Synthesis and characterization of degradation impurities of Flucloxacillin and Dicloxacillin

A series of degradation impurities of Flucloxacillin and Dicloxacillin were synthesized. The formation and a facile synthesis of each impurity were presented in detail, namely penicilloic acids of Dicloxacillin (3) (Ph.Eur. Impurity-A), Dicloxacillin glycine analog (4), Dicloxacillin penilloic acids (5) (Ph.Eur. Impurity-B), Dicloxacillin Pencillamide (6), N-Acetylated penicilloic acid of Dicloxacillin (7), DCMICAA adduct of Dicloxacillin penicilloic acid (8), Flucloxacillin glycine analog (Ph.Eur. Impurity-F) (9), penicilloic acids of Flucloxacillin (10), penilloic acids of Flucloxacillin (11), CFMICAA adduct of Flucloxacillin penicilloic acid (Flucloxacillin Ph.Eur. Impurity-H) (12), Flucloxacillin Penicillamide (Flucloxacillin Ph.Eur. Impurity-E) (13), and N-Acetylated penicilloic acid of Flucloxacillin (14). These impurities are extensively characterized by various analytical techniques.