Palladium-mediated synthesis of [carbonyl-11C]amides and hydrazides using [11C]carbon monoxide

Abstract

Low concentrations of [¹¹C]carbon monoxide, a palladium complex, aryl halides and ammonia or hydrazine were used for the synthesis of five benzamides and seven hydrazides. Some of the selected compounds (e.g. nicotinamide and benzamide) are biologically active. The reactivity of the bromo- and iodoheteroaryls was studied for similar ¹¹C-carbonylation reactions. Furthermore, the impact of tetrabutylammonium iodide on the reactivity of 2-bromo-5-nitrofuran has been investigated. The radiochemical yield of the ¹¹C-labelled compounds was in the range of 40–90% and the specific radioactivity was up to 1700 GBq μmol⁻¹. The radiochemical purity of the target compounds was determined by analytical HPLC and exceeded 95%. In a typical experiment starting with 7.0 GBq [¹¹C]carbon monoxide, 2.1 GBq of HPLC-purified thiophene-2-[carbonyl-¹¹C]carbohydrazide were obtained within 27 minutes of the start of the carbonylation reaction (75% decay-corrected radiochemical yield). (carbonyl-¹³C)Benzohydrazide was produced to verify the position of the label (δ 165.9 ppm) using ¹³C NMR.