Synthesis of 1,2-benzoxathiine 2,2-dioxide derivatives using aliphatic aldehydes and assessment of their antimicrobial activity

Abstract

Nowadays the problem of the antimicrobial resistance promotes the search of new chemical core-structures with the antimicrobial properties.Aim. To study the interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with active methylene nitriles and aliphatic aldehydes and assess the antimicrobial activity of the compounds obtained.Results and discussion. 1,2-Benzoxathiin-4(3H)-one 2,2-dioxide as a structural analog of 1,3-dicarbonyl compounds was used in the three-component interaction with aliphatic aldehydes and active methylene nitriles. In the case of malononitrile the target compounds were formed. When using ethyl cyanoacetate the only isolated product was triethylammonium salt that could be also obtained by the two-component reaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with aliphatic aldehydes. The study of the antimicrobial properties showed the higher activity of the compounds studied than in the reference drugs, especially against gram-positive strains.Experimental part. The series of 2-amino-4-alkyl-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)alkyl]-1,2-benzoxathiin-4-olate 2,2-dioxides was synthesized. The antimicrobial activity of the compounds obtained was determined by the agar “well” diffusion method.Conclusions. It has been shown that 1,2-benzoxathiin-4(3H)-one 2,2-dioxide as a structural analog of 1H-2,1-benzothiazin-4-one 2,2-dioxide can be used in similar three- and two-component reactions, but its reactivity is less due to the replacement of the 1-N-R-group with an O-atom. The novel compounds obtained exceeded the antimicrobial activity of the reference drugs, and were more active against gram-positive bacteria in contrast to isosteric derivatives of 1H-2,1-benzothiazin-4-one 2,2-dioxide that were active against gram-negative strains and fungi.