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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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KBS28-2 - Click coupling of 1-azido-naphthyl and propargyl alcohol #55

Closed KlementineJBS closed 1 year ago

KlementineJBS commented 1 year ago

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 #53.

Need to use GSP 7.3.1 ii - this involves heating the reaction to 50 C overnight (instead of rt for 1 hr). Will also use purified KBS23.

Reaction scheme

KBS28 - Click coupling of 1-azidonaphthalene and propargyl alcohol

Outcome

243.4 mg, 67% (improvement of ~ 20% on #53)

KlementineJBS commented 1 year ago

01.02.23

  1. Added sodium ascorbate (165 mg, 0.83 mmol, 0.5 equiv) and copper sulphate pentahydrate (84.6 mg, 0.339 mmol, 0.2 equiv) to a 2-neck flask
  2. Backfilled with N2 x 5
  3. Added 1-azido-naphthyl (#56) (274.4 mg, 1.62 mmol) dissolved in sparged THF (5 mL)
  4. Added propargyl alcohol (0.2 mL, 194.4 mg, 3.47 mmol, 2.1 equiv)
  5. Added sparged distilled water (1.6 mL)
  6. Heated to 50 C and left stirring from 4.30 pm
KlementineJBS commented 1 year ago

02.02.23

TLC'd at 10.30 am and found SM was still evident.

Eluent is 60% ethyl acetate in hexanes, stain is PMA. Spots are UV visible. Azide SM = top spot, product (?) = lower spot>

  1. Added additional propargyl alcohol (0.2 mL, 194.4 mg, 3.47 mmol, 2.1 equiv) and left stirring at 50 C

TLC'd at 4.45 pm. Still evidence of SM, so added more propargyl alcohol (0.46 mL, 7.8 mmol, 4.8 equiv) for a total of 9 equiv.

KlementineJBS commented 1 year ago

03.02.23

TLC'd at 10.30 am. Still evidence of SM but decided to work up anyway.

  1. Quenched with ammonium chloride (10 mL)
  2. Extracted with DCM (4 x 10 mL)
  3. Washed with water (40 mL) and brine (40 mL)
  4. Dried over mag sulphate

Crude vial weight: 15.6322 Full vial: 16.0528 Mass: 420.6 mg

Obtained as a dark orange/reddish liquid.

KlementineJBS commented 1 year ago

06.02.23

Over the weekend the reddish liquid has crystallised (?) into a fungal-looking grey solid.

image image image

NB. 40% TLC eluent in top left presumed to be inaccurate -- remade fresh batch for TLC on bottom left.

image
Fractions Vial weight Mass Moles % Compound
1-5 15.6698 37.7 0.22 14 Azide SM
16-22 15.5998 22.1 n/a - nil
26-27 15.3850 20.4 n/a - nil
28-33 15.6481 243.4 1.08 67 product

Product obtained as a fine, pale orange powder.

image
KlementineJBS commented 1 year ago

07.02.23

H NMR

KBS28-2.pdf

KBS28-2 F1-5_1.zip KBS28-2 F6-9_1.zip KBS28-2 F16-22_1.zip KBS28-2 F26-27_1.zip KBS28-2 F28-33.1.zip

LRMS

KBS28-2.pdf KBS28-2.d.zip

Peaks at 226.15 [M+H]+ and 248.14 [M+Na]+ - in agreement with previous attempts.