KlementineJBS / USYD_PhD_ELN

This repository forms the electronic laboratory notebook (ELN)for Klementine Burrell-Sander's PhD's

2 stars 0 forks source link

KBS24-1 - Click coupling of bis-propargyl diaminohexane and azidomethylferrocene #44

Closed KlementineJBS closed 1 year ago

KlementineJBS commented 1 year ago

Link to HIRAC, original method and [master page].

KBS24 Linear amine click coupling with azidomethylferrocene.docx

Reaction scheme

KBS24 linear amine click coupling with azidomethylferrocene

Outcome

62.1 mg (0.071 mmol), 70%

KlementineJBS commented 1 year ago

Amounts:

40 mg (0.102 mmol) linear amine
need 2.3 equiv. azidomethylferrocene = 0.234 mmol = 56.5 mg
reduce solvent to 2 mL each water/THF
need 0.2 equiv. copper sulphate = 0.0204 mmol = 5.1 mg
need 0.5 equiv. NaAsc = 0.051 mmol = 10.1 mg

Checked azide was OK before using - see NMRs.

KBS16-4 25-10-22_1.zip KBS16-4 25-10-22 processed.pdf

KlementineJBS commented 1 year ago

25.10.22

Sparged water and THF.

Added copper sulfate pentahydrate (10.0 mg) and sodium ascorbate (23.2 mg) to flask, evacuated and backfilled with N2 three times. Added sparged water (2 mL).

Added azidomethylferrocene (58.2 mg, 0.241 mmol, 2.3 equiv.) and bis-propargyl diaminohexane (42 mg, 0.107 mmol), each dissolved in 1 mL sparged THF.

Initially the reaction mixture settled into two layers - mostly green with a ring of orange on top. Adding 1 mL water increased the amount of green, adding 3 mL THF reduced the ring of orange. Left stirring from 6pm.

KlementineJBS commented 1 year ago

26.10.22

TLC'd at 12 pm. Appears to show that while starting material is consumed, there is a mixture of mono and bis click products.

SM = azidomethylferrocene solvent = 95:4.5:0.5 DCM:methanol:NH4OH

LRMS

KBS24-1 RM 26-10-22.pdf KBS24-1 RM 26-10-22.d.zip

Peaks indicate formation of mono click product (656.30, [M+Na]) and bis click product (897.34, [M+Na]). Small amounts of boc-protected amine and bis propargyl amine present (339, 415). Unsure about 495, 510, 41, 822, 1021 peaks.

Worked up at 4.30 pm - removed THF by rotary evaporation, extracted with DCM (4 x 5 mL) and washed with brine (20 mL). Left in conical over long weekend.

KlementineJBS commented 1 year ago

26.10.22

At 2.30 pm, added more sodium ascorbate (28.7 mg) as the green colour of reaction indicated oxidation of copper. Green colour gradually lessened.

KlementineJBS commented 1 year ago

31.10.22

Dried over MgSO4 and rotovapped down.

Empty vial: 15.7889 Full vial: 15.9281 Mass: 139.2 mg

LRMS

KBS24-1 cr.pdf KBS24-1 cr.d.zip

Peak at 897.32 [M+H]. Unsure what peaks at 959.45, 981.42 and 1021.33 represent - 1021 was also seen in reaction mixture earlier, but other two were not.

H NMR

KBS24-1 cr_1.zip KBS24-1 cr.pdf

Initial analysis indicates product has formed - boc peaks at 1.44, ferrocene peaks around 4.14 - 4.40.

KlementineJBS commented 1 year ago

08.11.22

Trying to find solvent system for columning.

TLCs in 2%, 3% and 5% MeOH in DCM

TLCs in 2%, 3% and 5% MeOH in DCM - MeOH contains 10% ammonium hydroxide

Determined on 0-5% then 5% using MeOH with 10% NH4OH.

KlementineJBS commented 1 year ago

09.11.22

Column conditions

Pooled fractions 5-7 to give a bright yellow coloured liquid. Rotovapped down.

Empty vial: 15.7074 Full vial: 15.7695 Mass: 62.1 mg

H NMR

KBS24-1 F5-7_1.zip KBS24-1 09-11-22.pdf

1H NMR (300 MHz, CDCl3) δ 7.49 (2H), 5.25 (4H), 4.39 (4H), 4.15-4.24 (18H), 3.18 (4H), 1.53 (2H), 1.43 (4H), 1.40 (18H), 1.19 (4H).

Partial assignment (using numbers from MestreNova prediction): δ 7.49 (triazole, 11 & 17), 5.25 (methylene, 34 & 48), 4.39 (methylene, 9 & 15), 4.15-4.24 (ferrocene, varied), 3.18 (hexane), 1.53 (hexane), 1.43 (hexane), 1.40 (boc groups), 1.19 (hexane).