One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Main Authors: Joseph L. Howard, William Nicholson, Yerbol Sagatov, Duncan L. Browne
• Format: Article
• Language: English
• Published: Beilstein-Institut 2017-09-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: fluorination; heterocycles; mechanochemistry; multistep; solid-state synthesis
• Online Access: https://doi.org/10.3762/bjoc.13.189

Solventless mechanochemical synthesis represents a technique with improved sustainability metrics compared to solvent-based processes. Herein, we describe a methodical process to run one solventless reaction directly into another through multistep mechanochemistry, effectively amplifying the solvent savings. The approach has to consider the solid form of the materials and compatibility of any auxiliary used. This has culminated in the development of a two-step, one-jar protocol for heterocycle formation and subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in moderate to excellent yields.