The selective synthesis of 2,3/2,5-dihydro-1,5-benzothiazepines was achieved by controlled reaction conditions. Detailed studies on reaction temperature, reaction time revealed that 2,3-dihydro-1,5- benzothiazepines (imine tautomers) (4) and 2,5-dihydro-1,5-benzothiazepines (enamine tautomers) (5) are speed-controlled and balance-controlled products, respectively. The imine-enamine tautomerism of 4 and 5 in different solvents was investigated by means of NMR spectroscopy. The result showed that 4 or 5 are almost stable in DMSO-d₆, C₆D₆, CD₃OD and purified CDCl₃. When 4 or 5 were disolved in unpurified CDCl₃, the equilibria were established between 4, 5 and 3 with the imine tautomers 4 as the major species. The interconversion of compounds 4, 5 and 3 was also observed in acidic solution of C₆D₆, but not in basic solution of the same solvent. The stability of 2,3/2,5-dihydro-1,5-benzothiazepine tautomers was studied by density functional theory at B3LYP/6-31G level. The theoretical results showed that enamine tautomers 5 are more stable than imine tautomers 4 which are consistent with the experimental results.

Key words: 1,5-benzothiazepine, speed-controlled product, balance-controlled product, imine, enamine, tautomerism