Aspects of the regiospecificity of homogeneous metal catalysed hydrogen isotope exchange reactions

The preparation of regiospecifically labeled compounds by homogeneous metal catalysed hydrogen isotope exchange reactions has been studied. The features of homogeneous hydrogen isotope exchange reactions are discussed along with other exchange methods; acid, base, heterogeneous metal, radiation, enzymic and zeolite catalysis. Homogeneous rhodium trichloride is investigated for regiospecificty of tritium labeling in a wide range of aromatic compounds. High regiospecificity of labeling ortho to carboxyl, carboxamide and methanamide groups is found, with the regiospecificity determined by H nmr spectroscopy. Also discussed is a study to determine whether any other Group VIII metal complexes will catalyse the ortho tritiation of benzoic acid, in addition to rhodium trichloride. The results of detritiation studies performed on benzoic acids using ruthenium acetylacetonate as catalyst as a model or rhodium trichloride are presented. Finally, an application of the rhodium trichloride system to the labeling of biologically useful molecules is discussed. The deuteration and tritiation of a number of drugs and metabolites containing known ortho directing groups is described. In a large number of cases, the regiospecificity for ortho labeling is very high. (author)