[clemi2310]

Hello everyone,

This is the first time I post here, thank you for what you do here. I hope you can help me. I am a french PhD student in 1st year and I already encounter troubles with chemistry !

Basically, I am trying to synthetize diverse diketoacids following this synthetic scheme:



The first step is ok I get my ester pure enough. But when it comes to the hydrolysis, I get the diketo acid but the methyl ketone (starting material) is regenerated... so my product isn't pure.

I made another test, is to leave the reaction during 24h, and I got full recovery of methylketone without any acid.
I also try the hydrolysis in acidic conditions (HCl 1M in water + dioxane, reflux), I still obtain the methyl ketone

Here my reactions conditions, maybe NaOH and MeOH play a role in the reapparition of the methylketone, the hydrogen between the 2 carbonyl is still enolisable so maybe that is why..




The thing is, my compounds are too polar to purify them by silica gel chromatography so i have to get them pure enough, or recrystallized (but depending on substrate it is difficult).

Could you help me to figure it out what is happening, in terms of mechanism maybe ? Do you have any solutions? For example changing the solvant...

Thanks a lot.

Clémence

[Doc Oc]

This is classical decarboxylation observed in malonic ester/acetoacetate syntheses. It's almost certainly what's happening here.

http://www.masterorganicchemistry.com/2012/08/14/the-malonic-ester-synthesis/

Are you making the oxalate esters or are you buying them? If you're making them you could try something like a benzyl ester, then hydrogenate to get your acid, that will avoid strongly acidic or basic conditions that can facilitate the decarboxylation.

[kriggy]

Cant you run the next reaction with ester instead of acid?
I can suggest basic hydrolisis - very carefuly add NaOH, do not heat if possible and isolate the salt, then carefuly  hydrolyze the salt with acid

[clemi2310]

Hello, thank you for your answers.

I buy the oxalate esters, Usually I use the dimethyl oxalate, but I've tried with diethyloxalate and di-tertbutyl oxalate, the same reaction occurs. It seems to be a retroclaisen reaction..

Unfortunately I dont have the facilities to proceed to an hydrogenation in my lab.

Kriggy, concerning running the next reaction with only the ester, no because this is the last reaction we want to keep the diketo pattern for their metal binding properties.

What do you think of a purification step by SPE or something like that?
I have tried to do the extraction of the diketo salt before acidification, it works a bit to remove the methyl ketone, but there's some left.