Chemical modifications of 6-allylsulfonyl- 4-methyl-1,2-dihydroquinolin-2-one as the approach for seaching new biologically active substances


  • T. O. Tsapko National University of Pharmacy, Ukraine



1, 2-dihydroquinoline-2-one, allylsulfone, heterocyclic sulfones, nucleophilic addition


To search biologically active substances among quinolone-2 sulfonyl derivatives the method for obtaining of the convenient intermediate, namely 6-allylsulfonyl-4-methyl-1,2-dihydroquinoline-2-one, has been developed. The synthesis has been carried out by alkylation of the initial 4‑methyl-2-oxo- 1,2-dihydroquinoline-6-sulfinic acid with allyl bromide in the acetonitrile medium and in the presence of potassium carbonate giving 73% yield of the product. The presence of the allyl fragment of 6-allylsulfonyl-4-methyl-1,2-dihydroquinoline-2-one allowed to carry out addition reactions with some C-, N- and O-nucleophiles. Addition to allyl sulfones occurs in accordance with Markovnikov’s rule despite of the strong electron withdrawing effect of the sulfonyl group. The reaction of 6‑allylsulfonyl- 4-methyl-1,2-dihydroquinoline-2-one with active methylene compounds has been carried out with diethyl malonate and ethyl cyanoacetate by refluxing in absolute ethanol in the presence of sodium ethoxide. As a result, 2-R-3-methyl-4-(4-methyl-2-оxo-1,2-dihydroquinoline-6-sulfonyl)butanoic acid ethyl esters have been obtained with 73-79% yields. 6-(2 Alkylaminopropylsulfonyl)-4-methyl-1,2- dihydroquinoline-2-ones are formed under the action of N-nucleophilic reagents, in particular primary aliphatic amines, on 6-allylsulfonyl-4-methyl-1,2-dihydroquinoline-2-one. This reaction takes place upon heating in dimethylformamide up to 50-60oC for 6 hours, the yields of the products are 35-40%. Hydration of the allyl fragment occurs in the same solvent when treated with sodium hydroxide at 20oC resulting in formation of 6-(2-hydroxypropylsulfonyl)-4-methyl-1,2-dihydroquinolin-2-one with 62% yield. The chemical transformations described open a prospect for synthesis of variety of new compounds with different functional groups in the alkylsulfonyl moiety of quinolones. This approach also allows to influence on such properties of new biologically active substances as molecular weight, lipophilicity, acidity, etc., which are essential for permeability of substances through biological membranes.


Зубков В.О., Гриценко І.С., Цапко Т.О. // ЖОФХ. – 2009. – Т. 7, вип. 3 (27). – С. 30-34.

Зубков В.А., Цапко Т.А., Гриценко И.С., Малоштан Л.Н. // ИзвАН. Серия хим. – 2010. – №12. – С. 2272-2275.

Получение и свойства органических соединений серы / Под ред. Л.И.Беленького. – М.: Химия, 1998. – 560 с.

Прилежаева Е.Н. // Успехи химии. – 2000. – Т. 69, №5. – С. 403-446.

Amewu R., Gibbons P., Mukhtar A., Stachulski A.V. et al. // Org. Biomolec. Chem. – 2010. – №8 (9). – Р. 2068-2077.

Cohen A., Crozet M.D., Rathelot P. // Molecules. – 2012. – Vol. 21, №18 (1). – P. 97-113.

Oja S., Saransaari P. // Proc. West. Pharmacol. Soc. – 2007. – Vol. 50. – Р. 8-15.

Padmavathi V., Thriveni P., Sudhakar Reddy G., Deepti D. // Eur. J. Med. Chem. – 2008. – Vol. 43, №5. – P. 917-924.

Samuele A., Kataropoulou A., Viola M., Zanoli S. et al. // Antiviral Res. – 2009. – Vol. 81, №1. – P. 47-55.

Shaaban M.R., Saleh T.S., Mayhoub A.S., Mansour A. et al. // Bioorg. Med. Chem. – 2008. – Vol. 16, №12. – P. 6344-6352.

Silvestri R., De Martino G., La Regina G. et al. // J. Med. Chem. – 2005. – Vol. 46, №12. – P. 2482-2493.

Tozkoparan B., Küpeli E., Yeşilada E., Ertan M. // Bioorg. Med. Chem. – 2007. – Vol. 15, №4. – P. 1808-1814.

Verbist B., Cleyn M., Surkyn M., Fraiponts E. et al. // Bioorg. Med. Chem. Lett. – 2008. – Vol. 18, №8. – P. 2574-2579.






Synthesis and Analysis of Biologically Active Substances