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25th January 2012 @ 02:52
Experiment concluded on 27/01/12.

Determining catalyst decomposition during previous experiments (KAB8-2, KAB1-1) or poor suitability for the particular reaction.


Hazard and Risk Assessment
Hazard and Risk Assessment KAB12-1

Following Experiments


Start: 25/01/12
Finish: 27/01/12

KAB8-2 (57 m, 16 mmol) was dissolved in toluene (2 mL) before MW45-3 (11 mg, 17 mol%) was added. The mixture was stirred and reflux heated at 70 °C from 15:10.

The reaction progress was monitored by TLC of the reaction mixture against the KAB8-2 starting material and the completely cyclised Pictet-Spengler product KAB12-1 (the same as previously made KAB8-1).

Monitoring the reaction progress by TLC
All TLCs were run in EtOAc/hexane, 3:1, v/v and stained with KMnO4.
TLC 1 --> +2 hours
TLC 2 --> +40 hours
TLC of reaction mixture (1)
TLC of reaction mixture (2)

TLC Legend: 12-1 - The KAB12-1 reaction mixture taken at the time at the bottom (sample number also circled at the bottom); Co - Co-spot of the reaction mixture, the KAB8-2 starting material and the expected product; SM - The KAB8-2 starting material; 8-2 - the expected product, identical to previously prepared KAB8-1
NOTE TLC 2: The circled areas mark the spots visible under long wave UV light, which were very intense, but did not resolve on staining.

The reaction mixture was removed from heat and allowed to cool at 08:50.
Cooled KAB12-1 reaction mixture

Summary and Conclusion
TLC suggested no formation of the expected dimethoxy N-benzoyl PZQ analogue. Distinct spots with lower Rf values than the starting material (in EtOAc/hexane, 4:1, v/v) may be the result of unwanted side reactions or decomposition of the reaction components. The crude product was not taken further.

Related Experiments
Acid-catalyzed PS* reaction to give the dimethoxy N-benzoyl PZQ analogue (KAB8-2)
Acid-mediated PS cyclisation to give racemic PZQ (KAB3-3), the dimethoxy N-benzoyl PZQ analogue (KAB8-1), the dimethoxy PZQ analogue (KAB1-2) and the N-benzoyl PZQ analogue (KAB7-1)
Acid-catalyzed Pictet-Spengler of MNR8-1 using binapthalenedisulfonic acid to give KAB1-1

NOTES 25/01/12
- Put as much in catalyst as I could get out of the vial but, couldn't quite get out 20 mol%.
-TLC 1 - The co-spots appearing in the reaction mixture suggest the catalyst is doing something, at least in the first couple of hours. Lowest spot could be impurities in the starting material, which were not present during the purification of KAB8-2.
- Left the reaction to continue for the next 2 days - unable to monitor over this time.

NOTES 27/01/12
- TLC 2 suggests the majority of the reaction mixture was the enediamide intermediate (starting material). There were some unknown spots.

Linked Posts
Attached Files
Scheme KAB12-1
Hazard and Risk Assessment KAB12-1
Table KAB12-1
TLC of reaction mixture (1)
TLC of reaction mixture (2)
Cooled KAB12-1 reaction mixture