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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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2023_BG_11D_1 - Bromination of 2-acetylpyridine #101

Closed KlementineJBS closed 1 year ago

KlementineJBS commented 1 year ago

Safety

HIRAC NBS reaction Breaking Good.docx

Reaction scheme

NBS reaction - formation of bromoketones

KlementineJBS commented 1 year ago
  1. Dissolved 2-acetylpyridine (1 g, 0.925 mL, 8.25 mmol) in acetonitrile (200 mL)
  2. Added p-toluenesulfonic acid monohydrate (2.360 g, 12.38 mmol, 1.5 equiv.)
  3. Put in ice bath and added N-bromosuccinimide (1.620 g, 9.08 mmol, 1.1 equiv.) slowly
  4. Heated to reflux from ~ 10.45 am

TLC's indicated that reaction was not complete.

  1. added more NBS (0.7514 g, 4.22 mmol, 0.5 equiv.) at 4.25

Some starting material still evident by TLC at 5.30 pm. Took reaction off anyway and rotovapped off excess solvent

20% ethyl acetate in hexanes, vanillin

KlementineJBS commented 1 year ago
  1. Dissolved sticky residue in DCM (45 mL) and washed with water (3 x 50 mL).
  2. Dried over mag sulphate and rotovapped down.

LRMS

Product not apparent.

2023_BG_11D_1.pdf 2023_BG_11D_1.d.zip

KlementineJBS commented 1 year ago

Realised that product is a salt and likely remained in aqueous phase.

  1. Basified aqueous phase to ~ pH 8 using sodium bicarbonate solution (sat.)
  2. Extracted with DCM (6 x 80 mL)
  3. Dried over mag sulphate and rotovapped down

H NMR

Inconclusive. This literature source quotes the following spectrum:

¹H NMR (500 MHz, CDCl3): δ = 8.70 (d, J = 4.6 Hz, 1 H), 8.11 (d, J = 8.0 Hz, 1 H), 7.90-7.87 (m, 1 H), 7.54-7.52 (m, 1 H), 4.87 (s, 2 H)

It appears that there is some amount of product in both the organic extract first obtained (labelled org extract) and that obtained after basification. However, the org extract sample also seems to contain SM as indicated by the peak at 2.75.

Note: the SM should contain a methyl peak at 2.75 and the product a methylene peak at 4.87 - see this literature source for NMR spectrum of 2-acetylpyridine.

2023_BG_11D_1 org extract_1.zip 2023_BG_11D_1_1.zip 2023_BG_11D_1.pdf

Actions

KlementineJBS commented 1 year ago

01.06.23

Combined extracts from above and re-reacted using p-toluenesulfonic acid (2.36 g, 12.4 mmol, 1.5 equiv) and NBS (9.09 mmol, 1.1 equiv.). Heated at ~85 C for a few hours.

TLC indicated that very little SM was left.

(Vanillin, 20% ethyl acetate in hexanes)

Removed excess solvent by rotary evaporation, added sodium bicarb solution (sat.) to convert product(s) to free base (adjusted to pH 8) and extracted with DCM (4 x 100 mL).

Washed with brine and dried over mag sulphate, then removed excess solvent by rotary evaporation and blowing down with nitrogen overnight.

Vial: 15.

KlementineJBS commented 1 year ago

H NMR

2023_BG_11D_1 + 11D_2.pdf 2023_BG_11D_1_1 (1).zip 2023_BG_11D_1 org extract_1.zip 2023_BG_11D_1_1.zip