Hydrogen-deuterium exchange of aromatic amines and amides using deuterated trifluoroacetic acid
The H-D exchange of aromatic amines and amides, including pharmaceutically relevant compounds such as acetaminophen and diclofenac, was investigated using CF3COOD as both the sole reaction solvent and source of deuterium label. The described method is amenable to efficient deuterium incorporation for a wide variety of substrates possessing both electron-donating and electron-withdrawing substituents. Best results were seen with less basic anilines and highly activated acetanilides, reflecting the likelihood of different mechanistic pathways.
General conditions: To the aniline or acetanilide (0.2 mmol) in a 2 dram vial was added CF3COOD (1.0 mL, 12.98 mmol). A stir bar was added and the sealed vial was heated to 110° C for 16 h. The solvent was evaporated in vacuo and the residue was stirred in 2 M KOH solution (0.5 mL) for 0.1–4.0 h. The deuterium-labeled substrate was extracted using CH2Cl2, Et2O, or EtOAc and purified using flash column chromatography with silica gel (hexanes/EtOAc).
Tetrahedron Letters Volume 56, Issue 5, Pages 747-749
