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23rd January 2014 @ 04:53

Reaction successful with 75% yield

Repeat of Synthesis of N,N-Dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (AEW 91-1) on twice the scale

Reaction scheme

Procedure

CT 4-1 (528 mg, 2 mmol, 1 equiv.), potassium acetate (785 mg, 8 mmol, 4 equiv.) and bis(pinacolato)diboron (762 mg, 3 mmol, 1.5 equiv.) were dissolved in anhydrous 1,4-dioxane (10 mL). Argon was bubbled through the suspension for 10 minutes before [1,1-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (73 mg, 0.1 mmol, 0.05 equiv.) was added and the suspension heated with reflux and stirring overnight. 

The crude reaction mixture was purified by flash column chromatography over silica (20-30% EtOAc/petroleum) to yield CT 5-1 as a white powder (467 mg, 1.5 mmol, 75%).

Data

-TLC

Crude reaction mixture after mini work-up in ethyl acetate/water. Solvent 50% EtOAc/hexane, stained with anisaldehyde. Major spot appears to be desired product upon comparison with AEW 91-1.

After column purification: 20-30% EtOAc/hexane, desired product eluted quickly and with other spots. Still need to check purity by 1H NMR, but lower polarity and a slower gradient required for future columns. Fractions 3-6 were combined (impure product, may require further purification), and fractions 7-16 (clean fraction). 

 -NMR

1H NMR of first fraction. No previous characterisation data in last attempt in this notebook (AEW ). However, signals are similar to CT 2-1, but consistent with the additional methyl group. Protons ortho- to the N,N-dimethylsulfonamide substituent are shifted slightly upfield relative to CT 2-1 due to extra electron donation from the additional methyl group. 

Sample is not quite dry, with ethyl acetate present in the spectrum, but otherwise looks pure with no other unexpected peaks. Sample needs to be further dried before taking another spectrum.

CT 5-1 column fraction 1 proton.pdf

Sample after drying

CT 5-1 fraction 1 dry.pdf

 

1H NMR of second fraction. Similar spectrum to first fraction, however there appears to be an impurity. Not sure if fraction was impure, or if flask/NMR sample was contaminated as the TLC straight after the column showed only one spot. Need to re-purify with a less polar solvent system. 

CT 5-1 column fraction 2 proton.pdf

After a second column using lower polarity (0-20% EtOAc).

'Major' fraction (concentrated fractions)

CT 5-1 fraction 2 major.pdf

'Minor' fraction (less concentrated fractions before/after major fraction)

CT 5-1 fraction 2 minor.pdf

Did not continue with trying to purify the second fraction from the first column, as obtained expected yield from the first fraction (see AEW 91-1)

HIRAC

CT 5-1 HIRAC.pdf

InChI strings

InChI=1S/C8H10BrNO2S/c1-10(2)13(11,12)8-5-3-4-7(9)6-8/h3-6H,1-2H3

and

InChI=1S/C12H24B2O4/c1-9(2)10(3,4)16-13(15-9)14-17-11(5,6)12(7,8)18-14/h1-8H3

to 

InChI=1S/C14H22BNO4S/c1-13(2)14(3,4)20-15(19-13)11-8-7-9-12(10-11)21(17,18)16(5)6/h7-10H,1-6H3

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Attached Files
CT 5-1 scheme.cdx
CT 5-1 HIRAC.doc
CT 5-1 HIRAC.pdf
CT 5-1 scheme.png
CT 5-1 column 1.JPG
CT 5-1 column 2.JPG
CT 5-1 column 3.JPG
CT 5-1 TLC crude.JPG
CT 5-1 column fraction 1 proton.pdf
CT 5-1 column fraction 2 proton.pdf
CT 5-1 column fraction 1.zip
CT 5-1 column fraction 2.zip
CT 5-1 fraction 2 minor.zip
CT 5-1 fraction 2 major.zip
CT 5-1 fraction 1 dry.zip
CT 5-1 fraction 1 dry.pdf
CT 5-1 fraction 2 major.pdf
CT 5-1 fraction 2 minor.pdf
Comments
Re: N,N-Dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (CT 5-1) by Matthew Todd
27th January 2014 @ 09:53
Looks like you have some nice fractions with pure product in there? Does the mass of the combined mixed fractions justify further purification?