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Selective Monophosphorylation of ethylenediamine; diisopropyl 2-aminoethylphosphoramidate

SyntheticPage 491
DOI: 10.1039/SP491
Submitted Mar 31, 2011, published Apr 01, 2011
Leandro Pedrosa (leandropedrosa@globo.com)


			Reaction Scheme: <IMG src="/images/empty.gif">Selective Monophosphorylation of <SPAN id=csm1305577892138 class="csm-chemical-name csm-not-validated" title=ethylenediamine grpid="1">ethylenediamine</SPAN><IMG src="/images/empty.gif">

Chemicals Used

ethylenediamine
ethanol
diisopropyl phosphonate
carbon tetrachloride

Procedure

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.

Author's Comments

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.

Data

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

 13C NMR (75.42 MHz, CDCl3) 23.75 (2d, CH3, JCCOP = 4.6); 42.71 (d, CH2CH2NP, JCCNP = 5.7); 43.68 (CH2NP); 70.79 (d, CH, JCOP = 5.7)

 31P NMR (121.42 MHz, CDCl3) 7.73


Lead Reference

M. C. Souza, W. P. Macedo, T. S. Torres, L. F. Pedrosa, H. G. Alt, Phosphorus, Sulfur and Silicon 2006, 181, 1885. doi:10.1080/10426500500543776

Other References

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

Supplementary Information

1H NMR (1H NMR - Diisopropyl 2-aminoethylphosphoramidate.pdf)
13C NMR (13C NMR - Diisopropyl 2-aminoethylphosphoramidate.pdf)
31P NMR (31P NMR - Diisopropyl 2-aminoethylphosphoramidate.pdf)

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Keywords: amines, organo phosphorous

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