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

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.

Key words

trialkyl phosphites - aldehydes - Meldrum’s acid - 2-[(dialkoxyphosphoryl)arylmethyl]malonates - phospha-Michael addition

• References and Notes

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• 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.
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