Synthesis and Structure (Z)-N-Aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides

Russian Journal of General Chemistry, Jun 2018

Reactions of 5-phenyl-2,3-dihydrofuran-2,3-dione with aromatic amines in anhydrous dioxane or methyl benzoylpyruvate with aromatic amines in the presence of sodium acetate in glacial acetic acid afforded (Z)-N-aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides.

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Synthesis and Structure (Z)-N-Aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides

RUSSIAN JOURNAL OF GENERAL CHEMISTRY 1070-3632 Synthesis and Structure (Z)-N-Aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides V. L. Gein 1 T. M. Zamaraeva 1 E. V. Gorgopina 1 N. M. Igidov 1 O. V. Bobrovskaya 1 M. V. Dmitriev 0 0 Perm State National Research University , Perm , Russia 1 Perm State Pharmaceutical Academy , ul. Polevaya 2, Perm, 614990 Russia -Reactions of 5-phenyl-2,3-dihydrofuran-2,3-dione with aromatic amines in anhydrous dioxane or methyl benzoylpyruvate with aromatic amines in the presence of sodium acetate in glacial acetic acid afforded (Z)-N-aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides. Aroylpyruvic acid amides are of obvious chemical interest. These polyfunctional reagents show high reactivity due to the presence of several reaction sites in their structure [1, 2]. They can act as C-nucleophiles and carbonyl electrophiles in the reactions, being promising starting materials for the synthesis of a variety of acyclic and heterocyclic compounds [1-4]. R = С6H5 (1), 4-BrС6H4 (2), 4-IС6H4 (3), 3-ClС6H4 (4), 4-C2H5OOCС6H4 (5), 4-CH3С6H4 (6), 4-CH3OС6H4 (7), 4-NH2SO2С6H4CH2CH2 (8). methyl benzoylpyruvate; 5-phenyl-2; 3-dihydrofuran-2; 3-dione; arylamines; aroylpyruvic acid amides - The most studied method for the preparation of N-substituted amides of aroylpyruvic acids is the ring opening of 5-aryl-2,3-dihydrofuran-2,3-diones under the action of N-nucleophiles in an inert solvent medium with an equimolar ratio of the reagents [5, 6]. Because of a number of drawbacks in this method [7], it remains urgent to find optimal conditions for the synthesis of amides of aroylpyruvic acids, which due to widely varying pharmacophore groups in their structure can be used further in the preparation of previously unknown and inaccessible functional heterocyclic compounds. A new simple method for the preparation of Narylamides of aroylpyruvic acids reported in [8] includes the reaction of arylamines with methyl aroylpyruvates in acetic acid in the presence of anhydrous sodium acetate. Later, arylamides obtained have been modified with 4-aminobenzenesulfonylacetamide sodium (sodium sulfacetamide) [9], 4-aminobenzenesulfonylguanidine (sulgine) [10], streptocide, and norsulfazole fragments [11]. Ph Ph O O O O O OH + NH2R O + NH2R CH3COONa O OH A 1_8 N H R Ph O O B O N H R Scheme 1. Ph O Continuing research in this direction, we apply this method for the synthesis of new N-arylamides of aroylpyruvic acids and studied their spatial structure. For the comparative study, (Z)-N-aryl-2-hydroxy-4oxo-4-phenylbut-2-enamides were prepared by reacting 5-phenyl-2,3-dihydrofuran-2,3-dione with anilines in an anhydrous dioxane. To establish the possibility of using alkylamines in the synthesis of aroylpyruvic acid amides, we performed the reaction with 4-(2-aminoethyl) benzenesulfonamide by two aforementioned methods. However, we did not succeed in obtaining compound 8 according to method b. Compounds 1–8 are yellow crystalline substances soluble in DMF, DMSO, soluble at heating in acetic acid, ethanol, and insoluble in water (Scheme 1). In the 1H NMR spectra of compounds 1–8, there were singlets of COCH2CO (4.53–4.64 ppm), CH= (7.02–7.17 ppm), CONH groups (8.99–10.78 pm), as well as the signals of aromatic fragments. In the spectrum of 8, the protons of both CH2 and NH2 groups were recorded in the regions of 2.86–3.51 and 7.32 ppm, respectively. Crystal structure of compound 5 was studied by single-crystal X-ray diffraction method (see the figure). The crystals were obtained by slow crystallization from acetic acid. The molecule of 5 crystallizes in the centrosymmetric spatial group of the monoclinic crystal system. The molecule is practically planar. The electron density of the keto-enol fragment is strongly delocalized, which is expressed in equalizing the lengths of multiple and single C–C and C–O bonds (see Table). The position of the hydrogen atom of the enol hydroxy group was refined taking into account the disordering due to the existence of tautomeric equilibrium [the ratio of the populations of the H4 and H5 atoms is 0.59( 7 ) to 0.41( 7 ), respectively]. In addition to the intramolecular hydrogen bond in the keto-enol fragment the molecule also has an intramolecular hydrogen bond of non-classical type С6–H6···O3 [H6···O3 2.329, С6···O3 2.927( 4 ) Å]. The crystal packing is stabilized by van der Waals interactions and several shortened С–H···O contacts. According to the studies performed, the most effective and convenient method for the synthesis of (Z)-N-aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides containing arylamine fragment with an electronwithdrawing group is the reaction of benzoylpyruvic acid methyl ester with arylamines in glacial acetic acid General view of the molecule of compound 5 in the crystal represented by thermal ellipsoids with 50% probability. in the presence of anhydrous sodium acetate. When using an aromatic amine with an electron-donor substituent or an alkyla (...truncated)


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V. L. Gein, T. M. Zamaraeva, E. V. Gorgopina, N. M. Igidov, O. V. Bobrovskaya, M. V. Dmitriev. Synthesis and Structure (Z)-N-Aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides, Russian Journal of General Chemistry, 2018, pp. 832-835, Volume 88, Issue 4, DOI: 10.1134/S1070363218040321