KBS28-3 - Click coupling of 1-azido-naphthyl and propargyl alcohol

[KlementineJBS]

Link to HIRAC and master page. Original method can be found in J. Batten's PhD thesis (2022).

KBS28 - Click coupling with 1-azidonaphthalene and propargyl alcohol.docx

Previous attempt is #55

Reaction scheme

Outcome

618 mg, 53%

[KlementineJBS]

16.02.23

Added sodium ascorbate (514 mg, 2.56 mmol) and copper sulphate pentahydrate (263 mg, 1.05 mmol) to a flask. Dissolved KBS23-4 (897 mg, 5.15 mmol) in THF (12 mL) and added to flask, then added propargyl alcohol (2.4 mL, 41.2 mmol, 8 equiv.) and water (4 mL).

Had to add additional water and THF to get phases to mix.

[KlementineJBS]

17.02.23

Reaction was a bright carrot orange.

Some starting material remained evident but it was thought this may be due to the highly UV active nature of the SM.

Ammonium hydroxide in methanol (1:9) was added by mistake. Ammonium chloride was then added (10 mL) to quench and then the methanol was removed via rotary evaporation.

The mixture was extracted with diethyl ether (4 x 20 mL), washed with water (2 x 50 mL) and brine (2 x 50 mL).

[KlementineJBS]

22.02.23

Columned but had difficulties dissolving. Ultimately used DCM but some material was left undissolved on the column bed.

Column 1

Column 2

Collected fractions 1-13 (azide SM) and 22-34 (product) from column 1, and fractions 1-14 from column 2.

SM vial weights Empty: 16.0912 Full: 16.3787 Mass: 287.5 mg (1.70 mmo, 33%)

Product vial weights (F22-34) Empty: 15.9967 Full: 16.5343 Mass: 537.6 mg (2.39 mmol, 46%)

Product vial weights (F1-14) Empty: 16.0504 Full: 16.1305 Mass: 80.1 (0.356 mmol, 7%)

Total mass recovered = 617.7 mg (2.74 mmol), 53%

Run in ethyl acetate in hexanes, 40%

H NMR

Azide SM

1H NMR (300 MHz, Chloroform-d) δ 8.06 – 8.00 (m, 1H), 7.78 – 7.72 (m, 1H), 7.56 (d, J = 8.3 Hz, 1H), 7.47 – 7.36 (m, 3H), 7.21 – 7.16 (m, 1H).

KBS28-3 SM_1.zip KBS28-3 SM (azide).pdf

Product

1H NMR (300 MHz, Chloroform-d) δ 7.99 (dd, J = 5.4, 4.1 Hz, 1H), 7.93 (d, J = 6.3 Hz, 2H), 7.62 – 7.44 (m, 6H), 4.98 (s, 2H).

KBS28-3_1.zip KBS28-3 2nd column_1.zip KBS28-3 product.pdf

[KlementineJBS]

Notes on appearance

Product was a reddish colour when warm but became a pale, orange-tinged powdery residue as it cooled.