Isosafrole --> MDP2P via performic and HCl with pictures

ApprenticeCook · DILLIGAF

As requested by Iodide, here is the writeup i refer to in the thread -->
https://www.synthetikal.com/synthforum/viewtopic.php?t=274

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Buffered Performic By OC (Octocambrium?)
I decided to take pictures of my last buffered performic. Ever since i’ve starting using this route, I’ve never looked back on a wacker.

Step 1 Safrole isomerisation at atmospheric pressure
I cant be running a vacuum pump all night so this is my way to go:
Set-up for a regular distillation. Place the safrole(purified by simple distillation under vacuum) along with 2-5% KOH under good stirring. I use about 2.5% and it works like a charm. The temp is brought up to around 180 to get rid of all water. 1 hour at that temp is usually fine, I dont really keep track so much. Then the solution is left to stir at around 140-150 overnight. You dont loose any safrole even without a refluxing column at that temperature . The next morning, vacuum is connected to the system and isosafrole distilled. Yields are always 95-98%. The easy part about this isomerisation is that you only have to rig one setup for the whole process. For those who have never prepared isosafrole, there are 2 distinct properties I use to discriminate. First isosafrole has a different smell then safrole, a lot weaker. Take sniff of safrole. Take a sniff of coffee beans. Smell iso. Its different isnt it? Then look at iso under light. It doesnt refract light as much as pure safrole. I even can see it in the receiver flask as it is distilled. Maybe you will end-up with 1% safrole, but it doesnt change a thing for later stages.

Step 2 Forming the glycol
Using a 2L flask, this is the most iso you can convert to keep control of the reaction IMHO.

300 grams iso
91 grams Sodium Bicarbonate(Arm n hammer )
800 ml DCM
279 grams H2O2 35%
461 grams Formic acid 88%

1. Forming the peracid
I suggest making 2 half batches of peracid for this reaction. So 140 grams peroxyde with 230 formic. To a stirring solution of peroxyde on a cool water bath is added the formic all at once. This is left to stir 30-45 minutes. The reaction isnt really exothermic.

2. The 2L flask
While the peracid is forming, place the iso, bicarb and dcm in this order in th 2L flask and leave to stir. Set-up a refluxing column along with an addition funnel on those 2 necks. The solution will look like that:

3. Adding the peracid
Place your freshly formed peracid in the addition funnel and start adding the peracid over the course of about 90 minutes. The solution will slowly start to turn yellow, it will reflux, and a lot of foam is usually produced in the early stages. Just adjust your drip rate a little slower and it will calm down. About 15 minutes in it looks like that:

The foam will subside and 1 hour into peracid addition it looks like that:

4. Forming the peracid(part 2)
When about 45 minutes into addition, start preparing your second batch of peracid. That way it will be fresh when you finish dripping in the first half.

I believe doing so cuts down on the amount of peracid that decomposes. Performic acid is not so stable so even after 2 hours, you see it starting to bubble, meaning its decomposing. At least thats always been my experience using ACS grade Formic and hydroponics store peroxyde( I wouldnt want to order formic and peroxyde from the same company)

5. Then leave to stir for an extra 24 hours. The solution progresses from white to yellow to orange, much like orange juice. This is what the solution looks like in the end. You can see that there is still enough breathing room in the flask. At least I’ve never add a problem.

6. Place in a sep funnel, sep off the dcm, extract with a little more dcm. In the sep, the layers look like that:

7. Distill off the dcm using a water bath. I like to do that overnight. Its a lot of dcm to be distilled out, so you can save-up some time there. Weight your glycol. From this one I got about 435 grams of glycol, its always been nearly quantitative. The glycol is red/dark orange and looks like:

Step 3 HCl hydrolysis
Thanks to Chromic I have never needed to do a sulfuric acid hydrolysis. HCl is really golden. In a 2L flask, you will have to do 2 hydrolysis by splitting the glycol in 2.

435 grams glycol
540 ml MeOH
900 ml water
900 ml muriatic acid

So 270 ml MeOH and 450 ml water are combined and warmed to about 60 degrees. The glycol is added(217.5 grams) followed by 450 ml muriatic acid. Upon acid addition the solution will turn a little pink/orange.

The solution is refluxed for 2.5 hours at about 80 degrees celcius. It will start to change color maybe 15 minutes after acid addition. You will see oil starting to stream on the top as it is stirring. One hour in, you will definitely see globules of oil floating around and the solution is more brown by now. Like that:

After 2.5 hours, cool down to room temp using a water bath to speed things up a bit. Place in sep funnel and sep off bottom layer. This is your oil, its dark red/black. The top layer is orange. Add a litle and extract the top layer again. 2 times 100 ml dcm is more then plenty I believe.

This step is repeated twice if you dont have anything bigger then a 2L flask

Take your dcm/oil( combine both hydrolysis then wash) layer and wash it a couple of times with 5%NaOH. Be patient and make sure all the dcm is out. This can take multiple sepp off/wait cycles. But if you want to increase your yield do so. Then wash with fresh water, followed by brine. You can then dry it even more with epsom salts if you want.
Distill dcm. Start vacuum and distill off your ketone.

I will look like that:

This run afforded 244 grams of ketone. 100 grams were used a la RoundBottom, final yield of recrystalized amine 85 grams.
So 900 grams of iso could end as about 600-650 grams of salt

I welcome any inputs, experiences from other bees that have experience with this synth as there is always room for improvement.

Comments by Abolt
Nice writeup.
The temp is brought up to around 180 to get rid of all water. 1 hour at that temp is usually fine, I dont really keep track so much. Then the solution is left to stir at around 140-150 overnight.
No need to go to 180. Just bring it to 140-150 and hit it with weak vacuum for 1 hour, then leave it to stir overnight. Or better yet, Turn on your vacuum and raise the temp until the Safrole starts to bubble, but not distill. Hold it at this temp. with the vac on until bubbling ceases, telling you your isomerisation is complete. Then simply turn up the heat and distill. The higher the temp, the quicker isomerisation will be completed.

This is left to stir 30-45 minutes.
You don't have to stir it for any longer than 3-4 minutes.

Just adjust your drip rate a little slower and it will calm down.
Exothermia subsides greatly after the first half of the peracid has been added. As a general rule, the second portion can be dripped in roughly half the time it took for the first portion.

Performic acid is not so stable so even after 2 hours, you see it starting to bubble, meaning its decomposing.
Impurities will also cause it to break down, always use SCRUPULOUSLY CLEAN GLASSWARE, for Peracids, or, if you are able to, have a specific set of glassware for peracids, and use it for nothing else.

Distill off the dcm using a water bath. I like to do that overnight. Its a lot of dcm to be distilled out, so you can save-up some time there. Weight your glycol. From this one I got about 435 grams of glycol, its always been nearly quantitative.
300 grams of Isosafrole is ~1.85 moles, therefore 1.85 mloes Isosafrole Glycol is ~ 363 grams. I would figure your yield of 435 grams has residual DCM in it. After you have distilled and emptied your DCM to it's container, apply weak vacuum to remove the rest.

Take your dcm/oil( combine both hydrolysis then wash) layer and wash it a couple of times with 5% NaOH. Be patient and make sure all the dcm is out.
An old post with some good advice from chromic and goiterjoe suggest doing a water wash before the NaOH washes. Try it and I am sure you will find your seperations are nicer and cleaner.

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That last comment by abolt is where the thread linked up the top of this post comes in handy, it has the chromic/goiterjoe thread in it.

Enjoy all!
-AC

2spun · The Resistor

Very sweet,

Thanks bro!

biobrew · Sun Jun 19, 2005 8:48 am

Great ref!!!!!! .......and pix

methyl_ethyl · Riedel De Haen

Good Find A_C,

Yes I believe this was "Ocotea Cymbarium's" pictorial, and if I recall correctly this was his first go at the synth, although I could be wrong.

I think the high 180C reccomendation was a "leftover" from the Leuckart days, and Abolt offers good advice concerning this. EDIT On second thought this probably has nothing to do with any Leuckart leftovers. (my mind is acting a little bit retro tonight Rolling Eyes

There has been some controversy concerning the HCL concentrations for hydrolysis. The above post uses the term "muriatic acid" I am not a very fond of this terminology as it does not describe what is really being used. Do I assume muriatic acid is 12N HCL? if so this would assume a 6N Hydrolysis correct? I have no idea if "muriatic acid" procured from a pool store is 12N. I see posts stating their muriatic acid is ~31.25% corresponding to ~10.41N HCL as opposed to true 12N ~36%. The HCL that I procure is usually fuming at 36-38%. Not that any of this will make a huge difference in yield AFAIK. I am just wondering if any yield junkies out there have optimized this hydrolysis for maximum yield, and what the proper concentration of HCL should be utilized in the Hydrolysis.

In the past I have run many different concentrations of HCL in the hydrolysis and have always achieved an "acceptable" yield. However back then acceptable yield had a different definition than it does now Smile

All in all, the pictures look just as I remember them, with exception to figure 5 as I recall my typical reaction products looking more orange in appearence than what is portrayed in the above post. That being said the colour I view on my screen may not be the colour of the actual product photographed.

This thread makes me want to crank out a performic and photograph / video capture it. I think pictures such as these can greatly help newbees to an extent. I wish I had photos of Leucky's back when I was first dabbling with them. Perhaps I can photograph the flasks I first used back in the day that are still charred with tar, that no solvent known on earth can remove, due to my first dabblings in leuckarts and heating mantles Crying or Very sad

.

things change...

much_love

methyl_ethyl

Soap · Sun Jun 19, 2005 11:34 am

this has to be the most useful post on safrole to mdp2p via performic that swim has seen as of yet. A friend of mine claims that the colors during the reactions of this performic are almost identical to his oxone reaction. Thank you very very much for posting this, swim will definetly try the performic on his next try. (just orderd a new hot plate/stirrer and 25g of hgcl2!!!! Very Happy

, and also found a site that sells formic in high concentrations for cheap! what sort of chems should be orderd with the formic to make it less supicious, is this necessasry?)

mucho points for the original poster! Wink

methyl_ethyl · Riedel De Haen

ApprenticeCook · DILLIGAF

Ocotea Cymbarium thats it... couldnt remember for the life of me how to spell it.. Thanks m_e.
I had this in my cache and completely forgot about it until iodide remninded me of my post in the thread on the hydrolysis topic, so here it is..

Hope it helps some newbees, photos always make it easier for the chemistry declined.
As for the method there are some more recent adjustments but i thought i had better post it in its original form, if o_c is watching from somwhere dont want to be mistaken as trying to steal the thunder (so to speak).

In the past i have seen store bought muriatic (yes m_e i hate the term to) acid used as described above with excellent results. But as with most industrial chemicals the conc would vary alot per batch (or per bottle even).

Soap, 25g HgCl2? goin the whole nine yards hey.. Thanks for the points man.

Take care all!
-AC

Soap · Sun Jun 19, 2005 11:50 pm

heh yeah look around, everyone 25g was the smallest this company sells, and it only cost swim $6... ill tell swim to go ahead and order the formic ($10 for 16 oz of 90-95%(%?) is that a deal or what???) as well as some lab glass and filter paper. no need to fear i guess. a.c. what sort of adjustments have been made?

ApprenticeCook · DILLIGAF

By adjustments i meant disputes, over temps, times etc... people put their own spin on things so this one method may not be globally accepted.
Swim would just use the above proceedure as is due to its simplicity and excellent yield attainment.

-AC