cationicNuisance - 20-11-2021 at 01:05
So I was looking over some random papers and i had the idea to propose a synthesis of N-methylpyrrolidine-N-oxide from proline. It has a similar
structure to N-methymorphiline-N-oxide which can apparently dissolve cellulose so I figure it might be interesting?
My idea is to start with proline, decarboxylate it with heat in the presence of an electron-deficient aldehyde/ketone, then methylate it using the
Eschweiler-Clark reaction. One interesting paper I found suggests that n-methylation can be done in excess molten oxalic acid and with 1:1
amine-to-polyformaldehyde, conditions which are very similar to the decarboxylation - does that imply that decarboxylation and n-methylation can take
place in one pot? (The authors didn’t try any alpha-aminoacids, so I’m gonna be hopeful and not rule it out). The prospect of doing this is what
motivated me to think about this synthesis in the first place.
Afterwards, I’d have to oxidize the n-methylpyrrolidine to the oxide, using peroxide/peracid. One intriguing thing is that since the reaction
mixture from the modified Eschweiler-Clarke would be a solid mass of excess oxalic acid and n-methylpyrrolidinium oxalate, what if I could just crush
up the mass and directly add it to a hydrogen peroxide-ice bath to make crude peroxalic acid in situ? This would be basically the dream reaction -
one-pot synthesis and workup without even having done any distilling yet.
I can’t imagine what the workup would look like, though. It’d probably have a high boiling point, so I probably can’t distill it directly. My
guess is it’d involve boiling down the solution (destroying any leftover peroxide/oxalic acid in the process).
What do you think?
Eschweiler-Clarke with oxalic acid and polyformaldehyde - https://www.researchgate.net/profile/Paul-Kosma/publication/...
clearly_not_atara - 20-11-2021 at 07:11
N-methyl amine N-oxides can undergo autocatalytic decomposition where the byproduct formaldehyde catalyzes further decomposition. I suggest you read
up about the safety issues with these compounds before proceeding.