ANTITUMOR BENZOTHIAZOLES .4. AN NMR-STUDY OF THE SITES OF PROTONATIONOF 2-(4-AMINOPHENYL)BENZOTHIAZOLES

The behaviour of the series of antitumour 2-(4-aminophenyl)benzothiazo les 1a-e in acid solution has been probed by C-13 and N-15 NMR methods and the sites of protonation determined. The parent compound 2-(4-ami nophenyl)benzothiazole la and the 2-(4-amino-3-methylphenyl) analogue 1b undergo initial protonation at the exocyclic amino group followed b y protonation at the N-3 atom of the benzothiazole nucleus: those anal ogues with a 3'-halogen substituent, compounds 1c-e, protonate initial ly at N-3. These observations have potential pharmaceutical significan ce.