Abstract
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-oxo1,2-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-allylsulfonyl4-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-1,2dihydroquinoline-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 50-60 o C 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 20 o C 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. According to the recent literature data, most of the studies is devoted to aryl sulfones, while heteryl sulfones have not been investigated so intensively. Nevetheless, some compounds of this class with the antimicrobial [8], antiviral [9, 11], antimalarial [5], anti-inflammatory and analgesic [10, 12, 13], antitumor [6] action have already been found. Therefore, sulfones is a promising class for study in order to develop medicinal substances. Continuing the research of 1,2-dihydroquinoline-2-one derivatives [2] that are carried out in the National University of Pharmacy a number of new potential biologically active substances in the range of 6-sulfonyl derivatives of 4-methyl-1,2-dihydroquinoline-2-one have been obtained by the reaction of nucleophilic addition to 6-allylsulfonyl-4-methyl-1,2-dihydroquinoline-2-one. Materials and Methods
Highlights
Materials and MethodsMethods of organic synthesis were used for obtaining new compounds
According to the recent literature data, most of the studies is devoted to aryl sulfones, while heteryl sulfones have not been investigated so intensively
Materials and Methods Methods of organic synthesis were used for obtaining new compounds
Summary
Methods of organic synthesis were used for obtaining new compounds. The structures of the compounds synthesized were proven by the methods of 1H NMR spectroscopy and mass spectrometry. 1H NMR spectra were recorded on a Varian Mercury VX-200 in DMSOD6 solution, the operating frequency was 200 MHz, the internal standard – TMS. Mass spectra were recorded on a Varian 1200L, the ionizing voltage was 70 eV. Melting points were measured by a Koffler device
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