Diethyl malonate fluorination: general reaction
Diethyl malonate (3.20 g, 20 mmol) and copper nitrate hydrate (Cu(NO3)2·2.5H2O; 0.46 g, 2 mmol) were dissolved in acetonitrile (17 mL) and placed into the fluorination reactor and the mixture was cooled to 0–5 °C. After purging the system with N2 for 5 minutes, fluorine gas (10% v/v in N2, 45 mL min−1, 22 mmol) was passed into the stirred mixture for 2 h. The reactor was purged with nitrogen for 10 minutes, the solvent was removed in vacuo and the residue partitioned between water (10 mL) and ethyl acetate (10 mL). The aqueous phase was extracted with ethyl acetate (10 mL) and the combined organic layers were washed with saturated brine (10 mL). After drying over sodium sulfate, the solvent was evaporated to leave diethyl 2-fluoromalonate (3.37 g, 94% yield, 93.5% purity) as a colourless liquid.IR (neat, cm−1): 2986, 1747, 1243, 1187, 1097, 1020;
δH (CDCl3, 400 MHz) 1.31 (6H, t, 3JHH 7.2, CH3), 4.31 (4H, q, 3JHH 7.2, CH2), 5.26 (1H, d, 2JHF 48.3, CHF); δF (CDCl3, 376 MHz): – 195.58 (d, 2JHF 48.3, CH–F);
δC (CDCl3, 100 MHz) 14.04 (CH3), 62.80 (CH2), 85.39 (d, 1JCF 198.2, C–F), 164.20 (d, 2JCF 24.1, C
![[double bond, length as m-dash]](https://lh3.googleusercontent.com/blogger_img_proxy/AEn0k_sQ5a2o6HvMkmVjbGmIAEPnsu3GyTHscVp2l4dOce8pA8NwXahJWCxN00ZRuAlCkOgQHS5Sm4hMJR-d4AyrsbKUWR5ehptTFay3VNXPvmkG3sK5-g=s0-d)
O); m/z (EI+) 179 (5%, [M + H]+), 133 (44%, [M − OEt]+), 105 (49%, [M − COOEt]+), 78 (100%, [CH2FCOOH]+).
Spectroscopic data were identical with those previously reported SEE and side products were identified from their reported 19F NMR shifts.
SEE.....
- (a) R. D. Chambers, J. Hutchinson and J. Thomson, J. Fluorine Chem., 1996, 78, 165–166 CrossRef CAS; (b) R. D. Chambers, M. A. Fox, D. Holling, T. Nakano, T. Okazoe and G. Sandford, Chem. Eng. Technol., 2005, 28, 344–352 CrossRef CAS; (c) R. D. Chambers and J. Hutchinson, J. Fluorine Chem., 1998, 92, 45–52
Diethyl fluoromalonate large scale fluorination
Diethyl malonate (40.0 g, 0.25 mol) and copper nitrate hydrate (Cu(NO3)2·2.5H2O; 5.81 g, 25 mmol) were dissolved in acetonitrile (200 mL) and placed in 500 mL fluorination vessel, cooled to 0–5 °C and stirred at 650 rpm using an overhead stirrer. After purging the system with N2 for 5 minutes, fluorine gas (20% v/v in N2, 80 mL min−1, 265 mmol) was introduced into the mixture for 6 hours and 30 minutes. The reactor was purged with nitrogen for 10 minutes, the solvent removed in vacuo and the residue partitioned between water (50 mL) and ethyl acetate (50 mL). The aqueous phase was extracted once more with ethyl acetate (50 mL) and the combined organic layers were washed with saturated NaHCO3 (25 mL) and brine (20 mL). After drying over sodium sulfate, the solvent was evaporated to leave diethyl 2-fluoromalonate (44.4 g, 99% yield, 95% purity) as a light yellow, transparent liquid. This crude product was distilled to afford high purity fluoromalonate (34.7 g, 77% yield, 99%+ purity) as a colourless liquid,bp. 102–103 °C (18 mbar), (lit.: 110–112 °C, 29 mbar), spectroscopic data as above.
N. Ishikawa, A. Takaoka and M. K. Ibrahim, J. Fluorine Chem., 1984, 25, 203–212
http://pubs.rsc.org/en/content/articlehtml/2015/gc/c5gc00402k
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