19F magnetic resonance probes for detecting formaldehyde

Abstract

Herein we report two separate 19F magnetic resonance (MR) probes responsive towards formaldehyde. Both agents were synthesized in a single step via aminoallylation of either 4-fluorobenzaldehyde (1FA) or 4-(trifluoromethyl)benzaldehyde (3FA) with ammonia and allylboronic acid pinacol ester. Condensation of the resulting homoallylic amines 1FA and 3FA with formaldehyde, followed by a 2-aza-Cope rearrangement and subsequent hydrolysis affords 4-fluorobenzaldehyde and 4-(trifluoromethyl)benzaldehyde, respectively. In the case of 1FA, this transformation is evidenced by a concomitant downfield shift in the 19F MR signal from −115 ppm to −103 ppm. Further, this transformation is selective towards formaldehyde over other reactive carbonyl species. While 3FA exhibits similar selectivity towards formaldehyde, this more sensitive probe is limited by the small chemical shift difference (0.7 ppm) following its activation.