Three-Component Reaction of Pyrrolediones, Malononitrile, and Acyclic Enols
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e-Component Reaction of Pyrrolediones, Malononitrile, and Acyclic Enols A. A. Sabitova, M. V. Dmitrieva, A. I. Belozerovaa, T. V. Sal’nikovaa, and A. N. Maslivetsa,* a
Perm State University, Perm, 614990 Russia *e-mail: [email protected]
Received February 10, 2020; revised March 31, 2020; accepted April 3, 2020
Abstract—Three-component condensation of ethyl 1-R-2-phenyl-4,5-dihydro-4,5-dioxo-1H-pyrrole-3-carboxylates, malononitrile, and acyclic enols (acetylacetone, alkyl acetoacetates, and ethyl benzoylacetate) afforded substituted ethyl 9-amino-10-cyano-1-oxo-3-phenyl-8-oxa-2-azaspiro[4.5]deca-3,6,9-triene-4-carboxylates. The products are interesting from the viewpoint of medicinal chemistry. Keywords: 1H-pyrrole-2,3-diones, malononitrile, 2-amino-4H-pyran-3-carbonitriles, 1,3-dicarbonyl compounds, enols, three-component reactions
DOI: 10.1134/S1070428020070155 We previously studied three-component reactions of 1H-pyrrole-2,3-diones with malononitrile and sixmembered carbo- and heterocyclic enols (5,5-dimethylcyclohexane-1,3-dione and 4-hydroxycoumarin), which led to the formation of spiro[chromene-4,3′-pyrroles] and spiro[pyrano[3,2-c]chromene-4,3′-pyrroles], respectively [1, 2]. Analogous reactions of 1H-pyrrole2,3-diones with malononitrile and five-membered carbo- and heterocyclic enols [indan-1,3-dione, cyclopentane-1,3-dione, and furan-2,4(3H,5H)-dione] afforded spiro[indeno[1,2-b]pyran-4,3′-pyrroles], spiro[cyclopenta[b]pyran-4,3′-pyrroles], and spiro[furo[3,4-b]pyran-4,3′-pyrroles], respectively [3, 4]. Threecomponent reactions of 1H-pyrrole-2,3-diones with malononitrile and acyclic enols have not been reported so far. By heating ethyl 1-R-2-phenyl-4,5-dihydro-4,5-dioxo-1H-pyrrole-3-carboxylates 1a–1d, malononitrile, and acyclic enols 2a–2d at a ratio of 1:1:4 in boiling anhydrous acetonitrile in the presence of triethylamine (20 mol %) for 19– 20 h (HPLC/MS monitoring) we obtained substituted 9-amino-10-cyano-1-oxo-3-phenyl-8-oxa-2-azaspiro[4.5]deca-3,6,9-triene-4-carboxylates 3a–3g (Scheme 1). Unlike similar reactions with cyclic enols [1–4], the reaction with enols 2a–2d required more severe conditions, i.e., prolonged heating and the use of excess enol (4 equiv). Compounds 3a–3g are high-melting colorless crystalline solids readily soluble in DMSO and acetone,
poorly soluble in ethanol and toluene, and insoluble in alkanes and water. Their IR spectra showed N–H stretching band at 3175–3502 cm–1), C≡N stretching band at 2185–2198 cm –1, and carbonyl stretching bands in the region 1626–1758 cm–1. The 1H NMR spectra of 3a–3g contained signals for aromatic protons, protons in the substituents R1, R2, R3, ester ethoxy group (δ 0.78–0.90 t and 3.73–3.96 ppm, m) and amino group (δ 7.11–7.28 ppm, br.s). In the 13C NMR spectra of 3a–3g we observed signals of lactam (δ C 178.1–179.0 ppm), ester (δ C 161.3– 165.0 ppm), and ketone (δC 197.1 ppm, 3b) carbonyl carbon atoms, as well as a signal of the spiro carbon atom at δC 49.8– 50.7 ppm. The structure of compound 3a was confirmed by X-ray analysis. According to the X
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