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

KBS30-4 - N-alkylation with KBS29 #165

Closed KlementineJBS closed 2 months ago

KlementineJBS commented 6 months ago

Link to HIRAC and master page.

Previous attempt is #149

KBS30 - Generic alkylation of 1,x-diaminoalkane with naphthalene-triazole pendant (updated).docx

Notes

Re-attempting alkylation on mono-alkylated product. Done in dry conditions this time.

Reaction scheme

KlementineJBS commented 6 months ago

7.12.23

added K2CO3 (62.5 mg, 0.452 mmol, 1.5 equiv.) to a flask on ice and backfilled with N2 x 3
Added mono-alkylated amine (202.4 mg, 0.292 mmol) dissolved in dry DMF (3 mL)
Added KBS29 (107 mg, 0.373 mmol, 1.3 equiv.) dissolved dry DMF (2 mL)
Left stirring on ice from 2.35 pm

KlementineJBS commented 6 months ago

First TLC'd after ~ 1 hour. Did a TLC with all starting materials to determine nature of spots (SM = mono alkylated product, 43 = nosylated amine, 29 = brominated pendant).

Pendant group is clearly still present, with no sign of hydrolysis this time. Not sure why SM has two spots.

KlementineJBS commented 6 months ago

Another TLC at 11.30 am the next day suggested that the pendant group was consumed (although this was added in excess), but amine SM remained. LRMS was employed to investigate.

KlementineJBS commented 6 months ago

LRMS

At least some of the mono-alkylated SM is present (692.24, [M-H]-). Unsure what the large peak at 939.26+ represents.

KBS30-4 RM.pdf KBS30-4 RM.d.zip

KlementineJBS commented 6 months ago

08.12.23

Quenched with 20 mL ammonium chloride and put in fridge over the weekend.

KlementineJBS commented 6 months ago

12.12.23

Crystals/salt had formed in fridge over weekend. Worked up with ethyl acetate (3 x 25 mL) and brine wash. Possibly some material was left in the sep funnel.

Too much DMF to read NMR, so washed with water x 5 and brine x 1. Doesn't actually dissolve well in ethyl acetate - toluene is better but not great, DCM works quite well.

vial: 15.7538 mass: 252.9 mg (0.281 mmol assuming complete conversion, 96%)

KlementineJBS commented 5 months ago

Column details

Fractions	Vial mass (g)	Mass obtained (mg)	Identity/notes
8-9	15.9410	-	too little to characterise
10	15.7455	3	contains SM/mono
11-16	15.6697	161.4	contains SM, mono, bis
17-18	15.5883	9.8	contains mono
19-20	15.7448	3	contains bis
21-36	15.7191	39.6	doesn't seem to contain SM, mono or bis

KlementineJBS commented 5 months ago

LRMS

Signs of bis product (as well as mono and SM) in F11-16.

Positive: 923.25 is bis product [M+Na]+, 716.14 is mono product [M+Na]+. Negative: 485.04 is SM [M-H]-, 692.17 is mono [M-H]-, unsure about 975.23.

No sign of product or SM in F21-36 - peaks at 413.29+, 623.38+, 1023.79+, 1123+.

KBS30-4 F11-16.pdf KBS30-4 F21-36.pdf KBS30-4 F11-16.d.zip

This is interesting as it suggests that the 939+ peak previously seen in the crude sample was indeed indicative of bis-product having formed.

KlementineJBS commented 5 months ago