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16th February 2012 @ 23:53
PS = Pictet-Spengler

START: 17/02/12
FINISH: 17/02/12

Background
Obtaining yield for the analogous reaction for the dimethoxy PZQ analogue.

Scheme%20KAB1-3.png
Table%20KAB1-3.jpg

Hazard and Risk Assessment
Hazard and Risk Assessment KAB1-3


Previous Related Experiments
The TfOH catalysed PS* reaction to give the dimethoxy N-benzoyl PZQ analogue (KAB8-11)
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)
Preparation of the PZQ peptide acetal Ugi-intermediate (KAB5-2)

Following Experiments
TfOH catalysed PS* reaction to give the dimethoxy PZQ analogue (KAB1-4)
TfOH catalysed PS* reactions to give the dimethoxy PZQ analogues (KAB8-14 & KAB1-5)
AgOTf catalysed PS reaction to give the dimethoxy PZQ analogue (KAB1-6)
AgOTf catalysed PS reaction to give the dimethoxy N-benzoyl PZQ analogue (KAB8-15)

Pre-Procedure
Molecular Sieve (MS) Activation. The beads were placed in a 100 mL beaker (~25 mL of volume) and microwaved (1000 W) in 30 second bursts until no water vapour was observed on the inside of the beaker.
Stock Acid Preparation. TfOH (88.7 mg, 0.591 mmol) was added to a volumetric flask (25 mL). The volume made up with dried toluene to give the TfOH/toluene stock acid solution (23.6 mM).

Procedure
MNR8-3 (540 mg) was dissolved in toluene (57 mL) before the addition of the activated MS (4 A). The mixture was cooled in an ice-bath and the TfOH/toluene stock (2.5 mL, 0.058 mmol, 5 mol%) was added at 0 °C at 11:15. The reaction mixture was allowed to warm, then reflux heated to 90 ° C. The reaction progress was monitored by TLC.

The reaction was terminated after the altered conditions from KAB8-11 to KAB8-12 efficiently promoted the Pictet-Spengler reaction. The following experiment, KAB1-4 was started immediately. No work-up was performed on the reaction mixture.

Monitoring the Reaction Progress by TLC
All TLCs were eluted with EtOAc/hexane, 5:3, v/v and stained with KMnO4. The time noted is from the addition of the acid.
TLC of reaction mixture (5 min)
TLC of reaction mixture (15 min)
TLC of reaction mixture (30 min)
TLC of reaction mixture (1 h)


The reaction was taken off heat after 1 hour. The product was taken no further.

Summary and Conclusion
See summary and conclusion from KAB8-11 (here).

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NOTES 17/02/12

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Linked Posts
Attached Files
Scheme KAB1-3
Table KAB1-3
Hazard and Risk Assessment KAB1-3
TLC of reaction mixture (5 min)
TLC of reaction mixture (15 min)
TLC of reaction mixture (30 min)
TLC of reaction mixture (1 h)