Heterocyclization of thioamides containing an active methylene group (review)

Abstract

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.

Synthesis of 2-(5-arylidene-4-oxo-3-arylthiazolydine-2)-N-phenylethanthiamides derivatives from malondithioamides

“…Известно, что тиоацетомиды яв-ляются удобными синтетическими блоками для получения различных гетероциклов, в том числе и тиазо-лов, содержащие двойные экзоци-клические связи [12,13]. Несмотря на это, реакция между хлоруксусным эфиром и дитиомалонамидами из-учена недостаточно [14].…”

“…Таким образом, в данной работе нами было показано, что исходя из N,N`-диарилмалондитиоамидов пу-тем последовательного проведения реакции Ганча и Кневенагеля мож-но получать производные 2-(5-ари-лиден-4-оксо-3-арилтиазолидин-2-илиден)-N-фенилэтантиоамида. Полученные соединения охарактери-зованы методами ЯМР 1 Н, ЯМР 13 С, а также УФ-спектроскопии.…”

Facile and efficient synthesis of 4'-thioxo-1',3,3',4,4',6' -hexahydro-1H,2'H-spiro[naphthalene-2,5'-pyrimidin]-1-ones in a three-component Mannich-type reaction

“…High reactivity of the thioamide group towards both electro-and nucleophilic agents, often in conjunction with that of other reactive centers in the molecule, made thioamides handy building blocks of particular importance in the synthesis of heterocyclic systems by inter-and intramolecular cyclization. [1][2][3][4][5] Saturated or partially saturated heterocyclic compounds with a thioamide group were found to be of interest as potential ionic liquid media. 6 Bogdanowicz-Szwed and co-workers reported the base-catalyzed reaction of β-ketothioamides with (E)-β-nitrostyrenes which yielded spiro(indane-1,3′-thiophenes).…”

Recyclization of 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydro-pyridin-2-ones into 1,6-annelated derivatives of 3-alkylcarbamoyl-5-benzoylpyridin-2-one

“…In the last two cases the reaction proceeds as a recyclization [3,4].The aim of the present work was to establish unequivocally the structure of the products of recyclization, to study the limits of its application, to investigate the effect of the ratio of starting materials on the direction of the reaction, and to clarify the sequence of formation of intermediate compounds.It was discovered that 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones 1a,b react with an excess of diaminoethane 2a and 1,3-diaminopropane 2b nonselectively. The reaction products are therefore not derivatives of 5-benzoyl-3-heteryl-2H-2-pyranone, as we proposed previously [3,4], but are 6-alkylcarbamoyl-8-benzoyl-5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridines 3a,b, 7-alkylcarbamoyl-9-benzo-yl-6-oxo-1,2,3,5-tetrahydro-2H-pyrido[1,2-a]pyrimidines 3c,d, and 1-alkyl-6-(1-alkyl-5-benzoyl-…”

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The structure of the recyclization products was demonstrated by spectral methods and X-ray structural analysis.Keywords: alkylamines, 1-(alkylamino)phenylmethylidene-3-methylcarbamoyl-4-oxo-1,4-dihydrobenzo [4,5]imidazo[1,2-a]pyridines, 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones, 3-alkylcarbamoyl-1-benzoyl-4-oxo-4H-benzo[4,5][1,3]thiazolo[3,2-a]pyridines, 3-alkylcarbamoyl-1-benzoyl-4-oxo-4,10-dihydrobenzo [4,5]imidazo[1,2-a]pyridines, 6-alkylcarbamoyl-8-benzoyl-5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridines, 7-alkylcarbamoyl-9-benzoyl-6-oxo-1,2,3,5-tetrahydro-2H-pyrido[1,2-a]pyrimidines, 1-amino-2-mercaptoethane, 1,3-diaminopropane, o-aminothiophenol, diaminoethane, o-phenylenediamine, recyclization X-ray structural analysis.We showed recently that 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones 1a,b are regiospecifically cyclocondensed with nitrogen-containing 1,2-, 1,3-, 1,4-, and 1,5-dinucleophiles [1-4]. In the last two cases the reaction proceeds as a recyclization [3,4].

The aim of the present work was to establish unequivocally the structure of the products of recyclization, to study the limits of its application, to investigate the effect of the ratio of starting materials on the direction of the reaction, and to clarify the sequence of formation of intermediate compounds.

It was discovered that 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones 1a,b react with an excess of diaminoethane 2a and 1,3-diaminopropane 2b nonselectively.

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