Yurii Vlasenko

Pummerer Reactions of Thiopyran Derivatives as a Method for the Preparation of Trifluoro-Methyl-Substituted Thiolanes with Antiviral Activity

2-(p-Tolylsulfanyl)-2-trifluoromethyl-3,6-dihydro-2Н-thiopyran 1-oxides undergo a vinylogous Pummerer reaction upon interaction with trifluoroacetic anhydride, forming 2-(p-tolylsulfanyl)-4-tri-fluoroacetoxy-2-trifluoromethyl-3,4-dihydro-2Н-thiopyrans. The hydrolysis, acetylation, and free radical desulfanylation of these compounds with a subsequent oxidation of the sulfur atom leads to 4-acetoxy-2-trifluoromethyl-3,4-dihydro-2Н-thiopyran 1-oxides. The Pummerer addition reaction of the latter with acetic anhydride and boron trifluoride etherate results in a ring contraction and formation of 3-acet-oxy-2-diacetoxymethyl-5-(trifluoromethyl)thiolanes, which could be converted with sodium boro-hydride to 3-hydroxy-2-hydroxymethyl-5-(trifluoromethyl)thiolanes having antiviral activity.

The synthesis and properties of 6-trifluoromethyl-substituted thiopyrano[3,4-d]isoxazole derivatives

The first representatives of the novel 4,7а-dihydro-3аН-thiopyrano[3,4-d]isoxazole heterocyclic system, containing an ester, carboxyl, or hydroxymethyl group at position 3 and a trifluoromethyl group at position 6 were obtained by [3+2] cycloaddition reaction of ethyl cyanocarboxylate N-oxide and 6-trifluoromethyl-2Н-thiopyran, followed by further transformations of the ethyl 6-trifluoromethyl-4,7а-dihydro-3аН-thiopyrano[3,4-d]isoxazole-3-carboxylate intermediate. The cleavage of the isoxazoline ring of the obtained compounds led to the formation of 6-trifluoromethyl-2Н-thiopyran derivatives with nitrile or carbonyl-containing functionality at position 3. Transformations of the thiopyran moiety in 4,7а-dihydro-3аН-thiopyrano[3,4-d]isoxazole were studied for the case of Pummerer reaction product with oxidized sulfur atom, ethyl 6-trifluoromethyl-4,7а-dihydro-3аН-thiopyrano[3,4-d]isoxazole-3-carboxylate 5-oxide, which was converted to ethyl 6-trifluoromethyl-4Н-thiopyrano[3,4-d]isoxazole-3-carboxylate.

Chemical properties of 5-(1,1,2,2-tetrafluoroethoxy)-4-phenylthiazole derivatives

In the present study, the possibility of converting [5-(1,1,2,2-tetrafluoroethoxy)-4-phenylthiazol-2-yl]amine to 2-halothiazoles and an azo compound via diazotation of the amine functionality was demonstrated. It was found that the reaction of [5-(1,1,2,2-tetrafluoroethoxy)-4-phenylthiazol-2-yl]amine with acyl and sulfonyl chlorides leads to products resulting from substitution exclusively at the exocyclic nitrogen atom. The halogen atom at position 2 of thiazole ring is substituted by S-nucleophiles or hydrogen atom upon catalytic hydrogenation on Pd/C. 2-Bromo-5-(1,1,2,2-tetrafluoroethoxy)-4-phenylthiazole was successfully employed in the synthesis of the corresponding α-thiazolylbenzyl alcohol and 2-formylthiazole via conversion to a organomagnesium intermediate. The stability of the tetrafluoroethoxy group in the above transformations was demonstrated.

CCDC 1444368: Experimental Crystal Structure Determination

Related Article: Alexander A. Shalimov , Tetyana I. Chudakova, Yurii G. Vlasenko, Anatoly D. Sinitsa, Petro P. Onys’ko|2016|Chemistry of Heterocyclic Compounds|52|267|doi:10.1007/s10593-016-1873-z

CCDC 1444371: Experimental Crystal Structure Determination

Related Article: Alexander A. Shalimov , Tetyana I. Chudakova, Yurii G. Vlasenko, Anatoly D. Sinitsa, Petro P. Onys’ko|2016|Chemistry of Heterocyclic Compounds|52|267|doi:10.1007/s10593-016-1873-z

Heterocyclization of N-(chlorosulfonyl)imidoyl chlorides with anilines, a new method of synthesis of 1,2,4-benzothiadiazine 1,1-dioxides

N-(Chlorosulfonyl)imidoyl chlorides react regioselectively with anilines, 2-aminomethylnaphthaline, or 1,2,3,4-tetrahydroquinoline leading to derivatives of 1,2,4-benzothiadiazine 1,1-dioxide. Heterocyclization occurs at the sterically less hindered C-6 atom in the case of 3-methoxy- and 3,4-dimethoxyaniline, while the reaction with 3-methylaniline leads to a mixture of cyclization products at the C-2 and C-6 atoms of aniline.