Breathing air as oxidant: Optimization of 2-chloro-2-oxo-1,3,2-dioxaphospholane synthesis as a precursor for phosphoryl choline derivatives and cyclic phosphate monomers

Greta Becker, Frederik R. Wurm*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)

Abstract

Phosphoryl choline derivatives are important compounds for drug development. Also other phosphoesters have received increased demand in recent years. Many of such compounds rely 2-chloro-2-oxo-1,3,2-dioxaphospholane (COP) as an intermediate. COP is available in a two-step reaction from the cyclic adduct of phosphorus chloride and ethylene glycol after oxidation. Although commercially available, in-house synthesis of COP is often required due to pricing, purity, and delivery issues. Air is a convenient and economical oxidizing agent, yet not used for synthesis of COP. While slow consumption of the P(III)-precursor 2-chloro-1,3,2-dioxaphospholane with molecular oxygen from a gas bottle, high amounts of unreacted oxygen are lavished and even may cause an explosion. Oxygen from air is a reasonable and safer alternative. Additionally, catalytic amounts of cobalt(II)chloride increase the reaction kinetics remarkably. The results presented allow a controlled and fast access to a variety of phosphoesters by optimized reaction conditions of COP and its derivatives.

Original languageEnglish
Pages (from-to)3536-3540
Number of pages5
JournalTetrahedron
Volume73
Issue number25
DOIs
Publication statusPublished - 22 Jun 2017
Externally publishedYes

Keywords

  • 2-Chloro-1,3,2-dioxaphospholane
  • 2-Chloro-2-oxo-1,3,2-dioxaphospholane
  • COP
  • Oxidation with air
  • Phosphorylcholine derivative
  • Poly(phosphoester)

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