pH Dependence of the Elimination of Isoquinolines from N-(2-Cyanoethyl)isoquinolinium Cations

Article abstract of DOI:10.1021/ja00188a047

The reactions of N-(2-cyanoethyl)isoquinolinium cations (1a (unsubstituted), 1b (4-bromo), 1c (4-aminocarbonyl), 1d (4-cyano), 1e (5-nitro)) have been investigated in basic aqueous solution (pH 9-13) at 25 deg C and ionic strength 0.1.In these solutions, these cations are rapidly equilibrated with their C-1 pseudobases, and pseudobase alkoxide ions, and pK_R(+) and pK_RO(-) have been evaluated.Subsequently, 1a-1c and 1e undergo hydroxide ion catalyzed eliminations to give the appropriately substituted isoquinoline and acrylonitrile.The pH rate profiles for thesereactions are very dependent upon pK_R(+) and pK_RO(-) for the isoquinolinium cation.It is shown that the nonreactivity of 1d under these conditions is readily rationalized in terms of the overwhelming predominance of the nonproductive pseudobase species (and/or its alkoxide ion) over the entire pH region under study.Second-order rate constants (k_OH) for the elimination reaction correlate with the pK_a of the isoquinolinium cation, with β_lg = -0.43.Elimination in basic D2O resulted in no observable incorporation of deuterium into the acrylonitrile product.These observations are shown to be consistent with either an E2 mechanism or an E1cB mechanism involving a hydrogen-bonded carbanionic intermediate in which internal return of the proton and loss of the nucleofuge are both faster than exchange with solvent.