Interaction of the O-Benzoyl-β-aminopropioamidoximes with Lawesson's Reagent and Spectral Characterization of the Products

Interaction of O-benzoyl-β-aminopropioamidoximes [β-amino group: pyperidin-1-yl; morpholin-1-yl; thiomorpholin-1-yl; 4-phenylpiperazin-1-yl; benzimidazol-1-yl] with Lawesson's reagent was done in tetrahydrofuran at heating to 70°C during 10 h. New O-thiobenzoyl-β-aminopropioamidoximes were obtained with the outputs 57–96%; they were characterized with the help of physicochemical, IR, and NMR spectra.


Introduction
Representatives of thion-containing compounds, in particular, ethionamide and prothionamide are used in medicine as anti-TB drugs [1]. A high anti-HIV activity of thion derivative of dibenzoyl substituted piperazine was revealed; thion derivative gives 100% inhibition of the HIV virus in comparison with 11% inhibition of the original carbonyl compounds [2]. In our group samples with high antitubercular activity were revealed within the row of β-aminopropioamides [3][4][5]. For us it was interesting to investigate the effect of replacing the oxygen atom in carbonyl group on a sulfur atom on the biological properties of studied compounds, primarily on the antitubercular properties.
The reaction products were characterized by physicochemical data, IR, and NMR spectra (Tables 1-3 and Scheme 3).
Thus compounds 6-10 in the resonance region of aromatic protons C sp2 H give signals at δ 6.80-9.25 ppm, whereas these signals of O-benzoyl groups in 1-5 are at δ 6.77-8.62 ppm.
Proton signals of NH 2 groups of 6-10 are situated in the area δ 6.87-6.97 ppm; analogous signals of 1-5 in the region δ 6.54-6.87 ppm with the highest shift to the low field Δδ 0.43 ppm for a pair of compounds 3 and 8.
Protons of α-methylene group of compounds 6-10 have a resonance at δ 2.69-3.15 ppm and compounds 1-5 in the area δ 2.26-2.74 ppm with a maximum shift to the low field Protons of methylene groups of β-heterocycles: (CH 2 ) 3 (6), as well as the protons attached to the heteroatom in the 4-position of compounds (7)(8)(9), have a resonance at δ 1.42 and 2.46 ppm and δ 3.73-3.93 ppm, respectively, while the similar protons of the oxygen analogues 1 and 2-4 at δ 1.37 and 1.50 ppm and δ 2.69-3.56 ppm with a maximum shift to low field Δδ 1.26 ppm for a pair of compounds 3 and 8.
Signals of methylene groups of heterocycles connected to the nitrogen atom (N1) -N(CH 2 ) 2 have the largest shifts to the low field: region δ 3.51-3.80 ppm (6-9) compared with the region δ 2.37-2.66 ppm (1)(2)(3)(4) with the maximum shift to low field Δδ 1.36 ppm which is characteristic for the pair of compounds 1 and 6.
Obviously such descreening effect of thiocarbonyl sulfur atom in the last three groups of protons reflects the spatial structure of thion derivatives 6-10 where the sulfur atom may be closed to these descreened groups of protons in the syn-isomer with the s-trans conformation as shown in Scheme 4.
A similar spatial structure with a syn-arrangement of N-O bond and the amino group NH 2 about C=N bond with s-trans conformation of the substituents with respect to N-O linkage was found in the hydrochlorides of aroylation products of O-β-aminopropioamidoximes with the help of X-ray analysis [15].

Conclusion
Thus, we have elaborated acceptable method of synthesis of O-thiobenzoyl-β-aminopropioamidoximes by using of interaction of O-benzoyl-β-aminopropioamidoximes with Lawesson's reagent at a ratio 1 : 0.5 at heating in THF at 70 • C for 10 h. NMR spectral characteristics of new O-thiobenzoyl-β-aminopropioamidoximes confirm the structure established on the basis of elemental analysis and infrared spectra and provide proof of the spatial arrangement of functional groups in the s-trans-syn-configuration.