[The stability of bromhexine and the structure of its degradation products]

Refluxed acid or neutral aqueous solutions of Bromhexine (1) show four degradation products. 1 is decomposed at room temperature (20 degrees C; 1 year) less than 1%. Degradation products of crystalline 1 are not detectable in the temperature-moisture-test. Under normal storage conditions a 5-year stability for aqueous solutions and a more than 10-year stability for crystalline 1 are estimated. Very small amounts of three degradation products were isolated by TLC. According to MS-, UV- and IR-analysis their structures are 3-cyclohexyl-6,8-dibromo-chinazoline-4-one (2a), 3-cyclohexyl-6,8-dibromo-chinazoline (2b) and 3-amino-4,6-dibromo-benzaldehyde (3). The structure of N-Methylcyclohexylamine is supposed for a further product. Ms fragmentation and degradation mechanisms are discussed.