154471-65-5 | 1-METHYL-3-(TRIFLUOROMETHYL)-1H-PYRAZOLE

CAS:154471-65-5 | 1-METHYL-3-(TRIFLUOROMETHYL)-1H-PYRAZOLE,Description

1-Methyl-3-(trifluoromethyl)-1H-pyrazole is a compound that belongs to the pyrazole class, characterized by a 5-membered ring containing two nitrogen atoms opposite each other. The trifluoromethyl group attached to the pyrazole ring significantly influences the compound's electronic properties and reactivity, making it a valuable moiety in various chemical applications, including medicinal chemistry and agrochemistry.

Synthesis Analysis

The synthesis of pyrazole derivatives, including those with trifluoromethyl groups, often involves the cyclization of hydrazines with 1,3-dicarbonyl compounds or their equivalents. For instance, the synthesis of 3,5-bis(trifluoromethyl)-1H-pyrazole starts from corresponding β-diketones, which are cyclized to form the pyrazole ring. Similarly, the synthesis of 3-substituted 5-hydroxy-5-trifluoro[chloro]methyl-4,5-dihydropyrazoles involves a cyclocondensation reaction of trifluoro[chloro]-substituted alkenones with isoniazid. These methods highlight the versatility of pyrazole synthesis, allowing for the introduction of various substituents, including the trifluoromethyl group.

Molecular Structure Analysis

The molecular structure of pyrazole derivatives can be elucidated using techniques such as X-ray diffraction, NMR spectroscopy, and computational methods. For example, the X-ray molecular structure of 3,5-bis(trifluoromethyl)pyrazole reveals that it forms tetramers through N–H···N hydrogen bonds in the solid state. The molecular geometry of pyrazole derivatives has also been optimized using computational methods, providing insights into their conformational flexibility and electronic properties.

Chemical Reactions Analysis

Pyrazole derivatives participate in various chemical reactions, leveraging their unique reactivity profile. For instance, the Vilsmeier–Haack reaction has been used to synthesize 1,2,3-triazolyl pyrazole derivatives, demonstrating the pyrazole ring's ability to engage in further functionalization. Additionally, the transformation of a carboxylic group in a pyrazole core into a trifluoromethyl group by sulfur tetrafluoride has been reported, showcasing the synthetic versatility of pyrazole derivatives.

Physical and Chemical Properties Analysis

The physical and chemical properties of pyrazole derivatives are influenced by their molecular structure. The presence of the trifluoromethyl group can enhance the compound's lipophilicity and electronic characteristics, which are crucial for biological activity. For example, some pyrazole derivatives have shown significant antifungal and antimycobacterial activities, attributed to their ability to inhibit specific enzymes or interfere with mycolic acid biosynthesis. The thermal properties of synthesized pyrazoles have also been characterized, indicating their stability and potential for various applications.

Scientific Research Applications

Application in Medicinal and Agrochemistry

• Summary of the Application : “1-Methyl-3-(trifluoromethyl)-1H-pyrazole” is a key intermediate for important building blocks relevant to medicinal and agrochemistry. It’s used in the synthesis of various pharmaceuticals and agrochemicals.
• Methods of Application or Experimental Procedures : A practical method for the synthesis of “1-Methyl-3-(trifluoromethyl)-1H-pyrazole” and “1-Methyl-5-(trifluoromethyl)-1H-pyrazole” has been developed. The process involves the reaction of 4-ethoxy-1,1,1-trifluorobut-3-en-2-one with methyl hydrazine hydrochloride. The functionalization of the 5-position is achieved by lithiation in flow followed by trapping in batch with a series of electrophiles.
• Summary of the Results or Outcomes : The method provides a high-yielding and practical synthesis of “1-Methyl-3-(trifluoromethyl)-1H-pyrazole” and "1-Methyl-5-(trifluoromethyl)-1H-pyrazole". This method represents an important advancement given the prominence of these motifs in both agrochemicals and pharmaceuticals.

Application in Synthesis of Functionalized Pyrazoles

• Summary of the Application : “1-Methyl-3-(trifluoromethyl)-1H-pyrazole” is used in the synthesis of functionalized pyrazoles. These functionalized pyrazoles are important motifs in both agrochemicals and pharmaceuticals.
• Methods of Application or Experimental Procedures : The synthesis involves the reaction of 4-ethoxy-1,1,1-trifluorobut-3-en-2-one with methyl hydrazine hydrochloride. The functionalization of the 5-position is achieved by lithiation in flow followed by trapping in batch with a series of electrophiles.
• Summary of the Results or Outcomes : The method provides a scalable synthesis of 3/5-trifluoromethyl pyrazole derivatives. This represents an important advancement given the prominence of these motifs in both agrochemicals and pharmaceuticals.

Application in Synthesis of Functionalized Pyrazoles

• Summary of the Application : “1-Methyl-3-(trifluoromethyl)-1H-pyrazole” is used in the synthesis of functionalized pyrazoles. These functionalized pyrazoles are important motifs in both agrochemicals and pharmaceuticals.
• Methods of Application or Experimental Procedures : The synthesis involves the reaction of 4-ethoxy-1,1,1-trifluorobut-3-en-2-one with methyl hydrazine hydrochloride. The functionalization of the 5-position is achieved by lithiation in flow followed by trapping in batch with a series of electrophiles.
• Summary of the Results or Outcomes : The method provides a scalable synthesis of 3/5-trifluoromethyl pyrazole derivatives. This represents an important advancement given the prominence of these motifs in both agrochemicals and pharmaceuticals.

Safety And Hazards

The safety and hazards of “1-Methyl-3-(trifluoromethyl)-1H-pyrazole” are not well-documented. It’s important to handle this compound with care and follow appropriate safety protocols.

Future Directions

The future directions for “1-Methyl-3-(trifluoromethyl)-1H-pyrazole” involve its potential applications in various fields. It’s expected that many novel applications of this compound will be discovered in the future.

More Information