Mechanochemical Conversion of Aromatic Amines to Aryl Trifluoromethyl Ethers
Michał Jakubczyk, Satenik Mkrtchyan*, Mohanad Shkoor, Suneel Lanka, Šimon Budzák, Miroslav Iliaš, Marek Skoršepa and Viktor O. Iaroshenko*
*Department of Chemistry, Faculty of Natural Sciences, Matej Bel University, Tajovského 40, Banská Bystrica 97401, Slovakia,
Email: viktor.iaroshenko
umb.sk
M. Jakubczyk, S. Mkrtchyan, M. Shkoor, S. Lanka, Š. Budzák, M. Iliaš, M. Skoršepa, V. O. Iaroshenko, J. Am. Chem. Soc., 2022, 144, 10438-10445.
DOI: 10.1021/jacs.2c02611
Abstract
A mechanochemical protocol enables a selective substitution of an aromatic amino group with a trifluoromethoxy group in the presence of pyrylium tetrafluoroborate and 1-methyl-1,4-diazabicyclo[2.2.2]octan1-ium trifluoromethanolate. The presented concise method opens a pathway to new chemical spaces for organic synthesis and medicinal chemistry.
see article for more examples
proposed mechamism
General procedure for the solid-state reaction
Inside a glovebox, a stainless steel 5 mL grinding vessel equipped with two balls (stainless steel, Ř=5 mm) was loaded consecutively with an appropriate aniline starting material (1.0 mmol, 1.0 equiv.), pyrylium tetrafluoroborate (1.1 mmol, 1.1 equiv.) and ZrO2 (grinding auxiliary) (1.0 mmol, 1.0 equiv.). Lastly, freshly prepared 1-methyl-1,4-diazabicyclo[2.2.2]octan-1-ium trifluoromethoxide (1.5 mmol, 1.5 equiv.) was added and the reaction vessel was properly sealed. The reaction vessel was installed on the ball mill and the contents were pulverized at 30 Hz for 1.5h. After completion of the reaction, the content of the vessel was directly subjected to flash chromatography on silica gel to isolate the desired compound using gradient elution. The gram scale synthesis was performed with 10 mmol of the starting amine in 25 mL grinding vessel using three Ř=10 mm balls.
Key Words
aryl ethers, mechanochemistry
ID: J48-Y2022
