[samuelima10]

Hello, I'm currently trying to characterize a macrocycle by NMR, but I'm having difficulty executing it.
My basic articles do the analysis using methanol-d4 or deuterium oxide.
However, in my tests, the molecule has extreme difficulty being solubilized in these solvents, causing the solution to precipitate with just a few milligrams added.
I filter the solutions when they present precipitation, but the NMR cannot capture the molecule, even when I use high frequencies.
I know that the molecule easily solubilizes in NaOH.
I'm thinking of preparing NaOH + D2O and doing the NMR later, could this solution cause any possible interference in the analysis?
I don't know how to proceed

[wildfyr]

Have you tried DMSO d6?

[rjb]

Hello, I'm currently trying to characterize a macrocycle by NMR, but I'm having difficulty executing it.
My basic articles do the analysis using methanol-d4 or deuterium oxide.
However, in my tests, the molecule has extreme difficulty being solubilized in these solvents, causing the solution to precipitate with just a few milligrams added.
I filter the solutions when they present precipitation, but the NMR cannot capture the molecule, even when I use high frequencies.
I know that the molecule easily solubilizes in NaOH.
I'm thinking of preparing NaOH + D2O and doing the NMR later, could this solution cause any possible interference in the analysis?
I don't know how to proceed

I have to be honest that I don't know a lot about macrocyclic compounds but it seems like yours have some solubility issues which is the root of the problem. Before I make a suggestion, is your molecule remotely soluble in any of the common (and not horrifically expensive) NMR solvents like DMSO (as suggested by Wildfyr) or is it (as I suspect) going to play hard ball? If you have enough of the stuff, I would try to determine solubility using a number of undeuterated solvents (ideally those which are also available as deuterated NMR solvents) first just to see if there is any possibility of sufficient solubility for NMR or not.

If not, then the NaOH idea is a possibility, but you would obviously end up with an increased residual H2O peak which might cause you some issues but is perhaps worth a try... I wonder if it might be possible to add a little Sodium metal into D20 to form NaOD soln.? That should work in theory and might solve your issues? Let us know how you get on.

R

[wildfyr]

 "Sodium metal into D20 to form NaOD soln."

the bazooka approach! I've never heard of such a thing, haha wow

[Babcock_Hall]

A long time ago I purchased some NaOD, but I have not checked to see whether or not it is still commercially available.

[RedViper9]

Cambridge Isotopes and Sigma both sell 40wt% NaOD in D2O, so it should be attainable.

D2O with addition of small portions of NaH will be more controllable, but still 'exciting'.

[rjb]

"Sodium metal into D20 to form NaOD soln."

the bazooka approach! I've never heard of such a thing, haha wow

Absolutely! The trouble is when you need to get something done and the lead times on what you need just don't work out (I'm still waiting on a compound I ordered from Sigma-Aldrich back in early March 2022!), sometimes, you've got go down the bazooka route... I figured that if the OP was doing NMR, they're going to have D2O and everyone has some Sodium tucked away in a cupboard somewhere; unconventional but I'll bet it works!

[wildfyr]

Note: Do not put Na sodium into contact with CDCl3 or any halogenated solvent, it can explode.