138343-94-9 | 4-Fluoro-1,3-dihydro-2H-indol-2-one

CAS:138343-94-9 | 4-Fluoro-1,3-dihydro-2H-indol-2-one,Description

4-Fluoroindolin-2-one is a fluorinated heterocyclic compound that has garnered interest due to its potential applications in medicinal chemistry and as a building block for more complex molecules. The presence of the fluorine atom can significantly alter the physical, chemical, and biological properties of molecules, making fluorinated compounds particularly valuable in drug design and development.

Synthesis Analysis

The synthesis of fluorinated isoindolines, which are closely related to 4-fluoroindolin-2-one, can be achieved through a tandem nucleophilic addition-intramolecular aza-Michael reaction. This method allows for the construction of isoindolines with varying degrees of fluorination, including mono-, di-, or trifluoromethyl groups, as well as heavier fluorinated groups, often resulting in single isomers. Additionally, the synthesis of related fluorinated compounds, such as 4-fluorobenzo[b][1,6]naphthyridines and 4-fluoroisoquinolines, can be performed using Ag(I)-catalyzed one-pot synthesis with Selectfluor as the fluorinating reagent. Moreover, a one-pot synthesis approach has been developed for 1-(trifluoromethyl)-4-fluoro-1,2-dihydroisoquinolines and 4,4-difluorotetrahydroisoquinolines, which involves a silver-catalyzed intramolecular aminofluorination of alkyne.

Molecular Structure Analysis

The molecular structure of fluorinated compounds can be elucidated using techniques such as X-ray crystallography. For instance, the structure of methyl 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate was determined to exist in a monoclinic P21/c space group with one molecule in the asymmetric part of the unit cell. Similarly, the structure of a fluoroalkylated 1,1-dimethoxy-3-iminoisoindoline acetal was revealed by X-ray structural analysis, providing insights into the stabilization of the amino tautomer.

Chemical Reactions Analysis

Fluorinated indolin-2-ones can undergo various chemical reactions, expanding their utility in synthetic chemistry. For example, the detrifluoroacetylative in situ generation of fluorinated amide enolates derived from 3-fluoroindolin-2-one can lead to asymmetric Mannich additions, affording α-fluoro-β-(fluoroalkyl)-β-aminoindolin-2-ones with high yields and diastereoselectivities. Additionally, gem-difluorosubstituted NH-azomethine ylides can be used in the synthesis of 4-fluorooxazolines via a three-component reaction involving imines, trifluoroacetophenones, and CF2Br2.

Physical and Chemical Properties Analysis

The introduction of fluorine atoms into the indolin-2-one framework can significantly influence the physical and chemical properties of the compound. Fluorinated compounds often exhibit increased stability, lipophilicity, and the ability to form unique intermolecular interactions due to the high electronegativity of fluorine. These properties are crucial for the development of pharmaceuticals, as they can affect the bioavailability and metabolic stability of drug candidates. For instance, fluorinated 4-hydroxyquinolinones have shown promising phototoxicity and cytotoxic activities against various cancer cell lines.

Scientific Research Applications

Synthesis and Pharmacological Evaluation

A study by Nirmal et al. (2010) focused on synthesizing novel derivatives of 4-fluoroindolin-2-one and evaluating them for analgesic and anti-inflammatory activities. The findings indicated that certain compounds exhibited significant anti-inflammatory activity, comparable to the reference standard diclofenac sodium, and displayed only mild ulcerogenic side effects (Nirmal, Prakash, Meenakshi, & Shanmugapandiyan, 2010).

Antitumor Activity

Another research by Chou et al. (2010) explored the design and synthesis of 5,6- (or 6,7-) disubstituted-2-(fluorophenyl)quinolin-4-one derivatives as potent antitumor agents. These analogues, including certain 4-fluoroindolin-2-one derivatives, exhibited significant inhibitory activity against various tumor cell lines. One of the derivatives selectively inhibited cancer cell lines, suggesting potential as a clinical candidate for cancer treatment (Chou et al., 2010).

Antibacterial and Antifungal Properties

Deswal et al. (2020) synthesized 5-fluoro-1H-indole-2,3-dione-triazoles using an environmentally friendly catalyst. The compounds showed considerable antibacterial and antifungal potency, demonstrating the application of 4-fluoroindolin-2-one derivatives in developing antimicrobial agents (Deswal, Naveen, Tittal, Vikas, Lal, & Kumar, 2020).

Cellular Imaging Applications

Fleming et al. (2015) conducted a study on a scriptaid analogue, 4-morpholinoscriptaid (4MS), which demonstrated rapid cellular uptake. This research provides insights into the potential use of 4-fluoroindolin-2-one derivatives in cellular imaging, enhancing the understanding of cellular processes (Fleming, Ashton, Nowell, Devlin, Natoli, Schreuders, & Pfeffer, 2015).

Safety And Hazards

The compound is labeled with the GHS07 pictogram and has a signal word of "Warning". The hazard statement is H302, indicating that it may be harmful if swallowed. Precautionary measures include avoiding contact with skin and eyes, using personal protective equipment, and ensuring adequate ventilation.

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