v 1.0 [Oct 16, 1998]
HTML by Rhodium
The Wacker process has been widely documented since the 1960s and is a relatively simple and easy process to perform. With respect to our desires, we are looking to take our olefin (safrole) and hydrogenize it (add an oxygen group). To do this we will be using a catalyst in the form of palladium(II) chloride (PdCl2). To help the palladium chloride do its job, we also require a co-catalyst. In this case, we'll be using cupric chloride (CuCl2). Copper chloride (CuCl) cannot be used in the procedure outlined here as it does not dissolve in methanol (MeOH) or ethanol (EtOH) and thus does not form the required complex. If you wish to use CuCl you would have to perform the following reaction in dimethylformamide (DMF) which tends to be more expensive and not quite as easily obtainable as MeOH or EtOH.
I've chosen to outline the method at a relatively small scale - a scale that would be suitable for personal research in a country that sanctioned this. You can probably use the same procedure to process 100mL or maybe even 150mL of olefin. Do be aware that processing more olefin requires even more air refills and more shaking.
The original inspiration goes to spiceboy and a big nod to him.
Note: Barq's root beer or cream soda bottles are the authors favorites. They have smooth sides unlike the contoured sides of a Coke bottle and thus are less prone to rupture due fatigue. Plus they're clear allowing you to easily see what's going on inside.
Take your soda bottle and wash it thoroughly in warm water and soap. Do not use water that is too hot. The label should gracefully fall off during the washing process. Do not place the cap back on the bottle after washing -- the warm air inside will contract as it cools causing the bottle to deform. Why is ketone harping-on about deforming so much? Well, it's like this kids. If the bottle deforms you're causing fissures to form in the plastic. You may not even be able to see them. Pump this baby up to pressure and BOOM!!! You may just create a pressure bomb that distributes a nice corrosive solution around your lovely home or over your body.
The next bit can be a bit tricky. You need to take that tubeless tire valve and insert it into the neck of the bottle. You may need to squeeze the rubber surround a bit to soften it up. It should fit very snuggly in the neck of the bottle. If it doesn't, go find a valve that will. Where I live, I was able to buy two packs of suitable valves for less than $4. Get several if you can.
Taking the bottle cap, remove the plastic liner that's inside the cap and throw it away. Apply heat from a candle to the top of the cap so that you can poke a hole in the soft plastic that the valve can poke through. Be careful! Hot plastic is napalm!!!.
Once you have a suitable hole in the cap, screw it down on the bottle so that the valve is secured but the valve threading protrudes through the cap allowing you to attach the tire pump. Pressurize the KRV to 40psi.
Fill a bucket or bath with water and place the KRV into the water. Squeeze gently. See a stream of bubbles? Nope? Good. If you do see bubbles you obviously have a leak that needs to be fixed.
You now have a KRV. Congratulations. He will serve your faitfully for several reactions.
The beauty of this reaction is it can be done with easily obtainable chemicals. PdCl2 is used in specialist photography (see my PdCl2 FAQ), cupric chloride can be made at a pinch but is not at all suspicious to buy, methanol and ethanol are often available at hardware or automotive stores (look for methanol, methyl alcohol, methyl hydrate, Everclear).
You will need:
A couple of points about these chemicals. Some photography suppliers will sell you sodium palladium chloride as a direct replacement for palladium chloride. Insist on straight palladium chloride. The most common form of CuCl2 is the dihydrate which has two water molecules attached to it. If you are using the anhydrous form, there is really no need to adjust the amount used as a 3-8 molar excess of CuCl2 is what's required.
If you are using anhydrous solvent you should add 1% (2.5mL) dH2O to the reaction. This reaction needs a bit of water to perform. If you're using anhydrous CuCl2 and not CuCl2·2H2O, add another 2.5mL of dH2O.
With respect to our favorite olefin, remember that garbage in equals garbage out. You should at least single distill to obtain relatively pure olefin. The other products in the oil have the capability to interfere with this reaction.
Take a glass, beaker, or flask and pour 100mL of solvent into it. Then add the 1g of PdCl2. If you have a magenetic stirrer, toss in a stir bar and let it stir for a bit (a bit is 15-30 minutes is normally good enough). The solution should turn a dirty brown color. Do not worry if it doesn't completely dissolve. Pour this liquid into the soda bottle.
Take the 5g of cupric chloride and throw it into the same beaker. You don't even need to wash it. Add 50mL of solvent and the cupric chloride should easily dissolve giving a bright green fluid. This gets poured into the soda bottle too.
Take that very same beaker and pour your safrole into it along with the remaining 100mL of solvent. Stir. Pour into the soda bottle. Add parsley. Serves two.
Now that you have all the goodies in the soda bottle, it's time to put the tubeless tire valve in the bottle neck and secure it with the modifed bottle cap. Be careful not to push the tire valve all the way through!
You're now ready to charge the bottle with air. Take your trusty pump and attach it to the valve. Pump until you have around 40psi in the bottle. You don't need that much pressure, what you really need is an large oxygen reserve and anything over atmospheric pressure. However, compressing the air gives you a large reserve of oxygen close to hand and also provides the pressure required.
Shake the bottle like crazy. How crazy? Well, you should see foam appear as you shake. Ideally, shake for at least 5 min. Preferably 10 min. The shaking is very important in this reaction, the more you do the better.
After shaking let the bottle stand for 20 minutes. De-pressurize the KRV and squeeze the bottle to expell all the gas inside. Some nasty gasses form during this reaction, and you want to get them out of the KRV. With a little bit of skill you can hold the valve open while you squeeze-release-squeeze the bottle a few times to pump the gasses out. Alternatively, you can remove the valve and the cap and remove the gasses that way, but it gets a little tiresome.
Replace the valve and cap if necessary and re-pressurize to ~40 psi. Shake again for at least 5 minutes. You will need to repeat this no less than 10 times at this scale. This reaction is time dependant too meaning that if you think you can get away with re-pressurizing once per day for 10-days and get the same results, you won't. What will happen is that you either won't get enough O2 into the olefin, or you will run out of O2 resulting in side products being formed instead of the ketone.Do the whole thing in a day including work-up of the final ketone and you'll be a happy camper.
In fact, if you can handle more shaking and more re-pressurizations at shorter time intervals you'll probably increase your yield and have a higher assurrance of getting final product.
When you're arms are falling off and you've re-pressurized at 10 times or so, add 500mL of distilled water (dH2O) to the solution in the bottle. This should be enough to precipitate the catalyst out of solution because the contents of the flask should already be acidic.
If you have a buchner funnel and vacuum source, filter this solution a couple of times to remove the catalyst. If you don't have a buchner and vacuum source, you can improvise with coffee filter and gravity.
The solution should now be relatively free of PdCl2 and CuCl2. You can extract the goodies from this solution using your favorite organic solvent. I quite like DCM (dichloromenthane) but you could also use ether or petroleum ether. Add 50mL of DCM (or ether or petroleum ether) to the solution, extract and repeat two or three times to get all the good stuff. Combine the extracts and then remove the solvent either under vacuum or at atmospheric pressure.
Once you've removed the solvent you'll be left with crude ketone which might well have some tar, isosafrole and other junk in it. If you have vacuum distillation equipment, then this is the optimum way to purify the crude ketone. If not, I'm afraid the bisulfite procedure is probably your only hope. It's pretty messy and you will lose some product doing it, but clean ketone is a good starting point for any amination or reduction.
And that's it. A simple, fairly inexpensive, easy to do reaction for making MD-P2P. Enjoy.
Question: Why is everyone afraid of pressure reactions? 'Cause they're dangerous, right?
Well, somewhat, yes, No more so than many other things, tho.
After having listened closely to Osmiums tales of power about his pressure dreams, I meditated on the problem and came up with a whole new approach to an old problem. I didnt want to use a champagne bottle because of a few different reasons, most of them having to do with it being glass. Plus you cant see color changes thru a green bottle. Well get ready everyone for a new dawn... Introducing the SRV (Spice Reactor Vessel) a 'ketone generator, if you will, its so simple that you'll scream....
What you need: one 2 L coke bottle. One valve stem for a car tire. I found it easily... fits in the neck tightly... what you have to do is squeeze the base and deform the rubber to a slight oblong shape. You will be able to pull the stem up and cork the bottle with it from the inside out, if you will. This is your pressure vessel. It is very easy to wire the stem in using the nice wide collar that runs around the top of the bottle. Try to visualize. I have tested the apparatus to 2.5 atm successfully. At about 40lbs the fuckin thing blew the valve stem out of the bottle like a .60 caliber shell. I never did find it. Oh well, they're only a buck. Thats why I mention wire. Anyway this is the setup for the dream that is the next part, entitled let there be ketone...
I want to thank Osmium for the original inspiration.
This process will allow the reacting of one hundred grams of olefin w/ 2g of PdCl2, and 8g of CuCl2. There will be no oxygen tank. The reference the main part of this is based on indicate that air will serve as an able reoxidant, and it will.
The SRV is pressurized with a tire pump. (37-40 psi)
The original reaction ran 21 hrs with 6-8 hrs standing time in the cool. So, actually, it ran about 14 hrs, with about 7 hrs standing.
Dont heat this stuff in any way while preparing. Heat favors aldehydes. The refs say that isomerization is decreased with control over 2 factors:
Contents are already acid, usually, but I like to hit it w/ some dilute acid before extraction.
This method is pretty close to OTC, and represents much testing and research. Not everyone had immediate results with it, but it is a very viable method.
This is an update on the SRV concept, including a detailed run with the unit. In this dream the ratios were as:
After mixing the copper salt w/ alcohol, it was chucked in the SRV.
Same for the PdCl2. Its probably better to put the palladium directly in the SRV via funnel, than to put it in a separate beaker and trying to do the mixing beforehand. The reason why is that the shit sticks to the beaker and is hard to recover when transferring containers.
When you get it all in there, assemble the unit and throw in a stirbarbefore you plug it up with the valve stem...this is a minor improvement that makes a big difference, because it enables you to get a much more turbulent agitation of the mixture...and that increases the oxygen uptake dramatically.
This was done next;
Plug the unit. Pressurize it w/ the pump.
I have found that you cannot run the electric tire pumps off of a small battery charger because it doesn't have the amps. Go out to your car and pressurize on the ground beside it. Or take a car battery and set up a work station at a bench, whatever.
Pressurize it for ten seconds. Shake it. Presurrize more. Shake it. Pressurize it until it rock hard, all the while shaking strongly. You can get a really good swirling-shaking action going on with the stir bar inside of the unit. If you think about it, this is the principle that engineers use to package spray paints in such a way that the contents can be readily mixed, while being under pressure. I really cant emphasize enough the difference this made in my dream. Your shaking effort is actually reduced, while your mixing efficiency is exponentially increased. Shake some more.
I shook the unit vigorously, nonstop for two hours. Well, stopped every ten minutes to relieve gases, and purge. Squeeze it while holding the valve open,and purge two or three times. Away from your face. Have cold water nearby to immerse the unit in intermittently, while repressurizing. This improves uptake. Shake it. Shake it. See?
When you first place everything in the unit, the stuff is a light, green-brown-golden. It evolves to gold-brown, then brown, then brick-red at the end. Really hard shaking was used, and never let up on.
At the end, when it was brick red, I noticed a fine suspension of Pd particles. Then, would purge and add new air. The particles would go away for a short time and come back, so this was done a few times, and, evidently, as the reaction finished, the catalyst quit going back into solution and would deposit as a fine, granular silt on the sides of the SRV as you slowly rotate it.
The character of the solution seemed to change right about the time the shit went from brown to dark red, too. It seemed less viscous, and kinda acted like it was more easily agitated. I dont know how objective Im being here, just thiught I'd add that.
Remember, Shake It Real Hard. There were vertical cracks appearing in the unit at the end of the Rx, indicating that it was a hearty shaking affair, replete with purge and binge...
Make up dilute acid. Others have said that it's not needed, but in my dreams a much more efficient separation is achieved with dilute HCl being used to bust everything up. Hit the stuff with about 200-300 ml of this. It gets cloudy and tan-crap-greenish color and a heavy red oil falls out to the bottom. But its full of catalyst. Get the buchner funnel and your patience together. Assemble them. Filter all this crap about 3-4 times with the paper I have, don't know about you. A clear red oil is obtained, and believe it or not, Zero tar. ZERO.
The result? 37 ml of ketone from 50 ml safrole. Thats over 70%. Its repeatable. It is not a fluke. There was extremely little iso and even less unconverted olefin. Removing the catalyst is a bitch, but its not really bad. You do need vaccuum. It seems like denatured ethanol is superior, in my dreams, to methanol as a substrate. Well, there you have it. If anyone is not afraid of shaking for two hours, this is a very viable way to get the stuff.
Low temps seem to favor a better all-round set of kinetics for this reaction.
After about 45 minutes of prssure/ shaking, 2ml of water was added to the mixture. This detail was added because it may have been important to anyone else finding themselves in this dream. It maybe wasn't necessary, but I have no way of knowing if/how much water is in the denatured (slx) alcohol. The dihydrate was used, salt-wise.
Well the final distilled product from these wacker/SRV's is a light, clear yellow-green. It comes over at 170-175°C. It smells weird, and post-purity yield is 55-60% with some messy technique. also, it glows a real cool green under black light, too...
The one important criteria in these reactions is the O2 to Pd ratio, IMHO. With more Pd, your results improve. With air, use less Pd. But air makes it easy for anyone.
This is a major finding in the sequence of SRV-type reactions.
I have found that in the using of Pd powered Wacker oxidations that there is a 'window' of Pd amount used that greatly influences factors such as pressure and shaking, and generally makes the air Wacker a little hard to predict.
I will tell you this; Using 1 g Pd to 50 g alkene will produce MDP2P, but only if you put out your max effort when it comes to shaking, and you make a top effort to keep the purge/binge thingy rollin'... (lotta air - a lot)!
If you do not perform with great vigor, you may not achieve conversion. I was confused when my new found reaction only returned the safrole to me one night, and I began wondering why... then I remembered that big humongous skunk joint that I smoked, and that, due to it, I really didn't get the full focus of my att'n span goin' on, so, was a little lax in the re-airing, and a little lax in the power of my shaking.
But the colors I posted werent right this time. They werent changing definitively. After the processing I got my oil back. I dreamed this dream again, and re-duped my original conditions, with earth-quake shaking, GONZO repressurizations, and attention to all details.
POW! (ketone appears) not the chemist, the chemical....
So, this means that I am onto something. But I am telling you that this is probably the most physically demanding method you could ever dream up. I started wondering, How about if you could get the results with your half-ass performance, and not have to feel like you've been at the deltoid machine at Golds Gym...
This took me back to J. Org. Chem. 34 [???] and the ratio 3:18:65 between PdCl2/CuCl2/Safrole (double distilled). I went the 'wimpy' process, which was still fairly robust shaking, and maybe 75% of the attention to the re-airing process. Guess What!?!? Ketone. Yes there was one bitch of an emulsion, but good lord, thats a lotta metal salt. It all cleaned up w/ a few passes thru the ol' Buchner....
Yield: After the processing, where I estimate I lost 10%, I got back 32 g of very light yellow oil that smells nothing like safrole. It has a heavier, softer smell, with an element of something spicy.
So, the moral of this story is: Use more Pd and get results that are more consistent.
Again, it will work with less, but you will work your ass off... and I am not sure, but I think I repressurized it (don't have my notes) 32 times. This was calculated by the volume of the bottle, the amount of O2 required, and the amount of O2 in air (~21%) - If you use 3g I'll just about guarantee it everytime...