goiterjoe (Title on BackOrder)
07-07-02 20:42
No 329636
      modifications to Oxone method  Bookmark   

Rhodium, on your site, you have listed:

The usual workup from the glycol
The more usual 65g batch is what most small-scale chemists do (after Shulgin, I suppose). In our case, we're just working with a mere 15g. Once you distilled out the DCM from the 250ml flask keep the glycol in and add:

25ml MeOH
120ml 15% H2SO4
Change the setup for reflux, and lightly reflux the mixture for
2h using a boiling hot water bath. The water bath should be kept at a light boil, and the reaction vapors will have a temp of around 65C.

The epoxide mixture will go from a light yellowish color to more of a darker brown color.

Let it cool. Load it into a sep funnel and tap off as much of the more dense ketone as possible (both PMP2P and MDP2P are more dense than water). Now extract with
3x20ml DCM.


It has been my experience that refluxing for 2 hours results in incomplete conversion of the epoxide to the ketone.  3 hours will result in almost no other fractions than the ketone upon fractional distillation.  The amount of DCM used for extraction also seems wrong.  It will get all of the ketone out, but you will have to add more DCM later to get the basic washes to separate correctly.  By doubling the amount of DCM used, it works better.


Turn off the stirrer, and let the mixture settle. The sediment will drop to the bottom. Pour off as much as possible into a beaker without getting any solids in. Suction filter the rest. The crystals will be off-white. A lot of your product will remain in the crystals. Rinse the crystals with fresh methanol to try and get as much product out as possible. The crystals should be bright white after rinsing twice.


When you wash the residual salt with methanol and add these extracts back to the mother liquid, more salt will fall out of solution.  It helps to flood the liquid with some more water to get these salts back into solution.  This also helps you extract more of the yellow color(presumably the epoxide) out of the liquid with your DCM washes.


All paths are the same: they lead nowhere
 
 
 
 
    Rhodium
(Chief Bee)
07-07-02 20:57
No 329642
      What file, and by whom? Chromic?  Bookmark   

What file, and by whom? Chromic?
 
 
 
 
    goiterjoe
(Title on BackOrder)
07-07-02 21:17
No 329645
      yes, Chromic's  Bookmark   

The oxone.epoxidation.html file.

All paths are the same: they lead nowhere
 
 
 
 
    Rhodium
(Chief Bee)
07-07-02 23:28
No 329704
      Okay, me go to work dat pronto!  Bookmark   

Okay, me go to work dat pronto!
 
 
 
 
    SiLiCoN7
(Newbee)
07-08-02 18:33
No 329958
      Extra extractions  Bookmark   

The 3 extractions of the epoxide is not enough IMHO SWIM dose more like 5 or even 8 especially if larger batches are done. SWIS7 thought the oxone didn't work in larger batches but realized that it dose, he was just not extacting well enough for the larger size. It is just all that volume of H2O and MeOH that make it hard for the DCM to pull the epoxide out.

Maybee you could add to the thread that the epoxide requires lots of extracting, like 5x plus in large batches.

Just saves newbees throwing away honey. Especially since the writeup says that all the color won't be extracted by the washes. SWIS7 found that after the 3rd extraction the color of the DCM after shaking and seperating will not bee very dark with oil like the 1st and 2nd. However the epoxide will continue to come across with subsequent extractions. The key here is repeated extractions as opposed to a large volume of solvent.
SWIS7 used 800ml DCM in 8 extractions for an 8x batch (129gr iso) this resulted in getting yields that correlated with those gotten in smaller batches.


the 21st of the 12th 2012......
 
 
 
 
    Chromic
(Synaptic Self-Mutilator)
07-08-02 19:26
No 329977
      Changes  Bookmark   

1) Three extractions get out all of the epoxide and get out all of the ketone. After boiling off the DCM, I always got a near quantitative amount of epoxide back.

2) I never needed more DCM to get the NaOH washes to work. They always took ~15 minutes to fully separate though. Give them time, not more DCM. I did notice that with asarone, it's important to rock gently on the first wash with NaOH (after acid hydrolysis) and only then shake on later washes.

3) I never did figure out an elegant way around the precipitate problem... IMHO, it doesn't matter. Osmium recommended in another thread to use DCM to wash it (I don't like that as the salts will hold onto some DCM).

However, I usually just went ahead and washed the salts with MeOH then extracted with DCM. It won't make a difference, the salts will come out in basic washes, plus if they do make it to the acid hydrolysis, it won't matter there either.
 
 
 
 
    goiterjoe
(Title on BackOrder)
07-09-02 00:06
No 330080
      15 minutes is a long time  Bookmark   

The ketone washes will separate out in 3 minutes if you double the amount of DCM.  Small amounts of DCM will recover all of the ketone, but they make the washing a bear.  Another thing that will help is if you do a plain water wash for your first wash, followed by NaOH washes.

This reaction scales up nicely IMHO.  you can get ~50g ketone back from 97.2g of isosafrole.  That's only around 40% yeild, but I think the yeilds could be higher.  at a 6x scaleup, I somehow always managed to end up with a >20g forerun of isosafrole.  I assumed it was isosafrole because it came over in the right temperature range, and when fed back to another Oxone/hydrolysis reaction would produce more ketone.  One theory I had was that it might not be a problem involving the amount of oxidant but instead a problem with methanol/water ratios.  I've wondered if adding a bit of acetone would help the mixture become more biphasic or not, but I no longer have the ability to experiment and find out.  If anyone doesn't mind playing around with your solvent ratios a bit, please do and report back with the results.

The precipitate salts are easy to deal with.  Just decant off your liquid, extract the remaining amount with 3 methanol pulls, add these to the mother liquor, and then add a little more than the required amount of water.  Another way to do it, if you're using a smaller separatory funnel and have to do multiple extractions anyway, is to decant off the mother liquor, extract this, then go back and do you methanol pulls of the precipitate salts.  Take that methanol and add 2-3x its volume of water and extract this with DCM separately.  Doing it this way prevents any salts from falling out of solution and clogging up your sep funnel.

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