Synlett 2004(5): 0866-0870  
DOI: 10.1055/s-2004-820022
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Tong-Shou Jin*, Jian-She Zhang, Jin-Chong Xiao, Ai-Qing Wang, Tong-Shuang Li
Department of Chemistry, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, P. R. China
Fax: +86(312)5016914; e-Mail: orgsyn@mail.hbu.edu.cn;
Further Information

Publication History

Received 2 January 2004
Publication Date:
04 March 2004 (online)

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.

    References

  • 1 Anastas P. Williamson T. Green Chemistry, Frontiers in Benign Chemical Synthesis and Procedures   Oxford Science Publications; Oxford: 1998. 
  • 2 Wender PA. Handy SL. Wright DL. Chem. Ind. (London)  1997,  765 
  • 3a Rideout DC. Breslow R. J. Am. Chem. Soc.  1980,  102:  7817 
  • 3b Breslow R. Maitra U. Rideout D. Tetrahedron Lett.  1983,  24:  1901 
  • 3c Eggelte TA. de Koning H. Huisman HO. Tetrahedron  1973,  29:  2491 
  • 4a Gajewski JJ. Jurayj J. Kimbrough DR. Grande ME. Ganem B. Carpenter BK. J. Am. Chem. Soc.  1987,  109:  1170 
  • 4b Brandes E. Grieco PA. Gajewski JJ. J. Org. Chem.  1989,  54:  515 
  • 4c Grieco PA. Brandes EB. McCann S. Clark JD. J. Org. Chem.  1989,  54:  5849 
  • 4d Severance DL. Jorgensen WL. J. Am. Chem. Soc.  1992,  114:  10966 
  • 4e Gao J. J. Am. Chem. Soc.  1994,  116:  1563 
  • 4f Gajewski JJ. Brichford NL. J. Am. Chem. Soc.  1994,  116:  3165 
  • 5a Lubineau A. J. Org. Chem.  1986,  51:  2143 
  • 5b Lubineau A. Meyer E. Tetrahedron  1988,  44:  6065 
  • 6a Kool ET. Breslow R. J. Am. Chem. Soc.  1988,  110:  1596 
  • 6b Breslow R. Acc. Chem. Res.  1991,  24:  159 
  • 7a Li CJ. Chem. Rev.  1993,  93:  2023 
  • 7b Grieco PA. Organic Synthesis in Water   Blacky; London: 1998. 
  • 7c Li CJ. Chan TH. Organic Reactions in Aqueous Media   Wiley; New York: 1997. 
  • 7d Jin TS. Xiao JC. Wang SJ. Li TS. Song XR. Synlett  2003,  2001 
  • 8 Manabe K. Mori Y. Kobayashi S. Tetrahedron  2001,  57:  2537 
  • 9 Horning EC. Horing MG. J. Org. Chem.  1946,  11:  95 
  • 10 Shi DQ. Lu ZS. Gao Y. Feng YJ. Zhou LH. Dai GY. Chinese J. Org. Chem.  1998,  18:  82 
11

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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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): νmax = 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.