Experimental and Computational Study on the Debenzylation of (2,4-dimethoxybenzyl)-protected 1,3-diazaoxindoles

The introduction and removal of the 2,4-dimethoxybenzyl (DMB) moiety was studied in order to use it as a protecting group in the synthesis of diverse drug candidates containing the 1,3-diazaoxindole scaffold. The debenzylation of C(5)-unsubstituted and C(5)-isopropylidene-substituted 1,3-diazaoxindoles was investigated under various conditions. The DMB group could only be removed from the latter derivative using triflic acid. This observation can most likely be explained with electronic effects. In order to get a deeper insight into the reaction mechanism, quantum chemical calculations have been performed.