497832-98-1Relevant articles and documents
Practical synthetic method for functionalized 1-methyl-3/5-(trifluoromethyl)-1H-pyrazoles
Tairov, Maxim A.,Levchenko, Vitalina,Stadniy, Ivan A.,Dmytriv, Yurii V.,Dehtiarov, Serhii O.,Kibalnyi, Mykola O.,Melnyk, Anton V.,Veselovych, Stanislav Y.,Borodulin, Yurii V.,Kolotilov, Sergey V.,Ryabukhin, Sergey V.,Volochnyuk, Dmitriy M.
, p. 2619 - 2632 (2020/12/29)
A new, high-yielding, and practical method for synthesis of 1-methyl-3-(trifluoromethyl)-1H-pyrazole and 1-methyl- 5-(trifluoromethyl)-1H-pyrazole, key intermediates for important building blocks relevant to medicinal and agrochemistry, is developed. A one-step procedure for synthesis of the regioisomeric mixture of target pyrazoles was proposed starting from 4-ethoxy- 1,1,1-trifluoro-3-buten-2-one. The procedure for separation of this mixture was elaborated on the basis of the boiling point vs pressure diagram analysis. The efficient synthetic strategies for regioisomeric building blocks bearing CF3 groups at the 3rd and 5th positions were demonstrated. A set of 1-methyl-3-(trifluoromethyl)-1H-pyrazoles containing such a functional group as aldehyde, acid, boron pinacolate, lithium sulfinate, and sulfonyl chloride was synthesized based on lithiation of 1-methyl-3-(trifluoromethyl)- 1H-pyrazole in a flow reactor. Bromination of both 1-methyl-3-(trifluoromethyl)-1H-pyrazole and 1-methyl-5-(trifluoromethyl)-1Hpyrazole by NBS in mild conditions was performed. The introduction of the functional group at the 4th position of 1-methyl-5- (trifluoromethyl)-1H-pyrazole was illustrated by the optimized synthesis of the corresponding aldehyde and acid based on the Br-Li exchange in an appropriate bromide. Alternatively, the introduction of the functional group (acid and boron pinacolate) at the 5th position of 1-methyl-5-(trifluoromethyl)-1H-pyrazole was performed based on the direct ortho-metalation (DoM) reaction of 4- bromo-1-methyl-5-(trifluoromethyl)pyrazole followed by catalytic reductive debromination.
