Domino-reactions of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide, hetarenecarbaldehydes and active methylene nitriles in the construction of new 2-amino-4H-pyrans and the study of their antimicrobial properties


  • G. V. Grygoriv National University of Pharmacy, Ukraine
  • D. A. Lega National University of Pharmacy, Ukraine
  • V. P. Chernykh National University of Pharmacy, Ukraine
  • T. P. Osolodchenko SI «Institute of microbiology and immunology n.I.I.Mechnikov NAMS», Ukraine
  • L. A. Shemchuk National University of Pharmacy, Ukraine



1, 2-benzoxathiin-4(3H)-one 2, 2-dioxide, domino reactions, 2-amino-4H-pyran, triethylammonium salt, antimicrobial activity


Multicomponent domino reactions are an effective modern approach in the synthesis of different types of organic compounds, including biologically active pyrans.
Aim. To study the three-component interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with different hetarenecarbaldehydes and active methylene nitriles in order to synthesize new 2-amino-4H-pyran derivatives, as well as the antimicrobial activity of the compounds obtained.
Results and discussion. 2-Amino-4-heteryl-4,6-dihydropyrano[3,2-c][2,1]benzoxathiin-3-carbonitrile 5,5-dioxides were obtained by stepwise and multicomponent reactions of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with hetarenecarbaldehydes and malononitrile. For the same interaction with ethyl cyanoacetate the reaction selectivity decreased and not only target ethyl 2-amino-4H-pyran-3-carboxylates were obtained, but also triethylammonium salts of bis(1,2-benzoxathiin-2,2-dioxo-4-ol-3-yl)(heteryl)methane. The latter were also purposefully synthesized by the two-component reaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with hetarenecarbaldehydes in the presence of triethylamine. The compounds obtained revealed a higher antimicrobial activity against gram-positive bacteria and fungi compared to the reference drugs.
Experimental part. 3-Amino-4-heteryl-4,6-dihydropyrano[3,2-c][2,1]benzoxathiin-3-carbonitrile 5,5-dioxides and triethylammonium 3-[1-(4-hydroxy-2,2-dioxido-1,2-benzoxathiin-3-yl)heteryl]-1,2-benzoxathiin-4-olate 2,2-dioxides were synthesized. The antimicrobial activity of the compounds synthesized was studied by the agar diffusion method.
Conclusions. It has been proven that the multicomponent format for the three-component interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with hetarenecarbaldehydes and active methylene nitriles is more favorable and convenient than the stepwise approach to obtain new derivatives of 2-amino-4H-pyrans. Triethylammonium 3-[(4-hydroxy-2,2-dioxido-2,1-benzoxathiin-3-yl)heteryl]-2,1-benzoxathiin-5-olate 2,2-dioxides have been also synthesized. The antimicrobial properties of the compounds obtained are higher than in the reference drugs, especially against gram-positive bacteria and fungi.


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How to Cite

Grygoriv, G. V.; Lega, D. A.; Chernykh, V. P.; Osolodchenko, T. P.; Shemchuk, L. A. Domino-Reactions of 1,2-Benzoxathiin-4(3H)-One 2,2-Dioxide, Hetarenecarbaldehydes and Active Methylene Nitriles in the Construction of New 2-Amino-4H-Pyrans and the Study of Their Antimicrobial Properties. J. Org. Pharm. Chem. 2018, 16, 3-10.



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