Premium
N ‐Difluorocyclopropyl‐Substituted Pyrazoles: Synthesis and Reactivity
Author(s) -
Nosik Pavel S.,
Poturai Andrii S.,
Pashko Mykola O.,
Melnykov Kostiantyn P.,
Ryabukhin Sergey V.,
Volochnyuk Dmitriy M.,
Grygorenko Oleksandr O.
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900123
Subject(s) - chemistry , moiety , reagent , bromine , reactivity (psychology) , aqueous solution , organic chemistry , catalysis , halogenation , pyrazole , alkali metal , combinatorial chemistry , medicinal chemistry , medicine , alternative medicine , pathology
Difluorocyclopropanation of N ‐vinylazoles with the CF 3 SiMe 3 –NaI system was studied. It was found that N ‐vinylpyrazoles could be transformed into the corresponding N ‐difluorocyclopropyl‐substituted derivatives. The method was efficient on a 100 g scale and could be applied for the preparation of various functionalized regioisomeric pyrazole derivatives bearing a gem ‐difluorocyclopropane moiety, such as amines, carboxylic acids, aldehydes, bromides, and boronic esters. It was found that N ‐difluorocyclopropylpyrazole moiety tolerated many common reagents including nitrating mixture, bromine, aqueous acids and alkali, KMnO 4 , LiBH 4 , and Pd 0 complexes; it was unstable towards AlCl 3 , catalytic hydrogenation and lithiation conditions. The products obtained are advanced building blocks which of potential importance to medicinal and agrochemistry.