Study On The Stability And Tautomerism In Solvents And Solid-state Thermal Properties Of Imine And Enamine Type Of1,5-benzothiazepines

Prototropy occurs frequently in natural products and influences the properties of thecompound importantly. Tautomerism of imine-enamine often related with the bioactivesubstances and drug molecule,that is why it attracted people’s wide attention.In the course ofthe study, we have found that3-acyl or ester1,5-benzothiazepines often exist as structures ofimine and enamine, and they always transforme into each other. Therefor the study on thetautomerism of imine and enamine not only can investigate the relationship with the structureand activity of1,5-benzothiazepines but also have some common sense.In this paper,we have delved into the tautomerism of imine and enamine based onbenzothiazepines.For this purpose,we have accomplished the following work:1、The synthesis method of imine and enamine type of1,5-benzothiazepines have beenstudied. A series of imine and enamine type of1,5-benzothiazepines are synthesized.Furthermore, the structures of these new compounds are determined by IR、1H NMR、13CNMR、MS(orHRMS) and elemental analysis.2、Spectroscopic characterization of the imine and enamine type of1,5-benzothiazepinesin solvents were investigated,include UV and1H NMR. It was found that the UV spectra ofthe imine and enamine type of1,5-benzothiazepine in aprotic solvent have obviouscharacteristics, and can be distinguished well, while in protic solvents (methanol as anexample), the spectra of two type chemicals are essentially coincident,but the1H NMR of thetwo type compounds have clear divisions. Accordingly, we developed the research methods.3、The tautomerism of imine and enamine type of1,5-benzothiazepines was studied byUV spectral methods and1H NMR spectral data, the effects of different solvents,temperatureand pH on the tautomerism of tautomers were investigated.The results show that underanhydrous conditions, imine and enamine type of1,5-benzothiazepine can exist stably indifferent polar aprotic solvents, different temperature, acid, alkali conditions, tautomerismdoes not occur,and no decomposition. Under the action of strong acid (trifluoro-acetic acid),imine type of benzothiazepine change to enamine type of benzothiazepine.4、The effects of solvent, temperature and time on the imine and enamine type of1,5-benzothiazepines tautomerism in protic solvents have been studied by1H NMR spectraldata, and it is found that ability to release protons of solvent, temperature and time influencedthe tautomerism of tautomers greatly. 5、The kinetic and thermodynamic characteristics of the conversion of imines toenamines in acetic acid were studied by taking compounds3a、3b、4a、4b as examples. Theresults showed that transformation from imines to enamines follows the second-order kineticequation.the the calculation of thermodynamics parameters showed that that transformationendothermic and thermodynamically feasible in the studied temperature range, and the valuesof entropy change are positive.6、The thermal properties of the tautomers were investigated by by taking compounds3a、3b、4a、4b as examples. The kinetic parameters of thermal decomposition for thecompounds were calculated. The thermodynamic parameters (H≠, G≠and S≠) at the peaktemperatures of the DTG curves were also calculated.