SYNTHESIS OF SYMMETRICAL METHYLENEBIS(ALKYL HYDROGEN PHOSPHONATES) BY SELECTIVE CLEAVAGE OF METHYLENEBIS(DIALKYL PHOSPHONATES) WITH MORPHOLINE.
GantlaVidyasagar Reddy, HollieK Jacobs, AravamudanS Gopalan, RichardE Barrans, MarkL Dietz, DominiqueC Stepinski, AlbertW Herlinger
Index: Synth. Commun. 34(2) , 331-344, (2004)
Full Text: HTML
Abstract
The preparation of partial esters of methylenebisphosphonic acids has been of recent interest due to their potential therapeutic applications. This paper describes a convenient method to prepare symmetrical methylenebis(alkyl hydrogen phosphonates) by the selective cleavage of the corresponding methylenebis(dialkyl phosphonate) with refluxing morpholine. The effects of structural variations on the amine as well as the substrate have been investigated to understand the scope and limitations of this reaction. A superior approach to hindered bisphosphonic acid esters involves the cleavage of their dimethyl esters, 4, using morpholine. This method is also useful to access a number of C-alkyl dialkyl methylenebisphosphonic acids such as 6. This study clearly shows that cleavage with morpholine is convenient, inexpensive, and allows for the preparation of a variety of P,P'-disubstituted partial esters in good yields and high purity.
Related Compounds
Related Articles:
2002-01-31
[J. Med. Chem. 45(3) , 703-12, (2002)]
A direct method for the synthesis of nucleoside 5'-methylenebis (phosphonate) s from nucleosides. Kalek M, et al.
[Tetrahedron Lett. 46(!4) , 2417-21, (2005)]
Facile high yielding synthesis of symmetric esters of methylenebisphosphonic acid. Stepinski DC, et al.
[Tetrahedron 57(41) , 8637-45, (2001)]