KlementineJBS / USYD_PhD_ELN

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

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KBS53-1 - Nosyl deprotection of KBS48 #190

Closed KlementineJBS closed 2 months ago

KlementineJBS commented 3 months ago

Link to HIRAC and master page #186

KBS44 Nosyl deprotection of linear amines.docx

Reaction scheme

KBS44 - Nosyl deprotection of linear amine

Outcome

Mass purified: 13.7 mg (0.026 mmol, 20%)

KlementineJBS commented 3 months ago

26.03.24

Dissolved SM KBS48-2 (116.4 mg, 0.129 mmol) in dry DMF (4 mL)
Added thiosalicyclic acid (123.2 mg, 0.799 mmol, 6.2 equiv.) as thiol is probably degraded (dimerised) to some extent
Added potassium carbonate (146.1 mg, 1.06 mmol, 8 equiv.)
Left stirring at 60 C from 2.50 pm
Heated to 80 C at 3.50 pm

KlementineJBS commented 3 months ago

27.03.24

TLC was somewhat difficult - needed to spot directly from flask to get clear definition.

Run in 5% MeOH + NH4 in DCM. Ninhydrin staining. Thiol sticks to baseline while SM amine is quite non-polar.

KlementineJBS commented 3 months ago

LRMS (reaction mixture)

Peak at 531.27+ indicates desired product [M+H]+. Tiny peak at 716.27+ indicates singly-denosylated product [M+H]+.

Impurities: 273.92- indicates nosyl/thiosalicyclic acid byproduct [M-H]-

KBS53-1 RM repeat.pdf KBS53-1 RM repeat.d.zip

KlementineJBS commented 3 months ago

Added more thiol using a different thiol this time: 2,2′-(ethylenedioxy)diethanethiol (84.2 uL, 4 equiv.).

This paper describes using this thiol and getting equivalent results to mercaptoethanol or thiophenol.

KlementineJBS commented 3 months ago

LRMS

KBS53-1 RM 28-03-24.pdf KBS53-1 RM 28-03-24.d.zip

KlementineJBS commented 3 months ago

28.03.24

Work up as in #188 using 25 mL for all volumes.

vial: 15.9099 mass: 51.3 mg (if this was all product, which it is not -- 0.097 mmol = 75%)

KlementineJBS commented 3 months ago

H NMR

Looks like product is there, along with lots of the second thiol used - will have to remove this to get accurate yields. Not clear whether singly deprotected product is present.

nmr300_20240328_KBS53-1 cr_1.zip nmr300_20240328_KBS53-1 residue_1.zip

KlementineJBS commented 2 months ago

Really struggled to column and realised this was due to the amines sticking to the column - needed to use a solvent system containing base to get them off. Had initially tried DCM/acetone which seems to have just separated the thiols/byproducts out.