Author Topic: Catalytic Transfer Hydrogenation: A review  (Read 368 times)

carl_nnabis

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #20 on: July 01, 2012, 09:45:16 AM »
wow really nice and such a high yield and all under atmospheric pressure! :o
its really impressive, but do you think it will work equally well with alpha-alkyl substituted nitroalkenes? 
Quote
and the flask warmed with a small flame (such a risk it's awesome)
you must be totally mad ;D
"It's like the drug trip I saw when I was on that drug trip!"

akcom

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #21 on: July 01, 2012, 05:09:38 PM »
Fantastic notes pyramid.  Any suggestions for recovering the catalyst?  I'd hate to ruin my sintered glass funnel filtering Pd/C and I have no idea how you'd get it out of the celite?

pyramid

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #22 on: July 01, 2012, 05:20:56 PM »
I believe the recovery of the catalyst is as simple as washing with dilute NaOH and then washing with a few portions of hot iPrOH or another suitable solvent. I would not try to reuse it more than a few times as I always noticed slower reaction times for other substrates where Pd/C was reused(under a balloon hydrogenation). I read somewhere (don't know where) that it is beneficial to keep the washed and recovered catalyst in dilute (few percent?) formic acid solution in water.

If you don't have good filter papers, it is possible to use one paper on the bottom of the funnel, then a layer of Celite poured on in a slurry then another paper on top once compacted. It is crude but allows better recovery. Alternatively you can use the Celite and Pd/C mixture but I have not tried this before. This is done in a Buchner funnel. I would not recommend using a sintered funnel just because of the possibility of the carbon going into it.. That is a hassle.
Then you could also just filter over 2-3 papers which also works. A few ways to go about it.

pyramid

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #23 on: July 02, 2012, 03:25:42 PM »
wow really nice and such a high yield and all under atmospheric pressure! :o
its really impressive, but do you think it will work equally well with alpha-alkyl substituted nitroalkenes?

Yes, it should work for the preparation of aminopropanes/butanes as well, from the corresponding nitroalkanes.

carl_nnabis

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #24 on: July 02, 2012, 03:40:50 PM »
I have totally overread that you reduced the nitroalkane and not the alkene  ::)
now this explains your awesome yield, i wondered a bit about it ;D
"It's like the drug trip I saw when I was on that drug trip!"

Sol Invictus

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #25 on: July 02, 2012, 11:24:23 PM »
Nice post pyramid- thanks for sharing notes. :-)
So going thru the nitroethene then forming the nitroethane via NaBH4 & reducing w Pd/C & Ammonium Formate really gives higher yields of the final phenethylamine vs. going thru the nitrostyrene & reducing w Al/Hg or other methods? Is there a reason why yr going from aldehyde to nitroethene to nitroethane to PEA, instead of from aldehyde to nitrostyrene to PEA? Sol would think that the extra step in the former would cause a yield decrease, even if just from mechanical losses...
And while it's a bit off topic- Pyramid are you aware of anything that could be substituted for the ButylLithium in the aforementioned 2-CE synth?

Thanks!

pyramid

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #26 on: July 03, 2012, 12:34:19 AM »
Nitrostyrene is just a general name for nitroethenes, propenes and butenes, stemming from the double bond (nitroethenyl, vinylbenzene etc). That intermediate is a nitrostyrene.

The yield is absolutely higher than using Al for reduction. Nearly all mechanical loss can be eliminated by using solvents to rinse your flasks and everything with every single transfer you do. I don't write it in these examples, but every time something is poured or transferred the original vessel is ALWAYS rinsed with 2 or 3 portions of solvent. The yield on producing the nitroalkane is very high, even if it contains a few percent of dimeric material.

Instead of using n-BuLi one can go through the 2,5-dimethoxyacetophenone, I don't know how else you could get the alkyl group on the ring.

Sol Invictus

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #27 on: July 03, 2012, 01:25:36 AM »
Oops- now I see. I thought for some reason that the nitroethene was a different type of nitrostyrene distinct from nitrostyrene itself. It makes total sense now- thanks for clearing that up!
Two quick questions- do you always isolate the nitroethane derivative prior to the reduction to the amine? In most of the examples on Rhodium the nitroethane is not isolated before reductive amination & the reported yields are less than or on par with other methods of directly red. aminating the nitrostyrene. Do you think isolating the intermediate might be at least partially the reason for yr good yields with process, even w/o purification of said intermediate?

Thanks for yr time & patience with my questions!  :)

pyramid

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #28 on: July 03, 2012, 01:52:14 AM »
We are not doing a reductive amination here since this is a regular phenethylamine, not N-methyl or other. First the double bond is reduced by NaBH4 and the nitro done by H2/Pd.

I think the yield is higher if you isolate the nitroalkane and at least give it a couple of washes in this case and any other reduction technique. In some other examples I have posted, you can reduce nitroalkenes one pot with NaBH4 then Zn/HCl but the yields can get a bit random sometimes, here there is no intermediate purification. If you isolate the intermediate and then do the Zn/HCl yield is always better.

You cannot directly reduce the nitroethene by hydrogenation without a parr shaker and high catalyst loading in eg. MeOH containing some HCl. Other methods for direct reduction, Al/Hg, LiAlH4 etc don't always yield well. Here the work up is always simple and the conditions mild, no sludges to deal with or anything, I would opt for the NaBH4 then CTH any day for any nitroalkene that can apply to this technique.

akcom

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #29 on: July 03, 2012, 06:35:41 PM »
fresh1: the use of n-butyl lithium puts this out of reach for 99% of the chemists here.  It's a great write up no doubt, but its utility in synthesizing 2C-E for the average home chemist approaches nil.  The other steps on the other hand are extremely useful and well written to boot.

pyramid: instead of using n-butyl lithium it's not hard to imagine a process using Cr(CO)3 to activate the benzene ring followed by nucleophillic addition.

pyramid

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #30 on: July 03, 2012, 07:11:57 PM »
One can make their own n-BuLi relatively easily, as long as you have the needed glass and an inert gas source. Nothing more than n-BuCl/Br (chloride preferred), dry hexanes, lithium and some sodium, info is online. I never made my own, I get it commercially, but if I could not I would just make it. It is too useful to deny to yourself if you have the needed equipment! 1.6M and 2.5M are not pyrophoric, but you must use dry inert gas as it decomposes on contact with air almost instantly.

Akcom, do you have a reference for that? It just seems even more work and hazard to use a chromium compound. I'm not about to try it, but I am interested. BTW did you ever use the CTH for anything?

Baba_McKensey

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #31 on: July 03, 2012, 09:15:20 PM »

akcom

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Re: Catalytic Transfer Hydrogenation: A review
« Reply #32 on: July 04, 2012, 06:13:04 AM »
Akcom, do you have a reference for that? It just seems even more work and hazard to use a chromium compound. I'm not about to try it, but I am interested. BTW did you ever use the CTH for anything?

The general information was gleaned from a book called Transition Metal in The Synthesis of Complex Organic Molecules.  Unfortunately my response was a bit off the cuff and after consulting the book, it looks as if nucleophillic attack would only occur at the 3 position with catechol derivatives, if not with the chromium center itself.  I'll look over it once more and see if there is anything that could be applied here, but I doubt it.