Metal-bearing and trifluoromethyl-substituted pyrimidines: generation and functionalization

5-Pyrimidyllithium species are fairly stable when the metal is flanked by two electron-withdrawing substituents such as trifluoromethyl and chlorine or bromine. Thus, the corresponding 5-carboxylic acids are produced in high yields from 4,5-dibromo-6-(trifluoromethyl)pyrimidine and 5-bromo-4-chloro-6-(trifluoromethyl)pyrimidine upon halogen/metal permutation accomplished with isopropylmagnesium chloride or butyllithium followed by carboxylation. Satisfactory or excellent yields of 5-carboxylic acids are equally obtained when 4-chloro-, 2,4-dichloro- and 2,4-dibromo-6-(trifluoromethyl)pyrimidine are deprotonated with lithium diisopropylamide before being allowed to react with dry ice. In contrast, consecutive treatment of 2-bromo-4-(trifluoromethyl)pyrimidine and 2-chloro-5-iodo-4-(trifluoromethyl)pyrimidine with butyllithium affords the expected carboxylic acids in only poor yields and not even trace amts. of acid were detected when 4-bromo-6-(trifluoromethyl)pyrimidine served as the substrate. The formation of bipyrimidines, emerging from either one of two competing mechanistic pathways, is a permanently menacing side reaction. [on SciFinder (R)]


Published in:
European Journal of Organic Chemistry, 6, 1593-1598
Year:
2006
Keywords:
Note:
CAN 144:488618
28-16
Heterocyclic Compounds (More Than One Hetero Atom)
Institute of Chemical Sciences and Engineering,Ecole Polytechnique Federale,Lausanne,Switz.
Journal
1434-193X
written in English.
672-45-7; 1546-78-7; 126538-81-6; 785777-87-9; 785777-94-8; 785777-99-3; 785778-00-9 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of pyrimidinecarboxylic acids by metalation of pyrimidines bearing electron-withdrawing substituents and subsequent carboxylation); 16097-64-6P; 37552-81-1P (4-Chloro-6-(trifluoromethyl)pyrimidine); 425392-76-3P (5-Bromo-4-chloro-6-(trifluoromethyl)pyrimidine); 887626-21-3P; 887626-22-4P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of pyrimidinecarboxylic acids by metalation of pyrimidines bearing electron-withdrawing substituents and subsequent carboxylation); 188781-17-1P; 220880-12-6P; 887626-20-2P; 887626-23-5P; 887626-24-6P; 887626-25-7P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of pyrimidinecarboxylic acids by metalation of pyrimidines bearing electron-withdrawing substituents and subsequent carboxylation)
Other identifiers:
Laboratories:




 Record created 2007-03-07, last modified 2018-01-27


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