[aranel]

i have this compound with a cbz which refuses to be cleaved off. tried 33% HBr in AcOH. even left overnight. got my still protected compound back, and a tiny amount of deprotected compound. tried hydrogenation with Pd/C. no change. added some more Pd, thinking the catalyst might have been poisoned or so. nothing.

how could this happen? any ideas?? or what else i could try you think? 

[Doc Oc]

How old is your Pd/C?  That stuff does go bad so if you have an old bottle it might be considerably degraded.  Either add a lot more (which should be no problem because you just filter the Pd off at the end anyways) or you can try a different Pd source, I've actually done this deprotection with Pd(OH)2 and a hydrogen balloon.

[aranel]

it is less than 2 years old. is that enough time for the Pd to go bad?

i thought that for the HBr in AcOH i used. so ordered a new bottle. but made hardly any improvement.

so you think it must be something with the reagents right? i cant see any reason for the compound to be stable to those conditions

[Doc Oc]

Yes, I would say that's enough time for the Pd to go bad, but it depends on how it's been stored.  If it's just sitting on a shelf, then it's probably bad.  If you're careful with it, parafilm it, and throw it in a dessicator, then maybe the substrate is stubborn.  Either *Ignore me, I am impatient* the amount or try a different Pd source.

Haven't done HBr deprotection so don't know about the ins & outs of that.

This definitely does sound reagent based and the Pd/C immediately sent up a red flag for me because I know from experience that stuff doesn't keep.  However, if multiple deprotection methods aren't working, it could be substrate problems.  If you're allowed, maybe posting the rest of the structure would help (although I don't think it should matter that much).

[aranel]

not in a dessicator, but parafilmed.

okay then i would go for a different Pd source. if still not working, then think of any other problems releated to substrate.

thank you!

[g-bones]

definitely give pearlman's catalyst a try, its really good for hydrogenolysis reactions (the first step of the deprotection)

[russellm72]

Try Pd-C (10%) Degussa type. 50% water content in EtOH under a balloon of hydrogen.

Sorry if stating the obvious but you are thoroughly degassing before introducing the H2 a few times under vacuum?

Anyway this method works well for me and the wet catalyst is easy to handle.

Regards

R

[Dan]

Do you have an amine elsewhere in the structure? Aliphatic amines are known to poison Pd catalysts and retard hydrogenolysis. I have encountered this problem many times. Usually it can be solved simply by protonating the problematic amine(s) - run your catalytic hydrogenolysis in dilute HCl (I tend to use 0.2-0.5 M HCl in either water, water/ethanol or water/1,4-dioxane in various ratios depending on solubility).

As has been suggested already, Pearlman's [Pd(OH)₂/C] is usually more active than Pd/C. Pd black is another option, but catches fire much more easily than the C-supported catalysts. I have seen preps for particularly stubborn benzyl groups using up to stoichiometric Pd black with acetic acid as the solvent!

[OldThrashbarg]

Solvent choice is pretty important for hydrogenolysis reactions and I've found it to make a lot more difference than trying out different bottles of Pd/C or using Pearlman's catalyst.  You'll probably have to screen a number of them, but using TFA as the solvent has saved me a couple of times.

If you're trying simple acidic cleavage, I've seen people have success using strong Lewis acids such as boron tribromide or trichloride.

[Med90]

for deprotection of Cbz, I have used Pd/c in EtOAc (<a href="http://medchemblog.blogspot.com/2009/11/hydrogenation-demonstration.html#more">using hydrogen balloon: demonstration</a>). and successfully deprotected Cbz...

Good Luck!