The Cu+ method, originally developed for aromatic compounds, has also been applied for radioiodination of pyridine rings. The aim of this paper is a more fundamental approach of the different parameters ruling the Cu+-assisted radioiodination of the regiomers of pyridine.
A mechanistic model is represented on the basis of the mutual complex-formation properties of pyridine for Cu+ and Sn++. It is proven that a part of the Cu+ catalyst, required for optimal labelling, is involved in a Halo-PyrN:Cu+-complex resulting in a lower labelling yield. In case of 3-Br-pyridine and 4-Br-pyridine, the Sn++ present in excess versus Cu+ in the general reaction conditions, can displace Cu+ from its pyridine complex rendering it available as catalyst, allowing a successful labelling.
A 2-Br-pyridine, with the halogen atom in ortho position of the N atom, is an exception to that rule: the Cu+ ions reversibly bound in the Br-Pyr-N:Cu+-complex are also involved in an intramolecular transfer to the ortho C-Br bond resulting in an effective molarity exceeding the bulk concentration and a high labelling yield.
Radioiodination of a 2-halo-pyridine analogue is preferentially performed in the absence of SnSO4, using only gentisic acid as reducing agent. Copyright © 2012 John Wiley & Sons, Ltd.