydrolysis of certain fluorinating agents, such as Fluolead, suggest that fluorinated indoles may also exhibit enhanced stability. The fluorescence properties of 4-cyanoindole-2'-deoxyribonucleoside (4CIN), a related compound, indicate that fluorinated indoles could have potential applications in fluorescent labeling and imaging.

Scientific Research Applications

1. Chemoenzymatic Synthesis of Indole-Containing Acyloin Derivatives

• Summary of Application: 4-Fluoroindole is used in the chemoenzymatic synthesis of indole-containing acyloin derivatives. These derivatives are key intermediates of many antimicrobial/antiviral natural products or building blocks in the synthesis of biologically active molecules.
• Methods of Application: The reaction was initiated by the addition of 4-fluoroindole in the Pf TrpB 6-mediated systems to provide 4-fluoro-tryptophan.
• Results or Outcomes: The results demonstrate that NzsH displays a considerable substrate profile toward donor substrates for production of acyloins with different indole ring systems.

2. Synthesis Intermediate for Dyes and APIs

• Summary of Application: 4-Fluoroindole is used as a synthesis intermediate for dyes and active pharmaceutical ingredients (APIs) in applications of drug discovery, OLEDs, DSSCs, and bioimaging.
• Methods of Application: The derivatization of indole is versatile. Substitution of 1-position (on the nitrogen) is achieved with sodium hydride or potassium hydride making it a nucleophile.
• Results or Outcomes: 4F-Indole improves the effectiveness of kanamycin (an aminoglycoside antibiotic) against Pseudomonas aeruginosa, a multi-drug resistant pathogen.

3. Preparation of Sodium-Dependent Glucose Co-transporter 2 (SGLT2) Inhibitors

• Summary of Application: 4-Fluoroindole is used as a reactant for the preparation of Sodium-Dependent Glucose Co-transporter 2 (SGLT2) Inhibitors for the Management of Hyperglycemia in Diabetes.

4. Preparation of Tryptophan Dioxygenase Inhibitors

• Summary of Application: 4-Fluoroindole is used as a reactant for the preparation of tryptophan dioxygenase inhibitors. These inhibitors are potential anticancer immunomodulators.

5. Preparation of Antifungal Agents

• Summary of Application: 4-Fluoroindole is used as a reactant for the preparation of antifungal agents.

6. Interference with Quorum Sensing

• Summary of Application: 4-Fluoroindole is one of several indole derivatives that have been found to interfere with quorum sensing, a type of bacterial communication. This interference can suppress the production of certain bacterial products.

4. Preparation of Tryptophan Dioxygenase Inhibitors

• Summary of Application: 4-Fluoroindole is used as a reactant for the preparation of tryptophan dioxygenase inhibitors. These inhibitors are potential anticancer immunomodulators.

5. Preparation of Antifungal Agents

• Summary of Application: 4-Fluoroindole is used as a reactant for the preparation of antifungal agents.

6. Interference with Quorum Sensing

• Summary of Application: 4-Fluoroindole is one of several indole derivatives that have been found to interfere with quorum sensing, a type of bacterial communication. This interference can suppress the production of certain bacterial products.

Safety And Hazards

4-Fluoroindole causes skin irritation and serious eye irritation. It may cause respiratory irritation and is harmful if swallowed or in contact with skin. It should be stored in a well-ventilated place and kept in a tightly closed container.

Future Directions

Indole-containing acyloins, like 4-Fluoroindole, are key intermediates in the synthesis of biologically active molecules such as carbazoles, β-carbolines, and other indole-containing molecules. They are also key precursors of antimicrobial/antiviral agents. Therefore, the development of straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying their fundamental properties and applications.

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