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KlementineJBS / USYD_PhD_ELN

This repository forms the electronic laboratory notebook (ELN)for Klementine Burrell-Sander's PhD's
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KBS16-5 - Azidation of ferrocenylmethanol #27

Closed KlementineJBS closed 1 year ago

KlementineJBS commented 1 year ago

Link to HIRAC, original method and master page.

KBS16 Ferrocenylmethanol to azidomethylferrocene DPPA.docx

Previous attempt was #17.

Reaction Scheme

Bromoadamantane to azidoadamantane (ELN)

Outcome

KlementineJBS commented 1 year ago

08.08.22

  1. Set up a flask under nitrogen
  2. Added KBS15-6 (#18) (341 mg, 1.58 mmol) by solution transfer (dry THF, 10 mL)
  3. Added DBU (0.3 mL, 2.01 mmol, 1.3 equiv.) and DPPA (0.4 mL, 1.86 mmol, 1.2 equiv.)
  4. After 10 minutes stirring, added NaN3 (116 mg, 1.78 mmol, 1.1 equiv.)
  5. Heated to 60 C and left from 4.45 pm
KlementineJBS commented 1 year ago

09.08.22

TLC indicated reaction was progressing but not yet complete - some SM remains. Noted that in previous attempt #17, reaction was worked up despite some SM remaining - however, wanted to see if increased reagents/further reaction time improved yield.

Extra products in SM lanes presumed to be due to degradation - sample used was #6, about 4 months old.

  1. Added extra DBU (0.15 mL, 1.00 mmol, 0.6 equiv.) and DPPA (0.2 mL, 0.93 mmol, 0.59 equiv.) at 11.15 am

Second TLC at 4.30 pm indicated reaction still not complete

KlementineJBS commented 1 year ago

10.08.22

TLC at 9.30 indicated reaction was complete.

  1. Diluted with water (40 mL)
  2. Extracted with toluene (3 x 50 mL)
  3. Washed with brine (100 mL)
  4. Dried over MgSO4 and rotovapped

Empty vial: 15.6728 Full vial: 16.4000 Mass: 727.2 mg (3.02 mmol, 191%)

H NMR

1H NMR (300 MHz, CDCl3) δ 4.22 (2H), 4.18 (2H), 4.15 (5H), 4.10 (2H).

KBS16-5 cr_1.zip KBS16-5 cr processed.pdf

Lots of solvent evident in NMR - ethyl acetate, toluene. Some minor peaks are unknown (3.33, 3.23, 3.01, 2.48, 2.34 and others).

Will column and re-NMR.

KlementineJBS commented 1 year ago

16.08.22

Fractions Empty vial Full vial Mass (mg) Yield (%) Compound
17 - 18 15.8661 16.0044 138.3 36 Product
19 - 21 16.2074 16.3144 107 - 28 Product (wet)
22 - 23 15.9654 15.9731 7.7 - 2 Uncertain
24 - 27 15.9252 15.9335 8.3 - 2 Uncertain
28 - 35 15.8950 15.9208 25.8 - 7 Uncertain
36 - 47 16.1763 16.1856 9.3 - 2 Uncertain

H NMR

1H NMR (300 MHz, CDCl3) δ 4.22 (2H), 4.18 (2H), 4.15 (5H), 4.10 (2H).

KBS16-5 F17-18_1.zip KBS16-5 F17-18 processed.pdf

Only impurity evident is small amount of water

KBS16-5 F19-21_1.zip KBS16-5 F19-21 processed.pdf

Some impurities - water, ethyl acetate, DCM. Also has small peak at 4.27 - integral of 0.22 suggests it is not part of compound.

Seems possible that minor spots on fractions are due to trace DPPA/DBU rather than SM or other ferrocenyl compounds. Can probably combine F17-18 with F19-21 for a total yield of 245 mg (1.02 mmol, 64%).

KBS16-5 F22-23_1.zip KBS16-5 F24-27_1.zip KBS16-5 F28-35_1.zip KBS16-5 F36-47_1.zip

KBS16-5 F22-47 processed.pdf

All of these fractions have miniscule quantities. Given the difficulty in determining whether they contain product or starting material, they will not be used further.

KlementineJBS commented 1 year ago

22.08.22

LRMS

Doesn't seem to work on ESI+

KBS16-5 F19-21.d.zip KBS16-5 F17-18.pdf KBS16-5 F19-21.pdf KBS16-5 F17-18.d.zip

KlementineJBS commented 1 year ago

23.08.22

IR

KBS16-5 F17-18.zip