The synthesis of pamidronic derivatives in different solvents: An optimization and a mechanistic study

Rita Kovács, A. Grün, Orsolya Németh, Sándor Garadnay, István Greiner, G. Keglevich

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The synthesis of pamidronic acid and sodium pamidronate dihydrate from β-alanine and P-reagents (phosphorus trichloride and phosphorous acid) was investigated at 75°C in different solvents, and the preparation was optimized. In sulfolane, the use of 2 equiv of phosphorus trichloride and phosphorous acid was found the optimum to lead to pamidronic acid in a yield of 63%. In methanesulfonic acid, 3.2 equiv of phosphorus trichloride was necessary without any phosphorous acid to give pamidronate dihydrate in the best yield (57%) after hydrolysis and pH adjustment. In the first case, the P-nucleophile may be (HO)2P-O-PCl-O-P(OH)2 or (HO)2P-O- PCl2, whereas in the second case, the P-reactant is probable Cl 2P-O-S(O)2Me. It can be said that the mechanism proposed for the formation of pamidronic acid is highly influenced by the solvent used, as it determines the necessary P-reagent(s). Our results promote the "on purpose" planning of the synthesis of dronates.

Original languageEnglish
Pages (from-to)186-193
Number of pages8
JournalHeteroatom Chemistry
Volume25
Issue number3
DOIs
Publication statusPublished - 2014

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pamidronate
Derivatives
Acids
Nucleophiles
Alanine
Hydrolysis
Sodium
Planning
phosphonic acid
phosphorus chloride

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

The synthesis of pamidronic derivatives in different solvents : An optimization and a mechanistic study. / Kovács, Rita; Grün, A.; Németh, Orsolya; Garadnay, Sándor; Greiner, István; Keglevich, G.

In: Heteroatom Chemistry, Vol. 25, No. 3, 2014, p. 186-193.

Research output: Contribution to journalArticle

Kovács, Rita ; Grün, A. ; Németh, Orsolya ; Garadnay, Sándor ; Greiner, István ; Keglevich, G. / The synthesis of pamidronic derivatives in different solvents : An optimization and a mechanistic study. In: Heteroatom Chemistry. 2014 ; Vol. 25, No. 3. pp. 186-193.
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