ethylenediamine
ethanol
diisopropyl phosphonate
carbon tetrachloride

A solution of the amine (45 mmol, 2.5 eq) in ethanol (9 mL) was added of recently distilled diisopropyl phosphonate (18 mmol, 1 eq) in carbon tetrachloride (4 mL) and ethanol (5 mL) dropwise. The temperature should not exceed 55–65°C during the addition. The mixture was stirred for 15 min until diisopropyl phosphonate wasn´t detected by TLC. The solution was evaporated under reduced pressure. Water (50 mL) was added to the residue, and the product was extracted twice with 20 mL portions of CH₂Cl₂; the organic phase was dried over MgSO₄ and evaporated giving a pale yellow oil (2.02 g, 50%) product of high purity. Additional washes with water can be performed if necessary.

A 2.5-fold excess of diamine must be used to neutralize HCl and still keep a basic pH necessary to catalyze the reaction. The addition of phosphonate to the amine should not exceed 10 min nor overtake the range 55–65°C; otherwise, bis-phosphorylation will occur preferentially. This particular reaction protocol can be applied to different aliphatic diamines ranging from the stated ethylenediamine up to 1,6-diaminohexane.

¹H NMR (300 MHz, CDCl₃) 1.31, 1.32 (12H, 2d, CH₃, J_HCCH = 6.1); 2.55 (2H, s, NH₂ broad); 2.84 (2H, t, CH₂NH₂, J_HCCH = 5.5); 2.99 (2H, m, CH₂NHP); 3.31 (1H, m, NH-P); 4.59 (2H, dhep, HCO, J_HCCH = 6.2, J_POCH = 7.6)

 ¹³C NMR (75.42 MHz, CDCl₃) 23.75 (2d, CH₃, J_CCOP = 4.6); 42.71 (d, CH₂CH₂NP, J_CCNP = 5.7); 43.68 (CH₂NP); 70.79 (d, CH, J_COP = 5.7)

 ³¹P NMR (121.42 MHz, CDCl₃) 7.73

T. S. Torres, W. P. de Macedo, L. F. Pedrosa, M. C. B. V. de Souza, V. F. Ferreira, A. C. Cunha, T. Fogel, F. C. Santos, I. P. Marques, I. C. P. P. Frugulhetti, M. C. de Souza, Lett.Org. Chem. 2008, 5, 644. doi:10.2174/157017808786857615