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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: oldmchorny on September 21, 2021, 09:00:38 AM

Title: How to functionalize polyallylamine?
Post by: oldmchorny on September 21, 2021, 09:00:38 AM
Dear everyone,

I've got a question regarding the functionalization of polyallylamine. I am not much of a polymer chemist, so please treat me with leniency.
As part of my PhD project I would like to functionalize the amines of polyallylamine (or any similar polymer that consists of a aliphatic backbone and has amines in the side-chains). Specifically I would like to react the amine with an Acylchloride, actually with a Fmoc-chloride derivative I synthesized. The reaction I try to achieve can be depicted as something like:

What would be a proper synthetic strategy to go about it? I know I can usually react amines with Fmoc-chloride in DCM in the presence of DIPEA as a base. But I can not really apply this procedure here, since the polymer behaves weirdly in DCM, as soon as it touches DCM it becomes a gum-like, insoluble, unusable blop. 
I've got two formulations of the polyallylamine: on the one hand the hydrochloride (which of course is not nucleophilic) as a solid and on the other hand I have a watery solution (which is messing with Acylchlorides)

I just naively tried to react the watery polymer solution with sulfonated Fmoc-Cl in water/dioxane with Na2Co3 as a base, but under these conditions the Fmoc-Cl would already start cleaving and causing troubles, also I had no proof the desired reaction actually took place.

Does anyone of you know a good strategy on how to functionalize polyallyamine side-chain amines? I would not need to react every single active site on the polymer, I think it would be sufficient if only like 20-40mol% of the amines would be reacted. But how to achieve that? How to access the active sites of these kind of polymers? I am grateful for any suggestion on how to go about it, as well as for any literature on the topic (I could not find lots of useful literature).


Title: Re: How to functionalize polyallylamine?
Post by: rolnor on September 21, 2021, 03:52:44 PM
I would try a two-phase system water/DCM, use NaHCO3 as base and Fmoc-Cl.
Title: Re: How to functionalize polyallylamine?
Post by: wildfyr on September 22, 2021, 06:02:04 PM
Don't be married to DCM, that reaction would work in MeCN, THF, DMF, DMSO, etc etc etc. However if you're starting with the allylamine hydrochloride then of course it won't be soluble in organics, and you'll NEVER get all the water out of that aqueous version, so it will always foul the reaction. Don't even try.

What I would do is take the powder, and add it to a solution of organic solvent and 2+ eq of a base (TEA, DIPEA, DMAP, whatever) and let it stir until it dissolves. Then add your acyl halide. This polymer amine salt COULD be soluble in DMF or DMSO btw. Keep in mind your basic salt might precipitate. You want to choose a base that is a stronger base than your allylamine.

I think two phase system is terrible for polymers. You'll get foaming, emulsions, poor conversion etc. It will be horrible. Schotten-Baumann condition is for small molecules because they are great at seperating between phases and staying there.

P.S. Even for the polyallylamine powder, consider drying the heck out of it with P2O5 setup, low heat + vacuum, or a dessicator. Its probably hygroscopic itself.
Title: Re: How to functionalize polyallylamine?
Post by: wildfyr on September 22, 2021, 06:12:28 PM
I just looked at your reaction, you recognize that your sulfonic acids will protonate any free amines and make this a lot harder... I think in light of that I would use more eq of your amine base, and definitely do it in DMF or DMSO to have a prayer of keeping that fmoc disulfonate salt dissolved. Workup will be painful. Typically the answer is precipiate, filter, then redissolve and precipitate. Repeat until amount of small molecule left trapped in the matrix is sufficiently low, or in this case, until most of the DMF is gone.

 Those sulfonic acids change this from a relatively straightforward operation to a b$*%( and a half though.
Title: Re: How to functionalize polyallylamine?
Post by: rolnor on September 23, 2021, 02:33:26 AM
wildfyr has more experience with polymers so listen to him. My point is that avoid strong base, this will cleave the Fmoc, use pyridine, DMAP etc instead.