Dextroamphetamine: Pharmacology and Synthesis Guide

Pharmacology of Dextroamphetamine: Unraveling Its Intricate Effects


Dextroamphetamine, a potent central nervous system stimulant, has gained attention for its diverse pharmacological properties. Understanding its synthesis is crucial for comprehending its intricate effects on the human body. Dextroamphetamine can be synthesized through various methods, including biosynthesis, direct synthesis, and the separation of optical isomers from racemic amphetamine. In this article, we delve into the synthesis process, shedding light on a simplified approach adaptable to "home conditions."


Dextroamphetamine Synthesis from P2NP via Al/Hg:

  1. Aluminum Amalgam Preparation: Begin by tearing 14 g of aluminum foil into small pieces (2x2 or 3x3 cm) and place it in a round-bottom flask, ensuring it's fully covered with water. This step aims to remove the oxide layer from aluminum.
  2. Mercury Salt Creation: Break the bottom tip of a mercury thermometer, collect all the mercury, and add 4 ml of nitric acid (70%). This step requires caution due to hazardous mercury vapors. Heat the glass to about 50 degrees Celsius, allowing all the mercury to dissolve over approximately 30 minutes.
  3. Cleaning the Aluminum: After the mercury salt is prepared, add it to the aluminum in the flask. Within 5 minutes, the aluminum will lose its shine and develop a layer of gray sludge at the bottom.
  4. Rinse and Add Reactants: Drain the liquid and rinse the aluminum with water three times. Then, add 30 ml of water to the flask and set up the apparatus for the reaction.
  5. Initiating the Reaction: Add a solution of 14% P2NP (1-phenyl-2-methyl-2-nitroethylene) to the reaction flask and initiate the reduction of P2NP. The reaction produces hydrogen, which is essential for the synthesis.
  6. Controlling Temperature: Carefully monitor and control the temperature during the reduction, keeping it around 50-55 degrees Celsius to avoid overheating, which can lead to reduced yields and colored products.
  7. Alkali Addition: Once the reduction is complete, add a cooled alkali solution to the reaction mixture until the pH reaches 11-12. This step dissolves the remaining aluminum and yields yellow oil.
  8. Layer Separation: Transfer the mixture to a separating funnel and wait for the layers to separate. Collect the oily fraction.
  9. Extraction: Extract amphetamine from the remaining sludge by washing it three times with petroleum ether. Combine the upper layers and cool them in ice water.
  10. Final Extraction: Separate any remaining water from the upper layer and dry it with anhydrous magnesium sulfate.
  11. Purification: Filter the product through a Buchner funnel to remove solid impurities.
  12. Acidification: Prepare a sulfuric acid solution in acetone (1:10) and add it drop by drop to the product to reach pH 6. This results in a white precipitate.
  13. Precipitate Collection: Cool the mixture in ice water, filter the precipitate, and rinse it with cold acetone.
  14. Drying and Weighing: Air-dry the filtered product and record its weight.

Through this synthesis process, 7.55 g (0.0205 mol) of amphetamine sulfate is obtained, with a reaction yield of 43.6%.

Extraction of D-Amphetamine

To obtain dextroamphetamine from the racemic mixture, the following steps are employed:

  1. Dissolve 6 g of racemic amphetamine in 6 ml of water and adjust the pH to 11 with an alkali solution.
  2. Extract with 5 ml of petroleum ether and warm the solution. Add d-tartaric acid in alcohol solution to the mixture, followed by alcohol until complete dissolution. Cool with stirring to precipitate l-amphetamine d-tartaric salt, leaving d-amphetamine in solution.
  3. Precipitate d-amphetamine with additional d-tartaric acid. Filter the precipitate to obtain the d-amphetamine base, then adjust the pH to 11 with alkali.
  4. Acidify the d-amphetamine base to pH 6 using a sulfuric acid solution in acetone, resulting in 2.63 g of d-amphetamine sulfate with a yield of 87.7%.

This extraction method is applicable to amphetamine synthesized through various routes.

  1. G.Patton

    Dextroamphetamine synthesis (Nabenhower, 1942)

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    Dextroamphetamine synthesis from P2P by (S)-(−)-α-Methylbenzylamine

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