Stability of the 1,4-bis(2′-haloethyl)-1,4-diazabicyclo[2.2.1]heptane dication

Abstract

Certain derivatives of the 1,4-bis(2′-haloethyl)-1,4-diazabicyclo[2.2.1]heptane dication system ranging from dibromide 2b to ethanesulfonate 2g were found to be quite stable under essentially neutral conditions. A very convenient synthesis of 1,4-bis(2′-chloroethyl)-1,4-diazabicyclo [2.2.1]heptane dichloride (2d) was developed in order to compare the relative stability of this system with that of dibromide 2b. While dichloride 2d was found to be less stable than dibromide 2b, it did prove very useful for rapid preparation of other anion derivatives such as dinitrate 2e, dihydrogen dimaleate 2h, diperiodate 2i, tetrachloroplatinate 2j, and tetrachloroaurate 2k. At temperatures near 150 °C, or upon ignition (in the open) or gentle shock, diperiodate2i detonated violently. The ethanesulfonate 2g was obtained from diperchlorate 2a employing an ion-exchange procedure. Stabilization of dication 2 provides an unusual heterocyclic system with exceptional anticancer properties.