Couple of quick questions:

Would piperazine (as the monohydrochloride salt) be a strong enough base to hydrolyse methyl acetate?

Also, whilst strong acids do so, are acyl halides sufficiently acidic to hydrolyse lower alkyl or aryl carboxylic esters?

I'm wondering from a point of view of using methyl acetate as a solvent for the N-acylation of piperazine using benzoyl and propionyl chloride.

Or would acetonitrile be a more suitable solvent (rather not use it, due to toxic potential, and price reasons.

Hmmm...interesting idea with the nucleophilic substitution.

So a simple reflux in a high boiling solvent with a combination of piperazine and a carboxylic ester of choice, with a sufficiently efficient condenser and prolonged rxn time, should, in theory, give an N-monoacylated piperazine? my end target is N1-propionyl-N4-benzoylpiperazine.

Use of the monohydrochloride salt+alkyl propionate should then selectively acylate the unprotected nitrogen, allowing subsequent freebasing, to expose the second N for either the same reaction with a benzoyl ester to afford the target compound?

That would be very convenient indeed, and save my using the acid halides, which are, by all accounts, not particularly cheap, or easy to obtain (I have both propionyl and benzoyl chloride, but to be able to substitute a dirt cheap ester instead would be most welcome)

I confess, I am an awful chemist, pharmacology and neurobiology are my personal forte, and these days I find it incredibly difficult to learn/understand new things, or cognitiely process things I am studying/memorise the results, due to what I suspect, excitotoxicity-mediated hippocampal/prefrontal cortical damage which is the entire point of the synthesis of the target compound (the AMPAkine sunifiram)

And truth be told, I don't know the difference between 1st order and second order reactions.

Anybody see a reason that acylation couldn't be done just fine using methyl/ethyl propionate as the solvent for the acylation (on piperazine monohydrochloride) that way, the potential side reaction with the solvent would produce, as a 'byproduct' the same compound as the reaction with the acid halide?

Hm, that link isn't working for me.

Could you be so kind as instead, to cite the reference in question, that way I can find the paper manually? unless you have direct access to it that is.

DOI+publishing journal and article name would do me just fine.

Having phenol as a byproduct wouldn't be too bad a thing either, no specific need for it right now, but its always good to have a reaction that produces something potentially useful as a 'waste' product

I'm all for economy that way.

Gah...beats experimenting when you have only a shitty govt disability income and still live with your damn parents for want of ability to move. i should have recognised the username, but these days, I can't retain a memory of much of anything at all anymore. Its frustrating as hell, my mind used to be sharp as a razor, now, its all gone, and functionally, not good for much except the most basic stuff, everything I knew I had to relearn, over years, reading the same old stuff over and over again, or try, being unsable to understand most of it now, I'm hoping the sunifiram might just be the answer, as there is nothing the medical establishment will do for me here, aside from offer endless repetitions of the same same test battery, and then eventually, when they finally tell me something at all in the way of a result, that I don't have a problem.

Ooops! bugger..I'm a blind bastard for not spotting that.

Thanks Atara.