Aldehyde to Methyl Ketone

[RollWitMe]

I can not seem to find in literature , or the search engine any practical reference for rearrangement of say
R-CH2-CH2-CHO to R-CH2-CO-CH3. This is basically in reference to the Pd(OAc)2 / H2O2 RxN. The theoritical aspects of this problem are intriguing and on paper it is messy. The bisulfite addition will and should precipitate out both the aldehyde and the ketone from this reaction. Once you have the purified carbonyl groups, how to rearrange the aldehyde that forms into the ketone. If you run the reaction in Acetic acid, not t-butyl alcohol w/ H2SO4 and HgCl2, on top of the peroxide and catalyst, it should be able to inhibit aldehyde formation. I can get references to that procedure if anyone is interested.
I like to cook!

[Rhodium]

If you just want to separate them, oxidize with a mild oxidant to make the acid of the aldehyde, which can be separated from the ketone by an A/B extraction.

[RollWitMe]

Not seperate, it seems that anyone who is getting a postive bisulfite is getting the aldehyde contrast to what they think. Any aldehyde will complex faster then the comparitive ketone w/ bisulfite. stereochemistry steric interference says so :-P . I'm looking for the theoritical  information for a procedure, that could transform the aldehyde to the methyl ketone. I found a few that involve Li-I and a couple more than involve fancy metallic PTC's but it seems more trouble than it's worth. running the Pd(Ac)2 w/ H2O2 in acetic/sulfuric COLD should kinetically favor the formation of the ketone R-C-CO-C over the aldehyde R-C-C-COH. I'm just pondering but i have some 1-Octene to try it on if anyone comes up with something. I'm legal now, but I still like to research etc etc. 10 yr suspended sentence over your head is nothing to f*ck with :/
I like to cook! . . . but some dudes in blue vests with yellow letters took my kitchen.

[PrimoPyro]

RWM, I like your style! Good luck to you! Keep us posted on your findings.

And if they are not thread worthy, please PM me anything chemically interesting that you find at all. I love theory. It's nice and clean.  

                                              PrimoPyro
Vivent Longtemps la Ruche!

[Ritter]

I have a few things to add to this Wacker subject (afterall, I think this reaction is how I got my nickname!).  Several tests of this rxn were run on the standard isoalkene in an attempt at synthesizing the propiophenone.  The only product recovered from these reactions was unreacted starting material.

The intended use of the propiophenone was nitrosation w/ t-butyl nitrite and HCl.  The resulting isonitrosopropiophenone hydrogenates to MDA w/ a little Pd/C and sulfuric acid catalyst in 80% yields.  Refs for this rxn are archived here.

I wonder if the hydrogen adjacent to the carbonyl on the aldehyde is acidic enough to undergo nitrosation much the same way the alpha hydrogen on the propiophenone does???  Probably not, but it sure would be nice!   Can anyone elaborate?

[RollWitMe]

Ritter, one quick question. You were running the wacker on the isoalkene or the terminal alkene? After some more research, it seems that water would be inhibiting the reaction? 30% H2O2 contains a lot of water and if the t-butyl alcohol is not dry it could also interfere. Has anyone ever tried using 98% t-butyl peroxide (C₄H₉)-O-O-(C₄H₉). It's a strong oxidizer as well and would produce more t-butyl alcohol in the RxN. Ritter, if you could also refer to the MDA RxN or where I could find info regarding the Pd/C part of it, I'd be interested in the theoritics behind it.

I'm getting some ideas for senior research in organics, I need some new legal synths to work on. Thanks. Everything my professor suggests is boring, I'd like to be able to relate it to something and post my findings on here
I like to cook! . . . but some dudes in blue vests with yellow letters took my kitchen.

[RollWitMe]

I also came across some t-butyl hydro peroxide in some old journal refs. It will be some time before any work gets done on the 1-octene, but we'll follow it w/ GC when it does happen.
I like to cook! . . . but some dudes in blue vests with yellow letters took my kitchen.

[Rhodium]

Ritter: I am very interested in this nitrosation of propiohenones/acetophenones as precursors to amphetamines/phenethylamines. However, I have not found a single reference where the tautomeric alpha-hydroximinoketone can be reduced to the phenylalkylamine without using catalytic hydrogenation under relatively high pressure.

I have seen CTH reductions with ammonium formate being used to reduce oximes, as well as phenyl-alkyl ketones, but never at the same time. Do you believe it is possible?

All other reductions which does not involve catalytic hydrogenations only produce the amino-alcohol, which is sad. I would look forward to such a reduction being performed at atmospherical pressure. It is one of my current holy grails, as it is so simple, and at the ame time being so unexplored.

The references you have on this reaction would be very nice to get some pointers to.

[Ritter]

Rhodium:

That mentioned ref is J. Med. Chem. 25, 1442(1982)
It uses HOAc/H2SO4/ 50psiH2(Pd/C) to get >80% yields of amine.  This ref also contains excellent oximation info along with some high yielding NaBH3(CN) reductions.  The paper is a must-have for your collection!

Rhodium, you should consider building a medium-pressure hydrogenator.  It is actually much easier than most people think.  A simple thick walled glass bottle will easily handle up to 50psi and serve as a reactor.  A good hydrogen source is one of those electrolytic generators, these are commonly available from used equipment vendors here in the states and I suspect the same is true in EU.  It would be sheer simplicity to use one of these to fill a small soda or beer keg then rig a valve and pressure guage system to fill the rxn bottle w/ hydrogen to the desired pressure.  Don't worry about shaking the reactor, mag stirring will suffice.  Let me know if you want more details.

As far as CTH rxns are concerned, I have not spent an exorbitant amount of time studying this topic.  However, I'm guessing that if it works at all, yields will be low.  Perhaps there is a NaBH4 reduction which will do the trick, I'm guessing this one may work:  Chem. Lett., 1029 (1981).  This ref uses NaBH4/ PdCl2 to completely reduce benzylic ketones and alcohols in decent yields.  I have not seen the paper myself, however I'm guessing that this catalyst system will also reduce the oximino function.  Please check it out and let me know if it looks promising, I currently have no library access.

In combination with the simple/high-yielding oximation quoted in the paper mentioned above, this reduction really has potential to shape up as one of the holy grails of phenylalkyl synthesis.  BTW, did you receive my PM last week?

[foxy2]

http://www.orgsyn.org/orgsyn/prep.asp?prep=CV1P0061

I hate my government, does this mean I'm a terrorist??