Switchable reactivity: the site-selective functionalization of trifluoromethyl-substituted pyrazoles

Modern organometallic methods enable the regioflexible conversion of simple heterocyclic starting materials into families of isomers and congeners. Depending on the choice of the reagent, 1-methyl-5-(trifluoromethyl)pyrazole undergoes deprotonation and subsequent carboxylation mainly or exclusively at either the 4-position of the heterocycle or at the nitrogen-attached Me group. Similarly, 1-phenyl-5-(trifluoromethyl)pyrazole and 3-methyl-1-phenyl-5-(trifluoromethyl)pyrazole are selectively attacked by lithium diisopropylamide at the heterocyclic 4-position and by butyllithium concomitantly at the 4-position and the ortho position of the Ph ring. In contrast, metalation of 1-methyl-3-(trifluoromethyl)pyrazole occurs only at the 5-position, whatever the organometallic or metal amide base. Further sites become accessible to functionalization if bromine is introduced into the heterocyclic or arom. ring. This has been demonstrated with 4-bromo-1-methyl-5-(trifluoromethyl)pyrazole, 4-bromo-1-methyl-3-(trifluoromethyl)pyrazole, 4-bromo-1-methyl-5-(trifluoromethyl)pyrazole and 1-(2-bromophenyl)-5-(trifluoromethyl)pyrazole. [on SciFinder (R)]


Published in:
European Journal of Organic Chemistry, 17, 2913-2920
Year:
2002
Keywords:
Note:
CAN 138:170121 28-8 Heterocyclic Compounds (More Than One Hetero Atom) Departement de Chimie, BCh, Ecole Polytechnique Federale,Lausanne,Switz. Journal 1434-193X written in English. 497833-12-2P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (debromination of; prepn. of trifluoromethyl-substituted pyrazoles via multistep site-selective functionalization routes); 129585-50-8P; 153085-15-5P; 154471-65-5P; 333363-79-4P; 497832-98-1P; 497832-99-2P; 497833-00-8P; 497833-01-9P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (lithiation and carboxylation of; prepn. of trifluoromethyl-substituted pyrazoles via multistep site-selective functionalization routes); 497833-06-4P Role: PRP (Properties), SPN (Synthetic preparation), PREP (Preparation) (prepn. and crystal structure of trifluoromethyl-substituted pyrazoles from multistep site-selective functionalization routes); 144219-75-0 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of trifluoromethyl-substituted pyrazoles via multistep site-selective functionalization routes); 98534-81-7P; 113100-53-1P; 119083-00-0P; 128694-63-3P; 272442-83-8P; 481065-92-3P; 497833-02-0P; 497833-03-1P; 497833-04-2P; 497833-05-3P; 497833-07-5P; 497833-08-6P; 497833-09-7P; 497833-10-0P; 497833-13-3P; 497833-14-4P; 497833-15-5P; 497833-17-7P; 497833-18-8P; 497833-19-9P; 497833-20-2P; 497833-21-3P; 497833-22-4P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of trifluoromethyl-substituted pyrazoles via multistep site-selective functionalization routes); 60-34-4 (Methylhydrazine); 100-63-0 (Phenylhydrazine); 16732-66-4 (2-(Bromophenyl)hydrazine) Role: RCT (Reactant), RACT (Reactant or reagent) (reaction with ethoxytrifluorobutenone; prepn. of trifluoromethyl-substituted pyrazoles via multistep site-selective functionalization routes); 17129-06-5 Role: RCT (Reactant), RACT (Reactant or reagent) (reaction with methylhydrazine; prepn. of trifluoromethyl-substituted pyrazoles via multistep site-selective functionalization routes)
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 Record created 2006-03-03, last modified 2018-01-27


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