Synlett 2014; 25(09): 1331-1334
DOI: 10.1055/s-0033-1341085
letter
© Georg Thieme Verlag Stuttgart · New York

Phospha-Michael Addition to In Situ Prepared 5-Arylmethylidene Meldrum’s Acids

Mehdi Adib*
a   School of Chemistry, University College of Science, University of Tehran, P. O. Box 14155-6455 Tehran, Iran   Fax: +98(21)66495291   Email: madib@khayam.ut.ac.ir
,
Ehsan Sheikhi
a   School of Chemistry, University College of Science, University of Tehran, P. O. Box 14155-6455 Tehran, Iran   Fax: +98(21)66495291   Email: madib@khayam.ut.ac.ir
,
Narjes Rezaei
a   School of Chemistry, University College of Science, University of Tehran, P. O. Box 14155-6455 Tehran, Iran   Fax: +98(21)66495291   Email: madib@khayam.ut.ac.ir
,
Hamid Reza Bijanzadeh
b   Department of Chemistry, Tarbiat Modares University, P. O. Box 14115-175, Tehran, Iran
,
Peiman Mirzaei
c   Department of Chemistry, Shahid Beheshti University, Tehran, Iran
› Author Affiliations
Further Information

Publication History

Received: 28 February 2014

Accepted after revision: 12 March 2014

Publication Date:
08 May 2014 (online)


Abstract

Knoevenagel condensation reaction of an aldehyde and Meldrum’s acid produces a 5-arylmethylidene Meldrum’s acid, which undergoes Michael addition of a trialkyl phosphite under solvent-free conditions to afford the title compounds in good yields.

 
  • References and Notes

    • 6a Alonso E, Solis A, del Pozo C. Synlett 2000; 698
    • 6b Camp NP, Hawkins PC. D, Hitchcock PB, Gani D. Bioorg. Med. Chem. Lett. 1992; 2: 1047
  • 7 Kido Y, Hamakado T, Anno M, Miyagawa E, Motoki Y. J. Antibiot. 1984; 37: 965
  • 8 Patel DV, Rielly-Gauvin K, Ryono DE. Tetrahedron Lett. 1990; 31: 5591
    • 9a Snoeck R, Holy A, Dewolf-Peeters C, Van Den Oord J, De Clercq E, Andrei G. Antimicrob. Agents Chemother. 2002; 46: 3356
    • 9b Hammerschmidt F. Angew. Chem., Int. Ed. Engl. 1994; 33: 341
    • 9c Jennings LJ, Macchia M, Parkin A. J. Chem. Soc., Perkin Trans. 1 1992; 2197
    • 9d Sikorski JA, Miller MJ, Braccoli DS, Cleary DJ, Corey SD, Font KJ, Gruys KJ, Han CY, Lin K.-C, Pansegrau PD, Ream JE, Shnur D, Shah A, Walker MC. Phosphorus, Sulfur 1993; 76: 115
  • 10 Peters ML, Leonard M, Licata AA. Cleve. Clin. J. Med. 2001; 68: 945
  • 11 Kaboudin B. Tetrahedron Lett. 2003; 44: 1051
  • 12 Firouzabadi H, Iranpoor N, Sobhani S, Amoozgar Z. Synthesis 2004; 1771
  • 13 Eymery F, Lorga B, Savignac P. Tetrahedron 1999; 55: 2671
  • 14 Nesterov VV, Kolodiazhnyi OI. Tetrahedron 2007; 63: 6720
  • 17 General Procedure for the Preparation of Compounds 4 and 5, Exemplified on 4a and 5a: A mixture of benzaldehyde (2 mmol), Meldrum’s acid (1 mmol), and trimethyl phosphite (2 mmol) was stirred at ambient temperature for 8 h. Progress of the reaction was monitored by TLC. After completion of the reaction, the products were purified by column chromatography using n-hexane–EtOAc (2:1) as eluent. The solvent was removed and the products were obtained. Dimethyl 2-[(Dimethoxyphosphoryl)phenylmethyl]-malonate (4a): yield: 0.149 g (45%); white powder; mp 80–81 °C. IR (KBr): 1735 (C=O), 1498, 1440, 1312, 1244, 1212, 1161, 1046, 1014 (PO), 916, 856, 829, 728 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 3.38 (s, 3 H, CO2CH3), 3.44 (d, 3 J PH = 10.7 Hz, 3 H, POCH3), 3.64 (d, 3 J PH = 10.9 Hz, 3 H, POCH3), 3.78 (s, 3 H, CO2CH3), 3.97 (dd, 3 J HH = 11.8 Hz, 2 J PH = 20.4 Hz, 1 H, PCHCH), 4.20 (dd, 3 J HH = 11.8 Hz, 3 J PH = 10.2 Hz, 1 H, PCHCH), 7.21–7.34 (m, 5 H, 5 × CH). 13C NMR (125.8 MHz, CDCl3): δ = 43.7 (d, 1 J PC = 139.2 Hz, PCH), 52.6 (CO2 Me), 52.9 (d, 2 J PC = 7.0 Hz, POMe), 53.0 (CO2 Me), 53.1 (PCHCH), 53.8 (d, 2 J PC = 6.5 Hz, POMe), 127.9, 128.6 (2 × CH), 129.6 (d, 3 J PC = 5.9 Hz, CH), 133.2 (d, 2 J PC = 7.0 Hz, C), 166.9 (d, 3 J PC = 21.2 Hz, C=O), 167.6 (C=O). 31P NMR (202.5 MHz, CDCl3): δ = 26.67 (P=O). MS (EI): m/z (%) = 330 (40) [M+], 299 (13), 271 (91), 266 (34), 239 (100), 211 (16), 189 (36), 177 (6), 161 (16), 149 (22), 131 (55), 121 (70), 109 (25), 103 (36), 93 (16), 77 (20), 59 (11). Anal. Calcd for C14H19O7P (330.27): C, 50.91; H, 5.80. Found: C, 50.7; H, 5.9. Diethyl 2-[(Diethoxyphosphoryl)(4-fluorophenyl)-methyl]malonate (4i): yield: 0.174 g (43%); colorless liquid. IR (KBr): 1740, 1735 (C=O), 1604, 1510, 1447, 1369, 1300, 1226, 1161, 1099, 1019 (PO), 962, 849, 794 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 0.93 (t, J = 7.1 Hz, 3 H, CH2CH 3), 1.12 (t, J = 7.0 Hz, 3 H, CH2CH 3), 1.22, 1.30 (2 × t, J = 7.1 Hz, 6 H, 2 × CH2CH 3), 3.75–4.05 (m, 7 H, 3 × CH 2CH3, PCHCH), 4.13 (dd, 3 J HH = 11.3 Hz, 3 J PH = 11.1 Hz, 1 H, PCHCH), 4.16 (q, J = 7.1 Hz, 2 H, CO2CH 2CH3), 6.98 (dd, 3 J HH = 8.0 Hz, 3 J FH = 8.5 Hz, 2 H, 2 × CH), 7.30–7.36 (m, 2 H, 2 × CH). 13C NMR (128.5 MHz, CDCl3): δ = 13.6, 14.0 (2 × CO2CH2 CH3), 16.2 (d, 3 J PC = 5.8 Hz, POCH2 CH3), 16.3 (d, 3 J PC = 6.2 Hz, POCH2 CH3), 43.1 (d, 1 J PC = 140.0 Hz, PCH), 53.5 (PCHCH), 61.7, 62.0 (2 × CO2 CH2CH3), 62.4 (d, 2 J PC = 6.9 Hz, POCH2), 63.1 (d, 2 J PC = 6.7 Hz, POCH2), 115.3 (d, 2 J FC = 21.3 Hz, CH), 129.5 (dd, 2 J PC = 7.1 Hz, 4 J FC = 2.7 Hz, C), 131.5 (dd, 3 J FC = 7.7 Hz, 3 J PC = 6.3 Hz, CH), 162.3 (d, 1 J FC = 250.3 Hz, CF), 166.5 (d, 3 J PC = 20.0 Hz, C=O), 167.1 (C=O). 31P NMR (202.5 MHz, CDCl3): δ = 24.25 (P=O). MS (EI): m/z (%) = 404 (38) [M+], 359 (20), 339 (11), 331 (100), 312 (28), 293 (16), 285 (91), 265 (28), 257 (43), 247 (16), 229 (67), 219 (43), 201 (13), 191 (15), 179 (34), 149 (94), 121 (32), 109 (31), 101 (21), 91 (9), 83 (38), 65 (8), 55 (13). Anal. Calcd for C18H26FO7P (404.37): C, 53.47; H, 6.48. Found: C, 53.5; H, 6.3.
  • 18 Texier-Boullet F, Foucaud A. Synthesis 1982; 165
  • 19 Seven O, Polat-Cakir S, Hossain MS, Emrullahoglu M, Demir AS. Tetrahedron 2011; 67: 3464
  • 20 Yang F, Zhao D, Lan J, Xi P, Yang L, Xiang S, You J. Angew. Chem. Int. Ed. 2008; 47: 5646
  • 21 Wu Q, Zhou J, Yao Z, Xu F, Shen Q. J. Org. Chem. 2010; 75: 7498