Data from the last six years on the heterocyclization of thioamides containing an active methylene group are analyzed and classified.At the present time there has been a considerable increase in the number of publications on the chemistry of thioamides, and this is explained by the value of the compounds as initial reagents for further transformations and particularly for the synthesis of various sulfur-and nitrogen-containing heterocycles [1][2][3][4][5][6][7][8]. The enormous practical significant of the latter is common knowledge -they have found application as drugs, pesticides, dyes, and preservatives.Thioamides with an active methylene group are attractive synthesis units for the production of heterocycles. These polyfunctional compounds can be represented by the formula R 3 -CH 2 CS-NR 1 R 2 (where R 1 , R 2 = H, Alk, Ar; R 3 is an electron-withdrawing group such as CN, AlkCO, ArCO, (AlkO) 2 PO, AlkSO 2 , ArSO 2 , NO 2 ). The presence of another reaction center (the methylene group) makes it possible to use them as N-С-С and S-C-C components for various condensations [1][2][3][4][5][6][7][8]. A special feature of such substrates is the ability to react both with dinucleophilic and with dielectrophilic and dipolar reagents. As a rule the products of these heterocyclizations contain functional groups, which makes it possible to achieve their modification or annelation. Such characteristics of thioamides with an active methylene group substantially increase their synthetic potential and extend the range of accessible heterosystems, while the use of modern physical methods of investigation (X-ray crystallographic analysis and 1D and 2D NMR spectroscopy) makes it possible to establish the structure of the obtained compounds unambiguously. The presence of biological activity in the products of these transformations also attracts investigators to this subject [5][6][7][8].The reason for the appearance of this review was the increasing need for generalization and classification of new information on the heterocyclization of such thioamides that had not been included in previous reviews [2][3][4][5] and also to define the trends in the study of these processes. Since one of the most important reports in this field is the review [1] we undertook an analysis of the literature that has appeared in the last six years.

The direction of the reaction is governed by the basicity of the medium as well as by the structure of the initial thiourea. Acylation of thioureas (I) and (VI) in acetone occurs selectively yielding heterocycles (III) and (X), respectively. On the other hand, acylation of (I) and (VI) in the presence of potassium carbonate proceeds nonselectively furnishing compounds of cyclic, (IV), and acyclic, (V) and (VII), structure, and phenyl isothiocyanate (VIII). Thiazinones (X) do not react with hydrogen peroxide in acetic acid at room temperature, but melting them with phenacyl bromides (XI) results in dehydrogenation and formation of compounds (XII). -(BRITSUN, V. N.; ESIPENKO, A. N.; LOZINSKII, M. O.; Russ.

Derivatives of 3-aroyl-2-(methylthio)pyridine are valuable starting materials for obtaining condensed nitrogen-containing heterosystems. In spite of the significant number of studies devoted to the synthesis of these compounds [1-7] their further conversions have not been studied. This is probably explained both by the nonselectivity of the reactions obtaining them [1-3] and the difficulty of availability of the initial reactants [4][5][6][7].

Keywords: 1-R-3-benzoyl-5-ethoxycarbonyl-6-oxo-1,2,3,6-tetrahydropyridine-2-thiones, diethyl ethoxymethylenemalonate, 6-ethoxycarbonyl-2-imino-8-methyl-4-phenyl-1,2,7,8-tetrahydropyrido[2,3-d]-pyrimidin-7-one, 5-ethoxycarbonyl-7-methy-3-phenyl-6,7-dihydroisoxazolo[3,4-b]pyridine-6-one, N-R-3-oxo-3-phenylpropanethioamides, 9-R-7-ethoxycarbonyl-5-phenyl-8,9-dihydropyrido[2,3-d][1,2,4]triazolo-[1,5-a]pyrimidin-8-ones, X-ray structural analysis, cycloacylation.The cycloacylation of thioamides by unsaturated carboxylic acid derivatives is a convenient and practical method for the synthesis of sulfur containing azoles and azines [1][2][3][4][5].One of these reagents is diethyl ethoxymethylenemalonate, the ethoxy group of which has good nucleofuge properties. None the less, there are only two studies in which the cyclocondensation of this compound with thioamides is discussed [6,7]. It is likely that the low interest of investigators in this area of reactions is explained by the fact that the reaction is carried out under forcing conditions [7] and forms two [7] or three products [6].The aim of this work was the discovery of conditions for the cycloacylation of the N-R-3-oxo-3-phenylpropanethioamides 1a,b by diethyl ethoxymethylenemalonate 2 and the exploitation of the synthetic potential of the products obtained.It was found that the N-R-3-oxo-3-phenylpropanethioamides 1a,b condense with diethyl ethoxymethylenemalonate 2 in the presence of sodium ethylate. The reaction occurs selectively and its products are the 1-R-3-benzoyl-5-ethoxycarbonyl-6-oxo-1,2,3,6-tetrahydropyridine-2-thiones 3a,b.In all likelihood the high selectivity of the process is explained by the high CH-acidity of the thioamides 1a,b [8] when compared with the N-aryl-2-thiocarbamoylacetamides. The latter react with diethyl ethoxymethylenemalonate non selectively to give three products [6].

Earlier we developed a general method for obtaining condensed heterocycles containing a 1,3-triazine ring, based on the reaction of nitrogen-containing thiones with 3-aryl-2-propenoyl chlorides in pyridine [1][2][3][4]. In this work, we have studied the reaction of 3-oxo-3-R 1 -N-R 2 -propanethioamides 1a-c with 3-aryl-2-propenoyl chlorides 2a-c. Since 3-oxo-3-R 1 -N-R 2 -propanethioamides 1a-c have several reaction centers [5,6], the products of this reaction can be 3,4-dihydro-2H-pyran-2-ones, 4H-pyran-4-ones, 4H-1,3-thiazin-4-ones, 6H-1,3-thiazin-6ones, 4H-thiopyran-4-ones, 2H-thiopyran-2-ones, 4H-piperidin-4-ones, and 6-thioxopiperidin-2-ones, which complicates isolation and identification of the compounds formed.The optimal conditions for carrying out the reaction involve stirring a solution of 3-oxo-3-R 1 -N-R 2propanethioamides 1a-c and 3-aryl-2-propenoyl chlorides 2a-c in acetone in the presence of K 2 CO 3 at 20-50°C for 2.5 h. The products of each reaction, according to TLC and 1 H NMR spectroscopy, are a mixture of two compounds which have the same elemental composition and were separated by treatment of the reaction mixture with a 5% aqueous NaOH solution. Detailed analysis of the 1 H NMR, 13 C NMR, and IR spectra of the reaction products, and also comparison of this information with the spectral data for 4H-thiopyran-4-ones and 4Hpiperidin-4-ones given in [7], showed that as a result of the reaction, 4-aryl-1-aryl(alkyl)-5-acyl-6thioxopiperidin-2-ones 3a-d, 2-aryl-6-aryl(alkyl)amino-5-acyl-2,3-dihydro-4H-thiopyran-4-ones 4a-d, and 2-acetonylidene-6-(4-nitrophenyl)-3-phenyl-5,6-dihydro-4H-1,3-thiazin-4-one (5) were formed.The type of heterocycles, their ratio and yield depend on the nature of the substituents R 1 , R 2 , and Ar 1 in the starting 3-oxo-3-R 1 -N-R 2 -propanethioamides 1a-c and 3-aryl-2-propenoyl chlorides 2a-c. Acylation of 3-oxo-N-phenylbutanethioamide 1a by 3-phenyl-2-propenoyl chloride (2a) and 3-(4-chlorophenyl)-2-propenoyl chloride (2b) leads to formation of 6-thioxopiperidin-2-ones 3a,b and 4H-thiopyran-4-ones 4a,b in 1:1 ratio, the products of condensation of thioamide 1a with 3-(4-nitrophenyl)-2-propenoyl chloride 2c are 6-thioxopiperidin-2-one 3c and 4H-1,3-thiazin-4-one 5, also in an equimolar ratio.

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