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18th January 2012 @ 03:00
Experiment concluded on 19/01/12

Background
Part of the Lewis acid catalyst screen for the isolation of the dimethoxy N-benzoyl PZQ enediamide intermediate via the incomplete Pictet-Spengler.
Analogous reaction to the silver(I) triflate catalyst screens (KAB11-1 and KAB11-2).

Scheme
Scheme%20KAB11-3.png
Table%20KAB1-3.jpg

Hazard and Risk Assessment
Hazard and Risk Assessment KAB11-3


Following Experiments
The copper(II) triflate catalysed PS to give the dimethoxy N-benzoyl PZQ analogue (KAB8-3)
The silver(I) triflate catalysed PS to give the dimethoxy N-benzoyl PZQ analogue (KAB8-4)

Procedure

18/01/12
The dimethoxy N-benzoyl PZQ analogue peptide acetal, MNR10-1 (33.2 mg, 72.4 umol), was dissolved in toluene (10 mL) before the addition of copper(II) trifluoromethanesulfonate (13.9 mg, 53 mol%). The mixture was stirred at room temperature from 15:20.
TLC of the reaction mixture:
TLC of reaction mixture (1)

From L to R: (1)Reaction mixture, (2) Co-spot of reaction mixture, MNR10-1 starting material and the complete PS cyclisation product KAB8-1, (4) The MNR10-1 starting material, (4) The complete PS cyclisation product, KAB8-1.
NOTE: The TLC suggested most of the reaction mixture contained the starting material. No sign of the enediamide, which has a higher Rf than either the starting material or the completely PS cyclised product.

The reaction mixture was left to stir at rt overnight.

19/01/12

A sample of the reaction mixture was taken at 09:00. TLC of the sample suggested complete PS cyclisation of the starting material (MNR10-1) to the dimethoxy N-benzoyl PZQ analogue. No sign of enediamide by TLC, which has a higher Rf than the starting material.

TLC of reaction mixture (2)

Eluent: EtOAc/hexane, 3:1, v/v.
Stain: KMnO4
From L to R: (1)Reaction mixture of simultaneously run KAB11-2 at 09:00, (2) Reaction mixture at 09:00, (4) The MNR10-1 starting material, (4) The complete PS cyclisation product, KAB8-1.

The reaction was terminated by quenching with water (50 mL). The organic and aqueous fractions were the separated, and the organic layer dried over magnesium sulfate. The aqueous layer had pH 5. The organic layer was filtered, then concentrated under reduced pressure to give crude KAB11-3 as a clear oil (5.1 mg), with maybe some white solid.

The sample was too dilute to get any conclusive information from the H-NMR (in CDCl3)
Raw H-NMR of crude KAB11-3


However, it was likely that the product was the completely cyclised product, the dimethoxy N-benzoyl PZQ analogue (see KAB8) and not the expected enediamide.

References
Todd, M. H., Ndubaku, C. & Bartlett, P. A., J. Org. Chem. 2002, 67, 3985-3988 - DOI: 10.1021/jo010990m (Paper)

Related Experiments
Lewis acid catalysed preparation of the dimethoxy N-benzoyl PZQ enediamide (KAB11-1)
Silver(I) triflate catalysed preparation of the dimethoxy N-benzoyl PZQ enediamide (KAB11-2)


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NOTES 18/01/12
-Not sure if the Cu(OTf)2 has gone slightly off. It was a blue -solid, of slightly non-uniform colour.
- The Cu(OTf)2 is poorly soluble in toluene. Must ensure solution keeps stirring.
- I would like to start refluxing the reaction mixture, but I'm out of space.

NOTES 19/01/12
The copper was visible as a solid in the bottom of the reaction mixture. It had gone greenish in colour. Oxidation? Considering doing the reaction under dry conditions.
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Linked Posts
Attached Files
Scheme KAB11-3
Hazard and Risk Assessment KAB11-3
Table KAB11-3
TLC of reaction mixture (1)
TLC of reaction mixture (2)
Raw H-NMR of crude KAB11-3