New methods for rapid radiohalogen labelling of organic molecules

The aim of this study was to develop new and rapid procedures for the incorporation of short-lived radiobromine and radioiodine isotopes into organic compounds. This was accomplished by the electrophilic cleavage of tin-carbon bonds with BrCl and ICl generated in-situ from bromide and iodide, respectively, in the presence of an oxidizing agent. The vinyl-tin derivatives, [4], [8], [12], [17], [18] and [19], were prepared by treatment of the corresponding acetylenic compounds with tri-n-butyltin hydride, in the presence of a radical initiator catalyst, in 51-98% yield. Each of the vinyl-tin derivatives, except [17], was brominated in high yield (89-100%) with sodium bromide oxidized by Chloramine-T under acidic conditions. Compound [17] was brominated in 13% yield; competing bromination of the A-ring of [17] was responsible for this low yield. The vinyl-tin precursors [4], [8], [17], [18] and [19] were iodinated with sodium iodide in the presence of acidified Chloramine-T in 88-99% yield, except [17], which was iodinated in 1.9% yield because of facile A-ring iodination. Compound [18] was subsequently radio-labelled with ⁸²Br, ¹²³I and ¹³¹I forming [41], [42] and [43], respectively, using the Chloramine-T method. Compound [41] was isolated in 77-81% radiochemical yield using low specific activity NH₄⁸²Br. Compounds [42] and [43] were obtained in 82-90% radiochemical yield, in relatively high specific activity. The major side-product formed during the no-carrier-added radioiodinations was the chlorinated derivative [38]. An alternate procedure, based on N-chlorosuccinimide as the oxidant, was developed which gave [41] and [42] in 85% and 62% (no-carrier-added ¹²³I radiochemical yields, respectively. [See Thesis for Diagram]Science, Faculty ofChemistry, Department ofGraduat