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5th February 2012 @ 21:36
PS = Pictet-Spengler

START: 06/02/12
FINISH: 10/02/12

Background
Reducing catalyst loading in the procedure of KAB8-4.

Scheme%20KAB8-10.png


Hazard and Risk Assessment
Hazard and Risk Assessment KAB8-10


Previous Related Experiments
The silver(I) triflate catalysed PS to give the dimethoxy N-benzoyl PZQ analogue (KAB8-4)
TfOH catalysed PS* reaction to give the dimethoxy N-benzoyl PZQ analogue (KAB8-7 & KAB8-8)

Following Experiments
AgOTf catalysed PS reaction to give the dimethoxy N-benzoyl PZQ analogue (KAB8-15)

Procedure
06/02/12. A mixture of MNR10-1 (95.5, 0.208 mmol) and AgOTf (13.7 mg, 53 μmol, 27 mol%) in toluene (30 mL) was reflux heated at 90 °C from 09:00.
MNR10-1 starting material
Reaction Setup

Progress was monitored by TLC of the reaction mixture against the MNR10-1 starting material and the expected product (identical to previously made KAB8-4).
09/02/12. The brown reaction mixture was removed from heat and allowed to cool to rt at 14:30 (+ 77 hours). After diluting with EtOAc (50 mL), the solution was washed with citric acid solution (0.5 M, 50 mL) then saturated sodium bicarbonate solution (50 mL). The organic layer was separated and the basic aqueous layer was extracted with EtOAc (2 x 30 mL). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a crude KAB8-10 as an orange oil. The product was placed in the freezer overnight to promote crystallisation.

Monitoring the Reaction Progress by TLC
Eluent: neat EtOAc
Stain: KMnO4
TLC at 3 hr
TLC at 24 hr
TLC at 32 hr
TLC at 50 hr


Summary and Conclusion
The reaction did not go to completion. The silver may have been poisoned halting the reaction. Alternatively, the reaction was not carried out under anhydrous conditions. Formation of TfOH in situ may have contributed to formation of the product.
At this stage, the role if any, of Ag(I) in the PS reaction to give the dimethoxy N-benzoyl PZQ analogue is unknown. The reaction must be performed under anhydrous conditions.

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NOTES 08/02/12
- 11:40. Reaction still shows some enediamide intermediate (by TLC) but otherwise clean.

NOTES 09/02/12
- The enediamide spot had not faded when the reaction was quenched. The bottom of the round bottom flask was coated in a fine dark brown, almost silty solid, presumably, silver (reduced?). Was unable to rinse out with either EtOAc or the aqueous acid/base.
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Linked Posts
Attached Files
Hazard and Risk Assessment KAB8-10
Scheme KAB8-10
TLC at 3 hr
MNR10-1 starting material
Reaction Setup
TLC at 24 hr
TLC at 32 hr
TLC at 50 hr