Synthesis of typical sulfonamide antibiotics with [14C]- and [13C]-labelling on phenyl ring for environmental studies

Abstract Background As a kind of widely used antibiotics, sulfonamide antibiotics (SAs) has become ubiquitous environmental contaminants that caused public concerns. The behavior of SAs in complex environmental system need to be elucidated, which is hampered by unavailability or high cost of isotope-labelled SAs. Results Using commercially available uniformly [l4C]- and [l3C]-labelled aniline as starting material, we synthesized [phenyl-ring-14C]- and [phenyl-ring-l3C]-labelled sulfamethoxazole (SMX), sulfamonomethoxine (SMM), and sulfadiazine (SDZ) using four-step (via condensation of labelled N-acetylsulfanilyl chloride and aminoheterocycles) or five-step (via condensation of labelled N-acetylsulfonamide and chloroheterocycles) reactions in good yields (5.0−22.5% and 28.1−54.1% for [14C]- and [13C]-labelled SAs, respectively) and high purities (> 98.0%). Conclusion The synthesis of [l4C]-labelled SAs could be completed on milligram-level, being feasible for preparation of labelled SAs with high specific radioactivity. This study provides efficient and maneuverable methods to obtain a variety of [14C]- or [13C]-labelled SAs for studies on their environmental behavior, such as fate, transformation, and bioaccumulation.