QM study on regioselectivity in the synthesis of pyrimido[4,5-b][1,4]benzothiazines: kinetic and thermodynamic point of view

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• 作者：Mina Ghiasi ; Mahmonir Aghawerdi ; Majid M. Heravi
• 关键词：Pyrimido[4 ; 5 ; b][1 ; 4]benzothiazine ; Tautomerism ; Solvent effect ; PCM ; DFT calculation
• 刊名：Journal of the Iranian Chemical Society
• 出版年：2017
• 出版时间：April 2017
• 年：2017
• 卷：14
• 期：4
• 页码：743-754
• 全文大小：
• 刊物主题：Analytical Chemistry; Inorganic Chemistry; Physical Chemistry; Biochemistry, general; Organic Chemistry;
• 出版者：Springer Berlin Heidelberg
• ISSN：1735-2428
• 卷排序：14

文摘

In the present study, the experimentally observed regioselectivity in pyrimido[4,5-b][1,4]benzothiazine synthesis has been modeled using density functional theory method at M06/6-311++G** level. Also the tautomerism of all four tautomers of 6-ethyl-2-thio(1H) pyrimidin-(3H)-4-one as an important intermediate through the reaction path in pyrimido[4,5-b][1,4]benzothiazine synthesis has been investigated extensively in the gas and solution phase. The stability order of tautomers was found as A > D > B > C, in gas and chloroform solvent; however, changing to more polar solvents this order was changed as A > B > D > C using polarized continuum model. In the next step, we focused on another significant feature of this synthesis which has major role in the observed regioselectivity. Two proposed reaction paths with two different transition states that it seems the mode of its intermolecular cyclization has a special role in regioselectivity of the final product have been considered. Comparison of our calculated NMR and IR spectrum with those already reported for some pyrimido[4,5-b][1,4]benzothiazines demonstrates a reliable agreement. Moreover, all obtained results in the gas and solution phase confirm that the synthesis of above-mentioned compound is thermodynamically more favorable than the possible regioisomeric product.