Experimental section. Amphetamine Sulphate Synthesis Via P2P With Ammonium Formate and Reduction With Mg
The reactions proceed according to Scheme 1.Scheme 1
Starting reagents and materials
Starting reagents and materials
- 5 g purified P2P (P2P obtained through the reduction of P2NP with sodium borohydride)
- 4.1 g Mg
- 30 г HCOONH4
- 10-15 ml H2O
- 50 ml EtOH 88%
- 30 ml HAc
- 100-150 ml DCM
- 5+5 ml Ethyl acetate
- 2-3 mL of concentrated sulfuric acid (83%)
- pH indicator paper
- 2 liters of technical-grade cold water
- 20-30 g of anhydrous sodium sulfate
- 50 mL of 25% NaOH (sodium hydroxide)
- 500 mL and 250 mL flasks
- Reflux condenser
- Separatory funnel
- Filter paper
- Funnels
- Beakers
- Heater
In Figure 1, the starting components are presented.
Figure 1
P2P is placed into a 1 L flask along with ammonium formate and ethanol, and the mixture is well stirred. Figure 2
Figure 2
Mg is added to the obtained mixture. The reaction starts almost immediately. Figure 3
Figure 3
During the reaction, 5 mL of acetic acid (HAc) is added. Figure 4
Figure 4
The reaction proceeds quite vigorously; the flask needs to be cooled by placing it in an ice bath. Figure 5
Figure 5
The reaction is completely finished within 30-40 minutes. Figure 6
Figure 6
After the reaction is complete, the mixture is filtered. Figure 7
Figure 7
After filtering, the paper filter is rinsed with 15-25 mL of acetic acid. Figure 8
Figure 8
50-70 mL of DCM is added to the filtrate for the extraction of the amine. Figure 9
Figure 9
Next, a 25% aqueous solution of NaOH is added until the pH reaches 8-10. During this process, a white precipitate of magnesium hydroxide will form, accompanied by the release of the amphetamine as a free base, characterized by a distinctive pleasant odor. Figure 10
Figure 10
The amphetamine free base from RM is further extracted with several portions of DCM. Figure 11
Figure 11
The extract in DCM is dried with anhydrous sodium sulfate. Figure 12
Figure 12
The DCM is distilled off. Figure 13
Figure 13
After DCM distilled off, the flask contains the oil of the amphetamine free base. Figure 14
Figure 14
The amine free base is transferred to a glass beaker, and the residues in the flask are washed with 5 mL of ethyl acetate. Figure 15
Figure 15
Sulfuric acid is added to the amphetamine free base solution in ethyl acetate until the pH 7. A precipitate of amphetamine sulfate is forms. Figure 16
Figure 16
The precipitate of amphetamine sulfate is filtered through a paper filter and washed with 5 mL of ethyl acetate. Figure 17
Figure 17
The precipitate is air-dried. Figure 18
Figure 18
The yield of amphetamine sulfate was 1.17 g or 17%. Figure 19
Figure 19
Conclusions and Recommendations
Conclusions and Recommendations
- The method is relatively simple for synthesizing the amine from P2P and ammonium formate through magnesium metal reduction.
- The method is suitable for scaling up by adding magnesium metal in portions to the reaction mass.
- A drawback of the method is the product yield of 17%.
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