Amphetamine Synthesis from phenylpropanolamine hydrochloride with reduction using I2 and H3PO2.
Starting reagents and materials
The process way presented on Scheme 1.
Starting reagents for amphetamine synthesis: phenylpropanolamine hydrochloride, I2 and H3PO2. Fig. 1
The powder of phenylpropanolamine hydrochloride is poured into the flask. Fig 2
The powder of I2 is added to the phenylpropanolamine hydrochloride in the flask and continuously mixing. Fig 4
The H3PO2 is added in very small portions (drops) to the mixture in the flask while continuously mixing. The H3PO2 acid is added within 1.5 hours. The reaction should not be very exothermic! Fig 5
Reflux connected to the flask. The mixture is heated to the temperature 100-160°C for 10-12 hours. Fig 6
The solution should become transparent and homogeneous. Fig 7
To the resulting reaction mixture, 20-50 ml of water is added. This solution has acidic pH and very bad smell! Fig 8
NaOH cooled solution is added to the RM until reaching an alkaline pH. Fig 9
Next, sodium thiosulfate solution is added. Fig 10
The mixture cooled and added 100 ml of DCM (boiling point of DCM is 40°C). Fig 11
The layer of DCM is dried with sodium sulfate. DCM was decanted. Fig 13
HCl 7% solution was added to the dried DCM in the separating funnel. Additionally, 2-3 extractions of AMP from DCM are carried out with some portions of HCl solution. DCM layer discarded. Fig 14
Finally obtained water acidic solution volume is 400-450 ml. Fig 15
To the obtained solution powder of aluminium oxide is added. Fig 16
The solution is filtered through a paper filter. Fig 17
Filtered solution is evaporated to crystallization. Crystals without filtration dried in desiccator with NaOH approximately 3-4 days. Fig 18
Petroleum ether 70-100 ml is added to dried crystals. Fig 19
The amphetamine hydrochloride crystals are filtered. Fig 20
Filtered and dried crystals of AMP hydrochloride. Fig 21
Standard test for AMP. (Left etalon AMP*HCl; right obtained crystals). Fig 22
AMP*HCl. Fig 23
Yield is 1.9 g or 43%. General yields in this method 40-60%.
Starting reagents and materials
- 10.4 g I2
- 9.4 ml H3PO2
- 20-50 ml H2O
- 50 ml 25% NaOH (15-20 г NaOH)
- 3 g sodium thiosulfate
- 250-300 ml DCM
- 30-50 g Na2SO4
- 400-450 ml HCl 7%
- 1-2 g Al2O3
- 100 ml Petroleum ether
- Flasks 250 and 500 ml
- Glasses
- Funnels
- Separating funnel
- Magnetic stirrer with heating
- Flask heater
- Reflux
- Paper filters
- Pipettes
- Porcelain filter for vacuum filtration
- TLC plate
- UV-lamp
- pH indicator paper
- AMP standard test
The process way presented on Scheme 1.
Starting reagents for amphetamine synthesis: phenylpropanolamine hydrochloride, I2 and H3PO2. Fig. 1
The powder of phenylpropanolamine hydrochloride is poured into the flask. Fig 2
I2 is ground into a powder. Fig 3
The powder of I2 is added to the phenylpropanolamine hydrochloride in the flask and continuously mixing. Fig 4
The H3PO2 is added in very small portions (drops) to the mixture in the flask while continuously mixing. The H3PO2 acid is added within 1.5 hours. The reaction should not be very exothermic! Fig 5
Reflux connected to the flask. The mixture is heated to the temperature 100-160°C for 10-12 hours. Fig 6
The solution should become transparent and homogeneous. Fig 7
To the resulting reaction mixture, 20-50 ml of water is added. This solution has acidic pH and very bad smell! Fig 8
NaOH cooled solution is added to the RM until reaching an alkaline pH. Fig 9
Next, sodium thiosulfate solution is added. Fig 10
The mixture cooled and added 100 ml of DCM (boiling point of DCM is 40°C). Fig 11
The mixture is transferred to a separating funnel. DCM is separated. Additionally, 2-3 extractions of DCM are carried out with portions of 40-50 ml each. Fig 12
The layer of DCM is dried with sodium sulfate. DCM was decanted. Fig 13
HCl 7% solution was added to the dried DCM in the separating funnel. Additionally, 2-3 extractions of AMP from DCM are carried out with some portions of HCl solution. DCM layer discarded. Fig 14
Finally obtained water acidic solution volume is 400-450 ml. Fig 15
To the obtained solution powder of aluminium oxide is added. Fig 16
The solution is filtered through a paper filter. Fig 17
Filtered solution is evaporated to crystallization. Crystals without filtration dried in desiccator with NaOH approximately 3-4 days. Fig 18
Petroleum ether 70-100 ml is added to dried crystals. Fig 19
The amphetamine hydrochloride crystals are filtered. Fig 20
Filtered and dried crystals of AMP hydrochloride. Fig 21
Standard test for AMP. (Left etalon AMP*HCl; right obtained crystals). Fig 22
AMP*HCl. Fig 23
Yield is 1.9 g or 43%. General yields in this method 40-60%.
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