Improved Richman-Atkins syntheses of cyclic polyamines particularly 1,4,7-Triazacyclononane (tacn) and 1,4,7-Triazacyclodecane (tacd), with the aid of cation-exchange in purification and isolation

Abstract

Richman-Atkins cyclization syntheses for the cyclic triamines 1,4,7-triazacyclononane (tacn) and 1,4,7-triazacyclodecane (tacd) with the alternative possible sets of reagents as tosyl derivatives have been examined in detail and compared. The cyclizations from the tritosyl derivative of diethylenetriamine (dientt) and the appropriate diols as ditosylates proceeded relatively cleanly, although there were small amounts of higher products and some carry through of dientt for tacn. The alternative cyclizations, from 2,2'-(tosy1imino)bisethyl ditosylate and a ditosyl diamine, gave little reaction to form tacn as the tritosyl derivative. The reaction to form tritosyl tacd proceeded further, but was accompanied by significant formation of higher condensation products, particularly the hexamines 1,4,7,11,14,17-hexaazacycloeicosane (2 : 2 cyclic dimer) and 3,7,10,13-tetraazahexade- cane-1,16-diamine. A cation-exchange procedure, applied after the detosylation stage, is described for obtaining the required pure 1 : 1 cyclic polyamines as their hydrochloride salts with high recovery. This is an effective method for removing higher co-products. These may be recovered, and by this means the above hexamines were isolated in admixture.