Sciencemadness Discussion Board

Novel synthesis of methyl ketones from terminal alkenes

Flip - 1-3-2006 at 21:56

I have devised a novel reaction scheme for the synthesis of methyl ketones from terminal alkenes. While the procedure is not directly referenced in the literature, it has been created using textbook reactions with IDENTICAL functional group chemistry. Each step has decent yeild, all products are major products, and most importantly, these reactions are proven to work and are taught in major college chemistry courses.

What I would like from you guys is some help in developing a base of references and advice that might help me work through some of the expected yeilds, ratios, and procedural details, with a particular focus on aromatics ; ) I hope to do a write-up here and would love to cite you guys as contributors.

The reaction scheme is in the attached file, but i'll give you rundown... the ketone is formed by the tautomerization of the enol, which is created by hydroboration of the internal alkyne in tetrahydrofuran. The internal alkyne is formed by the alkylation of the terminal alkyne with bromomethane. The terminal alkyne is synthesized from the starting alkene by bromination, followed by dehydrohalogenation.

This reaction scheme has potential, especially those of us that migrated here from another board some time ago.

What do you guys think? Can I get some help?

Feel free to PM me on this topic as well.

- Flip

novelsyn2propanone.gif - 4kB

budullewraagh - 2-3-2006 at 16:23

KOH and the dibromoalkane would produce the corresponding vicinal diol, not an alkyne. perhaps you were missing an E1 step?

that's an interesting concept with the vicinal en-diol (if that really is a term) causing the removal of water. well done.

chochu3 - 2-3-2006 at 18:55

It will produce the alkyne after additon of a strong base KOH or NaNH2. The hydroboration would cause a an alcohol on the benzyl carbon. I don't think you will get a ketone unless you use mercury sulphate on an alkyne or you oxidate the alcohol from the hydroboration, but you will still get a mixture of products.

Tautomerization

Flip - 2-3-2006 at 19:25

Quite right about the hydroboration, the initial product will have an -OH on the 2 position of the double bond. This is an enol, which will tautomerize spontaneously to the ketone. (keto-enol tautomerization)

I thought about mercury sulfate, but that would put the carbonyl on the wrong carbon of the internal alkyne. I've considered HgSO4 for the conversion of terminal propynes to methyl ketones, however, but to my knowledge mercury sulfate is a watched reagent. Anyone know if there is an easy preparation for it?

Back to the reaction though, I am certain, in agreement with chochu3, that treatment with a strong base will yeild the alkyne via dehydrohalogenation. The hydroboration will yeild the enol, which will tautomerize to the ketone.

I don't suppose that anyone has any references that I might use to work up the procedure and stoichiometry for these reactions?

[Edited on 3-3-2006 by Flip]

Regiochemistry of BH3 addition

Flip - 2-3-2006 at 19:41

The hydroboration is an anti-markovnikov addition, and so the BH3, and therefore the OH, should add to the less stable of the two sites where we might imagine a carbocation. This would be the two position, if we consider the hyperconjugation and resonance from the R group. I believe that it also makes sense in terms of the steric crowding that could be caused by say, for instance, an aromatic ring.

And in case no one else thought of it, this opens up some interesting new possibilities for styrofoam : )

Triple bond isomerization with KOH

Flip - 3-3-2006 at 17:45

Actually, I would like to tweak the above procedure a little bit.

If the R group is cyclic, this wouldn't matter, but if the R group is an alkyl chain, KOH could actually cause an isomerization of the triple bond to the next carbon over on the chain (within the R group).

Now the reaction is still solid if the R group isn't a straight chain, but because the dehydrohalogenation can also be accomplished with sodamide, I'm going to tweak the procedure to utilize the NaNH3 instead of KOH. It's just one less neccessary reagent, the way I see it.


I do believe that I have devised a whole new route to 2-propanones. : )

The_Davster - 3-3-2006 at 18:01

Other than sticking the methyl on the alkyne, this is almost exactly like a question I got on my intoductory o-chem final. It was something like prepare R-CO-CH3 from R-CH=CH2, obviously in this case oxymercuration was used instead of hydroboration though. So I am afraid its not a completly new idea, but the addition of the methyl step is very nice in that one would not have to work with mercury compounds.

Flip - 3-3-2006 at 21:23

Of course I didn't invent the reactions, just the synthesis strategy ; ) It's kinda like building with legos, each reaction you learn adds to your collection of legos until eventually you can build any molecule you want. : )

For the record though, no one to my knowledge in or out of the realm of "amateur experimentalism" has ever synthesized 2-propanones from ethenes using this strategy... especially the ones that I have in mind. And for all I know, there could be a more efficient strategy that is preferred by the Phd crowd.

However, giving credit where credit is due, I do have to thank my professor, who judging by his orations is probably also reading this. : )

[Edited on 4-3-2006 by Flip]

Flip - 3-3-2006 at 21:42

Actually I should thank you though rogue... because that's exactly what I need... people who have seen something similar to this before, and who might be able to cite journal articles that could give me some more insight into the procedural details of each step.

Surely the same reactions on similar or equivalent functional group chemistry are performed and published all over the place... I have searched JACS but my queries haven't turned up as much as i'd like. Does anyone know any ref's that might help me work out ratios, etc? Would anyone be willing to collaborate with me on this?

Thanks,

Flip

[Edited on 4-3-2006 by Flip]

Ionium - 9-3-2006 at 14:22

Quote:
Originally posted by Flip
Quite right about the hydroboration, the initial product will have an -OH on the 2 position of the double bond. This is an enol, which will tautomerize spontaneously to the ketone. (keto-enol tautomerization)

I thought about mercury sulfate, but that would put the carbonyl on the wrong carbon of the internal alkyne. I've considered HgSO4 for the conversion of terminal propynes to methyl ketones, however, but to my knowledge mercury sulfate is a watched reagent. Anyone know if there is an easy preparation for it?

Back to the reaction though, I am certain, in agreement with chochu3, that treatment with a strong base will yeild the alkyne via dehydrohalogenation. The hydroboration will yeild the enol, which will tautomerize to the ketone.

I don't suppose that anyone has any references that I might use to work up the procedure and stoichiometry for these reactions?

[Edited on 3-3-2006 by Flip]


Well thought out.

AFAIK vil mercury sulfate form spontanously when concentrated sulfuric acid is mixed with mercury.