Electrolytic Hydrogenation of Ephedrine, Pseudoephedrine and PPA"Festerlytic Hydrogenation" by Bozakium
[ Back to the Chemistry Archive ]
PrefaceAs those of you who have been following the chem scene this year know, the new book from Uncle Fester has been promised and promised by Loompanics since March or so of this year, with the release date continually being pushed back, despite the word that it was "at the printer's" in June. I have been privy to the manuscript of a very,dare I say, revoloutionary chapter of this book since much earlier this year, and out of respect for the author's need to make a living, not divulged any "trade secrets" though I have told of said formula's most vital element, and teased of the simplicity this new Fester Method.
Now several months later, and nearly a year since the book was written it is still not available and we are now told by 'Panics to expect it in September sometime. Yeah, right (sarcasm here folks). Anyway, while discussing this with Fester, I mentioned how I had teased the swarm with hints of the new method, but hadn't divulged any "trade secrets". The embittered Fester, pissed at the gravelly hand-job Loompanics has been giving him(allegedly due to management changes or something) defiantly trumpeted "Divulge Trade Secrets!" I nearly busted at nut with both excitement and relief that I could now share this breakthrough with you, the scientific world. My shit-eating grin still aglow, Uncle excitedly gave me two new references which promise to significantly shorten reaction time. It is now my great honor to share this knowlege in the interest of the furtherment of science. Enjoy.
Reduction of the hydroxyl group of various 1-phenyl-2-aminopropanols and their substituted amino variants are easily and efficiently carried out by electrocatalytic hydrogenation of their respective acetic esters at a palladium or palladium-plated electrode in a divided electrolytic cell. Use of a lamb's skin prophylactic as an inexpensive yet effective cell divider is also demonstrated in this experiment.
One gram of ephedrine, pseudoephedrine or PPA hydrochloride is placed in a large test-tube along with 5-7 mL of glacial acetic acid. The test tube is heated in a water bath until all the ephedrine (in this case) hydrochloride is dissolved. A few drops of concentrated sulfuric acid are added. Mix it all together and LOOSELY stopper the end of the test tube to prevent steam from entering. Heat the water bath to just about boiling, and use it to heat the test tube and its contents for a few hours. This forms the acetic ester of the ephedrine, pseudoephedrine or PPA used in the reaction.
The solution should appear clear and water-like, completely homogenous. After heating, the reaction mixture can be kept stoppered as is for a few days, but it's best to use it immediately after it's cooked.
Next, mix up a solution of 5 mL of concentrated sulfuric acid in 100 mL of water. Take a 250 mL beaker, and place it on a magnetic stirrer. Clip a well-scrubbed Kling-Tite Naturalamb condom in one side of the beaker, and place a piece of lead 1/2 inch in diameter and a few iches long inside the condom. On the other side of the beaker, stand up a one-ounce ingot of palladium. Using alligator clips, make contact with the ingot, and wth the piece of lead. They are your two electrodes. Next, pour most of the dilute sulfuric acid solution into the beaker. Save enough that some can be poured into the condom so that the solution levels are about equal inside the condom and the beaker. The ingot of palladium should be almost completely immersed. The alligator clip should be up out of the solution, and there should be enough space left to add the ester reaction mixture from the test tube to te beaker without causing the solution level to reach the alligator clip.
The surface of the palladium ingot should be lightly sanded prior to use. This increases its surface area a little and exposes fresh, clean metal. The piece of lead should be scrubbed free of grease and dirt. The wire lead to the palladium ingot can be clipped to the side of the beaker with a clothes pin or paper clip to prevent the ingot from falling over during the course of the reaction. A DC current meter (ammeter) should be put in series with the wiring. A good one can be had at Radio Shack for under $50.00.
The wires are first hooked up so that the palladium ingot is connected to the positive pole of the DC power supply, and the piece of lead to the negative. The typical one- ounce ingot will have a face with an area of about six square centimeters immersed in the solution and one square centimeter up out of the solutuion. Only count the area on the side facing the lead piece. The back side doesn't count because significant current doesn't reach it. With this typical ingot apply about two amps for 30 seconds to one minute. Oxygen will bubble freely from the ingot, and hydrogen from the piece of lead. Blackening will be noted on the edges of the ingot, where the current is most intense, and a lighter discoloration on the flat face of the ingot. This pre-treatment is called anodizing. It has been found that anodizing increases the ability of the palladium ingot to adsorb hydrogen when the wiring is turned around, and the ingot is made the cathode.
Next, redo the wiring so that the palladium ingot is attached to the negative pole of the DC power supply, and the piece of lead to the positive. Turn the juice back on and run between one and two amps of current for about 20 minutes. At first, the amount of hydrogen generated at the palladium ingot will appear small. This is because the Pd adsorbs hydrogen so well. After about five minutes of current passage, the whole surface of the ingot will freely bubble off hydrogen.
After the 20 minute charging with hydrogen, begin magnetic stirring of the solution, and pour in about half of the ester reaction mixture from the large test tube. Adjust the current flow from the variable power supply so that a current of about 50 milliamps per square centimeter of palladium surface flows. If one has about six square centimeters of the ingot facing the piece of lead immersed in the solution, a current of about 300 milliamps is called for. This will result in some gassing off of hydrogen from the edges of the ingot, but over the rest of its surface the hydrogen will react before it bubbles off. The lead anode will form a brown layer of lead oxide, and will not dissolve at all in the sulfuric acid solution. Some surface particles will be kicked off the lead when it's first charging, but they don't make it through the condom. The lead anode can be replace with a piece of platinum if desired, but lead is a lot cheaper. Graphite is amother possibilty.
Keep an eye on the current meter, as the current flow can change as the reaction progresses. Keep the current flow around 300 mA (0.3 amp) for the size ingot given in this example. When 1000 coulombs ( a coulomb is a unit of charge equalling one amp-second) have passed into the solution, add the other half of the ester reaction mixture from the test-tube., and continue at 300 milliamps until 3000 coulombs have passed through the solution. Let us use the 300 mA current to show an example of these calculations: At 300 milliamps, 1000 coulombs pass in 1000 / 0.3 Amps = 3333 seconds, or a little under one hour. 3000 coulombs pass in 10,000 seconds, or two hours, 45 minutes.
3000 coulombs per gram of feed material has been found to give good yields of a fine product, but by no means consider this number to be optimal. It may well be that a greater yield would be obtained by passing more current. It may also be that pseudoephedrine and PPA differ from ephedrine in their ease of electrocatalytid hydrogenation. I don't think that any harm can come from passing more current, within reasonable limits, so by all means experiment with the amount of current passed.
During the course of thi reduction, the color slowly changes from its initially clear color to slightly tinted with yellow. It's not known whether this color change is due to some of the condom soaking out, or if it's a byproduct of the reaction. In any case, it's a remarkably clean reaction.
When the desired amount of current has passed, the work-up and isolation of the product is very simple. The Kling-Tite condom is removed from the beaker. after pulling out (no pun intended) the lead electrode, the jimmy hat is, as is custom in some parts, flushed down the toilet. The anode can be used over and over. The palladium cathode is then rmoved and rinsed off. It too can be reused an INNUMERABLE (Bozakium's emphasis) number of times. The process of anodizing the palladium will have to be repeated prior to each run. Some fresh metal may have to be exposed on occasion by light sanding of the metal surface. An ingot of palladium should last for a lifetime.
The reaction mixture should be poured into a sep funnel, and a 20% NaOH solution should be added with shaking until the solution is strongly (13 + pH) alkaline to pH paper.
Extract with two 50 to 100 mL portions of toluene. This should be plenty for one-gram of product. THe toluene extracts are then bubbled with dry HCl to get the crystalline hydrochloride product. After rinsing them off with some fresh toluene, they are spread out to dry.
The most pleasantly surprising finding is that crank produced by this method doesn't give one the body and soul-wrenching hangovers so typical of the product made by the iodine-red phosphorous method.. This is a highly desirable way to keep one's own party rocking and rolling.
If one should wish to produce more than a gram or so at a time, a larger palladium cathode should be used. Linking together more ingots of palladium would get pretty expensive, so a more economical alternative will be detailed. That alternative is electroplating some copper or brass screen with a thick coating of palladium.
The simplest way to get this section of screen electroplated with palladium is to go to the yellow pages, look under electroplaters and find one who plates palladium. Ask for a plate build-up of several thousandths of an inch, so that enough Pd is deposited to last a while.
The Pd plated screen would then be used exactly like the ingot. First it must be anodized, then charged up with hydrogen in exactly the same way. The sole difference is that the greater surface area of the screen facing the condom-encased anode requires a correspondingly greater amount of current to be passed. Then, during the course of the reduction, again 50 milliamps per square centimeter of surface area facing the anode is used. The total of 3000 or so coulombs per gram of feed material doesn't change by increasing the size of the electrode.
An alternative to this is plating the screen yourself, anodically dissolving a portion of the ingot to form a PdCl2 solution then..... sorry folks, this all of the manuscript I have, but I'm sure palladium plating is no national secret (yet).
There is a company that sells an electroplating kit consisitin of a power supply, metal solution and a 'pen' electrode. As soon as I find their paperwork among my rubble I will post it.
The lastest word from Fester is a couple of references from Indian journals on electroplating graphite electrodes with palladium, essentially giving a Pd black on C catalyst in the cell!
On the Electrochemical Reduction of Benzyl Cyanide to Phenethylamine with a Pd/C Electrode (note: The title may not be exact due to the illegibility of my chickenscratch transcription of my conversation with UF.)
2) Krishnan, Journal of Applied Chemistry, Vol 5, Pg 125-128 (1975)
The greater activity of Pd on C (over straight Pd) results in a shorter reaction time.
If anyone manages to find these references, please post them at the hive. I'd also be happy to answer anyone'e electrical questions, as long as you are not doing anything illegal of course. Enjoy.
Addendum by Readyeddie:
Rhodium,I think you need to change something on the fester formula on your site.The problem is the ester it says add half of it then wait 45 min or so then add the other half.Witch is wrong because a gram needs 3000 coulombs to be passed.If you add the ester in two parts it will leave half of the product unreacted.Why because the second half will not have the right amount of time to be hydrogenated.Witch will give a mix of meth and starting feed. The ester should be added all at one time and ran until 3000 coulombs has passed.But on the other hand some people think why not just run longer to let the second half have the right amount of time to react. Wrong why because the first half of the ester will more and likely be changed back to the starting feed. Just trying to help other where others have failed.