Formaldehyde: A Reagent for Simultaneous Protection of Heterocyclic NH and Activation of Alternative Locations to Electrophilic Attack. Part II. A New Synthetic Method for the 5(3)-Substitution of N-Unsubstituted Pyrazoles

Article abstract of DOI:10.1016/S0040-4020(01)81320-X

N-Unsubstituted pyrazole 1 is readily converted into 5-substituted derivatives 2 in moderate to good overall yields in a one-pot sequence, using formaldehyde both for N-protection and to mediate lithiation at the 5-position.The dilithiohemiaminals 5 react with electrophiles at the pyrazole 5-position to give 5-substituted 1-lithioxymethylpyrazoles 6 which undergo smooth dehydroxymethylation under mild conditions (acid hydrolysis or silica gel) to give N-unsubstituted 5(3)-substituted pyrazoles.