Lone Ranger Methcathinone synthesis via Jones reagent.
Here is the Jones Oxidation method I posted in ADC. My Grandma tried it, and found no flaw. You guys can tell me if there are typos or any problems with it. It is the best oxidation process for secondary alcohols that I know of. It even has been used on Codeine (a tert alcohol) with limited success. OK, here it is:
Part 1 - Some Boring(?) Chemistry
'Reduction' is the addition of hydrogen to a molecule, and 'oxidation' is the removal of hydrogen. The pseudo or ephedrine that we are starting with is our 'substrate'. Our first task will be to oxidize the 'OH' (hydroxyl group) to 'O'. To remove the unwanted hydrogen, we will use a powerful oxidizing solution, known as 'Jones Reagant'.
Jones reagent is prepared by dissolving 26.72 grams of chromium trioxide (CrO3) in 23ml of concentrated sulfuric acid, and then diluting the mixture to 100ml with water. One mL of the reagant oxidizes 4 'millimoles' of an alcohol. Secondary alcohols (like we have) are oxidized to ketones in excellent yields.
A 'mole' is very large number of molecules (6X10^23). The actual number is not important, what is important is that a mole of one substance contains the exact same number of molecules as a mole of any other. A mole of lead weighs 207.2 grams, and its molecular weight is 207.2. A mole of ibuprofen weighs 206.28 grams, mw=206.28. A mole of pseudoephedrine (mw=165.23) weighs 165.23 grams. So if I choose to start with 2 grams of pseudoephedrine, (or 2 X 1/165.23 moles = .0121 moles = 12.1 millimoles), and each mL of the jones reagant oxides 4 millimoles, I will need 12.1 / 4mL of Jones reagant, or 3.03 mL. I will prepare exactly 4mL of the reagent, since I am bound to lose a small amount in the glassware and on the table!
So we only need 4/100 of the 26.72 grams of CrO3 (chromium trioxide) and 23ml H2SO4 (sulfuric acid) to make our needed 4mL of reagent. Half molar amounts of sodium dichromate, potassium dichromate or ammonium dichromate may be substituted. This is because each molecule of CrO3 (mw=99.994) has one chromium atom in the +6 state (that is with 6 bonds, 2 to each of 3 oxygens). Each molecule of sodium dichromate - Na2Cr2O7.2H2O (mw 298) has 2 chromiums in the +6 state (and the chromium is our oxidant in this case). In this example the 1.068 (4/100 X 26.72) grams of CrO3 = 1.068/99.994 or 10.68 millimoles. 10.68/2 mmoles is needed of sodium dichromate. So 5.34 mmoles = 298 X .00534 = 1.59 grams. So 1.59 grams of sodium dichromate may be used in place of 1.068 grams of CrO3 (chromium trioxide).
Part 2 - Oxidizing the Alcohol to a Ketone
Lets get to work. 1.068 grams (I used just over 1 gram) CrO3 are added to .92ml H2SO4, and distilled water is added to bring the total volume to 4ml. 2 grams of pseudoephedrine are dissolved in 20ml acetone, and cooled in an ice bath. The Jones reagant is slowly added to the pseudoephedrine, dropwise and with stirring. The mixture becomes a reddish brown.
Since we used just about the exact number of molecules required, and under very mild conditions, the reaction will proceed slowly, but very smoothly. Just let the ice melt and the stirred solution warm over night.
Part 3: Extracting the Ketone
About 12-18 hours later the reaction is complete, the color is now a very dark green. We now have to neutarlize and extract our ketone. Add about 20mL of water, and chill in an ice bath. Dropwise and with stirring add about 1 gram of lye (Sodium Hydroxide - NaOH) in a solution with as little water as possible (highly concentrated). Check the pH regularly, and stop at pH=12. The now basic solution is shaken with 50ml of toluene. Allow to stand and two layers will form. The ketone will move into the toluene layer. Let the mix settle and remove the acetone/toluene/ketone and put it aside. Add another 50mL portion of toluene to the aqueous (water-based) portion, shake, filter (which breaks the emulsion and removes some chromium salts), and remove and put aside the toluene. Ensure that pH is still 12, and repeat again with another 50mL portion of toluene.
Combine the three toluene extractions and evaporate them with a hair dryer. The result is the impure ketone of pseudoephedrine, also know as methcathinione or ephedrone.
We used very gentle oxidation, neutralization, extraction, and evaporation conditions. Shortcuts can be used (no ice, evaporate with some heat, ect.), but good lab practice is never to stress the substrate needlessly. So we were careful.
The raw "dirty" methcathinone weighs about 1.7 grams
It is purified by adding just enough tolene to redissolve it. Some particles will not dissolve, and are left in the drying dish. The toluene is filtered to remove any additional particles, poured back into the separation funnel and shaken with an equal amount of distilled water. This removes any small amount of water solubles. The toluene is put into a clean dish and dried once again. The impurities are more soluble in acetone than the ephedrone, so a very small amout of acetone is added, and sloshed around. Pour this off into the waste (original green mix). What's left is a little over 1 gram (about 60% yield) of relatively pure, slightly off-white methcathinone.
Better chemists can expect a much higher yield. This is a general procedure. The example given - Pseudoephedrine or Ephedrine to Methcatinone - is for illustrative purposes only. Oxidizing cold pills is illegal, and makes a lousy drug anyway.
Further Reading:"Oxidation and Reduction of Organic Compounds" - Kenneth Rhinehart, Prentice-Hall, 1973 - Jones Reagant and other oxidation and reduction methods "Selection of Oxidants in Synthesis" - Leland Chinn, Marcel Dekker, 1971 - detailed mechanism and preparation of Jones Reagant on page 42 --------------------------------------------------------------------------------
Addition by anonymous contributor:
After the oxidation/stirring-time has expired and the methcathinone is in solution ready to be extracted, before adding 25% NaOH, add about five milliliters of isopropylalcohol (store bought of any concentration is fine, exact measurements not really needed [ballpark figure is fine]) to the mix. Stir for about ten minutes more (mixture may or may not get warm) and then cool the solution which hasn't changed much in appearance, add a volume of toluene equivalent to the solution, start stirring mixture while in an ice-bath, and add the appropriate amount of base. Stirring should be done for about two minutes only. Allow the layers to separate (the top toluene layer should be cloudy and the bottom chromium solution should be totally green) and do final work-up as usual. Yes, you bet your ass that there is NO SLUDGE! What happens is this: The IPA neutralizes the remaining chromic acid in solution that normally, if based, would form the sludge. But since there is no remaining chromic acid, the only thing that forms is the water soluble basic chromium hydroxide. Two SMOOTH layers will form. All you have to do is separate the bottom one, and you're good to go. Trust me on this one. It took forever to figure out, but it does work. There are a few problems that can arise but only if your starting ephedrine isn't pure. Aside from that, you should have no trouble. Really.
Synthesis of methcathinone from ephedrine (from unknown patent)
A solution composed of 0.99g of sodium dichromate and 1.33g of concentrated sulfuric acid dissolved in 4.46mL of water is added slowly with stirring to 1.65 g of l-ephedrine dissolved in 4.7mL of water and 0.52mL of concentrated sulfuric acid at room temperature. The mixture is stirred at room temperature for an additional 4-6 hours and then made alkaline with sodium hydroxide solution. The aqueous mixture is extracted with two volumes of chloroform and then with two volumes of ether. The organic extracts containing the free base of l-methcathinone are combined, treated with an excess of dry hydrogen chloride gas and the solvents evaporated. The residual l-methcathinone hydrochloride is stirred with petroleum ether, collected and purified by dissolving in ethanol and reprecipitating with ether; mp 182-184°C.