Synthesis of [¹¹C]cyanoalkyltriphenylphosphoranes via [¹¹C]cyanide substitution on haloalkylphosphonium salts

Abstract

The synthesis of the 11C-labelled bifunctional precursors 3-[1T]cyanoeth y ltripheny lphosphonium bromide (1 ' ) , 4-[ 1 1 C] cyanopropyltriphenylphosphonium bromide (2'), 5-[11C]cyanobutyltriphenylphosphonium bromide (37, 4-[~~C]cyanopropyltphenylphosphonium iodide (4') and 5-[llC]cyanobutyltriphenylphosphonium iodide (5') is presented. The label was introduced using [llC]cyanide in a substitution reaction on the o-haloalkyltriphenylphosphonium salt (bromide or iodide salt). The phosphonium salts 1'-5' were formed in 33-99% radiochemical yield in 5-10 min reaction time. After addition of epichlorohydrin as generator of base, the precursors 1-3 were formed. The potential of the intermediates 1-3 in Wittig reactions was shown in model reactions with aromatic and aliphaticaldehydes. The aromatic olefins obtained from 1'-5' were formed in 85-96 % radiochemical yield, with ZIE ratios between 67/33-75/25. The aliphatic olefins were obtained in 60-78% radiochemical yield from 4' and 5'. In the reaction with 1' and an aliphatic aldehyde, the yield decreased to 510%. The ZIE ratios were 100/0 for the aliphatic olefins. In an experiment starting with 2,7 GBq (73 mCi) hydrogen IllCIcyanide, 451 MBq (12.2 mCi) olefin from 3' and 4-nitrobenzaldehyde was obtained in 44 min from hydrogen [llCIcyanide production, with a 55 % decay corrected radiochemical yield, the radiochemical purity was 96%.