The latter, as their potassium salts, were esterified in water or DMF by dimethyl sulfate or various
reactive halides, and in this case a series of novel esters 3a-m was formed.
In studying hydrazinolysis of compounds 1a-c, we observed that only compound 1a is readily converted
to the expected hydrazide 4 when treated with excess hydrazine hydrate at room temperature. When this
reaction is carried out at elevated temperature, as described for the methyl ester of 2-methyl-5-
phenylthiazolecarboxylic acid [4], breakdown of the thiazoline ring occurs.
We synthesized new potentially biologically active hydrazones 5a-e from respectively hydrazide 4 and
benzaldehyde, furfural, 5-nitrofurfural, acetophenone, or p-benzoquinone.
EXPERIMENTAL
The 1H NMR spectra were recorded on a Mercury-300 spectrometer (300 MHz) in DMSO-d6.
The composition and structure of the synthesized compounds were confirmed by the results of elemental
analysis and 1H NMR spectra (see Table 1).
3,4-Dimethyl-2-thioxo-1,3-thiazolinyl-5-carboxylic Acid (2a) was obtained according to the known
procedure in [3].
3-Aryl-4-methyl-2-thioxo-1,3-thiazolinyl-5-carboxylic acid 2b,c. Ester 1b,c (10 mmol) was added to
a solution of 84% KOH (10 mmol) in ethanol (10 ml) and the reaction mixture was refluxed for 3 h. Then the
ethanol was distilled off and the residue was dissolved in H2O (10 ml) and the solution was filtered; the filtrate
was acidified with HCl to pH 4 and the precipitate formed of product 2b,c was filtered out.
Esters of Acids 2a-c (3a-m). Acid 2a-c (10 mmol) was added to a suspension of 84% KOH powder
(10 mmol) in DMF (10 ml); the mixture was stirred for 1 h, and then the halide (10 mmol) was added in
portions. The reaction mass was held for 3 h at 50-60°C and then cooled, and the potassium halide was filtered
out. The filtrate was evaporated down, the residue was treated with H2O (10 ml), the precipitate of product
3a-m was filtered out and dried in air.
3,4-Dimethyl-2-thioxothiazolinyl-5-carboxylic Acid Hydrazide (4). Ester 1a (2.2 g, 10 mmol) was
added with stirring to 55% hydrazine hydrate (10 ml), and the reaction mixture was held for 24 h at 20°C. Then
the product 4 was filtered out and washed with water (10 ml).
N-(3,4-Dimethyl-2-thioxothiazolinylcarbonyl)hydrazones of Benzaldehyde (5a), Furfural (5b),
5-Nitrofurfural (5c), Acetophenone (5d), and p-Benzoquinone (5e). 36% HCl (0.86 ml) was added to
compound 4 (2.03 g, 10 mmol) in H2O (30 ml) and then the carbonyl compound (10 mmol) were added to the
solution obtained at 0°C. The mixture was held for 4 h at 20°C, and the precipitate of product 5a-e was filtered
out, washed on the filter with H2O (10 ml) and dried in air. Compounds 5 were purified by grinding with
acetone and then filtered out.
REFERENCES
1.
N. N. Mel'nikov, K. P. Novozhilov, and T. N. Pylova, Chemicals for Plant Protection [in Russian],
Khimiya, Moscow (1980), p. 263.
2.
3.
M. D. Mashkovskii, Drugs [in Russian], Meditsina, Moscow (1984), Pt. 1, p. 202.
V. V. Dovlatyan, K. A. Eliazyan, V. A. Pivazyan, E. A. Kazaryan, A. P. Engoyan, R. T. Grigoryan, and
R. G. Mirzoyan, Khim. Geterotsikl. Soedin., 677 (2000).
4.
V. A. Mamedov, N. A. Nuretdinov, and F. G. Sigbatulina, Izv. Akad. Nauk SSSR. Ser. Khim., 2835
(1991).
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