KlementineJBS / USYD_PhD_ELN

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

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KBS52-3 - Nosyl deprotection of KBS51 #200

Open KlementineJBS opened 1 month ago

KlementineJBS commented 1 month ago

Link to HIRAC and master page #186

Reaction scheme

KlementineJBS commented 1 month ago

07.05.24

Added potassium carbonate (318 mg, 18 equiv.) to a 2-neck flask
Evacuated and backfilled x 3
Added KBS51-1 (140 mg, 0.127 mmol) dissolved in dry DMF (5 mL)
Added thiophenol (0.11 mL, 9 equiv.)

Left stirring at 80 C from 3.30 pm

KlementineJBS commented 1 month ago

H NMR - reaction mixture

Crude NMRs taken from RM at ~5pm yesterday and ~10 am this morning.

First indicates some SM remaining, in second there is no sign of it.

nmr300_20240509_KBS52-3 RM 09-05-24_1.zip nmr300_20240508_KBS52-3 RM_1.zip KBS52-3 RM.pdf

KlementineJBS commented 1 month ago

09.05.24

Workup - dilute with ethyl acetate (40 mL), washed with LiCl solution (3 x 20 mL), Na2CO3 solution (2 x 20 mL) and dried.

Vial:

Massive amounts of thiophenol and DIAD hydrazine make it difficult to pick out peaks from product. Maybe try basic purification before attempting analysis.

Later attempted to remove excess thiophenol by adjusting to pH 8 and re-extracting (amine should be nonpolar, thiol should be deprotonated and polar). Didn't seem to make any difference to amount of thiol by TLC - possibly suggesting that excess is of diphenyl sulfide or thiol-nosyl side product instead of unreacted reagent.

KlementineJBS commented 1 month ago

LRMS of crude

Peaks at 434+ and 845+ don't correspond to anything well known. Maybe thiophenol or related products?

KBS52-3 cr.d.zip KBS52-3 cr.pdf

KlementineJBS commented 1 month ago

10.05.24

Attempted another workup using acid/base. Performed LLE with ~60 mL DCM and 3 x 60 mL of hydrochloric acid (0.1 M, pH 1). Aqueous layer was clear, but upon basifying to pH > 14 the combined aqueous layers went cloudy. Followed with an extraction with DCM (3 x 60 mL) and brine wash. DCM extract was straw yellow in colour.

Vial: 15.9109 g

KlementineJBS commented 1 month ago

H NMR

Looks really good - some junk but almost no SM remaining (integral of 0.2 vs 4 for peak at 4.74 vs 4.05). Need to hivac, LCMS and HPLC.

nmr300_20240510_KBS52-3 crude_1.zip KBS53-2 crude.pdf

KlementineJBS commented 1 month ago

LRMS

KBS52-3 check.d.zip KBS52-3 check.pdf

KlementineJBS commented 1 month ago

13.05.24

Tried working up the remaining aqueous extracts to see if any more product was to be found. Followed same procedure as before but used ethyl acetate to extract at the end.

Note: initial DCM extract from acid/base workup was found to contain product along with either DIAD, thiol or both. Ethyl acetate extract contained no obvious product.

nmr300_20240513_KBS52-3 DCM extract_1.zip nmr300_20240513_KBS52-3 2nd extract_1.zip

KlementineJBS commented 1 month ago

No longer sure what this NMR is from - believed to be DCM extract from second acid/base workup but not 100% certain. Contains product.

KBS52-3 mystery.pdf nmr300_20240515_KBS52-3 2nd DCM_1.zip

KlementineJBS commented 1 month ago