52222-73-8 | 4-(trifluoromethyl)-1H-pyrazole

CAS:52222-73-8 | 4-(trifluoromethyl)-1H-pyrazole,Description

4-(Trifluoromethyl)-1H-pyrazole is a chemical compound that has gained attention due to its potential applications in various fields, including pharmaceuticals and agriculture. The trifluoromethyl group attached to the pyrazole ring is of particular interest because of its ability to influence the biological activity of the molecule.

Synthesis Analysis

The synthesis of 4-(trifluoromethyl)-1H-pyrazoles has been achieved through several methods. A copper-mediated domino cyclization/trifluoromethylation/deprotection process using TMSCF3 as the CF3 source has been described, which allows the synthesis of the pyrazole cores under mild conditions. Another approach involves the copper-catalyzed cycloaddition of 2-bromo-3,3,3-trifluoropropene with N-arylsydnone derivatives, yielding the desired pyrazoles with excellent regioselectivity. Additionally, synthetic protocols have been developed for the preparation of bis- and tris(trifluoromethyl)pyrazoles, highlighting the versatility of the trifluoromethyl group in pyrazole chemistry.

Molecular Structure Analysis

The molecular structure of 4-(trifluoromethyl)-1H-pyrazoles and their derivatives has been extensively studied. Quantum mechanical calculations and spectroscopic investigations have provided insights into the vibrational frequencies, molecular orbital, and electrostatic potential of these compounds. X-ray crystallography has been used to determine the structure of related dihydro-1H-pyrazoles, revealing planar structures and the influence of substituents on molecular packing.

Chemical Reactions Analysis

4-(Trifluoromethyl)-1H-pyrazoles exhibit interesting reactivity patterns. For instance, they can undergo Diels–Alder reactions, with fluorinated pyrazoles showing regiospecificity and varying reactivity depending on the degree of fluorination. The presence of the trifluoromethyl group can also influence the electron delocalization and hyperconjugation effects within the molecule, affecting its reactivity.

Physical and Chemical Properties Analysis

The physical and chemical properties of 4-(trifluoromethyl)-1H-pyrazoles are influenced by the trifluoromethyl group. This group can enhance the lipophilicity and stability of the molecule, which is beneficial for developing new insecticides with good activity against various pests. The introduction of the trifluoromethyl group into pyrazole derivatives has also been shown to affect their antimicrobial and antioxidant activities.

Scientific Research Applications

Synthesis Methods

• Copper-Mediated Synthesis : Copper-mediated synthesis of 4-(trifluoromethyl)pyrazoles has been achieved through a remarkable domino sequence from α,β-alkynic tosylhydrazones. This method provides a one-step route to 4-CF3 N-H pyrazole cores with good functional group compatibility, using trifluoromethyltrimethylsilane as the CF3 source, and can be used to synthesize analogs of drugs like celecoxib (Wang et al., 2017).
• Copper-Catalyzed Chemoselective Synthesis : A series of 4-trifluoromethyl pyrazoles have been prepared via copper-catalyzed cycloaddition, offering a new protocol that provides these compounds with moderate to excellent yields and excellent regioselectivity (Lu et al., 2019).

Chemical Properties and Applications

• Nematocidal Evaluation : Novel 3-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives, synthesized from ethyl 4,4,4-trifluoroacetoacetate, exhibit weak fungicidal but good nematocidal activity against M. incognita (Zhao et al., 2017).
• Insecticidal Activities : 1-Substituted-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives have shown good insecticidal activities against various pests, suggesting their potential as alternative insecticides (Wu et al., 2017).
• Synthesis of Fluorinated Pyrazoles : Trifluoromethylazoles, including 4-(trifluoromethyl)-1H-pyrazoles, have been synthesized, providing potential applications in measuring pH in biological media by 19F NMR spectroscopy (Jones et al., 1996).
• Antimicrobial Agents : 1,2,3-Triazolyl pyrazole derivatives, including those containing 4-(trifluoromethyl)-1H-pyrazole, have been synthesized and displayed broad-spectrum antimicrobial activities and moderate to good anti-oxidant activities (Bhat et al., 2016).
• High Thermal and Chemical Stability : Pyrazolate-bridged metal–organic frameworks featuring 4-(trifluoromethyl)-1H-pyrazole show exceptional thermal and chemical stability, making them suitable for applications like catalysis (Colombo et al., 2011).
• Organometallic Chemistry : Switchable reactivity studies demonstrate the regioflexible conversion of 4-(trifluoromethyl)-1H-pyrazoles in organometallic methods, offering a range of functionalization possibilities (Schlosser et al., 2002) .

Safety And Hazards

The safety and hazards associated with “4-(trifluoromethyl)-1H-pyrazole” would depend on its specific properties. It’s important to refer to the relevant safety data sheets for specific information.

Future Directions

The future directions for research involving “4-(trifluoromethyl)-1H-pyrazole” could include further exploration of its potential applications in pharmaceuticals and agrochemicals, as well as the development of new synthetic methods.

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