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Pictet-Spengler route to Praziquantel
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5th February 2012 @ 23:03
*PS = Pictet-Spengler

START: 06/02/12
FINISH: 06/02/12

Scheme%20KAB3-11.png


Hazard and Risk Assessment
Hazard and Risk Assessment KAB3-11


Previous Related Experiments
The metal triflate catalysed Pictet-Spengler to give racemic PZQ (KAB3-9 & KAB3-10)
TfOH catalysed PS* reaction to give the dimethoxy N-benzoyl PZQ analogue (KAB8-7 & KAB8-8)

Following Experiments
TfOH catalysed PS* reaction to give PZQ (KAB3-12 to KAB3-16)

Procedure
KAB5-2 (0.065 g, 0.16 mmol)* was dissolved in toluene (30 mL) before addition of TfOH (1 drop, ~10 mg, 60 mol%). The clear, colourless mixture turned pale yellow immediately following addition of the acid. The mixture was stirred at room temperature from 11:07.
Reaction mixture before after the addition of TfOH
Just after the addition of TfOH
Reaction mixture at ~1 hr

Reaction was terminated at 14:05 (+ 3 hours). The reaction mixture was diluted with EtOAc (30 mL) then quenched with saturated sodium bicarbonate solution (50 mL). The organic layer was separated and the aqueous layer further extracted with EtOAc (30 mL). The organic layers were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give crude KAB3-11 as a yellow oil (99 mg).
TLC of the crude product (in EtOAc/hexane, 3:1, v/v) showed three spots with lower Rf values than the KAB5-2 starting material.

Monitoring the Reaction Progress by TLC
TLC at 30 min

Eluent: EtOAc/hexane, 3:1, v/v.
Stain: KMnO4

Summary and Conclusion
TLC of the crude oil showed multiple spots with no sign of the expected enediamide intermediate (as was present in the KAB3-9 and KAB3-10 reactions), or the expected product (praziquantel). The product was taken no further. See following experiment (here)


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NOTES
- Currently +1 hr since reaction start. I think the acid has been consumed and a side reaction has occured. No product spot. But major reaction component is spot with Rf 0.14 in neat EtOAc. Remainder of reaction mixture is the KAB5-2 starting material. Suspect 60% to be unknown spot and 40% to be starting material.
- *The KAB5-2 used in the reaction was not dry (NMR showed solvent peaks). The amount added is incorrect.
- Obtained >100% yield. Possibly formed TfOH adduct?
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Linked Posts
Attached Files
Scheme KAB3-11
Hazard and Risk Assessment KAB3-11
Reaction mixture before after the addition of TfOH
Just after the addition of TfOH
Reaction mixture at ~1 hr
TLC at 30 min