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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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Abstract

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.

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Acknowledgements

The authors are thankful to Alzahra University Research Council. MMH is thankful also to Iran National Scientific Foundation (INSF) for partial financial support, allocated for his individual research chair.

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  1. Department of Chemistry, Faculty of Physics and Chemistry, Alzahra University, Vanak, Tehran, 19835-389, Iran

    Mina Ghiasi, Mahmonir Aghawerdi & Majid M. Heravi

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  1. Mina Ghiasi
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  2. Mahmonir Aghawerdi
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  3. Majid M. Heravi
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Correspondence to Mina Ghiasi or Majid M. Heravi.

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Ghiasi, M., Aghawerdi, M. & Heravi, M.M. QM study on regioselectivity in the synthesis of pyrimido[4,5-b][1,4]benzothiazines: kinetic and thermodynamic point of view. J IRAN CHEM SOC 14, 743–754 (2017). https://doi.org/10.1007/s13738-016-1014-8

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