Synthesis and cathodic cleavage of a set of substituted benzenesulfonamides including the corresponding tert-butyl sulfonylcarbamates: pKa of sulfonamides

Abstract

From a series of substituted benzenesulfonic acids, most of which have previously been employed for the protection of amino functions and including a few such known to facilitate cleavage by acid, benzylamides 1a–k have been derived and studied. Initially their electrochemical cleavage potentials were determined by cyclic voltammetry in order to further explore selective deprotection within this substance group. In parallel, the corresponding tert-butyl sulfonylcarbamates 2a–k have also been prepared and studied. Among the sulfonamides investigated S–N bond cleavage was found to take place over a wide range of potentials from –1.67 to –2.64 V (excluding the nitro derivative), the most acid-labile groups requiring more negative potentials, whereas this cleavage was facilitated by 0.19–0.30 V for the sulfonylcarbamates. Small scale electrolyses of 2 at controlled potential with determination of the cleavage products formed were subsequently performed. For the N-benzylbenzenesulfonamides 1, the pK_as in DMSO and in some cases also in water have been determined and found to be in the range 14.0–16.4 and 10.07–11.53, respectively.