N. S. Akhmadiev

Heterocyclization of dimethyl malonate with SH acids and formaldehyde in the presence of catalysts

Three-component heterocyclization of dimethyl malonate with SH acids (H2S, ethane-1,2-dithiol) and formaldehyde in the presence of 5 mol % of transition metal chlorides (FeCl3, CoCl2, NiCl2) gave dimethyl 1,3-dithiane-5,5-dicarboxylate and dimethyl 1,4-dithiepane-6,6-dicarboxylate. The reactions in the presence of transition metal chlorides hydrates were accompanied by Krapcho decarboxylation with formation of methyl 1,3-dithiane-5-carboxylate and methyl 1,4-dithiepane-6-carboxylate.

One-pot synthesis of bis-1,5,3-dithiazepanes and their sorption properties toward silver(I) and palladium(II)

The possibility of one-pot synthesis of bis-1,5,3-dithiazepanes by multicomponent condensation of amines (NH4Cl, hydrazine, and 1,2-ethylenediamine) with formaldehyde and 1,2-ethanedithiol was described. Their sorption properties relative to Ag(I) and Pd(II) were studied by a static method. It was shown that at room temperature bis-1,5,3-dithiazepanes recovered with high efficiency silver(I) and palladium(II) from nitrate solutions and hydrochloric acid solutions, respectively.

Silica-alumina catalyzed of 2,4-pentanedione with formaldehyde and α,ω-dithiols

Depending on the character of initial reagents the condensation of 2,4-pentanedione with aldehydes and thiols in water environment leads to the formation in 15–98% yields of β-sulfanyldiketones exhibiting a wide range of pharmacologic characteristics [1, 2]. We presumed that the condensation of 2,4-pentanedione (I) with formaldehyde and α,ω-dithiols would allow the synthesis of cyclic III [3] or linearly bound β,β′-disulfanyldiketones IV (see the scheme). Preliminary experiments showed that the reaction without catalyst of diketone I with formaldehyde and 1,2-ethanedithiol (IIb) (Н2О, 80–100°С, 8 h [1]) afforded 3,10-diacetyl5,8-dithiadodecane-2,11-dione (IVb) in a yield ≤20% (conversion ~30%). Aiming at increasing the yield we carried out the reaction in the presence of heterogeneous catalysts. Poly-(4-vinylpyridine)alumina-silica (PVP/Al2O3–SiO2) at the molar ratio Al2O3–SiO2 0.31–0.83 catalyzed the Knoevenagel condensation of 1,3-dicarbonyl compounds with aldehydes [4]. In view of these data we applied to the reaction alumina-silica catalysts obtained from ethyl silicate-40 [5] in the presence of surfactant Reapon-4 (see the table, samples nos. 1–4), and samarium silicates (samples nos. 10, 11), and also catalysts obtained by annealing and deposition of elements in the pores of thermohydrated silica gel (samples nos. 5–9, 12). Among the tested alumina-silica catalysts (samples nos. 1–5) the sample Al2O3–SiO2 with the molar ratio 0.0125 : 1 exhib-

Catalytic multimolecular reactions of 1,3-dicarbonyl CH acids with CH2O and S- and N-nucleophiles

The literature data on the synthesis and properties of oxo-functionalized acyclic and cyclic sulfides obtained by the catalytic multicomponent reactions of 1,3-dicarbonyl compounds with formaldehyde and S-nucleophiles are summarized. An approach to the multimolecular four-component heterocyclization of 1,3-dicarbonyl compounds with CH2O and S- and N-nucleophiles in the synthesis of sulfanyl-substituted azaheterocycles is discussed.

Directed Aminomethylation of Pyrrole, Indole, and Carbazole with N , N , N′ , N′ -Tetramethylmethanediamine

Catalytic aminomethylation of pyrrole and indole with N,N,N′,N′-tetramethylmethanediamine in the presence of 5 mol % of ZrOCl2·8H2O proceeds selectively at the positions 2, 5 of pyrrole and 1, 3 of indole. Carbazole under the same conditions affords 3-formyl-9-aminomethyl derivative. The reaction in the presence of 5 mol % of K2CO3 occurs as monoaminomethylation: for pyrrole at the position 2, for indole at the position 3, and for carbazole at the nitrogen atom of the substrate. Water-soluble 1,1′-(1H-pyrrole-2,5-diyl)bis(N,N-dimethylmethanamine) exhibits a fungistatic activity with respect to phytopathogenic fungi Rhizoctonia solani.

Transition metal-catalyzed C,C- and C,N-cycloaminomethylation reactions of pyrrole and indole

Catalytic cycloaminomethylation of pyrrole with bis(methoxymethyl)alkylamines or a mixture of alkyl(phenyl)amines and paraformaldehyde in the presence of [Ni(Py)4Cl2]·0.76H2O or NiCl2·6H2O catalysts proceeded at positions 2 and 5 of pyrrole ring. Cycloaminomethylation of indole was accomplished effectively at positions 1 and 3 in the presence of ZrOCl2·8H2O catalyst. When carbazole was treated with bis(methoxymethyl)alkylamine in the presence of ZrOCl2·8H2O catalyst, it was converted to N-aminomethylated product – N-[(9H-carbazol-9-yl)methyl]-N-(methoxymethyl)alkylamine.

Nickel-catalyzed multicomponent heterocyclization of 2,4-pentanedione to sulfanylmethyl-1 H -pyrazoles

A one-pot synthesis of new sulfanylmethyl-substituted 3,5-dimethyl-1H-pyrazoles with fungicidal activity was based on a nickelcatalyzed four-component condensation of 2,4-pentanedione with formaldehyde, thiols, and hydrazine hydrate.

Synthesis of Bis(Isoxazol-4-Ylmethylsulfanyl)Alkanes and Some Metal Complexes as a Hepatoprotective Agents

Purpose: This research is devoted to designing the synthesis of sulfanyl-substituted 3,5-dimethylisoxazoles, which contain structural analogues of the SAM drug in the molecule. SAM (S-adenosyl-L-methionine), formed in the biosynthetic process, is used as an effective hepatoprotective drug. Complexation and hepatoprotective properties of the combinatorial series of bis(isoxazolylsulfanyl)ethane have been studied. Methods: Bis(isoxazol-4-ylmethylsulfanyl)alkanes were synthesized using the one-pot method. The structures of compounds were established by one-dimensional (1H,13C) and two-dimensional (COSY, HCQS, HMBC) NMR spectroscopy, mass-spectrometry and X-ray diffraction. The biological activity of the combinatorial series of sulfanyl derivatives of diketones, azoles and their metal complexes has been studied by in vivo method. Simulation of the animal associated processes was carried out in accordance with the principles of bioethics. Screening studies of hepatoprotective activity were carried out in a model of acute CC14 intoxication after a single injection intraperitoneally as a 50% solution in olive oil. The pharmacologically known hepatoprotective drug SAM served as a control. Results: Two-step synthesis of novel α,ω-bis(isoxazol-4-ylmethylsulfanyl)alkanes was carried out via the multicomponent reaction between 2,4-pentandione, CH2O and α,ω-dithiols, then the resulting α,ω-bis(1,3-diketone-2-ylmethylsulfanyl)alkanes were transformed by hydroxyl amine to obtain bis-isoxasole derivatives. Promising precursor 1,2-bis(isoxazol-4-ylmethylsulfanyl)ethane was converted to metal complexes by interaction with PdCl2 or CuCl. The obtained compounds were found to be practically non-toxic compounds (1001 - 3000 mg/kg) according to the classification of K.K. Sidorov, but copper complex refers to low-toxic compounds substances (165 mg/kg). Compounds of sulfanyl ethane series demonstrate hepatoprotective activity. Conclusion: Palladium(II) complex being almost non-toxic possesses hepatoprotective activity comparable to the drug like SAM.