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24th August 2012 @ 06:26
Sc: 1-10
Synthesis of SC3-1 and SC3-2 from SC2-1.

HIRAC


SC3-1 and SC3-2 synthesis.pdf


Procedure followed:

The procedure was identical to that used for MNR41-9, with the following temperature and starting material modifications: The reaction was performed at ambient temperature (not -5 degrees Celsius) without the addition of PZQ, and the amount of starting material was downscaled to 100 mg.

SC2-1 (0.1010 g, 0.34 mmol) was reacted with acetyl chloride (0.05 mL, 0.61 mmol) in the presence of 2,6-lutidine (0.05 mL, 0.48 mmol) in acetonitrile (0.03 M, 13 mL), under argon gas and with stirring, to give SC3-1.
SC2-1 (0.1008 g, 0.34 mmol) was again reacted under the same conditions, with the addition of Yb(OTf)3 (0.0085 g/mL, 1.3 mL, 0.017 mmol) to give SC3-2.

SC3%20revised.png

SC3-1%20and%20SC3-2.png

24th August 2012

It was noticed that both solutions decolourised from a dark orange to light yellow upon addition of acetyl chloride. There was no visible difference between the two reactions due to the presence of Yb(OTf)3.

TLC analysis confirmed that both reactions had gone to completion after 6 hours.

Products were extracted in ethyl acetate (3 x 10mL) using sodium hydrogen carbonate. During the extraction of SC3-1 minor bubbling was observed, which was attributed to residual acid in the glassware. The products were obtained as oils in yields of greater than 100%, possibly indicative of residual reactants.

29th August 2012

SC3-1 was purified using silica column chromatography using ethyl acetate/hexane eluent. TLC analysis showed that fractions 40-48 contained a single product, but co-spotting was observed for fractions 14-23. Samples within these ranges were combined and solvent was removed. 1H NMR analysis of fractions 40-48 indicated a single product with clear signals in the aromatic region. A noticeable shift in the triplet signals previously observed at 3.2 and 4.0 ppm was also observed (indicative of cyclisation). Fractions 14-23 did not contain product, which was deduced from a lack of 1H NMR signals in the aromatic region. However, these fractions were retained in the interests of identifying this compound, as hydrolysis product(s) have been generated in similar experiments.

TLC analysis of SC3-1 crude sample:
SC3-1 fractions 1-20.JPG
SC3-1 fractions 21-40.JPG
SC3-1 fractions 41-60.JPG


NMR analyses:
11.09.12_SC3-1_column frac 14-23_1H.pdf
30.08.12_SC3-1_column frac 40-48_1H.pdf


3rd September 2012

SC3-2 was purified in the same way as SC3-1. Fractions 9-20, 21-26 and 27-42 were pooled, respectively. It was found that the latter two combined samples contained an aromatic species. Based on TLC analysis, fractions 21-26 appeared to contain an additional compound (similar co-spotting was observed during SC3-1 column separation). 1H NMR analysis elucidated the presence of a contaminant in fractions 27-42, whereas fractions 21-26 were cleaner. Fractions 9-20 did not contain an aromatic species. The contaminant was suspected to be residual 2,6-lutidine. TLC analysis supported this possibility. 2,6-lutadine is a clear, oily liquid with a boiling point of 144 degrees Celcius, which might explain the oily nature of the substance that was obtained post solvent evaporation. We intend to repeat these reactions due to a contamination of the laboratory hexane supply, which was used for the column purification described above. Contaminant is thought to have been octane (or some other high-boiling point hydrocarbon).

TLC analysis of SC3-2 crude sample:
SC3-2 fractions 1-20.JPG
SC3-2 fractions 21-40.JPG
SC3-2 fractions 41-57.JPG


NMR analyses:
06.09.12_SC3-2_column frac 21-26_1H.pdf
06.09.12_SC3-2_column frac 27-42_1H.pdf


Mass accounting...
Total yield for SC3-1: 0.1234 g, 0.368 mmol, 108% (N.B. lutidine contamination is thought to have caused this).

  • 24-39: 0.105g
    40-48: 0.0184g

Total yield for SC3-2: 0.0882 g, 0.263 mmol, 77%.

  • 9-20: 0.0101g
    21-26: 0.0431g
    27-42: 0.0350g

11th September 2012
TLC of SC3-2 with lutidine and SC2-1 indicates lutidine contamination:
lutidine contamination of SC3-2.JPG


Attached Files
SC3-1 and SC3-2 synthesis.pdf
SC3-1.png
SC3-2.png
SC3 revised.png
SC3-1 and SC3-2.png
SC3-1 fractions 1-20.JPG
SC3-1 fractions 21-40.JPG
SC3-1 fractions 41-60.JPG
SC3-2 fractions 1-20.JPG
SC3-2 fractions 21-40.JPG
SC3-2 fractions 41-57.JPG
11.09.12_SC3-1_column frac 14-23_1H.pdf
06.09.12_SC3-2_column frac 21-26_1H.pdf
06.09.12_SC3-2_column frac 27-42_1H.pdf
11.09.12_SC3-1_column frac 14-23_1H.pdf
30.08.12_SC3-1_column frac 40-48_1H.pdf
lutidine contamination of SC3-2.JPG