3-乙酰基-2,3/2,5-二氢-1,5-苯并硫氮杂卓的选择性合成及其互变异构

Selective Synthesis and Tautomerism of 3-Acetyl-2,3/2,5-dihydro-1,5-benzothiazepines

研究了温度、时间等因素对合成反应的影响,发现亚胺型杂卓4和烯胺型杂卓5分别为速度控制产物和平衡控制产物,并且实现了两种互变异构体的选择性合成.用核磁共振法研究了溶剂、酸碱度对4,5互变异构的影响,发现两种异构体在CD3OD,DMSO-d6,C6D6以及精制的CDCl3中比较稳定,在未精制的CDCl3中容易发生互变及开环反应,形成3,4,5的平衡混合物,并以4为主要组分.4,5在酸中不稳定,但在弱碱(吡啶)中能稳定存在.采用密度泛函理论方法在B3LYP/6-31G基组水平上对四组(八种)不同取代基的上述异构体进行了几何优化和计算.结果表明,烯胺型杂卓5比亚胺型杂卓4稳定,理论计算结果与实验结果基本一致.

The selective synthesis of 2,3/2,5-dihydro-1,5-benzothiazepines was achieved by controlled re-action 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 al-most 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.