Science of Synthesis

Whitehead, A.; Sieck, S. R.; Mukherjee, S.; Hanson, P. R., Science of Synthesis, (2005) 21, 916.

Bis(acylphosphonates) are of great interest as effective anticalcification[‌30‌] and antiresorption[‌31‌] agents both in vitro and in vivo. In an attempt to study the biological effect of chain length of such bis(acylphosphonates), a synthesis was reported[‌32‌] utilizing S-ethyl (diisopropoxyphosphoryl)thioformate (‌31‌), which is easily obtained from the corresponding chlorothioformate (‌Scheme 10‌). Tetraester ‌32‌ is obtained by the reaction of ethane-1,2-diamine with thioformate ‌31‌. Subsequent dealkylation with bromotrimethylsilane produces the disodium salt of the N,N′-bis[(dihydroxyphosphoryl)carbonyl]ethylenedi­amine species. After recrystallization (MeOH), diacid ‌33‌ is obtained in 90% yield. Longer chain bis(acylphosphonates) were synthesized in a similar fashion.

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References