[Bendzo]

Hello everybody!

Sometimes, when you are too involved in one process, you need to ask people with a fresh set of eyes and ideas, to help you find a solution. This is one such case.

Here is my problem. Among other things at work, I am also involved with overseeing a catalytic hydrogenation reaction, where an aromatic acyl group is transformed to en ethyl group using 5 mass % of Pd/C with regards to the starting compound. The reaction procedure is as follows: First you dissolve the starting compound in EtOH, add active charcoal and heat up the mixture at reflux temperature for some time. After that, filtration over celite follows and the mother liquor is transferred to a hydrogenation autoclave, the catalyst is added and the hydrogen pressure is applied. Looks like a no-problem reaction. And there are or should not be any problems at all.
So here's what's happening:
The reaction sometimes takes place leading to the final product, then sometimes, only the alcoholic intermediate of the hydrogenation is formed and the product is not obtained. I monitor the reaction progress with chromatography.
So I began solving the predicament and concluded that the obvious culprit was an unknown poison, which deactivates the Pd/C catalyst. So I sticked to this statement, and already proved it on some experimental data, that is...untill this week.
So what happened no?
We started the reaction, it did not proceed. So I stated, that the EtOH was to blame. We ran the reaction in MeOH without the pre-workup with active charcoal, and the reaction proceeded. Then we ran it in EtOH again, without active charcoal workup... And it proceeded!?!
So we said, OK, maybe a flask was dirty and we got a pollutant in to the system there. We cleaned every bit of glassware and equipment, ran the whole reaction again, this time with work up with active charcoal, and we found that the reaction proceeded far far slower than usual. Usually the reaction proceeded within 3 h. This time we ran it for 4,5 h and there was still 60 % of the alcoholic intermediate present and none of the starting material. So to test if the EtOH is poisoned, we added more catalyst, which should not make a difference if there is a catalyst poison in the system. But after adding some more catalyst, the reaction was complete in 30 min. The pressure, mixing speed, shape of stirrer, temperature and sampling intervals were the same in all cases, but the reaction progress was different in every case.
Another interesting observation in the process: in 99% of the cases, the reaction proceeded so that the starting compound was not firstly reduced to the alcoholic intermediate and then in to the product, but the product was already gradually forming, untill all matter was product after 3 h. But in this later case, the whole product was transformed to the alcoholic intermediate in the first 30 min of the reaction, then this was intermedate was very very slowly transfromed to the product.

So same reaction, different reaction kinetic profiles and unpredictable reaction time and outcome.
What did I miss?!
In some cases the reaction goes in EtOH, then again sometimes no.

Thank you for your suggestions and your opinions.

[zarhym]

If you think EtOH is the problem, you should distillate it and try again. From my experience, there are several things important in this reaction. The most important is the oxygen in the air. If the reaction is not well degased, the Pd can be oxidized, and there will be no reaction. The pressure of H2 and tempreature is also important.

[zarhym]

From your observations, I think you didn't degas your reaction. That's the reason the more Pd/C you add, the better reaction you have.