Amphetamine Synthesis of alpha-PVP (1 to 10 kg scale). Full tutorial

[ireshop]

Introduction

This topic presents the method of alpha-PVP synthesis on a medium scale from 1 to 10 kg. There are elaborate video tutorials, which allow anyone to produce this substance. You can also find here a list of the necessary equipment and reagents.

Laboratory Equipment and Materials:

• Round bottom flask.
• Stand and clamp for securing.
• Reflux condenser.
• Dropping funnel.
• pH indicator papers.
• Beakers.
• Vacuum source.
• Laboratory balance (1-2000 g is suitable).
• Measuring cylinders of 100, 500 and 1000 mL.
• Magnetic stirrer with heating plate.
• Glass rod and spatula;
• 1 L separatory funnel.
• Laboratory grade thermometer.
• Büchner flask and funnel.
• Vacuum source.
• Filter paper.
• Rotary evaporator.
• Conventional funnel.

Reagents:

• Valerophenone (CAS 1009-14-9) 1 kg.
• Hydrobromic acid (HBr) 1 kg 48%.
• Hydrogen peroxide (H2O2) 300 g 35%.
• Pyrrolidine 1100 ml (CAS 123-75-1).
• Ethyl acetate 4 L.
• Sodium carbonate (Na2CO3) 20% aqueous solution.
• Diethyl ether (Et2O) 50 ml.
• EtOH (ethyl alcohol) 50 mL.
• Dibenzoyl-D-tartaric acid 12.7 g, 35.5 mmol.
• Dichloromethane (CH2Cl2) 830 mL.
• Hexane 1100 mL.
• Concentrated hydrochloric acid 35% (HCl).

Stage 1. Halogenation.

1. Weigh 1 kg of valerophenone (CAS 1009-14-9) and pour into the reactor.
2. Add 1000 g of 48% hydrobromic acid (HBr).
3. The reaction mixture is stirred vigorously for 5 minutes.
4. Hydrogen peroxide (H2O2) 300 g at 35% is added into the dropping funnel installed in the reactor neck.
5. The drip funnel tap is opened and the hydrogen peroxide is added dropwise with vigorous stirring.
6. Observe the colour of the mixture, which may vary from yellow to red. Hydrogen peroxide is added until the mixture is discoloured.
7. The temperature is kept below 65 ℃. The H2O2 drip is stopped if the temperature rises.
8. The reaction mixture is stirred vigorously for 1,5 hours.
9. Distilled water is added and the reaction mixture is stirred for 5 minutes.
10. The stirring is stopped and the reaction mixture separates into two layers. The target layer is at the bottom, the water is in the upper layer.
11. The water layer is removed with the help of a vacuum pump through the reactor neck.
12. An aqueous alkaline solution is added and stirred for 5 minutes.
13. Steps 9, 10 and 11 are repeated.
14. The resulting product is left in the reactor.

Step 2. Amination.

1. Place 4 L of ethyl acetate in a reactor with 1.5 kg of 2'-Bromovalerophenone and stir for 5 minutes.
2. A dropping funnel is installed in the reactor neck and pyrrolidine 1150 ml (CAS 123-75-1) is added into this funnel.
3. The tap of the dropping funnel is opened and the pyrrolidine is added dropwise with vigorous stirring.
4. The temperature is kept below 65 ℃.
5. The reaction mixture is stirred vigorously for 1 hour after completion of the addition of pyrrolidine.
6. The reactor vacuum pump and the reflux condenser cooling pump are switched on.
7. Most of the ethyl acetate is distilled off.
8. The vacuum pump is stopped and acetone is added to the reactor. Stirring is continued.
9. Hydrochloric acid is added into the dropping funnel at the neck of the reactor.
10. Hydrochloric acid is added until a pH of 5 is reached. A small amount of the reaction mixture is drained from the bottom tap of the reactor to check the pH with indicator paper (a glass rod can also be used for this purpose). The sample is returned to the reactor.
11. After that, the reaction mixture is poured into a beaker and placed in a freezer for 12 hours.

Step 3. Filtration.

1. A vacuum filtration system (nutsche filter, filter cloth, vacuum pump) is installed.
2. The vacuum pump is switched on.
3. The reaction mixture is poured from the beaker (from step 13 of step 2) into the Büchner funnel.
4. The reaction mixture is filtered and pressed to a solid.
5. Cold acetone is poured into the Büchner funnel to cover the solid.
6. The acetone is filtered off and the product is washed. Step 5 is repeated if the solid substance is not white.
7. The contents of the Büchner funnel are poured into a Pyrex dish for the drying procedure after acetone filtration and obtaining the white solid.
8. The Pyrex dish is placed in a dry place at room temperature.
9. The product is dried to a constant mass. The product is mixed and periodically triturated to increase the drying rate.

Step 4. Diastereomeric.

1. Dissolve 10.0 g a-PVP HCl, 35.5 mmol in the minimum volume of distilled water.
2. Add 20 % aqueous Na2CO3 solution to a pH of 8-9.
3. The mixture is extracted with 50 ml Et2O.
4. The ether extract is separated in a separatory funnel, then the Et2O is distilled off.
5. The free a-PVP base is dissolved in EtOH (50 ml).
6. The ethanol solution of the free a-PVP base is heated to 70 ℃.
7. Dibenzoyl-D-tartaric acid 12.7 g, 35.5 mmol is added.
8. The solution is refluxed with a reflux condenser for 1 min and cooled to room temperature.
9. The solvent is distilled off.
10. The residue is dissolved in CH2Cl2 (530 mL). Hexane (700 mL) is added with stirring.
11. The resulting crystals (9.1 g) are collected by filtration through a Büchner flask and funnel after 3 days.
12. Three consecutive recrystallisations from CH2Cl2/hexane (300/400 mL) give a single diastereoisomer (6.1 g, 61%).
13. Steps 1, 2, 3 are repeated with the salt from step 11.
14. Cold acetone is added.
15. Hydrochloric acid (HCl) is added until a pH of 5 is reached.
16. The crystals produced in step 15 are filtered off and air dried.

 

[islandgato]

And for A-PHP?

 

[RegulierTier]

For a-PHP you have to replace the valerophenone with hexaphenone.

 

[themonkeytown]

I did yesterday and went all the way wrong, in the alpha bromination I had to discard all the mix because the two layers suddenly become again one after the second wash of H2O2

 

[RegulierTier]

what do u mean? which 2nd h2o2 wash?
what have u done exactly and at which step have u been?

 

[themonkeytown]

Sorry! The last 2 is a typo I washed it with distilled water not ‘oxigenada’

 

[RegulierTier]

Ok thats weird af, when it's seperated first in two layers and you removed only the water layer, then it shouldn't mix to one layer when you give another water to it.

 

[themonkeytown]

I will give another try today, the thing is that I probably missed some step all the way because I am synthesizing almost all the elements and the 4 steps in my case is a couple more, fingers crossed!

 

[ireshop]

You have all this info in the main threads

 

[OreoBetor]

My aphp

 

[The-Hive]

Tune fits perfectly

 

[ireshop]

Gran aporte