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RESEARCH PRODUCT

“Twin” phosphorous atoms of tetraethyl 2-methyl-piperyd-1-ylmethylenebisphosphonates

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Recently, bisaminophosphonates found applications as therapeutic agents for curing bone disorders. When trying to relate the structures of substituted piperid-1-ylmethylenebisphosphonic with their biological properties, non-typical findings that in 31P NMR spectra of 2-methyl-piperid-1-ylmethylenebisphosphonic and 2-ethyl-piperid-1-ylmethylenebisphosphonic acids, two separate singlets from each of the phosphonic groups were observed, while their analogues bearing substituent in position 3 exhibit only one signal. Their presence was explained by freezing of the molecular motions by strong hydrogen bonding between NH and P = O atoms. In this work, synthesis as well as spectroscopic and theoretical investigations of the tetraethyl esters of 2-methyl-piperid-1-ylmethylenebisphosphonic in its racemic and enatiomerically pure forms are reported. Their 31P NMR spectra revealed two sets of dublets, which indicate the presence of two non-equivalent phosphorous atoms. More detailed NMR and theoretical studies indicated that the nonequivalent phosphorous signals in 31P NMR spectra may results from the absence of C2 symmetry of the molecule along with the presence of large ester groups blocking the internal molecular motion around C—N bond, and thus blocking the interchange of ring conformation. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:774–781, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20349