Introduction
At the moment, there are many ways to synthesize dextroamphetamine. They can be divided into 3 types: biosynthesis (using biomass), direct synthesis, and synthesis of racemic (the sum of l- and d-isomers) amphetamine followed by separation of optical isomers. In our case, a synthesis was chosen, in which simple reagents and rapid synthesis were used, which is maximally adapted to «home conditions». The process is as follows: we obtain the racemic amphetamine in the classical way, then we divide it into 2 optical isomers (l- and d-) by the Nabenhower method [US patent 2276508, Nabenhauer FP, "Method for the separation of optically active alpha-methylphenethylamine", published 17 March 1942, assigned to Smith Kline French].
Synthesis
Synthesis of amphetamine from P2NP via Al/Hg. First, we make an aluminum amalgam. It is needed in order to clean the aluminum from the strong oxide layer that forms when interacting with air. We take 14 g of aluminum foil and tear it with our hands into pieces of 2x2, 3x3 cm in size. Be sure to tear, not cut, to increase the surface area. Place into a 3-necked round-bottomed flask and fill the foil completely with water.
Now we are preparing the mercury salt. We take a mercury thermometer from the pharmacy, wrap it in paper, break it at the bottom tip. Pour all the mercury into a glass, where then add 4 ml of nitric acid (70%). Do not forget that mercury vapors are hazardous to health! To initiate the reaction, the glass had to be heated to about 50 degrees, stirring occasionally. All the mercury dissolved about for 30 minutes, and an orange gas, nitrogen oxide (IV), was released from the glass. The reaction equation is as follows:
Hg + 4HNO3 ----> Hg(NO3)2 + 2NO2 + 2H2O
2
Pipette 2 ml of the solution and place it in a round-bottom flask with foil. After about 5 minutes, the foil lost its shine, became dull, and a small layer of gray sludge (aluminum hydroxide) collected at the bottom of the flask.
Pour 30 ml of water into the flask, insert a thermometer into the left throat of the flask, insert a reflux condenser into the central throat, and insert a dropping funnel with 110 ml of 14% P2NP (it is phenylnitropropene; 1-phenyl-2-methyl-2-nitroethylene) solution into the right throat.
Acetic essence is often used to produce hydrogen, but I "start" the reaction to produce hydrogen with water. Less acidic medium, which means less alkali must be added later. Many people ask the question: "How to remove this water?" There is no need to remove water anywhere, it reacts with aluminum and hydrogen is obtained:
2Al + 6H2O ---> 2Al (OH) 3 + 3H2
It is very important to remember that the reaction of P2NP reduction comes with a very! large exotherm. It is necessary to carefully monitor the temperature and prevent overheating above 60 degrees. Personally, I kept the temperature around 50-55 degrees. Failure to comply with this technology reduces the yield of the product and gives a colored (pink, orange) product. The infusion of the entire P2NP took about 50 minutes. Change the dropping funnel to a glass stopper. We got just such a gray solution.
We cool the mixture to room temperature, put a plug instead of the thermometer, remove the reflux condenser. We make an alkali solution based on 1 part of sodium hydroxide - 2 parts of water. Dissolution proceeds with heating, so we wait until the solution cools down. It is not worth pouring solid alkali into the reaction mass or pouring a hot solution, as this reduces the yield, like any overheating. Pour alkali cooled to room temperature to the reaction mass until pH = 11-12, wait 30-40 minutes until all the floating aluminum dissolves, yellow oil floats up. At the same time, we also monitor the temperature. Reaction equations:
2Al + 2NaOH + 6H2O ==> 2Na[Al(OH4)] + 3H2
NaOH + Al (OH)3 ---> Na[Al(OH)4]
We pour everything into a separating funnel. We are waiting for the separation of layers. Take the oily fraction.NaOH + Al (OH)3 ---> Na[Al(OH)4]
A large drop of water remains in the bottom of the glass, which is separated on a separating funnel. Pour the top layer into a glass and dry over anhydrous magnesium sulfate. There we clean the amphetamine from the remnants of mercury and water.
I take concentrated 98% sulfuric acid. Prepare a solution of sulfuric acid in acetone in a volume ratio of 1:10. I took the technical acetone, in the hardware store, and distilled it, taking away the "heads" and "tails". Then I dried it with anhydrous magnesium sulfate. Many people ask whether is it possible to make a solution in IPA. Yes, you can, but IPA (isopropyl alcohol) is evaporated longer than acetone.
Cool the reaction mass in ice water, filter the precipitate on a Buchner funnel, rinse with 3 ml of cold acetone.
7.55 g (0.0205 mol) of amphetamine sulfate was obtained.
Calculations:
m (P2NP) = 110 * 0.14 = 15.4 g.
n (P2NP) = 15.4 / 163.17 = 0.094 mol.
n (amphetamine sulfate) = n (P2NP) = 0.094 mol.
n (amphetamine base)= 0.0205 * 2 = 0.0410 mol.
The reaction yield is 0.0410 /0.094 = 43.6 %.
You will carry out different reaction with sulfuric acid. Amphetamine free base 2 mole + 1 mole of sulfuric acid = 1 mole of amphetamine sulphate. When you count amph. sulphate, you have to multiply by two your mole result of amph. sulphate cuz you take 2 mole amph. base for one mole of amph sulfate.
Calculations:
m (P2NP) = 110 * 0.14 = 15.4 g.
n (P2NP) = 15.4 / 163.17 = 0.094 mol.
n (amphetamine sulfate) = n (P2NP) = 0.094 mol.
n (amphetamine base)= 0.0205 * 2 = 0.0410 mol.
The reaction yield is 0.0410 /0.094 = 43.6 %.
You will carry out different reaction with sulfuric acid. Amphetamine free base 2 mole + 1 mole of sulfuric acid = 1 mole of amphetamine sulphate. When you count amph. sulphate, you have to multiply by two your mole result of amph. sulphate cuz you take 2 mole amph. base for one mole of amph sulfate.
Extraction of d-amphetamine
We've got racemic amphetamine. It contains 1 molecule of d-amphetamine per 1 molecule of l-amphetamine. Next, 6 g of racemate is taken and dissolved in 6 ml of water, an alkali solution is added to reach pH = 11.
Extract with 5 ml of petroleum ether and warm the solution, add 2.45 g of d-tartaric acid in alcohol solution to the mixture. Then add alcohol until completely dissolved and cool with stirring. The l-amphetamine d-tartaric salt precipitates. The d-amphetamine remains in the solution. You can repeat procedure of cleaning precipitate of l-amphetamine d-tartaric salt by methanol to increase yield.
Source
Nabenhauer, Fred P. "Method for the separation of optically active alpha-methylphenethylamine." U.S. Patent No. 2,276,508. 17 Mar. 1942.
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I was looking at the numbers in the procedure as still waiting for some solvents to arrive. When starting the D-amphetamine purification, the 6ml of water given seems way too little. The solubility of the sulphate salt is given as 8.8 part water to one part amph. sulphate. Is it not a typo, did you not mean 60ml? Here is a link, but haven`t double-checked in the Merck:
