Reddy Gantla Vidyasagar, Jacobs Hollie K, Gopalan Aravamudan S, Barrans Richard E, Dietz Mark L, Stepinski Dominique C, Herlinger Albert W
Department of Chemistry and Biochemistry, MSC 3C, New Mexico State University, Las Cruces, NM 88003.
Synth Commun. 2004 Jan 1;34(2):331-344. doi: 10.1081/SCC-120027271. Epub 2011 Oct 18.
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.
由于亚甲基双膦酸的部分酯具有潜在的治疗应用，近年来对其制备方法颇感兴趣。本文描述了一种通过用回流的吗啉选择性裂解相应的亚甲基双（二烷基膦酸酯）来制备对称亚甲基双（烷基氢膦酸酯）的简便方法。研究了胺以及底物结构变化的影响，以了解该反应的适用范围和局限性。制备受阻双膦酸酯的一种更好方法是使用吗啉裂解其二甲酯（4）。该方法对于制备多种C-烷基二烷基亚甲基双膦酸（如6）也很有用。这项研究清楚地表明，用吗啉裂解既方便又便宜，并且能够以高收率和高纯度制备各种P，P'-二取代的部分酯。
