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

Background
Slight upscale of the test reaction in the attempted isolation of the enediamide intermediate (see KAB11-1) in the Pictet-Spengler reaction to give the dimethoxy N-benzoyl PZQ analogue. Monitoring by TLC.

Scheme
Scheme%20KAB11-2.png
Table%20KAB11-2.jpg

Hazard and Risk Assessment
As for KAB11-1 (here)

Following Experiments
Copper(II) triflate catalysed preparation of the dimethoxy N-benzoyl PZQ enediamide (KAB11-3)

Procedure

18/01/12
A mixture of MNR10-1 (45.6 mg) and AgOTf (14.2 mg, 56 mol%) in toluene (18 mL) was heated to 40 °C from 12:05.
A 0.1 mL aliquot was extracted at 13:30. A TLC of the aliquot was run against the starting material (MNR10-1) and the complete Pictet-Spengler cyclised product (KAB8-1) in EtOAc/hexane, 3:1, v/v. The TLC was eluted twice in the same eluent to the same solvent line in an attempt to achieve clearer separation of the spots.
TLC of reaction mixture (1)

The TLC suggested the reaction had not progressed and a large composition of the mixture was starting material.

At 17:30, TLC indicated no formation of the enediamide. The temperature setpoint was increased to 90 oC.

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.
Final TLC of reaction mixture

Eluent: EtOAc/hexane, 3:1, v/v.
Stain: KMnO4
From L to R: (1)Reaction mixture of KAB11-2 at 09:00, (2) Reaction mixture of simultaneously run KAB11-3 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 KAB11-2 as a clear solid/oil (27.7 mg).

H-NMR of crude KAB11-2
Raw H-NMR crude KAB11-2


Proton NMR agreed with TLC 2, that the product of the reaction was the dimethoxy N-benzoyl PZQ analogue and not the expected enediamide. Despite being "crude," the NMR suggested the product was quite clean (also suggested by TLC in lieu of co-spotting).

****Experiment concluded

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)
Copper(II) triflate catalysed preparation of the dimethoxy N-benzoyl PZQ enediamide (KAB11-3)
Linked Posts
Attached Files
Scheme KAB11-2
Table KAB11-2
H-NMR of crude KAB11-2
Raw H-NMR crude KAB11-2
Final TLC of reaction mixture
TLC of reaction mixture (1)