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5th January 2012 @ 00:04
Further attempts to sort out the problems of the Newman-Kwart Rearrangement using a microwave assisted procedure and DMA as a solvent.

Burns, M.; Lloyd-Jones, G. C.; Moseley, J. D.; Renny, J. S. Journal of Organic Chemistry 2010, 75, 6347.
Moseley, J. D.; Lenden, P. Tetrahedron 2007, 63, 4120.

MNR20-11%20scheme.png



Hazard and Risk Assessment:
HIRAC MNR20-11.pdf


Procedure
MNR20-11


Recovered MNR19 from MNR20-10 (0.50 g, 1.09 mmol) in DMA (2 mL) was sealed in a microwave tube and heated at 200 °C for 10 minutes followed by 250 °C for 10 minutes (mistake in starting experiment and should have been at 250 °C for the entire run)

The brown solution was then poured into 1% aqueous KOH solution (30 mL) where a off white solid precipitated out instantly. The solid was filtered and washed with water and dissolved in DCM, dried over magnesium sulfate, filtered and concentrated to give a brown crystalline solid (0.522 g, >100%)

TLC showed incomplete reaction.

SANY0111.JPG


TLC 50% EtOAc/Hex

Column 1, MNR19-2
Column 2, co-spot MNR19-2 and Reaction mixture after work up
Column 3, Reaction mixture after work up
Column 4, co-spot Reaction mixture after work up and MNR20-7 (Product)
Column 5, MNR20-7 (Product)

Unknown spot sitting between starting material and product - possible compound that's only rearranged at one site?

Proton NMR shows starting material, possible proposed intermediate and product in a ratio of 1:0.75:1.5. NMR also shows traces of DMA which shows up between 2-3 ppm when the new peaks are expected to be found.

mnr20-11_crude nmr

overlay of starting material, crude and product

zoomed in overlay

Next step - repeat with longer reaction time and possible higher temperature.

Procedure
MNR20-12


Recovered MNR19 from MNR20-10 (0.25 g, 0.55 mmol) in DMA (1.5 mL) was sealed in a microwave tube and heated with the gaol to reach 300 °C for 30 minutes. Actual heating resulted in a 5 minute ramp reaching 230 °C then the cooling was turned off and the raction was left on hold for 30 minutes during which the temperature rose to 290 °C.

The brown solution was then poured into 1% aqueous KOH solution (30 mL) where a off white solid precipitated out instantly. The solid was filtered and washed with water and dissolved in DCM, dried over magnesium sulfate, filtered and concentrated to give a light brown, fluffy crystalline solid (0.220 g, 88%)

*reaction carried out on a smaller scale to conserve starting material


mnr20-12_crude nmr greater conversion than for mnr20-11

Column - 25% EtOAC/Hex

Frac 5-6 tare 48.133 - SM and unknown spot (by TLC)

Frac 7-11 0.105 g, 42 % - mainly product and trace of unknown spot

Procedure
MNR20-13


Recovered MNR19 from MNR20-10 (0.25 g, 0.55 mmol) in DMA (1.5 mL) was sealed in a microwave tube and heated with the gaol to reach 300 °C for 1 hour.

The brown solution was then poured into 1% aqueous KOH solution (30 mL) where a off white solid precipitated out instantly. The solid was filtered and washed with water and dissolved in DCM, dried over magnesium sulfate, filtered and concentrated to give a light brown, fluffy crystalline solid (0.120 g)

TLC did not correspond to previous attempts.

** NMR needs added **

Conclusion, even in DMA reaction can be left too long. Let's just try and tweak the mnr20-12 conditions a little.

Procedure
MNR20-14


MNR19-4 (1.0 g, 3.49 mmol) in DMA (3 mL) was sealed in a microwave tube and heated with the goal to reach 300 °C for 30 minutes - 5 minute ramp time followed by hold for 25 minutes, no cooling during the reaction.

Microwave printout for MNR20-14

The brown solution was then poured into 1% aqueous KOH solution (30 mL) where a off white solid precipitated out instantly. The solid was filtered and washed with water and dissolved in DCM, dried over magnesium sulfate, filtered and concentrated to give a light brown, fluffy crystalline solid. ** (need dry mass) **

2012-01-17 17.03.24.jpg


TLC 50% EtOAc/Hex

Column 1, MNR19-2
Column 2, co-spot MNR19-2 and Reaction mixture after work up
Column 3, Reaction mixture after work up
Column 4, co-spot Reaction mixture after work up and MNR20-7 (Product)
Column 5, MNR20-7 (Product)

Again, as for MNR20-13, the TLC did not correspond to previous attempts.

Conclusion, let's repeat the conditions for MNR20-12, looks like increasing the concentration is not favoured although the literature suggests it should help the reaction.

Procedure
MNR20-15
18/01/2012

MNR19-4 (0.25 g, 0.55 mmol) in DMA (1.5 mL) was sealed in a microwave tube and heated with the gaol to reach 300 °C for 30 minutes. Actual heating resulted in a 5 minute ramp reaching 160 °C then the cooling was turned off and the raction was left on hold for 30 minutes during which the temperature rose to 262 °C.

Microwave printout for MNR20-15

The brown solution was then poured into 1% aqueous KOH solution (30 mL) where a off white solid precipitated out instantly. The solid was filtered and washed with water and dissolved in CHCl3, dried over magnesium sulfate, filtered and concentrated to give a light brown, fluffy crystalline solid (XXXXXX?)

Column - 25% EtOAC/Hex
Attached Files
MNR20-11 scheme.png
HIRAC MNR20-11.pdf
SANY0111.JPG
mnr20-11_crude.pdf
mnr20-11_sm_prod.pdf
mnr20-11_sm_prod_zoom.pdf
mnr20-11.zip
mnr20-12.zip
mnr20-12_crude.pdf
mnr20-12_frac7-11.pdf
2012-01-17 17.03.24.jpg
2012-01-18 16.15.41ed.jpg
mnr20-14.pdf
mnr20-15.pdf