The thesis is devoted to the development of a preparatively convenient and effective method for the synthesis of novel functionally substituted sultams: 3-iodomethyl- and 3-aminomethyl derivatives of isothiazolidine 1,1-dioxides.
An approach to previously unknown 3-iodomethyl substituted sultams based on the iodocyclization of alkenylsulfonamides has been developed. Optimal conditions for halogen-initiated intramolecular cyclization were developed: 3-(iodomethyl)isothiazolidine 1,1-dioxides were obtained in almost quantitative yields when carrying out the reaction of but-3-ene-1-sulfonamides with molecular iodine in acetonitrile in the presence of sodium bicarbonate.
The limitations of the potential application of the iodocyclization of unsaturated sulfonamides were investigated, using the example of C- and N-substituted substrates, molecules with different lengths of unsaturated hydrocarbon chains, functionally substituted and bicyclic compounds.
Based on the obtained experimental data, a probable reaction mechanism of intramolecular aminoiodination of alkenylsulfonamides was proposed.
The reaction of 3-iodomethyl derivatives of sultams with nucleophilic reagents was studied. The influence of the basicity of nucleophiles on the course of the reaction of substitution of the active iodine atom in 3-(iodomethyl)-2-methylisothiazolidine 1,1-dioxide was determined. It was established that in the case of highly basic nucleophiles, products of hydrogen iodide elimination - unstable enamines - are formed along with substitution products.
Hydrolysis of in situ formed N-sulfonylated enamines with a diluted hydrochloric acid led to the formation of 3-oxobutane-1-sulfonamides.
A series of 3-(aminomethyl)isothiazolidine 1,1-dioxides was obtained by the reaction of 3-(iodomethyl)-2-substituted isothiazolidine 1,1-dioxides with sodium azide followed by reduction of the obtained azidomethyl derivatives with hydrogen.
The reaction of but-3-ene-1-sulfonyl chloride with α-, β-, and γ-aminoesters yielded a set of N-sulfonylated derivatives with different saturated chain lengths. Cyclization of these compounds under standard conditions and subsequent reaction of the formed iodomethylsultams with sodium azide led to the formation of the corresponding azidomethylsultams – derivatives of α-, β-, and γ-amino acids. The subsequent catalytic reduction of α- and β-aminoesters was accompanied by spontaneous intramolecular interaction of the formed amino group with the ester group, which led to the formation of bicyclic systems - tetrahydro-2H-isothiazolo[2,3-a]pyrazin-6(7H)-one 1,1-dioxide and hexahydroisothiazolo[2,3-a][1,4]diazepin-6(2H)-one 1,1-dioxide. These compounds were readily reduced to the corresponding amines by the action of lithium aluminum hydride in tetrahydrofuran.
When D- and L-alanine esters were used as starting compounds, as a result of such a series of transformations, all four possible stereoisomers of 7-methyltetrahydro-2H-isothiazolo[2,3-a]pyrazin-6(7H)-one 1,1-dioxide were obtained. Moreover, chromatographic separation was performed only at the stage of obtaining methyl 2-(3-(iodomethyl)-1,1-dioxydoisothiazolidin-2-yl)propanoate.
