25199-84-2 | 2-Hydroxy-4-(trifluoromethyl)quinoline

CAS:25199-84-2 | 2-Hydroxy-4-(trifluoromethyl)quinoline,Description

2-Hydroxy-4-(trifluoromethyl)quinoline is a chemical compound that belongs to the quinoline family, characterized by the presence of a trifluoromethyl group at the 4-position and a hydroxy group at the 2-position of the quinoline ring system. This structure imparts unique physical and chemical properties, making it a valuable intermediate for various chemical reactions and potential applications in medicinal chemistry.

Synthesis Analysis

The synthesis of 4-amino-2-(trifluoromethyl)quinolines, which are closely related to 2-hydroxy-4-(trifluoromethyl)quinoline, can be achieved via an intramolecular Friedel–Crafts reaction. This reaction involves 2-(1-(arylamino)-2,2,2-trifluoroethylidene)malononitrile derivatives, which are synthesized from N-aryl-2,2,2-trifluoroacetimidoyl chlorides and malononitrile. Additionally, the synthesis of various trifluoromethyl quinoline derivatives has been reported using different synthetic routes, such as the Sonogashira cross-coupling reaction, Buchwald–Hartwig amination, and radical cyclization of trifluoroacetimidoyl chlorides with alkynes.

Molecular Structure Analysis

The molecular structure of trifluoromethyl quinoline derivatives has been characterized by spectral studies, including X-ray crystallography for certain compounds. The presence of the trifluoromethyl group significantly influences the electronic properties of the quinoline ring, affecting its reactivity and interaction with other molecules.

Chemical Reactions Analysis

Trifluoromethyl quinoline derivatives participate in various chemical reactions. For instance, they can undergo hydrolysis under alkaline conditions to yield imidazoquinolines. They also exhibit reactivity towards the formation of carbohydrazide and 1,3,4-oxadiazoles, as well as the potential to form liquid crystalline phases. The reactivity of the [1,2,4]triazino ring in related quinoline derivatives has also been explored.

Physical and Chemical Properties Analysis

The physical and chemical properties of trifluoromethyl quinoline derivatives are influenced by their molecular structure. For example, the introduction of various substituents can lead to compounds with antimicrobial properties, liquid crystal behavior, and strong interactions with biomolecules such as ct-DNA. The crystal structures of certain derivatives have been studied, revealing insights into their conformation and potential interactions in the solid state. Optical and morphological studies of Y-shaped trifluoromethyl substituted quinoxalines, which share structural similarities with quinolines, have shown interesting properties such as solvatochromism, aggregation-induced emission, and distinct morphologies under scanning electron microscopy.

Scientific Research Applications

Organic Synthesis

• Field : Organic Chemistry
• Application : 2-Hydroxy-4-(trifluoromethyl)quinoline is used in the synthesis of new organofluorine compounds. These compounds are very effective in biological substances.
• Method : The synthesis involves the reaction of ethyl 2-cyanoacetate with trifluoroacetimidoyl chloride derivatives using sodium hydride in acetonitrile. This is followed by intramolecular cyclization of these products in nitrobenzene under reflux conditions.
• Results : This method affords a new series of substituted (trifluoromethyl)quinoline-3-carbonitrile derivatives in quantitative yields.

Drug Design

• Field : Medicinal Chemistry
• Application : Quinoline, which includes 2-Hydroxy-4-(trifluoromethyl)quinoline, is used as a core template in drug design due to its broad spectrum of bioactivity.
• Method : Various derivatives of the bioactive quinolines have been harnessed via expeditious synthetic approaches.
• Results : Quinoline is an indisputable pharmacophore due to its tremendous benefits in medicinal chemistry research and other valuable areas of human endeavor.

Fluorescent Probes

• Field : Biochemistry
• Application : 2-(trifluoromethyl)quinolines have been used as fluorescent probes in vivo.
• Method : The specific method of application is not mentioned in the source.
• Results : The use of these compounds as fluorescent probes has potential therapeutic value for the treatment of cancers and the Zika virus.

Synthesis of Analgesic Compound

• Field : Medicinal Chemistry
• Application : 4-Hydroxy-8-(trifluoromethyl)quinoline may be used in the synthesis of an analgesic compound, floctafenine.
• Method : The specific method of application is not mentioned in the source.
• Results : The use of this compound in the synthesis of floctafenine, an analgesic compound, is mentioned.

Fluorinated Quinolines

• Field : Organic Chemistry
• Application : Fluorinated quinolines, including 2-Hydroxy-4-(trifluoromethyl)quinoline, have found application in agriculture, and also as components for liquid crystals.
• Method : The synthesis of 6,7-difluoro-3-nitro-4-hydroxy-2-quinolone and 2,3,4-trichloro-6,7-difluoroquinolone from 4,5-difluoro-2-nitrobenzoic acid has been mentioned.
• Results : A number of fluorinated quinolines have found application in agriculture, and also as components for liquid crystals.

Synthesis of Pthalonitrile

• Field : Organic Chemistry
• Application : 4-Hydroxy-7-(trifluoromethyl)quinoline has been used in the synthesis of 4[[7-(trifluoromethyl)quinolin-4-yl]oxy]pthalonitrile.
• Method : The specific method of application is not mentioned in the source.
• Results : The use of this compound in the synthesis of 4[[7-(trifluoromethyl)quinolin-4-yl]oxy]pthalonitrile is mentioned.

Anticancer Assessment

• Field : Medicinal Chemistry
• Application : Quinoline derivatives, including 2-Hydroxy-4-(trifluoromethyl)quinoline, have been synthesized and assessed for their anticancer activity.
• Method : The specific method of application is not mentioned in the source.
• Results : The synthesized quinoline derivatives showed cytotoxic activity against human tumor cells.

Safety And Hazards

The compound is labeled with the GHS07 pictogram and has the signal word "Warning". The hazard statements include H315 (Causes skin irritation), H319 (Causes serious eye irritation), and H335 (May cause respiratory irritation). Precautionary measures include avoiding breathing dust/fume/gas/mist/vapors/spray (P261), washing thoroughly after handling (P280a), and if in eyes, rinsing cautiously with water for several minutes and removing contact lenses if present and easy to do (P305+P351+P338).

Future Directions

The interesting pharmaceutical and biological activities of 4-hydroxy-2-quinolones make them valuable in drug research and development. Hence, many publications have recently dealt with their synthetic analogous and the synthesis of their heteroannelated derivatives. This suggests that 2-Hydroxy-4-(trifluoromethyl)quinoline and its derivatives could have potential applications in the field of medicinal chemistry.

More Information