Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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Synthesis of Substituted Benzodifuran Derivatives from Benzene Diols and α-Chloro-α-(methylthio)acetone

벤젠 다이올과 알파-클로로-알파-(메틸싸이오)아세톤으로부터 치환 벤조다이푸란 유도체의 합성

  • Published : 2006.08.20
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Abstract

Keywords

EXPERIMENTAL

General. Melting points were measured by an electrothermal digital melting point apparatus IA 9100 and uncorrected. IR spectra were obtained on a JASCO FT IR-300E spectrometer. NMR spectra were recorded on a JNM-ECP 400 spectrometer using tetramethylsilane as an internal standard. Mass spectra were obtained by electron impact (EI) method using a Hewlett Packard 5970 GC-MS system. TLC was run on a Merck precoated silica gel plates. Silica gel 60 (70-230 mesh, E. Merck) was used for all column chromatographic separations.

α-Chloro-α-(methylthio)acetone (1): N-Chlorosuccinimide (10.5 g, 0.08 mol) was added to a stirred solution of α-(methylthio)acetone (8.2 g, 0.08 mol) in CCl4 (40 mL) in small portions at 0 ℃ and the stirring was continued at room temperature for 3 h. The prepcipitated succinimide was filtered off and the solvent was removed in vacuo. The residual oil was distilled to give 1 (6.8 g, 63%), bp 55-56 ℃/7 mmHg (lit.7 76-77 ℃/15 mmHg); 1H NMR (400 MHz, CDCl3) δ 2.19 (s, 3H), 2.37 (s, 3H), 5.38 (s, 1H).

Typical procedure for the synthesis of substituted benzodifurans (2,3): To a stirred solution of 1 (1.53 g, 11.0 mmol) and hydroquinone (550 mg, 5.0 mmol) in CH2Cl2 (30 mL) and THF (5 mL) was added ZnCl2 (1.50 g, 11.0 mmol) at room temperature, and the stirring was continued at the same temperature for 40 min. The mixture was quenched with water and organic layer was separated. The organic layer was dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (CCl4) to afford 2 (348 mg) and 3 (458 mg) as white solids in 25% and 33%, respectively, The other compounds 4-8 were synthesized similarly and the spectroscopic data of the products 2-8 are as follows.

2,5-Dimethyl-3,4-dimethylthiobenzo[1,2-b:4,3-b']difuran (2): Rf=0.68 (CCl4); 25%; white solid, mp 170-171 ℃; IR (KBr) 2982, 2914, 1572, 1406, 1308, 1267, 1216, 1143, 1038 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.43 (s, 6H), 2.62 (s, 6H), 7.30 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 12.65, 22.05, 106.99, 108.97, 122.28, 150.80, 159.67; EI-MS m/z 278 (M+, 100%), 263, 247, 230, 217, 199, 188, 139, 115, 106, 89, 75.

2,6-Dimethyl-3,7-dimethylthiobenzo[1,2-b:4,5-b']difuran (3): Rf=0.60 (CCl4); 33%; white soild, mp 179-180 ℃; IR (KBr) 2917, 1588, 1424, 1351, 1176, 1137, 1052 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.31 (s, 6H), 2.57 (s, 6H), 7.55 (s, 2H); 13C NMR (100MHz, CDCl3) δ 12.61, 18.50, 100.32, 108.63, 127.56, 151.08, 158.78; EI-MS m/z 278 (M+, 100%), 263, 248, 216, 203, 187, 139, 131, 124, 115, 95, 77.

2,6-Dimethyl-3,5-dimethylthiobenzo[1,2-b:5,4-b']difuran (4): Rf=0.65 (CCl4); 52%; white soild, mp 94-95 ℃; IR (KBr) 2983, 2919, 1595, 1431, 1374, 1274, 1173, 1113, 1067 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.35 (s, 6H), 2.56 (s, H), 7.46 (s, 1H), 7.68 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 12.56, 18.58, 94.20, 107.65, 108.39, 126.52, 151.96, 158.34; EI-MS (m/z) 278 (M+, 100%), 263, 248, 216, 203, 187, 159, 131, 124, 115, 98, 69.

2,7-Dimethyl-3,6-dimethylthiobenzo[1,2-b:6,5-b']difuran (5): Rf=0.68 (CCl4); 17%; white soild, mp 96-97 ℃; IR (KBr) 2919, 2859, 1644, 1442, 1390, 1354, 1282, 1182, 1124 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.19 (s, 6H), 2.38 (s, 6H), 7.36 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 8.11, 11.93, 92.99, 106.02, 109.37, 126.57, 150.03; EI-MS m/z 278 (M+, 100%), 263, 247, 214, 199, 171, 155, 128, 115, 92, 77.

2,6,8-Trimethyl-3,5-dimethylthiobenzo[1,2-b:5,4-b']- difuran (6): Rf=0.67 (CCl4); 53%; white soild, mp 130-131 ℃; IR (KBr) 2920, 1588, 1429, 1372, 1276, 1198, 1140, 1095, 1043 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.34 (s, 6H), 2.57 (s, 6H), 2.61 (s, 3H), 7.52 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 8.36, 12.60, 18.58, 104.62, 104.78, 108.56, 126.06, 150.76, 158.09; EI-MS m/z 292 (M+, 100%), 277, 262, 245, 230, 217, 201, 171, 131, 115, 95, 69.

2,4,6-Trimethyl-3,5-dimethylthiobenzo[1,2-b:5,4-b']difuran (7): Rf=0.71 (CCl4); 27%; white soild, mp 121-122 ℃; IR (KBr) 2916, 1592, 1430, 1382, 1215, 1136, 1072 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.30 (s, 6H), 2.55 (s, 6H), 3.37 (s, 3H), 7.28 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 11.44, 12.37, 20.99, 91.62, 108.55, 123.28, 123.58, 151.86, 159.18; EI-MS m/z 292 (M+, 100%), 277, 262, 245, 229, 201, 187, 171, 146, 115, 89, 59.

2,4,7-Trimethyl-3,8-dimethylthiobenzo[1,2-b:5,6-b']- difuran (8): Rf=0.66 (CCl4); 24%; white soild, mp 102-103 ℃; IR (KBr) 2919, 1609, 1496, 1336, 1282, 1236, 1171, 1113, 1007 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.29 (s, 3H), 2.47 (s, 3H), 2.53 (s, 3H), 2.64 (s, 3H), 2.89 (s, 3H), 7.09 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 12.25, 12.41, 18.23, 19.29, 21.04, 106.47, 108.28, 109.35, 113.27, 122.59, 127.10, 145.70, 152.66, 155.89, 158.36; EI-MS m/z 292 (M+, 100%), 277, 261, 245, 231, 201, 187, 171, 146, 115, 87, 59.

Typical procedure for the synthesis of desulfurized benzodifuran (9):

Compound 2 (195 mg, 0.7 mmol) was heated under reflux in ethanol (40 mL) containing Raney nickel (W-2, ca. 2.5 g) for 3h. The Raney nickel was removed by filtration and the solvent was evaporated off. The residue was purified by column chromatography (CCl4) to afford 9 (108 mg) as white solid in 83%. The other compounds 10-14 were prepared similarly from substituted benzodifurans (3-4, 6-8) and the spectroscopic data 9-14 are as follows.

2,5-Dimethylbenzo[1,2-b:4,3-b']difuran (9): Rf= 0.66 (CCl4); 83%; white solid, mp 109-110 ℃; IR (KBr) 3114, 2913, 1585, 1419, 1269, 1221, 1155, 1043 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.49 (s, 6H), 6.50 (s, 2H), 7.25 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 14.22, 101.60, 105.74, 120.79, 151.16, 155.40; EI-MS m/z 186 (M+, 100%), 171, 157, 128, 115, 92, 77.

2,6-Dimethylbenzo[1,2-b:4,5-b']difuran (10): Rf=0.61 (CCl4); 85%; white solid, mp 117-118℃; IR (KBr) 2957, 2912, 1612, 1428, 1374, 1283, 1171, 1112 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.45 (s, 6H), 6.38 (s, 2H), 7.40 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 14.27, 100.46, 102.74, 125.98, 151.74, 155.49; EI-MS m/z 186 (M+, 100%), 171, 157, 128, 115, 92, 77.

2,6-Dimethylbenzo[1,2-b:5,4-b']difuran (11): Rf=0.71 (CCl4); 82%; white solid, mp 83-84 ℃; IR (KBr) 2964, 2914, 1609, 1435, 1349, 1277, 1125, 1084 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.45 (s, 6H), 6.37 (s, 2H), 7.42 (s, 1H), 7.43 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.18, 93.41, 102.31, 109.04, 125.45, 152.47, 155.21; EI-MS m/z 186 (M+, 100%), 171, 157, 143, 128, 115, 92, 77.

2,6,8-Trimethylbenzo[1,2-b:5,4-b']difuran (12): Rf=0.69 (CCl4); 87%; white solid, mp 94-95 ℃ (lit.2a 91.5-92℃); IR (KBr) 2917, 1603, 1436, 1372, 1270, 1202, 1144, 1099 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.45 (s, 6H), 2.62 (s, CH3, 3H), 6.35 (s, 2H), 7.25 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 8.62, 14.25, 102.61, 103.89, 105.99, 125.01, 151.32, 154.95; EI-MS m/z 200 (M+, 100%), 185, 171, 159, 141, 128, 115, 99, 77.

2,4,6-Trimethylbenzo[1,2-b:5,4-b']difuran (13): Rf=0.64 (CCl4); 86%; white solid, mp 88-90℃; IR (KBr) 2916, 2856, 1599, 1436, 1366, 1269, 1211, 1092, 1049 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.45 (s, 6H), 2.54 (s, 3H), 6.40 (s, 2H), 7.28 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.23, 15.42, 90.92, 100.84, 118.97, 124.76, 152.28, 154.47; EI-MS m/z 200 (M+, 100%), 185, 171, 167, 128, 115, 100, 77.

2,4,7-Trimethylbenzo[1,2-b:5,6-b']difuran (14): Rf=0.65 (CCl4); 85%; white solid, mp 64-65℃; IR (KBr) 2918, 2736, 1587, 1439, 1395, 1271, 1200, 1067 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.48 (s, 3H), 2.49 (s, 3H), 2.52 (s, 3H), 6.42 (s, 1H), 6.54 (s, 1H), 7.09 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.06, 14.09, 18.88, 98.64, 101.75, 106.32, 111.89, 123.39, 124.60, 144.17, 153.25, 153.56, 154.02; EI-MS m/z 200 (M+, 100%), 185, 171, 157, 128, 115, 100, 84, 63.

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