A Novel Efficient Four- and Five-Component, One-Pot Synthesis of 4-Semicarbazonoalkyl-2-Naphthols

Abstract

One-pot, multicomponent coupling reaction of two or three molecules of aldehydes with 2-naphthols and semicarbazide hydrochloride is described for the preparation of 4-semicarbazonoalkyl-2-naphthols using PTSA/NaOAc as an efficient catalyst system in THF at room temperature or solvent-free conditions at elevated temperature.

Key words

4-semicarbazonoalkyl-2-naphthols - multicomponent - one-pot reaction - naphthol - solvent-free

References and Notes

• 1 Tietze LF. Chem. Rev.  1996,  96:  115 
• 2a For a special issue on MCR, see: Tetrahedron  2005,  61:  11299 
• 2b Ramon DJ. Yus M. Angew. Chem. Int. Ed.  2005,  44:  1602 
• 2c Zhu J. Eur. J. Org. Chem.  2003,  1133 
• 3a Menendez JC. Synthesis  2006,  2624 
• 3b Devi I. Bhuyan PJ. Tetrahedron Lett.  2004,  45:  8625 
• 3c Mashraqui SH. Patil MB. Mistry HD. Ghadigaonkar S. Meetsma A. Chem. Lett.  2004,  33:  1058 
• 3d Chetia A. Saikia CJ. Lekhok KC. Boruah RC. Tetrahedron Lett.  2004,  45:  2649 
• 3e Wang LM. Xia J. Qin F. Qian C. Sun J. Synthesis  2003,  1241 
• 4a Biginelli P. Ber. Dtsch. Chem. Ges.  1891,  24:  1317 
• 4b Bose AK. Pednekar S. Ganguly SN. Chakraborty G. Manhas MS. Tetrahedron Lett.  2004,  45:  8351 
• 4c Prajapati D. Sandhu JS. Synlett  2004,  235 
• 4d Shimokawa J. Shirai K. Tanatani A. Hashimoto Y. Nagasawa K. Angew. Chem. Int. Ed.  2004,  43:  1559 
• 5a Yamada T. Omote Y. Yamanaka Y. Miyazawa T. Kuwata S. Synthesis  1998,  991 
• 5b Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 5c Cristau P. Vors JP. Zhu JP. Org. Lett.  2001,  3:  4079 
• 5d Ross GF. Herdtweck E. Ugi I. Tetrahedron  2002,  58:  6127 
• 5e Ugi I. Werner B. Dömling A. Molecules  2003,  8:  53 
• 6a Passerini M. Gazz. Chim. Ital.  1921,  51:  121 
• 6b Bossio R. Marcaccini S. Pepino R. Torroba T. J. Chem. Soc., Perkin Trans. 1  1996,  229 
• 6c Bossio R. Marcos CF. Marcaccini S. Pepino R. Tetrahedron Lett.  1997,  38:  2519 
• 7a Micova J. Steiner B. Koos M. Langer V. Gyepesova D. Synlett  2002,  1715 
• 7b Martins FJC. Viljoen AM. Kruger HG. Roscher J. Joubert AJ. Wessels PL. Tetrahedron  2001,  57:  1601 
• 8a Cimarelli C. Palmieri G. Volpini E. Tetrahedron: Asymmetry  2002,  13:  2417 
• 8b Nots W. Tanaka F. Watanabe S. Chowdari NS. Turner JM. Thayumanaran R. Barbas CF. J. Org. Chem.  2003,  68:  9624 
• 8c Akiyama T. Itoh J. Yokota K. Fuchibe K. Angew. Chem. Int. Ed.  2004,  43:  1566 
• 8d Zhao G. Jiang T. Gao H. Han B. Huang J. Sun D. Green Chem.  2004,  6:  75 
• 8e Akiyama T. Matsuda K. Fuchibe K. Synlett  2005,  322 
• 8f Rondot R. Zhu J. Org. Lett.  2005,  7:  1641 
• 9 Khosropour AR. Khodaei MM. Moghanian H. Synlett  2005,  955 
• 10 Khodaei MM. Khosropour AR. Moghanian H. Synlett  2006,  916 
• 11a Shaterian HR. Yarahmadi H. Ghashang M. Tetrahedron  2008,  64:  1263 
• 11b Shaterian HR. Yarahmadi H. Ghashang M. Bioorg. Med. Chem. Lett.  2008,  in press

12

General Experimental Procedure (Method A) A mixture of aldehyde (2 mmol or 3 mmol), 2-naphthol (1 mmol), semicarbazide hydrochloride (1 mmol), PTSA (0.1 mmol), and NaOAc (1 mmol) at r.t. in THF (2 mL) was stirred for time as showed in Table [3] . The progress of the reaction was monitored by TLC. After completion of the reactions, the organic solvent evaporated and a mixture of EtOH-H₂O (2:1, 2 mL) was added to it, the suspension was stirred for 5 min and the precipitate filtered. The crude products were purified by recrystallization from EtOH.

13

General Experimental Procedure (Method B) A mixture of aldehyde (2 mmol or 3 mmol), 2-naphthol (1 mmol), semicarbazide hydrochloride (1 mmol), PTSA (0.1 mmol), and NaOAc (1 mmol) was magnetically stirred at 80 °C in an oil bath for an appropriate time as indicated in Table [3] . The reaction was followed by TLC. When the reaction was completed, the mixture was washed with EtOH-H₂O (2:1, 2 mL). The crude products were purified by recrystallization from EtOH.

14

Selected Characterization DataTable 3, Entry 8: Mp 222 °C. IR (KBr): ν_max = 3375, 3236-2962, 1651, 1599, 1545, 1342, 1273, 1124, 879, 814 cm^-1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 10.75 (s, 1 H), 10.41 (s, 1 H), 8.45 (br, 1 H), 8.09 (s, 1 H), 7.92-7.79 (m, 3 H), 7.53 (s, 1 H), 7.36-6.76 (m, 11 H), 3.77 (s, 3 H), 3.65 (s, 3 H). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 160.0, 159.6, 155.6, 153.5, 145.4, 140.4, 136.3, 132.5, 130.4, 130.8, 129.7, 129.2, 128.7, 127.5, 123.2, 122.4, 120.1, 119.6, 119.3, 118.9, 115.7, 113.1, 111.5, 111.3, 55.5, 55.3, 49.0. Anal. Calcd for: C₂₇H₂₅N₃O₄: C, 71.19; H, 5.53; N, 9.22. Found: C, 70.95; H, 5.58; N, 9.08.
Table 3, Entry 15: Mp 228-229 °C. IR (KBr): ν_max = 3385, 3219-2928, 1659, 1546,1340, 1273, 879, 814 cm^-1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 10.62 (s, 1 H), 10.55 (s, 1 H), 8.40 (br, 1 H), 8.13 (s, 1 H), 8.03 (s, 1 H), 7.88-7.50 (m, 5 H), 7.32-6.95 (m, 8 H), 2.32 (s, 3 H), 2.21 (s, 3 H). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 155.6, 154.0, 140.6, 140.4, 139.5, 136.0, 132.2, 131.2, 131.7, 130.8, 130.2, 129.9, 129.2, 128.9, 126.8, 126.4, 125.0, 120.4, 120.0, 116.0, 48.9, 21.5, 21.0. Anal. Calcd for C₂₇H₂₄BrN₃O₂: C, 64.55; H, 4.81; N, 8.36. Found: C, 64.15; H, 4.79; N, 8.20.
Table 3, Entry 19: Mp 194-195 °C. IR (KBr): ν_max = 3396, 3227-2964, 1649, 1556, 1435, 1340, 1273, 814, 754 cm^-1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 10.35 (s, 1 H), 10.10 (s, 1 H), 8.04 (d, 1 H, J = 8.8 Hz), 7.85-7.68 (m, 3 H), 7.48-7.25 (m, 4 H), 5.71-5.62 (m, 2 H), 2.24-2.10 (m, 2 H), 1.98-1.83 (m, 2 H), 1.81 (s, 3 H), 0.96 (t, 3 H, J = 6.6 Hz), 0.82 (t, 3 H, J = 7.2 Hz). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 155.8, 153.6, 145.2, 139.1, 132.8, 132.6, 129.0, 128.7, 128.4, 126.7, 122.8, 122.5, 120.1, 119.2, 47.9, 28.5, 21.6, 14.1, 11.7, 11.5. Anal. Calcd for C₂₀H₂₅N₃O₂: C, 70.77; H, 7.42; N, 12.38. Found: C, 70.35; H, 7.46; N, 12.14.