Pyrazolinium structures have practically valuable biological properties. Their methods of synthesis mainly consist in the reactions of cyclization of steroid compounds containing an enone fragment with a variety of hydrazines. We have previously obtained new spiropyrazolinium compounds by hydrolysis of 3-(β-heteroamino)ethyl-5-aryl-1,2,4-oxadiazoles and by arylsulfochlorination of β-aminopropioamidoximes. The aim of the work is to reveal the dependence of the structure of the final β-aminopropioamidoximes tosylation products from the structure of the starting amidoxime and strength of base. Methodology. The tosylation of β-aminopropioamidoximes was carried out in chloroform using diisopropylethylamine as a base. The synthesis was carried out at room temperature for 15–20 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the precipitate was filtered off, followed by evaporation of the filtrate and additional precipitation of the product; the combined precipitates were recrystallized from isopropanol. Results and discussion. The products of tosylation of β-aminopropioamidoximes were obtained in 45‒65% yields and identified using physicochemical and spectral [IR, NMR (1H and 13C)] characteristics, tosylation of β-aminopropioamidoximes (β-amino group: piperidin-1-yl, morpholine -1-yl, thiomorpholin-1-yl, 4-phenyl-piperazin-1-yl) proceeds with the formation of spirocyclic compounds ‒ arylsulfonates of 2-amino-1,5-diazaspiro [4.5]-dec-1-ene-5-ammonium; tosylation of β-(benzimidazol-1-yl)propioamidoxime gives the product on the oxygen atom of the amidoxime group.
Nitrobenzenesulfochlorination of β-aminopropioamidoximes leads to a set of products depending on the structure of the initial interacting substances and reaction conditions. Amidoximes, functionalized at the terminal C atom with six-membered N-heterocycles (piperidine, morpholine, thiomorpholine and phenylpiperazine), as a result of the spontaneous intramolecular heterocyclization of the intermediate reaction product of an SN2 substitution of a hydrogen atom in the oxime group of the amidoxime fragment by a nitrobenzenesulfonyl group, produce spiropyrazolinium ortho- or para-nitrobenzenesulfonates. An exception is ortho-nitrobenzenesulfochlorination of β-(thiomorpholin-1-yl)propioamidoxime, which is regioselective at room temperature, producing two spiropyrazolinium salts (ortho-nitrobezenesulfonate and chloride), and regiospecific at the boiling point of the solvent, when only chloride is formed. The para-Nitrobezenesulfochlorination of β-(benzimidazol-1-yl)propioamidoxime, due to the reduced nucleophilicity of the aromatic β-amine nitrogen atom, is regiospecific at both temperatures, and produces the O-para-nitrobenzenesulfochlorination product. The antidiabetic screening of the new nitrobezenesulfochlorination amidoximes found promising samples with in vitro α-glucosidase activity higher than the reference drug acarbose. 1H-NMR spectroscopy and X-ray analysis revealed the slow inversion of six-membered heterocycles, and experimentally confirmed the presence of an unfavorable stereoisomer with an axial N–N bond in the pyrazolinium heterocycle.
The reaction of β-(thiomorpholin-1-yl)propioamidoxime with tosyl chloride in CHCl3 in the presence of DIPEA when heated at 343 K for 8 h afforded the title hydrated salt, C7H14N3S+·Cl−·H2O, in 84% yield. This course of the tosylation reaction differs from the result of tosylation obtained for this substrate at room temperature, when only 2-amino-8-thia-1,5-diazaspiro[4.5]dec-1-ene-5-ammonium tosylate was isolated in 56% yield. The structure of the reaction product was established by physicochemical methods, spectroscopy, and X-ray diffraction. The single-crystal data demonstrated that the previously reported crystal structure of this compound [Kayukova et al. (2021). Chem. J. Kaz, 74, 21–31] had been refined in a wrong space group. In the extended structure, the chloride anions, water molecules and amine groups of the cations form two-periodic hydrogen-bonded networks with the fes topology.
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