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3rd November 2011 @ 00:20
Attempts to sort out the probelms of the Newman-Kwart Rearrangement

MNR20-1%20scheme.png

MNR20-1%20table.PNG

Hazard and Risk Assessment:
As for HIRAC-MNR17

Procedure
MNR20-1

MNR19-1 (20 mg, 0.04 mmol) was placed in a round bottom flask and heated in a sand bath set to reach 250°C under argon. Heating was very slow and took over an hour to reach 175°C. After 80 minutes from the start of heating, the flask was removed from the heat and allowed to reach room temperature.

Crude 1H NMR - MNR20-1 - Signs of a very slow conversion

MNR20-2
MNR19-1 (20 mg, 0.04 mmol) was placed in a round bottom flask and heated in a sand bath set to reach 250°C under argon. Heating was very slow and took over an hour to reach 175°C and then only reached 185°C after a total of 3 hours. At which time the flask was removed from the heat and allowed to reach room temperature.

Crude 1H NMR - MNR20-2 - slightly more conversion than MNR20-1

MNR20-3
MNR19-1 (20 mg, 0.04 mmol) was placed in a round bottom flask and heated in a sand bath (heavily insulated with tin foil) set to reach 200°C (not under argon, I forgot). Heating was quicker than the previous attempt and 200°C was achieved within 1 hour. Heating continued overnight due to time of starting the reaction. After a total of 17 hours the flask was removed from the heat and allowed to reach room temperature.

Crude 1H NMR - MNR20-3 - 40-60% conversion

MW45-2 clean product - broad peak at 2.767 integrating to 12 protons

MNR20-4
MNR19-1 (20 mg, 0.04 mmol) was placed in a round bottom flask and heated in a sand bath (heavily insulated with tin foil) set to reach 200°C under argon. Heating was quicker than the previous attempt and 200°C was achieved within 1 hour. Heating continued overnight due to time of starting the reaction. After a total of 17 hours the flask was removed from the heat and allowed to reach room temperature.

Crude 1H NMR - MNR20-4 - looks like less conversion than MNR20-3


By the looks of it, the reaction proceeds slowly but cleanly at lower temperatures. This is as hot as the stir-plates with temperature probe can get the sand bath. Also, the reaction does not appear to need to be under argon to proceed cleanly. The previous attempts using the heating mantles have just over cooked the compound.

Scale up the reaction and increase reaction time so crude can be columned and a yield calculated.

MNR20-5%20table.PNG

MNR20-5
MNR19-1 (250 mg, 0.54 mmol) was placed in a round bottom flask and heated in a sand bath (heavily insulated with tin foil) set to reach 250°C. Heating continued for X hours then flask was removed from the heat and allowed to reach room temperature.

on at 12pm, 4/11/11
off at 830 am, 7/11/11
total - 68.5 hours - reaction had started to turn black like original attempts and was not totally as soluble as 20-3 and 20-4.

Crude 1H NMR - MNR20-5 - no product

MNR20-6
MNR19-1 (250 mg, 0.54 mmol) was placed in a round bottom flask and heated in a sand bath (heavily insulated with tin foil) set to reach 200°C. Temperature was not reached overnight and starting material remained unchanged in the flask. The hot plate was reset and heating contiuned at 200°C for 20 hours. The flask was then removed from the heat and allowed to reach room temperature.

Column, 20-70% EtOAC/Hex

Frac 29-36 0.073 g, 0.16 mmol, 29 % - Very poor yield but extending the reaction time appears to destroy the product.

1H NMR - MNR20-6 frac 29-36 -
Attached Files
MNR20-1 scheme.png
MNR20-1 table.PNG
mnr20-1.pdf
mnr20-2.pdf
mnr20-3.pdf
mnr20-4.pdf
MW45-2d_column.pdf
MNR20-5 table.PNG
mnr20-6_frac 29-36.pdf
mnr20-5_crude.pdf