In organophosphorus chemistry, phosphoramidates (sometimes also called amidophosphates) are a class of phosphorus compounds structurally related to phosphates (or organophosphates) via the substitution of an −O− group for an amine group (−N−). They are derivatives of phosphoramidic acids, which possess the structure O=P(OH)(NR2)2 or O=P(OH)2(NR2).
A phosphorodiamidate is a phosphate that has two of its hydroxyl (−OH) groups substituted by amine (NR2) groups to give a species with the general formula O=P(OH)(NH2)2. The substitution of all three OH groups gives the phosphoric triamides (O=P(NR2)3), which are commonly referred to as phosphoramides.1
Synthesis
In the Stokes method, phosphoramidates are synthesized from phosphorus oxychloride. The compound reacts with phenol to form a chlorophosphonate ester or diester, depending on stoichiometry. The remaining chlorine substituents then react with an amine compound to give the phosphoramidate.2
Examples
Two examples of natural phosphoramidates are phosphocreatine and the phosphoramidate formed when histidine residues in histidine kinases are phosphorylated.3 An example of a phosphorodiamidate is morpholino which is used in molecular biology.
References
References
- IUPAC, Compendium of Chemical Terminology, 5th ed. (the "Gold Book") (2025). Online version: (2006–) "phosphoramides". doi:10.1351/goldbook.A00484
- Klement, R. (1963). "Phosphorus". In Brauer, Georg (ed.). Handbook of Preparative Inorganic Chemistry. Vol. 1. Translated by Riley, Reed F. (2nd ed.). NY, NY: Academic Press. pp. 579–590. LCCN 63-14307.
- Stock, Ann M.; Robinson, Victoria L.; Goudreau, Paul N. (2000-07-01). "Two-Component Signal Transduction". Annual Review of Biochemistry. 69: 183–215. doi:10.1146/annurev.biochem.69.1.183. PMID 10966457.