This is a parent page for improving the current methods for the purification of PZQ.
This page details attempts to optimise the purification of praziquantel by chromatography, with an emphasis on preparative, rather than analytical, work. Anybody can add to/edit this page.
Literature
1. This paper describes the purification of enantiopure PZQ using "chloroform/methanol 0–0.3% MeOH as a solvent system."
2. This paper uses 1:1 EtOAc/petroleum ether ramping to pure EtOAc.
3. This paper uses "thick layer preparative chromatography [prep TLC] benzene/ethyl acetate 1/1, silica gel."
Proton NMR assignment for PZQ has been carried out twice in the literature. Once in a review article: Analytical Profiles of Drug Substances and Excipients, 1998, 25, 463, and once in Arch. Pharm. (Weinheim), 1989, 322, 795-799. Of interest are the large differences in chemical shift between the diastereotopic protons on positions 1 and 6. Need image capture from the pdfs posted below...
Ryan has posted NMR data in a separate post.
This page details attempts to optimise the recrystallization of praziquantel. Anybody can add to/edit this page.
Literature
1. This patent (US patent 4,523,013) recrystallizes PZQ from "a mixture of petroleum ether and acetone," obtaining a 95% yield on the reaction.
2. This paper recrystallizes from ethyl acetate and hexanes to obtain a 70% yield on the reaction.
The best system the Todd lab has observed for the recrystallization of racemic praziquantel, as of Oct. 26, 2009, is the following:
Praziquantel is dissolved in a minimal amount of 50 ± 2ºC ethanol (solubility ca. 190 mg/mL; some results as high as 240 mg/mL; comfortably, 200 mg PZQ/mL 50ºC EtOH). This solution is allowed to cool to rt, and is left at 5ºC overnight before filtration, rinsing the crystals minimally with 5ºC EtOH. After drying under high vacuum, purity can be determined by melting temperature (138-139ºC, ref. RyanPakula blog, supporting NMR spectra coming soon) and proton NMR spectroscopy (CDCl3 works well).