Antitumour benzothiazoles. Part 4. An NMR study of the sites of protonation of 2-(4-aminophenyl)benzothiazoles

Abstract

The behaviour of the series of antitumour 2-(4-aminophenyl)benzothiazoles 1a–e in acid solution has been probed by ¹³C and ¹⁵N NMR methods and the sites of protonation determined. The parent compound 2-(4-aminophenyl)benzothiazole 1a and the 2-(4-amino-3-methylphenyl) analogue 1b undergo initial protonation at the exocyclic amino group followed by protonation at the N-3 atom of the benzothiazole nucleus: those analogues with a 3′-halogen substituent, compounds 1c–e, protonate initially at N-3. These observations have potential pharmaceutical significance.