Cycloacylation of 3-oxo-3-R1-N-R2-propanethioamides by 3-aryl-2-propenoyl chlorides

Esipenko

Lozinskii

2008

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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.

Section: [3+3] Cyclization Of 3-oxopropanethioamides With 13-dielectmentioning

confidence: 99%

Heterocyclization of thioamides containing an active methylene group (review)

Esipenko

Lozinskii

2008

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“…

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mentioning

confidence: 99%

“…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].…”

mentioning

confidence: 99%

Synthesis and reactions of 1-R-3-benzoyl-5-ethoxycarbonyl-6-oxo-1,2,3,6-tetrahydropyridine-2-thiones

Esipenko

Chernega

et al. 2007

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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].

“…However, the amide bond in these compounds is weak, as a result of which they are readily hydrolyzed by water to the corresponding 3-aryl-3-(5-thio-1H-1,2,4-triazol-5-yl)propionic acids 98 [82]. If a compound containing an active methylene group -N-phenyl-3-oxobutanethioamide (99) -is used as substrate, the reaction takes place nonselectively with the formation of three groups of compounds, i.e., thioxopiperidin-2-ones 100, 2,3-dihydro-4H-thiopyran-4-ones 101, and 5,6-dihydro-4H-1,3-thiazin-4-ones 102 [4,83]. The type of heterocycles, their ratio, and the yields depend on the nature of the substituents present in the phenyl ring of the initial 3-aryl-2-propenoyl chlorides.…”

Section: Reactions With 3-aryl-2-propenoyl Chloridesmentioning

confidence: 99%

“…The type of heterocycles, their ratio, and the yields depend on the nature of the substituents present in the phenyl ring of the initial 3-aryl-2-propenoyl chlorides. It was also shown [4,83] that the thioxopiperidin-2-ones 100 are prospective starting materials for the synthesis of condensed heterocycles -6H-thieno[2,3-b]-pyridin-6-ones and pyrazolo [3,4-b]pyridin-6-ones.…”

Section: Reactions With 3-aryl-2-propenoyl Chloridesmentioning

confidence: 99%

Cycloacylation of thioamides and their derivatives by compounds containing an activated multiple bond (review)

Lozinskii

2007

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The cycloacylation reactions of thioamides and their derivatives containing an activated multiple bond are analyzed and summarized.The cycloacylation of thioamides and their derivatives containing an activated multiple bond is an accessible and convenient method for the synthesis of five-and six-membered sulfur-and nitrogen-containing heterocycles -primarily 4H-1,3-thiazin-4-ones [1] and thiazolidin-4-ones [2], and also 2-thioxopiperidines [3], thiopyran-4-ones [4], and pyrimidin-4-ones [5]. Heterocyclic compounds of these types exhibit a wide spectrum of biological activity and have extensive practical applications [1,2,6].This group of reactions is also of interest from the theoretical standpoint since they make it possible to study, analyze, and predict the relationships between the reactivity of substrates containing the ambident NH─C═S group and their structure, reaction conditions, and the nature of substituents at the heteroatoms. Therefore, in spite of the fact that the first papers on this subject were published 50 of more years ago [7,8] synthetic investigations in the field are continuing to this day [9][10][11][12].Nevertheless, no reviews have been published on this subject. It should be mentioned that certain methods for the cycloacylation of thioamides by derivatives of unsaturated carboxylic acids were analyzed in reviews on the synthesis of 1,3-thiazines [1] and thiazolidin-4-ones [2, 13], reactions of N-aminoazolinethiones and N-aminoazinethiones [14], thioamides [15][16][17], and carbon suboxide [18]. However, the information on this subject in these publications has not been coordinated and is not exhaustive.New publications on the cycloacylation of thioamides, in which the range of both reagents and substrates has been extended, have appeared recently. Modern physical methods of establishing the structure of the synthesized products were used, and this made it possible to prove their structure unequivocally.For this reason we attempted to fill the gap and to analyze the information concerning the cycloacylation of acyclic and cyclic thioamides by compounds containing an activated multiple bond. This reviews covers papers not examined in [1,2,[13][14][15][16][17][18] and also papers that have appeared more recently.