Dextroamphetamine Synthesis

Dextroamphetamine Synthesis


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 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 °C, 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

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.

We drain the liquid and rinse the foil with water 3 times.

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 °C. Personally, I kept the temperature around 50-55 °C. 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.

To increase the yield, you can heat the reaction mass at a temperature of 50-60 °C for 30 minutes in a water bath.

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.

We extract amphetamine from the sludge, washing it 3 times with 10 ml of petroleum ether. Divide the upper part with a separating funnel. Combine all extracts with "oil" and put them in ice water for cooling.

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.

We filter the liquid from solid magnesium sulfate on a Buchner funnel.

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.

Drop by drop, carefully and with stirring, acidify with sulfuric acid in acetone to pH = 6. A white precipitate forms at the bottom.

Cool the reaction mass in ice water, filter the precipitate on a Buchner funnel, rinse with 3 ml of cold acetone.

Air dry the filtered product and weight.

7.55 g (0.0205 mol) of amphetamine sulfate was obtained.

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.

We precipitate d-amphetamine with an additional amount of d-tartaric acid. We filter the precipitate, get the base of d-amphetamine, adding alkali to pH 11.

We acidify the d-amphetamine base to pH = 6 with a solution of sulfuric acid in acetone. This gives 2.63 g of d-amphetamine sulfate. Yield is 2.63 / 3 = 87.7%

This extraction method valid to amphetamine, which was synthesized by any routes. There is an another way to obtain dextroamphetamine.


  1. G.Patton

    One Step Dextroamphetamine Synthesis

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  2. G.Patton

    Dextroamphetamine synthesis (Nabenhower, 1942)

    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...
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