Steric Effect of Methyl Group in Regioselective Tritiation of Toluamides

Abstract

Tritiation by the hydrogen isotope exchange in toluamides with HTO was studied in the presence of RhCl₃⋅3H₂O as a catalyst. It was established by chemical degradation that the exchange reaction occurred with virtually 100% regioselectivity at the o-position (s) (C₂ and C₆ positions) of all the toluamides. The methyl group was not tritiated. The exchange in m-toluamide was very strongly hindered at the C₂ position between the methyl and the amido group. The exchange at the C₆ position was more strongly prevented in o-toluamide than in m-toluamide. These findings are explained on the basis of the steric effect of the methyl group in agreement with the previously suggested mechanism that the exchange proceeds via initial coordination of the substrate compound to rhodium (III) chloride trihydrate.