MDP2P via Alkene Hydration/Tautomerism

[PrimoPyro]

Yep, that's right. Another P2P thread.  

Was thinking in the shower, as always, and got a couple ideas. Gotta love those hot showers taken for no other reason than because they feel good and stimulate thought, at least for me.  

I'll draw some pictures if necessary, but I'm pretty sure everyone who reads these threads can get along fine without pretty pics. I was thinking about safrole homologs like MDP-allene and MDP-CH2-C#CH where # is a triple bond, so that makes it an alkyne.

Acidic hydration of alkenes, when done on safrole and alkynyl-safrole, would give the carbocation in the 2-propane position primarily, with a possible rearrangement to the benzyl position. If the alkynyl-safrole, MDP-CH2-C#CH were hydrated, MDP-CH2C(OH)=CH2 would result, which would tautomerize in the acidic solution to MDP-CH2COCH3, which is MDP2P.

Now, for the allene homolog, MDP-CH=C=CH2, hydration of either bond could occur. If hydration of the terminal bond occurred, the 2-position would bear the initial carbocation. At first I thought that if the first alkenyl bond was hydrated, the 2-position would also bear charge, but now Im uncertain, the benzyllic carbon would likey bear charge, and that fucks things up a bit for this compound, lol.

In either case, the formed enol then tautomerizes to the ketone. The allene probably would not form MDP2P, but rather MD-Propiophenone instead. But the alkynyl homolog should form MDP2P I think.

Now what about addition of Br to safrole, not as in HBr addition, but addition with NBS so that the Br gets added to the 2-position carbon, with the alkene remaining intact. This has been carried out on acrolein or acryl esters (can't remember which) with NBS to produce the same effect.

Removal of the Br by treatment with alcoholic KOH would afford either the allene or the alkyne, which I do not know.

Even better, reaction of safrole with H2O/Br2 would produce MDP-CH2-CH(OH)-CH2Br which could be treated with alcoholic KOH to remove HBr forming MDP-CH2-CH(OH)=CH2 which tautomerizes to MDP-CH2-CO-CH3 of course. Perhaps this can be done with H2O and Ca(OCl)2 which is the same reaction essentially.

It would be really easy. React safrole with H2O/Ca(OCl)2 and then treat with KOH in ethanol.

Comments on any of the above?

Let me know if pictures are needed. By the way, does anyone else have weird periods of chemical thought while enjoying hot showers?  

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

[X_Stacy]

I am in the process of aminating a pot-o-ketone not unlike mdp2p. I tried a method for adding h2o to safrole via an old, given up method of 80% aqueous h2so4. Almost every post I read on it claimed that it either hydrated on the wrong spot or failed completely, but there were a few that claimed it worked fine, along with some interestingly simple oxidation methods from that point. I tried a procedure (I forget where I saw it, but it is in the database) that utilized the solution straight from hydration (mdp2p-ol+h2o+h2so4!) adding kmno4 (little at a time, with good stirring) until titrated. The author claimed that the h2so4 prevented the permanganate from attacking the methylenedioxy ring. I have to say, I think it worked! after cleanup suspected ketone was pale yellow and slimy, and did not have the overpowering smell of safrole. It is now (hopefully!) reductively aminating right beside me. I will post results, but am extremely interested in other methods of safrole hydration as well.
   P.S. If ANYONE tries this method, make sure that ingredients are COLD and KEPT COLD. On my first attempt I chilled h2so4 and safrole (separately) to 0°C. While adding the h2so4, I could see the reaction occurring, everything was going smooth, and then I heard a little fizzle. This was followed by an explosion that covered my lab with black acidic tar. I read later that MD rings in highly acidic solutions polymerize explosively if temp gets too high (somewhere above 0°!) Next try I used same procedure except kept in ice-salt bath. My most creative thinking is done in the shower
"I laugh in the face of danger, and then I hide until it goes away."

[Flip]

The tautomerization you speak of, enol>ketone, does not look feasable to me.  Then again you may have some way of changing the parameters in mind.

The tautomerization is a two step process, and each step is a reversible reaction.  First, the opening of that first pi bond is reversible, and then the loss of the hydroxyl and the formation of the new pi bond with the oxygen molecule would be a reversible reaction as well.

Someone with more knowledge than I might know how to make this work but I can't think of how this would be a feasable synthesis.

Plus I can't even imagine where to obtain or how to synth those homolouges.  Then again i'm not quite as well read as other bees here.

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

[Osmium]

> reaction of safrole with H2O/Br2 would produce MDP-CH2-CH
>(OH)-CH2Br which could be treated with alcoholic KOH to
> remove HBr forming MDP-CH2-CH(OH)=CH2 which tautomerizes
> to MDP-CH2-CO-CH3 of course.

Recheck these structures, you can't exchange a H for Br with alcoholic KOH.
I'm not fat just horizontally disproportionate.

[PrimoPyro]

I dont understand what you mean. Im not wanting to exchange anything, really.

The first reaction is standard halohydrin formation, going from safrole to MDP-CH2CH(OH)CH2Br.

The second step is an elimination reaction where HBr is abstracted from the molecule. I have read that aqueous basic solutions will substitute the halogen for a hydroxyl, but alcoholic solutions are much more prone to elimination reactions. This produces an alkene of course.

An alkenol, aka enol, will tautomerize in acidic solutions to a ketone. So work up the base with dilute HCl, forming the ketone and the alkalai chloride salt and water.

Where is the problem that you see at? I don't see it.

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