Selectivity in the Metalation of Polymethylpyrazines

Article abstract of DOI:10.1021/jo00161a002

The selectivity in the LDA-promoted lithiation of 2,3,5-trimethylpyrazine was studied by using the perdeuterated substrate 1-d₉.Quenching of the lithium salts of the latter with H2O gave a 1-d₈ isomer mixture which was analyzed by NMR.The order of reactivity of the three CH3 groups in 1-d₉ was found to be 3 > 2 > 5.The metalation studies were extended also to isomeric dimethylpyrazines.It was established that the two ortho CH3 groups in 2,3-dimethylpyrazine are more easily metalated than either of the CH3 groups in the other isomeric dimethylpyrazines.