Clean Synthesis of 1,8-Dioxo-octahydroxanthene Derivatives Catalyzed by p-Dodecylbenezenesulfonic Acid in Aqueous Media

Abstract

An efficient and convenient approach to the synthesis of 3,3,6,6-tetramethyl-9-aryl-1,8-dioxo-octahydroxanthene derivatives using p-dodecylbenezenesulfonic acid (DBSA) as the catalyst (10 mol%) is described. This method provides several advantages such as being environmentally friendly, processing high yields and simple work-up procedure. In addition, water was chosen as a green solvent.

octahydroxanthene - p-dodecylbenezenesulfonic acid - clean synthesis - aqueous media

References

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General Procedure for the Preparation of 1,8-Dioxo-octahydroxanthene: A mixture of an aromatic aldehyde (1.0 mmol), 5,5-dimethyl-1,3-cyclohexanedione (2.0 mmol) and DBSA (10 mol%) in H₂O (20 mL) was stirred at refluxing for 6 h. The progress of the reaction was monitored by thin layer chromatograph. After completion of the reactions, the mixture was cooled to r.t. and solid was filtered off and washed with H₂O (40 mL) and the crude products isolated. The crude products were purified by recrystallization by EtOH (95%). Data of the compounds are shown below:
Compound 3a, 3,3,6,6-Tetramethyl-9-benzene-1, 8-dioxo-octahydroxanthene. Mp 202-204 °C (from EtOH). IR (KBr): ν_max = 3030, 2980, 1685, 1670, 1470, 1360, 1200, 1170, 1140, 1005, 740, 700 cm^-1. ¹H NMR (CDCl₃): δ = 098 (s, 6 H, 2 × CH₃), 1.12 (s, 6 H, 2 × CH₃), 2.20 (dd, 4 H, J = 1.6 Hz, J = 2.4 Hz, 2 × CH₂, H-4, H-5), 2.45 (s, 4 H, 2 × CH₂, H-2, H-7), 4.66 (s, 1 H, H-9), 7.21 (m, 5 H, Ar-H). Anal. Calcd for C₂₃H₂₆O₃: C, 78.83; H, 7.47. Found: C, 78.95; H, 7.42.
Compound 3b, 3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-1,8-dioxo-octahydroxanthene. Mp 228-230 °C (from EtOH). IR (KBr): ν_max = 3025, 2980, 1680, 1660, 1620, 1490, 1480, 1360, 1200, 1170, 1140, 1090, 1010, 1000, 850, 840 cm^-1. ¹H NMR (CDCl₃): δ = 0.98 (s, 6 H, 2 × CH₃), 1.10 (s, 6 H, 2 × CH₃), 2.23 (dd, 4 H, J = 1.6 Hz, J = 3.6 Hz, 2 × CH₂, H-4, H-5), 2.50 (s, 4 H, 2 × CH₂, H-2, H-7), 4.64 (s, 1 H, H-9), 7.26-7.43 (m, 4 H, ArH). Anal. Calcd for C₂₃H₂₅ClO₃: C, 71.77; H, 6.54. Found: C, 71.89; H, 6.45.
Compound 3c, 3,3,6,6-Tetramethyl-9-(3-chlorophenyl)-1,8-dioxo-octahydroxanthene. Mp 183-184 °C (from EtOH). IR (KBr): ν_max = 3030, 2980, 1685, 1660, 1620, 1490, 1475, 1365, 1200, 1170, 1135, 1095, 1000, 850, 840 cm^-1. ¹H NMR (CDCl₃): δ = 1.02 (s, 6 H, 2 × CH₃), 1.12 (s, 6 H, 2 × CH₃), 2.30 (dd, 4 H, J = 1.6 Hz, J = 3.6 Hz, 2 × CH₂, H-4, H-5), 2.49 (s, 4 H, 4 × CH₂, H-2, H-7), 4.74 (s, 1 H, H-9), 7.11-7.25 (m, 4 H, ArH). Anal. Calcd for C₂₃H₂₅ClO₃: C, 71.77; H, 6.54. Found: C, 71.92; H, 6.41.
Compound 3d, 3,3,6,6-Tetramethyl-9-(2-chlorophenyl)-1,8-dioxo-octahydroxanthene. Mp 228-230 °C (from EtOH). IR (KBr): ν_max = 3030, 2980, 1680, 1665, 1620, 1495, 1470, 1360, 1200, 1170, 1140, 1100, 1000, 850, 840 cm^-1. ¹H NMR (CDCl₃): δ = 0.98 (s, 6 H, 2 × CH₃), 1.10 (s, 6 H, 2 × CH₃), 2.06 (dd, 4 H, J = 1.6 Hz, J = 3.0 Hz, 2 × CH₂, H-4, H-5), 2.49 (s, 4 H, 2 × CH₂, H-2, H-7), 4.64 (s, 1 H, H-9), 7.26-7.35 (m, 4 H, ArH). Anal. Calcd for C₂₃H₂₅ClO₃: C, 71.77; H, 6.54. Found: C, 71.88; H, 6.35.
Compound 3e, 3,3,6,6-Tetramethyl-9-(2,4-dichlorophenyl)-1,8-dioxo-octahydroxanthene. Mp 253-254 °C (from EtOH). IR (KBr): ν_max = 3035, 2980, 1685, 1660, 1633, 1490, 1480, 1410, 1360, 1210, 1195, 1155, 1100, 1000, 850, 770 cm^-1. ¹H NMR (CDCl₃): δ = 1.03 (s, 6 H, 2 × CH₃), 1.12 (s, 6 H, 2 × CH₃), 2.21 (dd, 4 H, J = 1.6 Hz, J = 3.2 Hz, 2 × CH₂, H-4, H-5), 2.46 (s, 4 H, 2 × CH₂, H-2, H-7), 4.96 (s, 1 H, H-9), 7.18 (s, 1 H, ArH), 7.39 (d, 2 H, J = 8.4 Hz, ArH). Anal. Calcd for C₂₃H₂₄Cl₂O₃: C, 65.87; H, 5.73. Found: C, 65.96; H, 5.59.
Compound 3f, 3,3,6,6-Tetramethyl-9-(2-nitrophenyl)-1,8-dioxo-octahydroxanthene. Mp 247-249 °C (from EtOH). IR (KBr): ν_max = 3035, 2980, 1685, 1673, 1620, 1533, 1360, 1211, 1173, 1152, 1010, 860, 800, 780, 745, 703 cm^-1. ¹H NMR (CDCl₃): δ = 0.99 (s, 6 H, 2 × CH₃), 1.12 (s, 6 H, 2 × CH₃), 2.16 (dd, 4 H, J = 1.6 Hz, J = 3.6 Hz, 2 × CH₂, H-4, H-5), 2.41 (s, 4 H, 2 × CH₂, H-2, H-7), 5.61 (s, 1 H, H-9), 7.36-7.45 (m, 4 H, ArH). Anal. Calcd for C₂₃H₂₅NO₅: C, 69.85; H, 6.37; N, 3.54. Found: C, 69.93; H, 6.54; N, 3.36.
Compound 3g, 3,3,6,6-Tetramethyl-9-(3-nitrophenyl)-1,8-dioxo-octahydroxanthene. Mp 168-170 °C (from EtOH). IR (KBr): ν_max = 3030, 2980, 1680, 1675, 1625, 1535, 1365, 1335, 1210, 11750, 1145, 1006, 830, 765, 730, 700 cm^-1. ¹H NMR (CDCl₃): δ = 1.02 (s, 6 H, 2 × CH₃), 1.13 (s, 6 H, 2 × CH₃), 2.22 (dd, 4 H, J = 1.6 Hz, J = 3.6 Hz, 2 × CH₂, H-4, H-5), 2.53 (s, 4 H, 2 × CH₂, H-2, H-7), 4.85 (s, 1 H, H-9), 7.43 (s, 1 H, ArH), 7.88-7.95 (m, 3 H, ArH). Anal. Calcd for C₂₃H₂₅NO₅: C, 69.85; H, 6.37; N, 3.54. Found: C, 69.90; H, 6.50; N, 3.42.
Compound 3h, 3,3,6,6-Tetramethyl-9-(4-nitrophenyl)-1,8-dioxo-octahydroxanthene. Mp 226-228 °C (from EtOH). IR (KBr): ν_max = 3030, 2980, 1665, 1650, 1623, 1530, 1360, 1340, 1200, 1070, 1042, 1005, 875, 833 cm^-1. ¹H NMR (CDCl₃): δ = 1.00 (s, 6 H, 2 × CH₃), 1.12 (s, 6 H, 2 × CH₃), 2.16 (dd, 4 H, J = 1.6 Hz, J = 3.6 Hz, 2 × CH₂, H-4, H-5), 2.41 (s, 4 H, 2 × CH₂, H-2, H-7), 4.46 (s, 1 H, H-9), 7.50-7.63 (m, 2 H, ArH), 8.06-8.16 (m, 2 H, ArH). Anal. Calcd for C₂₃H₂₅NO₅: C, 69.85; H, 6.37; N, 3.54. Found: C, 69.89; H, 6.46; N, 3.40.
Compound 3i, 3,3,6,6-Tetramethyl-9-(4-hydroxy-phenyl)-1,8-dioxo-octahydroxanthene. Mp 246-248 °C (from EtOH). IR (KBr): ν_max = 3360, 3025, 2980, 1795, 1725, 1700, 1633, 1613, 1525, 1390, 1375, 1260, 1233, 1200, 1196, 850, 843 cm^-1. ¹H NMR (CDCl₃): δ = 0.99 (s, 6 H, 2 × CH₃), 1.10 (s, 6 H, 2 × CH₃), 2.13 (dd, 4 H, J = 1.6 Hz, J = 4.0 Hz, 2 × CH₂, H-4, H-5), 2.47 (s, 4 H, 2 × CH₂, H-2, H-7), 4.62 (s, 1 H, H-9), 6.77 (d, 2 H, J = 8.0 Hz, ArH), 6.98 (d, 2 H, J = 8.0, ArH). Anal. Calcd for C₂₃H₂₆O₄: C, 75.38; H, 7.15. Found: C, 75.26; H, 7.09.
Compound 3j, 3,3,6,6-Tetramethyl-9-(4-methoxy-phenyl)-1,8-dioxo-octahydroxanthene. Mp 242-244 °C (from EtOH). IR (KBr): ν_max = 3025, 2980, 1685, 1660, 1620, 1513, 1450, 1375, 1360, 1260, 1235, 1170, 1142, 1032, 1003, 840 cm^-1. ¹H NMR (CDCl₃): δ = 1.01 (s, 6 H, 2 × CH₃), 1.09 (s, 6 H, 2 × CH₃), 2.20 (dd, 4 H, J = 1.6 Hz, J = 2.0 Hz, 2 × CH₂, H-4, H-5), 2.46 (s, 4 H, 2 × CH₂, H-2, H-7), 3.73 (s, 3 H, CH₃O), 4.70 (s, 1 H, H-9), 6.67-7.28 (m, 4 H, ArH). Anal. Calcd for C₂₄H₂₈O₄: C, 75.76; H, 7.41. Found: C, 75.85; H, 7.31.
Compound 3k, 3,3,6,6-Tetramethyl-9-(4-dimethyl-aminophenyl)-1,8-dioxo-octahydroxanthene. Mp 226-228 °C (from EtOH). IR (KBr): ν_max = 3035, 2980, 2195, 1687, 1665, 1580, 1500, 1454, 1400, 1234, 1195, 1040, 811, 743 cm^-1. ¹H NMR (CDCl₃): δ = 1.02 (s, 6 H, 2 × CH₃), 1.11 (s, 6 H, 2 × CH₃), 2.21 (dd, 4 H, J = 1.6 Hz, J = 2.4 Hz, 2 × CH₂, H-4, H-5), 2.46 (s, 4 H, 2 × CH₂, H-2, H-7), 2.88 [s, 6 H, -N(CH₃)₂], 4.67 (s, 1 H, H-9), 6.62 (s, 2 H, ArH), 7.15 (s, 2 H, ArH). Anal. Calcd for C₂₅H₃₁NO₃: C, 76.34; H, 7.89; N, 3.56. Found: C, 76.48; H, 7.86; N, 3.43.
Compound 3l, 3,3,6,6-Tetramethyl-9-(4-methylphenyl)-1,8-dioxo-octahydroxanthene. Mp 217-218 °C (from EtOH). IR (KBr): ν_max = 3035, 2980, 1685, 1665, 1633, 1515, 1470, 1365, 1200, 1165, 1140, 790, 775cm^-1. ¹H NMR (CDCl₃): δ = 1.03 (s, 6 H, 2 × CH₃), 1.12 (s, 6 H, 2 × CH₃), 2.07 (dd, 4 H, J = 1.6 Hz, J = 2.4 Hz, 2 × CH₂, H-4, H-5), 2.40 (s, 4 H, 2 × CH₂, H-2, H-7), 2.43 (s, 3 H, CH₃Ar), 4.69 (s, 1 H, H-9), 6.80-7.28 (m, 4 H, ArH). Anal. Calcd for C₂₄H₂₈O₃: C, 79.08; H, 7.74. Found: C, 79.25; H, 7.59.
Compound 3m, 3,3,6,6-Tetramethyl-9-(4-hydroxy-3-methoxyphenyl)-1,8-dioxo-octahydrox-anthene. Mp 226-228 °C (from EtOH). IR (KBr): ν_max = 3443, 3030, 2985, 2195, 1687, 1660, 1580, 1500, 1454, 1400, 1234, 1195, 1040, 811, 743 cm^-1. ¹H NMR (CDCl₃): δ = 1.02 (s, 6 H, 2 × CH₃), 1.12 (s, 6 H, 2 × CH₃), 2.24 (d, 4 H, J = 3.6 Hz, 2 × CH₂, H-4, H-5), 2.47 (s, 4 H, 2 × CH₂, H-2, H-7), 3.91 (s, 3 H, OCH₃), 4.68 (s, 1 H, H-9), 5.49 (s, 1 H, OH), 6.60 (s, 1 H, ArH), 6.74 (s, 1 H, ArH), 7.03 (s, 1 H, ArH). Anal. Calcd for C₂₄H₂₈O₅: C, 77.84; H, 7.57. Found: C, 77.98; H, 7.43.
Compound 3n, 3,3,6,6-Tetramethyl-9-(3,4-dioxy-methylenephenyl)-1,8-dioxo-octahydrox-anthene. Mp 224-226 °C (from EtOH). IR (KBr): ν_max = 3030, 2980, 1725, 1680, 1560, 1510, 1495, 1445, 1383, 1360, 1320, 1275, 1230, 1045, 945, 920, 890, 812, 790 cm^-1. ¹H NMR (CDCl₃): δ = 1.00 (s, 6 H, 2 × CH₃), 1.13 (s, 6 H, 2 × CH₃), 2.16 (dd, 4 H, J = 1.6 Hz, J = 2.8 Hz, 2 × CH₂, H-4, H-5), 2.41 (s, 4 H, 2 × CH₂, H-2, 7), 4.58 (s, 1 H, H-9), 5.90 (s, 2 H, OCH₂O), 6.75-6.86 (m, 3 H, ArH). Anal. Calcd for C₂₄H₂₆O₅: C, 73.07; H, 6.64. Found: C, 73.16; H, 6.68.
Compound 3o, 3,3,6,6-Tetramethyl-9-(2-phenylethylene)-1,8-dioxo-octahydroxanthene. Mp 175-177 °C (from EtOH). IR (KBr): ν_max = 3035, 2980, 1710, 1670, 1600, 1580, 1500, 1454, 1400, 1375, 1310, 1264, 1210, 1040, 970, 740, 700 cm^-1. ¹H NMR (CDCl₃): δ = 1.14 (s, 12 H, 4 × CH₃), 2.32 (s, 4 H, 4 × CH₂), 2.46 (s, 4 H, 4 × CH₂), 4.42 (s, 1 H, H-9), 6.25-6.33 (m, 2 H, -CH=CH-), 7.18-7.28 (m, 5 H, ArH). Anal. Calcd for C₂₅H₂₈O₃: C, 79.79; H, 7.45. Found: C, 79.91; H, 7.30.
Compound 8b, 2,2′-(4-Chlorophenyl)methylene-bis(3-hydroxy-5,5-dimethyl-2-cyclohexene- 1-one). Mp 141-143 °C (from EtOH), 140-142 °C(reported).¹⁰ IR (KBr): ν_max = 3443, 3000˜2500, 2980, 2922, 1635, 1490, 1480, 1380, 1290, 1230, 1140, 1090, 1000, 745 cm^-1. ¹H NMR (CDCl₃): δ = 1.06 (s, 6 H, 2 × CH₃), 1.17 (s, 6 H, 2 × CH₃), 2.21 (d, 4 H, J = 2.8 Hz, 2 × CH₂), 2.53 (s, 4 H, 4 × CH₂), 5.62 (s, 1 H, CH), 7.09-7.40 (m, 4 H, ArH), 9.63 (br, s, 1 H, OH, enol), 11.88 (br, s, 1 H, OH, enol). Anal. Calcd for C₂₃H₂₇ClO₄: C, 68.59; H, 6.75. Found: C, 68.66; H, 6.53.