A. M. Sipyagin

Synthesis of pyridines with fluoro-containing superlipophilic substituents

Abstract Methods have been developed for the introduction of superlipophilic groups into the pyridine molecule via the polychloropyridine thiols (PCPT, 1) reaction with fluorogenated inorganic oxidizers (XeF2, IF5). Under the action of XeF2 in perfluoro-carbonic acid PCPT undergoes perfluoroalkylation to form 4-per-fluoroalkylthio-PCP (2) in 50–85% yields; oxidation products formed in aqueous HF are sulphofluorides PCP (3 and 4). PCPT when heated with IF5 involves fluorination of the SH group to form 4-pentafluorothio-PCP in 30–40% yields. Interaction of compounds (2) and (5) various nucleophilic agents has been studied. It is shown that the SRF and SF5 groups are easily substituted by 0 and S-bearing nucleophiles and are stable to a range of nitrogenated nucleophiles. A number of compounds with high biological activity have been developed.

Polyfunctional action of biologically active compounds in antitumor chemotherapy of cyclophosphamide

Combinations of the known cytostatic cyclophosphamide (cyclophosphan) with hydroxamic acids (asparagylhydroxamic and salicylhydroxamic), nitric oxide donor (sodium nitrate), and an original hybrid non-steroidal anti-inflammatory compound, viz., diclofenachydroxamic acid nitrate salt (DHA·HNO3), were studied. The use of cyclophosphan in combination with these substances increases the efficiency of chemotherapy and elongates the life of animals with leukemia P-388. The dynamics of changes in the signal from cytochrome P-450 in the liver samples after the administration of DHA·HNO3 to the animals was studied by ESR spectroscopy. The mechanism of the action of DHA·HNO3 enhancing the chemotherapeutic effect of cyclophosphan was proposed.

Unusual nucleophilic substitution reaction of tetrachloropyridine N-oxide

Abstract The reaction between 2,3,5,6-tetrachloropyridine N -oxide and sodium dimethyldithiocarbamate in acetone forms 1-[6-(3′,5′,6′-trichloropyrid-2′-ylthio)-3,5-dichloropyrid-2-ylthio]propan-2-one as the main product.

Reactions of polyhalogenopyridines. 14. Reaction of isomeric dichlorocyanopyridines and pentachloropyridine with potassium ethylxanthate

The reactions of isomeric tetrachlorocyanopyridines with potassium ethylxanthate were studied. It was found that tetrachloro-2-cyanopyridine was converted successively into 4-mono- and then 3,4-bisethylxanthate derivatives. In the presence of potassium ethylxanthate the last derivative undergoes intramolecular cyclization with the formation of derivatives of 1,3-dithiolo[4,5-c]pyridine. In the case of other initial polychloropyridines processes involving substitution of the chlorine atoms by the ethylxanthate fragment, sometimes accompanied by the loss of COS molecules, were observed instead of heterocyclization.

Reactions of Polyhalopyridines. 16. Synthesis and Reactions of 2,3,5,6-Tetrafluoro-4-perfluoroalkylthiopyridines

Identical reaction products, viz. 2,3,5,6-tetrafluoro-4-perfluoroalkylthiopyridines 3a-c, were obtained on thermal decomposition of Xe(II) bisperfluoroalkylcarboxylates in the presence of mercaptotetrafluoropyridine and bis(2,3,5,6-tetrafluoro-4-pyridyl) disulfide. Compounds 3a-c readily interact with N-, O-, and S-containing nucleophiles, though with the first two types of reactant only with substitution of fluorine atoms in position 2 of the pyridine ring. In the latter case products are obtained both with retention of the perfluoroalkylthio group on interaction with sodium N,N-dimethyldithiocarbamate, and with total fission of that group in the case of alkali metal methanethiolate and toluenethiolate.

Reactions of polyhalogenopyridines. 15. Reaction of isomeric tetrachlorocyanopyridines and pentachloropyridine with potassium isopropyltrithiocarbonate

The reaction of isomeric tetrachlorocyanopyridines and pentachloropyridine with potassium isopropyltrithiocarbonate was investigated. It was found that the structure and composition of the reaction products depend both on the initial polychloropyridines and on the solvent in which the process is carried out. The intramolecular transformations of the isopropyltrithiocarbonate derivatives of tetrachloro-2-cyanopyridine in acetonitrile solution lead to 1,3-dithiolo[4,5-c]pyridines. In other cases heterocyclization was not observed. If the reactions were conducted in ethanol (except with tetrachloro-3-cyanopyridine) thioalkylation of the pyridine ring occurred.

Reaction of polyhalopyridines 4. Reaction of mercaptopolychloropyridines with fluorine-containing xenon compounds

A method has been developed for the perfluoroalkylation of mercaptopolychloropyridines by the thermolysis of xenon(II) perfluoroalkanecarboxylates, obtained by the reaction of xenon difluoride and aperfluoroalkanecarboxylic acids, in the presence of the appropriate thiol. Perfluoroalkylthio derivatives of polychloropyridines have been synthesized. The fluorosulfonyl derivatives of tetrachloropyriidne and of tetrachloropyridine N-oxide were obtained by the action of XeF2 on mercaptotetrachloropyridine dissolved in aqueous HF.

Perfluoroalkylation of 2-Thiopyrimidine Derivatives

The method of perfluoroalkylation of heterocyclic thiols and disulfides by thermolytic reaction with xenon(II) bisperfluoroalkylcarboxylates has been extended to sulfur-containing pyrimidines, including 2-mercaptopyrimidines, symmetrical disulfides, and S-trifluoroacetyl derivatives obtained from the corresponding thiols. The main reaction products are 2-SCnF2n+1 (n = 1, 2)-substituted pyrimidines. Their formation proceeds only via disulfides into which the initial thiols and S-trifluoroacetyl derivatives are converted in the reaction medium. Side reactions occurred in the case of trifluoromethylation linked with the perfluoroalkylation of the pyrimidine nucleus at the free 5 position (in the case of the 4,6-dimethyl derivative), or at position 4 or 4 and 5 (for unsubstituted pyrimidine). In addition, the introduction of the CF3 group at one of the methyl substituents was confirmed by the formation of CH2CF3 fragment.

Reactions of Polyhalopyridines. 17. Synthesis of 2-, 3-, and 4-Perfluoroalkylthiopolychloropyridines

Abstract2-, 3-, and 4-Perfluoroalkylthiopolychloropyridines have been synthesized using perfluoroalkylated thiol and disulfide derivatives of polychloropyridines via the thermal decomposition of Xe(II) bisperfluoroalkylcarboxylates. It was shown that their formation takes place from the starting thiols only through the formation of the disulfides. It was found that 3,4,5,6-tetrachloro-2-trifluoromethylthiopyridine reacts with potassium p-tolylthiolate with retention of the fluorine containing fragment and substitution of the chlorine atom in position 4 of the pyridine ring by the tolythio group.

Reactions of polyhalogenopyridines. 12. Reactions of 4-pentafluoroethylthio-2,3, 5,6-tetrafluoropyridine with nucleophilic agents

The reactions of 4-perfluoroethylthio-2,3,5,6-tetrafluoropyridine with various nucleophilic agents were investigated. It was shown that the pentafluoroethylthio group is inert toward N- and O-nucleophiles.