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Evaluation of aromatic radiobromination by nucleophilic substitution using diaryliodonium salt precursors
Author(s) -
Zhou Dong,
Kim Sung Hoon,
Chu Wenhua,
Voller Thomas,
Katzenellenbogen John A.
Publication year - 2017
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3519
Subject(s) - chemistry , bromide , nucleophilic substitution , nucleophile , nucleophilic aromatic substitution , electrophilic substitution , electrophile , base (topology) , substitution reaction , combinatorial chemistry , reactivity (psychology) , salt (chemistry) , organic chemistry , catalysis , medicine , mathematical analysis , alternative medicine , mathematics , pathology
Radiobromine‐labeled compounds can be used for positron emission tomography (PET) imaging (ie, 76 Br) and for radiation therapy (ie, 77 Br). However, the commonly used electrophilic substitution reaction using no‐carrier‐added radiobromide does not always afford the desired product due to the high reactivity of the brominating intermediate. A nucleophilic substitution by bromide, such as radiobromination of iodonium precursors, provides an alternative route for the synthesis of bromo‐radiopharmaceuticals. The applicability of aromatic radiobromination by nucleophilic substitution using diaryliodonium salt precursors was evaluated using iodonium model compounds and [ 76 Br]/[ 77 Br]bromide. Radiobromination was observed under all conditions tested, in up to quantitative yields. A QMA cartridge treatment method and a base‐free method have been developed, and no extra base is needed for either methods. The base‐free conditions are mild and afford much cleaner reactions. Up to 20% water is tolerated in the reactions without reducing the radiochemical yields. No‐carrier‐added and carrier‐added reactions afforded similar results. 4‐Bromobenzaldehyde and 4‐bromobenzoate have been radiosynthesized reliably and in good yields. These results indicate that this method is robust and efficient and thus will provide a route for radiobromination of electron‐deficient arenes and an alternative route for the synthesis of bromo‐radiopharmaceuticals for biological evaluations.