Sciencemadness Discussion Board - pre-reduction of Pd/C in CTH?

pre-reduction of Pd/C in CTH?

joe_aldehyde - 3-7-2005 at 03:27

is it a must to pre-reduce Pd/C using pressurized hydrogen before use in a CTH? i never see any references to this in the corresponding literature, but still i am told that Pd absolutely needs to be loaded with hydrogen. could someone please clear things up? thanks alot!

Transfer Hydrogenation

Kinetic - 3-7-2005 at 07:18

Of course not. If it was, there would be no advantage to using CTH over the traditional molecular hydrogen. Pd is often saturated with hydrogen before a reduction, but only when the reduction itself uses molecular hydrogen.

What is the reaction you intend to use the Pd/C to catalyse? Is it the reduction of an aliphatic nitro group to an amine by any chance? This reaction was successful for me using commercially avaliable 10% Pd/C and potassium formate, and I did not pre-load the catalyst with hydrogen. The procedure I followed was essentially the same as that written by Barium: A great CTH method. Likewise, the hydrogenolysis in Patent US6399828 works perfectly well without saturation of the catalyst with H2 before the reaction.

joe_aldehyde - 4-7-2005 at 07:50

yes, this is my goal you clairvoyant scientist you!

my catalyst is from degussa, but it hasn't been stored in a tightly sealed container since i obtained it so i don't know if it retained the original activity level. did you dry your catalyst before use?
may i ask for the yields you got?
i am also thinking about low pressure hydrogenolysis as i have a bottle of H2 at my disposal, but i am not yet comfortable with pressurizing anything.

Chemical Telepathy

Kinetic - 4-7-2005 at 10:55

Your previous posts suggested this may be what you had in mind.

I didn't dry my catalyst before use; it was used straight from the container which, although it had a screw-top lid, was surely not impenetrable to air. The bottle was first opened at least several months before I used it in this reaction.

I got an 80% overall yield on my first (and only, for this particular method) attempt at the reduction of the nitroalkene 5-(2-nitropropenyl)indane to IAP. The nitroalkene was added to NaBH4 in water/IPA, then after the (exothermic!) reduction was over, it was carefully quenched with AcOH and the phases separated with the aid of brine. The IPA layer was placed back in the flask with some water, and 10% w/w Pd/C. About 5 eq. HCOOK were then added and the reaction was stirred for 2 h at 70 C. The method is simple and striaghtforward. CTH is great.

Be careful if you do decide to use hydrogen in a non-professional setting. Having said that, there is often no reason to pressurise anything at all when using H2. Many reactions will still proceed under 1 atm of hydrogen, although they may take longer.

joe_aldehyde - 5-7-2005 at 06:30

since you say it was your only attempt at this method, which other ones have you tried out, regarding the reduction of nitropropenes to aminoalkanes? i'm working in a professional environment so to speak (and i have proper licenses for everything i do).
some vitride is on the way, which might be a nice (but fucking expensive) one-step reduction to go with since i have great fears of using LAH, probably without cause since i have never performed a reduction using LAH myself. there are myths of it catching fire upon exposure to slightest atmospheric moisture.

IAP...what is it like?

ah i forgot something: i also have another catalyst, namely Pt with Pd on Al2O3 (in the form of d=3mm pearls) , do you think it would be a good or even better substitute for Pd/C? i know that the activity of the Pt/Pd couple is greater than Pd alone, but still...i'm a real novice when it comes to hydrogenations.

[Edited on 5-7-2005 by joe_aldehyde]

daeron - 5-7-2005 at 09:04

Quote:

Originally posted by joe_aldehyde
ah i forgot something: i also have another catalyst, namely Pt with Pd on Al2O3 (in the form of d=3mm pearls) , do you think it would be a good or even better substitute for Pd/C?

there are some you cant use cos they are industrial catalyts,and the activation procedures are a bitch.whats the commercial name?

hmph,not that i could say something smart if i had the commercial name,lol.Never used pt/pd,but i know from the industrial exp,their activity can vary greatly

[Edited on 5-7-2005 by daeron]

joe_aldehyde - 5-7-2005 at 14:24

there's no such thing as a commercial name on it, just says what it is. it was distributed by some environmental research lab. obviously repackaged from a bigger batch/bottle/whatever.

if nobody can tell me, i'll just use it as it is, maybe it will work

if not...hell uh...got enough nitroalkenes to reduce.

maybe it will turn out to be the killer catalyst for that reaction, yeah! then i'll have 99% yields! woo hoo! and i only paid 10$ for 10g catalyst

[Edited on 6-7-2005 by joe_aldehyde]

IAP

lahthffire - 6-7-2005 at 19:08

Kinetic:

I also have experience with the reduction product of 5-(2-nitropropenyl)indane and I would be extremely interested in hearing about yours.

joe:

I also have experience with LAH (and fire with such! hence the name

). It's not really so difficult to work with if you just be careful, plan everything out before opening it, and use dry solvents. And whatever you do, DON'T add it to a flask full of solvent through the only opening in the flask (i.e. funnel in the neck of a one-neck flask). Even with a dry solvent, LAH fizzes upon introduction. And with just a little bit of moisture, you can end up with a lot of vapor trying to escape the flask. If you have a funnel with LAH powder blocking the only opening in the flask, you will end up with a cloud of finely dispersed LAH bursting out of the funnel propelled by a jet of (usually highly flammable) solvent vapor.

The finely dispersed LAH reacts readily with the moisture in the air leading to far more excitement than you would usually want at that kind of time!

joe_aldehyde - 6-7-2005 at 22:01

lahthffire: i don'T have THF, just ether and 1,4 dioxane (can the latter be used for LAH reductions? i only hear about ether and THF but hey, dioxane is a cyclic ether!) i googled for it and some reductions turned up, but other references i found say "DON'T USE LAH WITH DIOXANE!!!" which startles me...a bit.

how did you dry your solvents before use in the reduction, is the use of drying agents and mol sieves (i can get 3A ones) enough, or will i have to use sodium dried ether?

i wonder how LAH can reduce nitroalkenes to aminoalkanes while http://en.wikipedia.org/wiki/Lithium_aluminium_hydride says that it doesn't reduce simple alkenes. how does the nitro/amino group affect this? convinces me even more that chemistry is still alchemy where you know things just work, but not how and why

sparkgap - 6-7-2005 at 22:07

As I remember it, the mech is:

1. LAH reduces nitro to amino group.

2. Resultant enamine tautomerizes to imine.

3. LAH reduces imine to amine.

Someone clunk me on the head if my memory is faulty.

sparky (°_°)

Clunk: electrophilic alkenes

Kinetic - 10-7-2005 at 10:19

5-(2-Nitropropenyl)indane was the only substrate I tried the method on. I only work with substrates that give non-controlled prooducts, and IAP is the only legal, centrally active amphetamine derivative I can reasonably make using this method. The 'other' method I mentioned having success with using CTH was the acetylation/reduction of the ephedrine homologue 2-methylamino-1-phenyl-1-butanol to 2-methylamino-1-phenylbutane as I mentioned in my earlier post. One attempt at the CTH reductive amination of phenyl-2-butanone with methylamine failed, although I suspect this was due to other factors rather than the transfer hydrogenation itself, as there was appreciable hydrogen evolution.

In my experience, LAH can be safely handled in air. It is simply not true that it will spontaneously burst into flames (or deflagrate, if you will) on exposure to the slightest atmospheric moisture. On standing for long periods in a damp enough environment, however, the picture is likely to change.

I have only added LAH to sodium-dried THF, but I'm sure that molecular sieves could dry the solvent to a suitable degree. Still, if you're working in a 'professional' environment, and have been awarded licenses for everything you do - making or extracting, I infer from your other posts, controlled phenethylamine and amphetamine derivatives - I am very surprised that you are not familiar with LAH and do not have access to THF.

In my opinion, and this is shared by some but not all of those who have tried it, IAP is not really worth taking. Given my compulsive nature, the fact that I made about 4g and now have some 3.9g left after about a year is somewhat telling. At the low dose of 30mg, I found a reasonable stimulation with a noticeable body load (feeling somewhat queasy). I did not take it further than this, and I have no real desire to do so. Essentially, I was disappointed, but I have a tendancy to set my hopes way too high when making 'new' things that few have tested before: the same happened with methylone. When I took it, I was still in a rather depressive state (as per usual, admittedly) and that in itself was not a particularly good time to be trying new drugs. Indane is a good substrate to try new methods on and if you do get some IAP out of it, try it; you may like it. But if you set out to make IAP from scratch you should not expect much back from the quite appreciable outlay it would entail.

LAH can only reduce electrophilic alkenes; that is, those that are conjugated with electron-withdrawing groups. LAH is a nucleophilic reducing agent, and so can not attack alkenes that do not have an electrophilic end. Hence I would like to modify sparky's mechanistic proposal. Instead, LAH would probably attack the electrophilic end of the nitroalkene to give the nitroalkane as an intermediate. I suspect this as the milder reducing agent NaBH4 will only attack the alkene and not the nitro group; it follows that the alkene most susceptible to this type of nucleophilic reducing agent. The resulting nitro group is then reduced by LAH to give the amine.

joe_aldehyde - 11-7-2005 at 07:04

i thought "having proper licenses" is a figure of speech in this kind of forums, isn't it? everybody in here has proper licenses, else they wouldn't be here

Sandmeyer - 31-7-2005 at 09:21

I think Zealot once said that he dries his ethers with KOH instead of sodium with even better results.

disable a kat

topdowner - 6-10-2005 at 00:57

Hey,
swim wanna make a cth with p2np but there´s a problem. If the reaction has come down and the catal. is filtered off, I´ve to disable him or??? Or is it ok to wasch him with water?

@Kinetic...which procedure did you used in this patent??? and whith which masses?

transformer - 6-10-2005 at 12:15

Out of interest does anybody have have any references on this LAH mechanism for the reduction of nitroalkenes to aminoalkanes, i always assumed that the oxime is formed first and then the oxime is reduced to the amine.

When it comes to the LAH reduction of phenyl-2-nitropropene for example a large excess of LAH has to be used or the major product will be phenyl-2-propanoxime.

[Edited on 7-10-2005 by samsung]

Nef Off

Kinetic - 9-10-2005 at 13:42

topdowner: The procedure in the patent I referred to was the reduction of the acetylated ephedrine analogue (homologue in my case). The masses are irrelevant, though I did this reaction on a small scale. The results were posted at the Hive when it was still alive.

samsung: I have no references, only chemical intuition. These nitroalkenes are powerful Michael acceptors. Conjugated nitroalkenes are attacked by the weaker nucleophile NaBH4 only at the alkene function, hence it follows that the more powerful nucleophile LiAlH4 should also preferentially attack at this position. The nitro group is a powerful electron-withdrawing group, but, probably due to conjugation, is not particularly susceptible to attack by nucleophiles.

A possible explanation for the formation of the oxime via this mechanism, if only a stoichiometric amount of t he reducing agent is used, is that LiAlH4 is a base. The thus formed anion of the nitroalkane, from the reduction of the nitroalkene, could possibly undergo the Nef reaction. To quote from Organic Chemistry:

Quote:

The hydrolysis of this intermediate must take place in strong acid, to prevent the formation of side products such as oximes or hydroxynitroso compounds

The nitroalkane could also be half-reduced to the nitroso compound. This is a tautomer of the more stable oxime, and I don't think it is unreasonable to expect the compounds to 'interconvert' - with the oxime being stable enough not to convert back to the nitrosoalkane in any appreciable amount.

I have no evidence for the above, and I am certainly open to reading any mechanistic studies of the above reduction.