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

Abstract

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].

Cyclocondensation of 5-benzoyl-3-ethoxycarbonyl-6-methylthio-1-R-1,2-dihydropyrid-2-ones with heterocyclic N,N-and N,C-1,3-dinucleophiles

“…Yield of compound 2a was 12.08 g (73%), and of 2b 11,21 g (65%). The melting points and 1 H NMR and IR spectra of products 2a,b were identical to those given in [8].…”

“….1 ppm [8]) was absent from the 13 C NMR spectrum of the reaction product of 1,2-dihydropyrid-2-one 2a with 2-amino-5-methylthiazole 7b, and a signal was observed for the sp 3 -hybridized C-N carbon at 86.7 ppm [11], which may be assigned only to the C-5 atom of pyrido [2,3-d] The structures of the products of reaction of 1,2-dihydropyridin-2-ones 2a,b with such highly basic aminoazines as 3-aminobenzimidazole 9 (pKa 7.39, [9]) and 2-(cyanomethyl)benzimidazole 11, were confirmed by 1 H NMR spectroscopy.…”

“…Recently we have developed a preparative method of synthesizing 5-benzoyl-3-ethoxycarbonyl-6-methylthio-1-R-1,2-dihydropyrid-2-ones from available starting materials and the possibility was shown of using them for cyclocondensation with nitrogen-containing 1,3-dinucleophiles, particularly with the aim of obtaining bi-and tricyclic heterosystems [8].…”

“…Development of a preparative one-step method of synthesizing 1-R-1,2-dihydropyrid-2-ones 2a,b enabled an investigation [8] of the regioselectivity of their cyclocondensations with heterocyclic N,N-and N,C-1,3-dinucleophiles to be continued. As such were used 5-amino-3-R 1 -4-R 2 -pyrazoles 3a,b, 3-amino-2H-pyrazolo[3,4-b]pyridine (5), 2-amino-5-R-thiazoles 7a,b, 2-aminobenzimidazole (9), and 2-(cyanomethyl)-benzimidazole (11).…”

“…We showed previously [8] by X-ray structural analysis that the cyclocondensation of 1-R-1,2-dihydropyrid-2-ones 2a,b with such an aminoazole as 3-amino-1,2,4-triazole (pKa 4.17 [9]) proceeds selectively and is effected as a nucleophilic attack of the exocyclic and endocyclic amino groups of the reactant at the methylthio and aroyl groups of the substrate respectively. On the basis of these data it may be concluded that the products of the interaction of 1-R-1,2-dihydropyridin-2-ones 2a,b with derivatives of 3(5)-aminopyrazole (pKa 4.11 [9] Since the products of cyclocondensation of 1,2-dihydropyridin-2-one 2a with 2-amino-5-R-thiazoles 7a,b may have both an acyclic and a cyclic structure, then for the unequivocal determination of their structure we recorded the 13 C NMR spectrum of compound 8b.…”