Studies on the Reactions of 4-Ethoxycarbonyl-5-phenyl-2,3-dihydro-2,3- furandione with Some NH Nucleophiles (pdf)

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Studies on the Reactions of 4-Ethoxycarbonyl-5-phenyl-2,3-dihydro-2,3- furandione with Some NH Nucleophiles

Turk J Chem 28 (2004) , 659 – 665. c TÜBİTAK Studies on the Reactions of 4-Ethoxycarbonyl-5-phenyl-2,3-dihydro-2,3-furandione with Some NH Nucleophiles Ahmet ŞENER1 , Hasan GENÇ2 , İsrafil TOZLU2 , M. Kasım ŞENER3 1 Yüzüncü Yıl University, Art and Science Faculty, Chemistry Department, 65080, Van-TURKEY e-mail: 2 Yüzüncü Yıl University, Faculty of Education, Department of Science 65080, Van-TURKEY 3 İstanbul Technical University, Art and Science Faculty, Chemistry Department, İstanbul-TURKEY Received 07.05.2004 4-Ethoxycarbonyl-5-phenyl-2,3-dihydro-2,3-furandione 1 was reacted with o-phenylenediamine, substituted ureas and methylcarbamate or acetamide to give quinoxaline 2, pyrimidine 3 and benzoylmalonic acid 4 derivatives, respectively. Benzoylmalonic acid derivative 4a was converted into a new oxozinedione derivative, 5, by refluxing its solution in xylene containing a catalytic amount of p-toluene sulfonic acid. In addition, triphenylpyrazole carboxylic acid derivative 6 was obtained from the reaction of 4a with diphenylhydrazine. Key Words: Cyclic oxalyl compounds, quinoxaline, pyrimidine, benzoylmalonic acid, oxazine, pyrazole carboxylic acid. Introduction 4,5-Disubstituted-2,3-furandiones are important starting materials for the synthesis of many different heterocyclic compounds since they are capable of undergoing thermolysis and nucleophilic addition reactions depending on the reaction conditions and structures of the nucleophiles [1,5]. Thermolysis of the furandiones leads to the in situ generation of acylketenes as intermediates, which are trapped with nucleophiles or by [2+4] cycloaddition reactions with heterodienophiles having double or triple polar bonds [6]. A simple synthesis of dioxine and 4-pyrone derivatives based on the [2+4] cycloaddition reactions of acylketene intermediate generated in situ from furandione 1 with some carbonyl compounds has been reported previously [7]. Here, in order to shed light partially upon the versatility of furandione 1, we investigated the chemical behavior of 1 towards various nucleophilic reagents. 659 Studies on the Reactions of 4-Ethoxycarbonyl-5-phenyl..., A. ŞENER, et al., Experimental Solvents were dried by refluxing with appropriate drying agents and distilled before use. Melting points were determined on an Electrothermal Gallenkamp apparatus and are uncorrected. Microanalyses were performed on a Carlo Erba Elemental Analyzer Model 1108. The IR spectra were obtained as potassium bromide pellets using a Mattson 1000 FTIR spectrometer. The 1 H and 13 C-NMR spectra were recorded on a Varian XL-200 (200 MHz) and a Varian XL-200 (50 MHz) spectrometer, respectively, using TMS as an internal standard. All experiments were followed using DC Alufolien Kieselgel 60 F 254 Merck and a Camag TLC lamp (254/366 nm). 3-Oxo-2-(3,4-dihydroquinoxalin-2-yl)-3-phenylpropionic acid ethyl ester (2) To a cold solution of compound 1 (0.246 g, 1 mmol) in dry benzene (15 mL) was added a cold solution of 1,2–phenylenediamine (0.140 g, 1 mmol) in dry benzene (15 mL) under stirring and the stirring was continued at room temperature for 30 min. The yellow product that precipitated from the reaction medium was isolated by filtration and washed with benzene, yield 0.262 g (78% ), mp 183o C; IR: 3400-3350 cm−1 (O-H and N-H); 3060 cm−1 (Ar-H); 2905-2861 cm−1 (R-H); 1687, 1635, 1620 cm−1 (C=O); 1 H-NMR (DMSO-d6 ): δ=11.8 (b, N-H), 10.6 (b, O-H); 8.1-7 (m, Ar-H), 6.3 (s, methine group), 5-3.2 (b, N-H), 4.19 (q, OCH2 ), 4.05 (q, OCH2 ), 1.15 (t, CH3 ), 1.06 ppm (t, CH3 ); 13 C-NMR (DMSO-d6 ): δ 194.1 (C=O, benzoyl); 169.4 (C=O, ester), 168.6 (C=O, ester), 156.9 (C=O), 155.5 (C=O), 145.2 (C-3), 137.8, 135.4, 133.9, 133.4, 133.3, 133.0, 132.5, 131.0, 130.6, 130.3, 130.0, 129.9, 129.6, 128.1, 127.9, 127.8, 126.8, 125.5, 125.3, 124.7, 117.5, 116.1, 110.2 (methine group), 63.5 (OCH2 ), 61.7 (OCH2 ), 15.7 ppm (CH3 ). Anal.Calcd. for C19 H16 N2 O4 : C, 67.85; H, 4.79; N. 8.33; found: C, 67.74; H, 4.80; N, 8.32 5-Ethoxycarbonyl-1-ethyl-4-phenyl-1H –pyrimidine-2-one (3a) Compound 1 (0.246 g, 1 mmol) and ethylurea (0.088 g, 1 mmol) were refluxed in xylene for 6 h. After the solvent was removed by evaporation, the oily residue was treated with ether and the formed crude product was crystallized from ethyl alcohol to give 0.117 g (48% ) of 3b; mp 156o C. 1 H-NMR (CDCl3 ): δ 8.4 (s, 1H, H-6), 7.43-7.25 (m, 5H, Ar-H), 3.99 (q, 2H, CH2 ), 3.93 (q, 2H, CH2 ), 1.32 (t, 3H, CH3 ), 0.93 ppm (t, 3H, CH3 ); 13 C-NMR (CDCl3 ): δ 175.6 (C=O), 165.9 (C=O), 156.4 (C-4), 154.4 (C-6), 139.7, 132.2, 130.3, 129.6, 110.6 (C-5), 63.2 (O-CH2 ), 48.9 (N-CH2 ), 16.2 (CH3 ), 15.7 ppm (CH3 ). Anal.Calcd. for C13 H12 N2 O3 : C, 63.93; H, 4.95; N. 11.47; found: C, 64.04; H, 4.93; N, 11.45 5-Ethoxycarbonyl-1-(3,4-dimethoxyphenylmethylenamino)-4-phenyl-1H–pyrimidine-2one (3b) An equimolar mixture of furandione 1 (0.246 g, 1 mmol) and semicarbazone of 3,4-dimethoxybenzaldehyde (0.239 g, 1.1 mmol) was heated to 115o C over approximately 40 min without any solvent. After cooling to room temperature, the residue was treated with ether for about 12 h with stirring and the formed crude product was crystallized from isopropanol to give 0.148 g (35% ) of a yellow solid, mp 150o C; IR: 3060 cm−1 (Ar-H), 2950-2844 cm−1 (R-H), 1749 cm−1 (C=O, ester), 1732 cm−1 (C=O), 1672 cm−1 (CH=N); 1 H-NMR (CDCl3): δ 9.5 (s, 1H, CH=N), 8.7 (s, 1H, H-6), 7.6-6.9 (m, 8H, Ar-H), 4.16 (q, 2H, OCH2 ), 3.98 (s, 3H, OCH3 ), 3.97 (s, 3H, OCH3 ), 1.5 ppm (t, 3H, CH3 ). Anal.Calcd. for C23 H25 N3 O5 : C, 65.24; H, 5.95; N, 9.92; found: C, 65.37; H, 5.93; N, 9.94 660 Studies on the Reactions of 4-Ethoxycarbonyl-5-phenyl..., A. ŞENER, et al., 2-Methoxycarbonylaminocarbonyl-3-oxo-3-phenylpropionic acid ethyl ester (4a) General procedure An equimolar mixture of 1 and methylcarbamate was refluxed in dry benzene for 4 h. After the solvent was removed by evaporation, the oily residue was treated with ether and the crude product formed was crystallized from ethyl alcohol. The yield was 0.191g (65% ) ; mp 167o C; IR: 3274 cm−1 (NH), 3029 cm−1 (Ar-H), 2985-2905 cm−1 (R-H), 1743, 1721, 1692, 1660 cm−1 (C=O); 1 H-NMR (CDCl3 ): δ 10.9 (b, 1H, NH), 7.9-7.4 (m, 5H, Ar-H), 6.0 (s, 1H, methine group), 4.2 (q, 2H, OCH2 ), 3.7 (s, 3H, OCH3 ), 0.9 ppm (t, 3H, CH3 ); 13 C-NMR (CDCl3 ): δ 191.4 (C=O, benzoyl), 172.6 (C=O), 166.9 (C=O), 153.8 (C=O), 138.7 (quarternary C, Ph), 134.5, 130.7, 129.8, 98.5 (methine carbon), 64.5 (OCH2 ), 55.3 (OCH3 ), 15.3 ppm (CH3 ). Anal.Calcd. for C14 H15 NO6 : C, 57.34; H, 5.16; N. 4.78; found: C, 57.23; H, 5.17; N, 4.76 3- Acetylamino-2-benzoyl-3-oxo-propionic acid ethyl ester (4b) Compound 4b was prepared according to the general procedure with a reflux time of 5 h (acetamide), resulting in a 55% yield (0.152 g) (ethanol); mp 209o C; IR: 3387 cm−1 (NH), 3064 cm−1 (Ar-H), 2989-2940 cm−1 (R-H), 1790, 1747, 1679, 1650 cm−1 (C=O); 1 H-NMR (CDCl3): δ 9.47 (b, 1H, NH), 7.4-7.2 (m, 5H, A (...truncated)