Author Topic: Notes from an amateur: MDP-2-Pol and MDP2P-epoxide  (Read 2106 times)

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HoneySuckle

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Notes from an amateur: MDP-2-Pol and MDP2P-epoxide
« on: July 14, 2000, 04:01:00 AM »
Okay, these are just ramblings for the most part. Ive spent a bit of time today refining these ideas, but they are all on paper. I havnt totally considered all the details of the actual lab work (ie expense and ease) but I think most of this stuff is pretty inexpensive and easily obtainable (most, not all).

Lets start with MDP-2-Pol:

safrol ---(hydration)---> MDP-2-Pol

This is acid catylized and in water (a required reagent). The double bond in safrol attacks the H+ and the carbon in the two position is now a carbocation (markovnikov addition). 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. 2) What of all this rearangement talk?

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.

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.***

Then of course: MDP-2-P + Me-NO2 --(Al/Hg)--> Sweet Honey

So theres one possible way to ketone (provided the above problems are delt with) using safrol, a strong acid, water, chlorox, and vineger.


----------------------------


Now for the really wacky stuff (not a pun). Im wondering if anyone has successfully explored an epoxide intermediate.

You can epoxidize alkenes (safrol) using peroxy acid (most commonly peroxyacetic acid):

Alkene + Peroxyacetic acid ---> Epoxide + Acetic acid

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. 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).

everyone says she has good taste, so I would love to nibble on her ear- HoneySuckle

Beaker

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Re: Notes from an amateur: MDP-2-Pol and MDP2P-epoxide
« Reply #1 on: July 14, 2000, 07:22:00 AM »
Let me guess, you went and got your hands on some of that high-quality sophmore-organic college edumacation, and now you're convinced you know your shit? Your post reminds me exactly of the type of analysis I'd to get from students when I TA'd that class. Unfortunately, a full year of a introductory college o-chem course(or a careful reading the textbook from one) leaves one with a rather shallow understanding of organic chemistry. However, I know you mean well, and your post is generally correct in the simplified terms of sophmore o-chem, so I will be gentle.


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.



HoneySuckle

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Re: Notes from an amateur: MDP-2-Pol and MDP2P-epoxide
« Reply #2 on: July 14, 2000, 09:07:00 AM »
Wow.. thats pretty harsh.. I dont claim to be any sort of expert beaker, these are just things I was thinking about. Let me reiterate the title: "notes from an amateur". If I thought all of this stuff was totally sound, I wouldnt be posting it here for feedback, Id be doing it. So just incase this post has inticed your aggressive nature, relax, its not neccesary.

regarding the hydride shift:
I dont doubt that the positive charge would be more stable on the 1 carbon, but is it that much more stable to cause a hydride shift? Even though water is a weak nucleophile, you dont need a strong one to attack a carbocation, weak nucleophiles will do fine. Looking at this carbocation again, i can see that the electrons from the aromatic ring might form a pi bond with the 1 carbon, distributing the positive charge into the ring. If this in fact does happen, a hydride shift is more likely to happen than i previously thought. This might not happen because the ring would lose its aromacy and the stability gained by moving the charge into the ring might less than the stability lost by taking away the rings aromatic property. In your post you say:

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


BrightStar

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Re: Notes from an amateur: MDP-2-Pol and MDP2P-epoxide
« Reply #3 on: July 14, 2000, 07:03:00 PM »
For the most part, Beaker is right.
Resonance and charge density can move right through a benzyl ring.

You have to understand that, the methods that are discussed here are here for a reason ...
1. They work, and a newbie can make them work, and 
2.  They are fairly in expensive (relatively speaking).

Your p-tolunidesulphonic acid is a bit expensive.  And count the steps ... you added a couple.

I think that Beaker was a bit harsh ... we try to teach here.    But most of what he said was right.

Beaker - Bee nice, K?


http://rhodium.lycaeum.org/chemistry/mdmasyn.txt


Beaker

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Re: Notes from an amateur: MDP-2-Pol and MDP2P-epoxide
« Reply #4 on: July 15, 2000, 08:18:00 AM »
Sorry, was in bad mood, Brightstar is right, anger bad. However, neither of your proposed routes is workable IMHO, much less superior to other proven ones. Thinking is good, but assuming that just because you don't know why something doesn't work doesn't mean it will. Making that assumption is very dangerous.


HoneySuckle

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Re: Notes from an amateur: MDP-2-Pol and MDP2P-epoxide
« Reply #5 on: July 15, 2000, 10:02:00 AM »
Since what we do is illegal and the man is always trying to catch us buying certain chems for a commonly used route to make illegal drugs, its good for us to explore new methods. Thats what i was trying to do... provide a constructive "what if?"

If its not workable... no big deal. Maybe someone briliant might develop some amazing trick. thanks for your help guys.

everyone says she has good taste, so I would love to nibble on her ear- HoneySuckle