10.1007/s11176-008-1029-7

Abstract

Aminophosphonic acids, being direct analogs of natural aminocarboxylic acids-building blocks of peptides and proteins, exhibit a broad-range biological activity [1]. In this connection a-aminoalkylphosphonate derivatives with structural fragments containing amino groups on the phosphorus atom present indubitable interest. The presence of two amino groups in such compounds opens up new possibilities for their modification and for preparation of various linear and cyclic compounds including the amino-ÄÄÄÄÄÄÄÄÄÄÄÄ phosphonate fragment. a-Aminoalkylphosphonates with the phosphorus atom bearing functional substituents can be synthesized via addition of the corresponding P-substituted phosphorous acids to imines. We have developed a method for synthesis of mixed phosphorous acids involving the aminoalkyl fragment, using the example of the reaction of cyclic silyl phosphoramidites [2] with phenols. The reaction involves ring cleavage and liberation of phenoxysilane. K O N POSiMe 3 g Ph + 2ArOH %$ P!H + ArOSiMe 3 o O e i PhNH(CH 2 ) 2 O ArO I IIa, IIb II, Ar = Ph (a); Ar = 4-MeOC 6 H 4 (b). ÄÄÄÄÄÄÄÄÄÄÄÄAcid IIa readily adds to imine III to form P-functional aminoalkylphosphonate IV. III IVThe addition reaction forms the second chiral center, and, as a result, compound IV is a mixture of diastereomers in a ratio of 76 : 24. The prevailing diastereomer was isolated from the mixture by fractional crystallization; its individuality was confirmed by the observation of a single signal in the 31 P NMR spec-trum and one doublet proton signal of the PCH group in the 1 H NMR spectrum. Bubbling dry HCl through a solution of compound IV provides salt V. IV %%$ 2HCl P!CH!NH 2 Ph, 2Cl ! o O e i PhNH 2 (CH 2 ) 2 O ArO g Ph + + V Phenyl 2-(phenylamino)ethyl phosphonate (IIa).A mixture of 3.82 g of silyl phosphite I and 2.82 g of phenol was heated at 60oC for 2 h, after which 1.92 g (77%) of phenoxytrimethylsilane was distilled off in a vacuum, bp 67oC (11 mm Hg), n D 20 1.4738 [3].