KBS38-3 - NBS reaction on 2-acetyl-6-bromopyridine

[KlementineJBS]

Link to HIRAC.

HIRAC NBS reaction Breaking Good.docx

Previous attempt using NBS is #115

Reaction scheme

Outcome

1.367 g total, calculated mass of product is 1.30 g = 89% yield

[KlementineJBS]

1. Dissolved 2-acetyl-6-bromopyridine (1.0121 g, 5.06 mmol) in MeCN (200 mL)
2. Added tosic acid (1.4464 g, 7.60 mmol, 1.5 equiv.) and NBS (1.0893 g, 6.12 mmol, 1.2 equiv.)
3. Left stirring at 82 C from 9.45 am

TLC at 2.30 pm indicated reaction was occurring but not yet complete.

Vanillin stain, 30% EA in hexanes

[KlementineJBS]

Note that TLC from previous day showed a much stronger orange spot in the RM lane after having been left out overnight. New TLC at ~ 12 pm indicated SM was consumed and a new product had formed. Was surprised that the product had a substantially different Rf to the SM in 10% ethyl acetate in hexanes. (UV/vanillin)

4. Removed MeCN via rotovap
5. Dissolved in DCM (100 mL)
6. Washed with water (2 x 100 mL). Clear yellow solution turned cloudy, pale white/yellow upon addition of water.
7. Washed with brine (100 mL)
8. Dried over mag sulphate and rotovapped

Vial: 15.6920 Full vial: 17.0592 Mass: 1.367 g

[KlementineJBS]

H NMR

NMR indicated 95% of mass is product (mono and di bromo), which corresponds to an 89% yield.

Bromination percentage calculations.xlsx KBS38-3.pdf KBS38-3 cr_1.zip