http://rhodium.lycaeum.org/chemistry/mdp2pol.txt (http://rhodium.lycaeum.org/chemistry/mdp2pol.txt)
BrightStar, the only rearangement that might take place is a hydride shift involving the carbocation intermediate. I dont think this would happen for a couple reasons: I think the water would attack the carbocation much faster than a hydride shift from one 2nd degree carbon to another 2nd degree carbon. The only reason the hydride might shift and the charge would move to the 1 carbon would be because the phenyl group could slightly stabilize the charge with its electron density. Hydride shifts usually involve carbons with different degrees; we dont have that in this case. Im wondering if all this "charge moving to the 1 position" business is observed emperically. My guess would be no.Easy enough, but there are a couple problems: 1)how soluble is safrol with water? the reaction may only take place at the interface, which might make for a slow and tedious process
That's actually the simple part. It doesn't matter. Alkenes dissolve in conc. sulfuric no problem.
the only rearangement that might take place is a hydride shift involving the carbocation intermediate. I dont think this would happen for a couple reasons: I think the water would attack the carbocation much faster than a hydride shift from one 2nd degree carbon to another 2nd degree carbon
You are right about the probable mechanism of rearrangement, I will give you that. However, 1,2-hydrogen shifts, should they be energetically and sterically predisposed to occur, are one of the fastest chemical processes known, right up there with proton transfer and three-membered ring closure, so I doubt that attack by water(no hydroxide here, acidic conditions!), which is a really shitty nucleophile, is going to be kinetically competitive with rearrangement. Intramolecular processes are almost always faster than intermolecular ones, that's one of the reasons why you get all sorts of funky unimolecular rearrangements that would never happen otherwise.
The only reason the hydride might shift and the charge would move to the 1 carbon would be because the phenyl group could slightly stabilize the charge with its electron density. Hydride shifts usually involve carbons with different degrees; we dont have that in this case.
Actually, the benzylic carbocation is muuuuuuch more stable than the initially formed one. Aside from the fact that it is benzyllic, which results in a goodly amount of stabilization, there is a large resonance effect from the oxygen in the 4 position, which results in a situation where the 1-carbocation is waaaaaay more stable than the 2-carbocation, which is of course the exact type of situation that favors rearragement.
Im wondering if all this "charge moving to the 1 position" business is observed emperically. My guess would be no.
The nuclear magnetic resonances never lie, and neither does Brightstar(We all hope :P ). That said, I don't know for sure that this method for making MDP-2-pol cannot under any circumstances be made to work, but it does not look promising. Also, if it did work(and nobody seems to have ever been able to confirm that it does), we would all know about it, because it is otherwise such an attractive-looking method for clandestine chemists.
So lets assume we get the charge (and then the hydroxyl group) in the two position (MDP-2-Pol). We could then oxydize this using a chromic acid (from K2Cr2O7 or Na2Cr2O7); that would be the old way (bad for the environment and the chemist's health). We could oxyidze it to MDP-2-P using the reagents described in the artical above.
I havnt looked this up yet, but it looks extremely promising:
R-CH2-CH(OH)-CH3 ---(NaOCl **chlorox**/acetic acid and water)---> MDP-2-P
***the details of this are apparently on page 71 of the Jan 91' edition of the Journal of Chemical Education.***
The last thing you would want to do would be to oxidize under acidic conditions. Wouldn't want to regenerate that nasty carbocation would we? Also, I suggest you NOT give references in that format in any setting.
You can epoxidize alkenes (safrol) using peroxy acid (most commonly peroxyacetic acid):
Alkene + Peroxyacetic acid ---> Epoxide + Acetic acid
Hell yes! Ever hear of the performic oxidation? You know, that thing Labtop is always talking about doing to 20L of isosafrole at a time!
Epoxides, of course, are very reactive because of ring strain. You could protinate the Oxygen in the ring with a strong acid, making the 2 carbon partially positive. Then, any weak nucleophile (methylamine for example!!!) can attatch to the two carbon, leaving a hydroxyl group on the 3 carbon.
Explain to me how you propose to protonate the epoxide oxygen without protonating the methylamine? Aside from that, assuming you could open the epoxide with methylamine under acidic conditions(you can't), the nucleophile would attack the 1-position(the most stable carbocation). You may be able to open the epoxide under basic conditions, but good luck trying to do that regioselectively. Better to just do a pinacol rearrangement like all the other good little boys and girls and then aminate your MDP2P
We could then treat this hydroxyl group with p-Toluenesulfonyl chloride, forming a p-toluenesulfonate substituent on the 3 carbon (my book says 72%). Then use NaBH4 or LAH in DCM to substitute a hydride (would this be called bimolecular electrohilic substitution? i think so maybe). And there you are.. ecstasy. I dont really know how pricey or difficult these reagents are to get a hold of, but the epoxide can be made quite easily, and to that MeAm can be added once the oxygen is protinated with a strong acid. The weird shit (tosul chloride, NaBH4/LAH) is neccesary to remove the hydroxyl group. Im not sure how fast all of these reactions take place, but i expect them to be pretty speedy (hehe).
Whatever.
there is a large resonance effect from the oxygen in the 4 position
Are you saying the charge moves into the ring? Are you sure this happens? I was thinking this wouldnt happen, which would reduce the likelyhood of a hydride shift; but if it does happen, im inclinded to believe a hydride shift would occur.
regarding oxydation:
Like I said, i havnt looked into it yet, but it said acetic acid so i wrote acetic acid. Besides, i havent compared pKas or anything, but i dont think acetic acid would be very good at protinating that hydroxyl group (although there are a ton of lone pairs in that mix, the acid wouldnt have to be too strong). Since I dont know the details of this reaction, Im not sure if you could modify the solvent or not. As far as my giving refences in that format, this isnt a research paper. If that is not what concerns you, please send me a message (id like to know what thats all about).
The epoxide:
Yes I have heard of the performic acid process, but Im not familiar with it. I will look into it. Although I never mentioned isosafrole and I dont know what it has to do with anything I said. The epoxide I suggested would be in the 2,3 position and the methylamine would attack the most stable partial positive at the 2 carbon (the 1 carbon would be neutral if not slightly negetive). I was thinking about the protonation of the Oxygen in the ring versus the protonation of the MeAm before I read your post, and had hoped that someone would comment on it. I realized that you couldnt attack with MeAm. Might it be possible to attack with a nitrogen that is sp2 or sp hybridized? It would absolutly be easier to just add the nitrogen in some form now rather than adding somthing else and then doing some sort of substitution (although i dont know if its easily done).
and to the whatever comment:
Lets just say hypothetically, you could add a nitrogen, wouldnt this be a resonable way to get rid of the hydroxyl group? I let my idea run its course, and when it was finished I had a hydroxyl group to get rid of. It seems to me that treating with tolsul-chloride and NaBH4 is a reasonable way to do this. I dont however know how practical it is.
I a greatly appreciate your feedback Beaker. Please dont bee too tough on me, I know what I know (or at least think so) and at least Im putting some thought into this. I know older bees can appreciate it when newbees use their heads and can at least get things "generally correct in the simplified terms" (I have to start somewhere).
everyone says she has good taste, so I would love to nibble on her ear- HoneySuckle
http://rhodium.lycaeum.org/chemistry/mdmasyn.txt (http://rhodium.lycaeum.org/chemistry/mdmasyn.txt)