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Updated: Jan 12, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Accessing trifluoromethylated SuFEx-able pyrazole via distortion-accelerated 1,3-dipolar cycloadditions
Bipin Khanal1, Mark Aldren M Feliciano2, Brian Gold1
1Department of Chemistry and Biochemistry, New Mexico State University Las Cruces New Mexico 88003 USA bgold@nmsu.edu.
None:
Fluorinated pyrazoles are valuable scaffolds with wide-ranging applications in medicinal chemistry, agrochemistry and materials science. We report the 1,3-dipolar cycloaddition of 2,2,2-trifluorodiazoethane and 1-bromoethene-1-sulfonyl fluoride for the concise synthesis of 5-(trifluoromethyl)-1H-pyrazole-3-sulfonyl fluoride. Computational analysis revealed that lowered distortion energies account for increased reactivity relative to other stabilized diazo compounds. The resulting trifluoromethylated pyrazole contains a SuFEx-able click handle, enabling orthogonal diversification pathways for diversity-oriented clicking. Together, these features support rapid functionalization and efficient access to structurally diverse analogs, offering a versatile platform for expansion of chemical space geared towards the development of bioactive molecules.
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