Hello board !
I'm planning on following the following methodologie in order to form hydroxamate from a carboxylic acid :
CDI (4.5 mmol, 1.5 eq) was added to a solution of carboxylic
acid 1 (3.0 mmol) in dry tetrahydrofuran (THF) (5 ml). The reaction mixture was
stirred for 1 h. Powdered hydroxylamine hydrochloride (417 mg, 6 mmol) was added.
The resulting mixture was stirred overnight (ca. 16 h). The mixture was diluted with
5% aq. KHSO4 (30 ml) and extracted with EtOAc (230 ml). The combined organic
phase was washed with brine (30 ml) and dried over Na2SO4. The extract was filtered
and concentrated in vacuo to give the product 3.
(Usachova, N. et al. Synthetic Communications, 2010, 40(6), 927–935.)
Since the rxn mixture is further diluted with aq. KHSO4 I guess here solvent as EtOAc or DCM are not an alternative ?
I am a bit pertubated with the whole solvent choice thing. How do you guys orientate your choice ?
DMF, MeCN ? What would you choose in this case ?
Now regarding the acidic work up ? The 5% aq. KHSO4 dilution objective is what ? Reprotonate products of the reaction ? Now I have a question as a phytochemist I often do A/B extraction aiming to selectively isolate alkaloids. In my reaction there I'll have N-containing compounds. Generally acidification of the solution will lead to a greater water solubility an a decreased apolar solvent solubility. Now in this case since the next step is an EtOAc partition in't that an issue ?
Another thing (sorry for my obsession with alternatives but I'm in a natural products lab ... crucial lack of reagents here ) What alternative do I have for the 5% aq. KHSO4 dilution ? Will aq. HCl do the trick ? What proportion then ?
Thanks again for all feedback