[asa029]

hi all!

I'm having some problems with a hydrogenation of a alkyne subsituted N-heterocycle. The reaction is done with hydrogen gas (both balloon and manifold) and Pd/C (5%) as the catalyst in EtOAC/EtOH. I have tried r.t. and elevated temperatures.

I only got my product once (50 min, 100% conv) and was never able to reproduce the results. I've tried different Pd/C and even bought a new one. I've also tried transfer hydrogenation with cyclohexene. None of these gave products, just unreacted starting materials.

We do not have the equipment for hydrogenation under pressure.

Anyone have any tips?

[Doc Oc]

Pd/C is finicky, but you bought a new bottle so that should have solved that.  You can try a couple things:

1) Increase the load.  I know it violates the "catalytic" part of the reaction, but just do it, especially since you don't have a Parr to do it under increased pressure.
2) I was always able to achieve debenzylation with a hydrogen balloon at room temp using Pd(OH)₂ and MeOH as the solvent.

[g-bones]

I would ditch the EtOAc and carry it out in straight methanol.  You can also add some trace HCl (or chloroform which makes trace HCl) or AcOH.  Increase catalyst loading like Doc Oc mentioned.  Also, try PtO2 or Rh/alumina, these have given me great results in the past.  Hope this helps.

[asa029]

I've tried increasing the catalyst loading to extreme amounts (about 100 w%) and also add trace amounts of AcOH. Still no product.

[discodermolide]

I've tried increasing the catalyst loading to extreme amounts (about 100 w%) and also add trace amounts of AcOH. Still no product.

I take it you wish to hydrogenate the alkyne? To what? All the way or stop at the olefin?
Anyway have a look at Houben-Weyl's volume on hydrogenation, plenty of hints in there.

[Dan]

I've tried increasing the catalyst loading to extreme amounts (about 100 w%) and also add trace amounts of AcOH. Still no product.

Try excess acid, and maybe something stronger - something like 2 equivs of HCl. The N may be poisoning the catalyst, protonation reduces the effect, this is well known for aliphatic amines. I used to work in aliphatic heterocycle synthesis (piperidines and pyrrolidines), and always found N-debenzylation would not proceed satisfactorily without addition of acid.

More here: http://www.chemicalforums.com/index.php?topic=54788.0

[OC pro]

Add dimethylacetamide (DMA). Always works fine when the Pd catalyst gets poisoned by any amine in the reaction mixture.

[asa029]

I've tried increasing the catalyst loading to extreme amounts (about 100 w%) and also add trace amounts of AcOH. Still no product.

Try excess acid, and maybe something stronger - something like 2 equivs of HCl. The N may be poisoning the catalyst, protonation reduces the effect, this is well known for aliphatic amines. I used to work in aliphatic heterocycle synthesis (piperidines and pyrrolidines), and always found N-debenzylation would not proceed satisfactorily without addition of acid.

More here: http://www.chemicalforums.com/index.php?topic=54788.0

That's a good tip and Im going to try it. Just wondering about the presence of HCl with an alkyne. Do you think it will survive?

[asa029]

The problem was finally solved with Pd(OH)2/C, MeOH and a ton of acetic acid. The reaction is sluggish and takes two days for completion, but at least I have my product for the next steps!

Champagne for everyone!