Ammonium [11C]thiocyanate: revised preparation and reactivity studies of a versatile nucleophile for carbon-11 radiolabelling

Abstract

Herein we report the preparation of ammonium [¹¹C]thiocyanate via the reaction of [¹¹C]CS₂ with ammonia. The [¹¹C]SCN^- ion is demonstrated as a potent nucleophile that can be used to readily generate a range of ¹¹C-labelled thiocyanate molecules in high conversions. Furthermore, novel ¹¹C-labelled thiazolone molecules can be easily prepared from the intermediate α-thiocyanatophenones via an acid mediated cyclisation reaction.

Scheme 1. A selection of organic molecules that can be prepared using the thiocyanate ion.

Scheme 2. Previously reported routes to [¹¹C]SCN^– relying on generating [¹¹C]HCN first (top); this work, which reports the synthesis of [¹¹C]SCN^–via [¹¹C]CS₂ (bottom).

Scheme 3. Substitution reaction of benzyl bromide with [¹¹C]NH₄SCN to generate benzyl [¹¹C]thiocyanate.

Chart 1. Radiolabelled thiocyanate molecules. Average of minimum n = 2.

Scheme 4. Acid mediated cyclisation of α-thiocyanatophenone which is hypothesised to proceed via the intermediate oxathiolium salt prior to thiazolone formation and elimination of sulfuric acid.

Scheme 5. One pot radiolabelling of 4-phenylthiazol-2-[¹¹C]one (10) via acid mediated cyclisation of the intermediate 1-phenyl-2-[¹¹C]thiocyanatoethanone (2), (*) denotes the ¹¹C labelling position.

Chart 2. ¹¹C-Radiolabelled thiazolone molecules. Average of minimum n = 2.