title: SYNTHESIS OF SYMMETRICAL METHYLENEBIS(ALKYL HYDROGEN PHOSPHONATES) BY SELECTIVE CLEAVAGE OF METHYLENEBIS(DIALKYL PHOSPHONATES) WITH MORPHOLINE.
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.
authors.affiliation: Department of Chemistry and Biochemistry, MSC 3C, New Mexico State University, Las Cruces, NM 88003.
authors.forename: Gantla Vidyasagar
authors.initials: GV
authors.lastname: Reddy
authors.forename: Hollie K
authors.initials: HK
authors.lastname: Jacobs
authors.forename: Aravamudan S
authors.initials: AS
authors.lastname: Gopalan
authors.forename: Richard E
authors.initials: RE
authors.lastname: Barrans
authors.forename: Mark L
authors.initials: ML
authors.lastname: Dietz
authors.forename: Dominique C
authors.initials: DC
authors.lastname: Stepinski
authors.forename: Albert W
authors.initials: AW
authors.lastname: Herlinger