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



## William Dampier

*Reagents:


*

Phenylacetone (cas 103-79-7) 1000 g;​
(S)-(−)-α-Methylbenzylamine (cas 2627-86-3) 904 g;​
Sodium borhydride 282 g;​
Boric acid (H3BO3) 461 g (or p-toluenesulfonic acid monohydrate 1418 g, or benzoic acid 911 g);​
Sodium bicarbonate (NaHCO3);​
Dichloromethane (CH2Cl2) (or ether, or petroleum ether) 2100 ml;​
Sodium sulphate (Na2SO4) anhydrous;​
Formic acid 1026 g;​
Potassium hydroxide (KOH) 1251 g;​
Ethanol (EtOH) L;​
Palladium on carbon (Pd/C 10%) 475 g;​
Acetone 3 L;​
Sulfuric acid (H2SO4 98%) concentrated ~750 ml;​

*Equipment and glassware:*

5 L Round bottom flask;​
Top stirrer and heating plate;​
Reflux condenser;​
Water bath;​
Vacuum source;​
Glass rod and spatula;​
Rotovap machine (optional);​
Laboratory scale (1-1000 g is suitable);​
Measuring cylinders 100 and 500 mL;​
1000 mL x3; 2000 mL x3; 500 mL x3 Beakers;​
5 L Separatory funnel;​
Boiling chips;​
Buchner flask and funnel [Schott filter may be used for small quantities];​
Pasteur pipette;​
pH indicator paper;​
Freezer;​
Vacuum desiccator (optional);​

*Step 1. Phenylacetone (P2P) reductive amination.*
*

*​*1.* Phenylacetone 1000 g and (S)-(−)-α-Methylbenzylamine 904 g are put into a 5 L round bottom flask;
*2.* The mixture is stirred at room temperature for 10-15 min;
*3.* Sodium borhydride 282 g is added slowly in several portions to the reaction mixture;
*4.* Then, boric acid (H3BO3) 461 g is added. It can be replaced by p-toluenesulfonic acid monohydrate 1418 g or benzoic acid 911 g;
*5.* The reaction mixture is stirred for 1 h at room temperature;
*6.* Next, the mixture is quenched with sodium bicarbonate (NaHCO3) saturated aqueous solution to alkaline pH 11-12;
*7.* Alkaline solution is extracted with dichloromethane (CH2Cl2) (or ether, or petroleum ether) 700 ml x3 in separatory funnel;
*8.* Extract is dried over anhydrous sodium sulphate (Na2SO4), filtered and concentrated under vacuum (optional) to get N-benzylamphetamine free base;​
*Step 2. Benzyl group removing from N-benzylamphetamine (debenzylation).*
*

*​*1.* Formic acid 1026 g, potassium hydroxide (KOH) 1251 g, N-benzylamphetamine free base 1000 g and ethanol (EtOH) 5 l are added into a 20 L flask, which is equipped with reflux condenser.
*2.* The reaction mixture is heated to a reflux temperature.
*3.* Palladium on carbon Pd/C 10% 475 g catalyst is added to the heated reaction mixture.​


*Pd/C catalyst*​*4.* The mixture is stirred at reflux temperature for 60 min.
*5.* The mixture is cooled to room temperature and filtered after reaction procedure.
*6.* Ethanol solution is evaporated under vacuum (optional) to get dextroamphetamine free base oil.
*7.* The catalyst powder is collected on the filter, washed with distilled water twice and washed with ethanol once.
*8.* An isolated catalyst is dried and used in a next batch.

*Step 3. Dextroamphetamine sulphate preparation.*
*1.* Amphetamine free base from *Step 2.6* is dissolved in acetone 2 l and stirred well.
*2.* Sulfuric acid (H2SO4) is added dropwise to reach pH 6.​

*3.* The mixture is put into a freezer for 12 h.
*4.* After that, the mixture is filtered and washed on a Buchner filter with cold acetone and dried on air or in vacuum desiccator to get Dextroamphetamine sulfate powder.​


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## Mr.Blanks00

hello sir, what is the percentage of the purity of the dextroamphetamine product for this method.


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## TotalSynthesis

ooh, that's a good one, didnt know it. i can directly source (S)-(−)-α-Methylbenzylamine quite easily.

@William Dampier how can this way be adopted to produce d-meth, do you maybe know that?

thx


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## G.Patton

TotalSynthesis said:


> ooh, that's a good one, didnt know it. i can directly source (S)-(−)-α-Methylbenzylamine quite easily.
> 
> @William Dampier how can this way be adopted to produce d-meth, do you maybe know that?
> 
> thx



TotalSynthesisHello, unfortunately no. You can use l- or d-tartaric acid for d-meth. Look at here. Procedure is the same, also read comment section.


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## cokemuffin

Yusuf said:


> hello sir, what is the percentage of the purity of the dextroamphetamine product for this method.



YusufIt just depends on the purity of your methylbenzylamine


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## cokemuffin

TotalSynthesis said:


> ooh, that's a good one, didnt know it. i can directly source (S)-(−)-α-Methylbenzylamine quite easily.
> 
> @William Dampier how can this way be adopted to produce d-meth, do you maybe know that?
> 
> thx



TotalSynthesisOnly way i could think of is to go from dexamphetamine to dexmethamphetamin via formaldehyde


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## G.Patton

cokemuffin said:


> Only way i could think of is to go from dexamphetamine to dexmethamphetamin via formaldehyde



cokemuffinHi, you'll get racemic mixture from this way.


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## cokemuffin

G.Patton said:


> Hi, you'll get racemic mixture from this way.



G.PattonOh sry didn't know that, does the same apply to fenethyline?


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## G.Patton

cokemuffin said:


> Oh sry didn't know that, does the same apply to fenethyline?



cokemuffinI think yes, it is Nucleophilic substitution reaction, which gives racemic product.


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## TotalSynthesis

@G.Patton 

using a cheaper catalyst should be possible. What would you expect which one could be a good substitution?
Raney?
Ni/C?


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## G.Patton

TotalSynthesis said:


> Raney?



TotalSynthesisI guess Ni/Re but I'm not 100% sure.


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