A new and simple synthesis of N‐succinimidyl‐4‐[127/125I]iodobenzoate involving a microwave ‐ accelerated iodination step

A short and simple method for the preparation of N‐succinimidyl‐4‐iodobenzoate 3 and its 125I analogue that is widely used for radioiodination of proteins is described. The method involves the reaction of in situ generated trimethylsilyl iodide [127I or 125I] from trimethylsilyl chloride with N‐succinimidyl‐4‐[3,3‐(1,4‐butanediyl)‐triazene] benzoate 2 available from the condensation of N‐hydroxysuccinimide and 1‐(4‐carboxyphenyl)‐3,3‐(1,4‐butanediyl)‐triazene 1 in the presence of dicyclohexyl carbodiimide (DCC). The new triazene 1 was prepared by precipitating the diazonium ion of 4‐aminobenzoic acid with pyrrolidine. A microwave‐mediated rate acceleration was observed during the iodination step and by applying this procedure the labelled compound 3 was obtained in 81% radiochemical yield in 8 minutes.