P2P's Via Pinacol Reactions

[PrimoPyro]

Hi.  

The following is a very interesting excerpt from March's Advanced Organic Chemistry, 5th Ed. pg.1599-1560. After the excerpt I will begin to discuss an obvious idea that came to me after reading this, and would love to get some feedback on it.  

Reductive Coupling: Bimolecular Reduction of Aldehydes and Ketones to 1,2-Diols

2 RCOR ==Na/Hg==> [R₂C(OH)]₂

1,2-Diols (pinacols) can be synthesized by reduction of aldehydes and ketones with active metals such as sodium, magnesium, or aluminum. Aromatic ketones give better yields than aliphatic ones. The use of Mg-MgI₂ mixture has been called the Gomberg-Bachmann Pinacol Synthesis. As with a number of other reactions involving sodium, there is a direct electron transfer here, converting the ketone or aldehyde to a ketyl, which dimerizes.



Other reagents have been used, including SmI₂, Yb, activated Mn, In with ultrasound, VCl₃(thf)₃/Zn, and a reagent prepared from TiCl₄ and Mg amalgam (a low-valent titanium reagent). Dialdehydes have been cyclized by this reaction (with TiCl₃) to give cyclic 1,2-diols in good yield. Unsymmetrical coupling between two different aldehydes has been achieved by the use of a vanadium complex, while TiCl₃ in aqueous solution has been used to couple two different ketones. Two aldehydes have also been coupled using magnesium in water. Coupling leads to a mixture of syn- and anti-diols. “Syn-selective” reagents are Cp₂TiCl₂/Mn and NbCl₃.

Then it goes on into photochemical combination. The same reaction, but using photons to induce a singlet state that facilitates the same reaction. But that is another subject.

So, I’m wondering to myself if one could react benzaldehyde with an excess of acetaldehyde, to form 1-phenyl-1,2-dihydroxypropane, which also happens to be the diol of propenylbenzene, not allylbenzene. Yum, you know what that means. Pinacol rearrangement with dilute H₂SO₄ like usual will afford the phenyl-2-propanone. If piperonal were used instead of benzaldehyde, the product would, after Pinacol rearrangement, be MDP2P of course.  

I do realize the drawback of needing things like sodium metal to perform the original reaction, but some of the reagents don’t seem that tough, like the Mg/H2O combination for example. This is a very cool possibility.

I also wanted to bring up the question of using the H₂SO₄ rearrangement on ethylene glycol to prepare acetaldehyde. Ethylene glycol is sold as common antifreeze for making coolant for automobiles, and is widely available in good purity. Get a brand without a dye added to it. Prepare the acetaldehyde any way you want, or buy it, but I’m pretty interested if this is possible, because ethylene glycol is very cheap in the USA, and widely available, as is sulfuric acid.

Then react your acetaldehyde with your benzaldehyde of choice, and rearrange the formed diol to the phenyl-2-propanone of your desire. Who needs nitroethane anyway?  

PrimoPyro
Will perform sexual favors for females in exchange for 1,2-dimethylaziridine. PM for details.

[Flip]

I wouldn't have believed it if I hadn't drawn it in ISISdraw.  Primo you are right, and this is a tight synth.  Unless there are procedural/yeild? complications than you got something really good here.  Just throw the two aldehydes together and bang you got yourself a propanediol and run the pinacol to yeild P2P/MDP2P.

I'll bet this has other good applications as well.

Primo you are the Hive McGuyver.     I bet we could send you out into the woods miles from civilization and you would come back with some P2P.

Flip
Conclusion /nm./: the place where you got tired of thinking.

[Flip]

Check it out:
From Ethanol to Acetaldehyde

Nosova T, Jousimies, Kaihovaara P, Jokelainen K, Heine R, Salaspuro M Alcohol Clin Exp Res (1997) 21(3): 489-94.Toulene --> Benzyl alcohol

Shaw JP, Harayama S Eur J Biochem (1992) 209(1): 51-61.Benzyl alcohol --> Benzaldehyde

Shaw JP, Rekik M, Schwager F, Harayama S J Biol Chem (1993) 268(15): 10842-50.
Then of course.....

Benzaldehyde + Acetaldehyde ---Gomberg-Bachmann--> propanediol ---pinacol---> P2P



Dunno these reagents but I pulled the ref's for you.  Of course you could also use oil of bitter almonds but what fun would that be?

My god man, go to the hardware store, pick up a pail of toulene and some denatured alcohol.  The cops would bust in on you and ask where the hell the precursors are.  You could just sit there laughing your ass of.

Flip
Conclusion /nm./: the place where you got tired of thinking.

[PrimoPyro]

Even simpler, I could be *busted* for precursors by simply buying a coke at a McDonald's via drive-thru. I have ethylene glycol running through my car's cooling system, and the cup the coke is in is made of polystyrene. As you know, oxidation of styrene monomer in certain reactions yields benzaldehyde.    

Oh, so someone has noticed that 99% of my threads revolve around some form of P2P production, one way or another, eh?  

I'm fairly interested in the Mg/H2O combination as the coupling agent, and my next interest would be sodium metal. All those exotic compounds, even the titanium complexes, are beyond my scope for something so simple as P2P. Almost defeats the purpose, so to speak, since the reaction is presented to be simple and uncomplex. But if anyone chose to use them, to each his own, and may luck be with you and your flasks.

Thanks for the info Flip, very very interesting. I don't think NADP is something very accessible, though... I believe it is a biological chemical is it not? A complex enzyme in cells is what I *want* to "remember" from somewhere.

PrimoPyro
Will perform sexual favors for females in exchange for 1,2-dimethylaziridine. PM for details.

[moo]

The -ase's are enzymes allright. The ethanol to acetaldehyde oxidation is done routinely by millions of alcoholists every day. Think of it, you could transform P2Pol to P2P in your own body!

[Flip]

>As you know, oxidation of styrene monomer in certain reactions yields benzaldehyde.

Working on that certain reaction.  Still need to spend some more $$$ for the equipment.  I've now built a 5 ft long s-d variation, and it seems to be extremely effective.  R&D is expensive but fun.  I got set back by some major automotive expenses but I should be able to try that soon enough.  Getting that monomer is the bitch.

>I believe it is a biological chemical is it not?

Yeah you would be surprised what you can do with some of that shit if you can get your hands on it.  Enzymes have been my research interest for about the past 14 hours.

Flip
Conclusion /nm./: the place where you got tired of thinking.

[GC_MS]

The -ase's are enzymes allright. The ethanol to acetaldehyde oxidation is done routinely by millions of alcoholists every day. Think of it, you could transform P2Pol to P2P in your own body!

Depending on the phenyl ring substituents, your body turns olefines into peroxides, followed by turning the epoxide into the ketone.
WOMAN.ZIP: Great Shareware, but be careful of viruses...

[hermanroempp]

Aldolcondensation (sorry, but this will happen) of benzaldehyde and acetaldehyde will give you cinnamaldehyde.
Quidquid agis, prudenter agas et respice finem!

[PolytheneSam]

How about

Post 40131

(Mastermind: "Re: Interesting patents found", Serious Chemistry) ?
http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

[PrimoPyro]

I forgot about that. So it seems the desired Mg/H2O route may have difficulty, I don't know. I suppose it depends on the quantities of reagents used.

Waterless/alcohol-less systems shouldn't have aldol side reactions, though.

PrimoPyro
Will perform sexual favors for females in exchange for 1,2-dimethylaziridine. PM for details.

[hermanroempp]

Waterless/alcohol-less systems shouldn't have aldol side reactions, though

If your intention would be to use only ketones, I'd agree. But I think aldehydes (benzaldehyde and acetaldehyde) are too reactive and give a heap of side reactions, even in non-polar, aprotic solvents. If you look for the "classic" pinacol synthesis (2,3-dimethyl-2,3-butanediol from acetone with Mg/Hg in dry benzene) in the literature, the authors always give yields of about 40-50% for the product. And this with a ketone, not with a far more reactive aldehyde!
No one would use the benzaldehyde/nitroethane route (aldol-like synthesis in the first step, nitroethane is CH-acidic like acetaldehyde) for P2P synthesis if there would be a much easier way by the pinacole.
But hopefully, I'm wrong...

Quidquid agis, prudenter agas et respice finem!