Dextroamphetamine Synthesis (Nabenhauer, 1942)
- Thread starter G.Patton
- Start date
I read the original patent. there they wrote that per 2mol of amphetamine they add 1mol of tartaric acid and dissolve it in the right amount of alcohol. heat to a boil and set aside to crystallize. they separate the aqueous phase from the crystals and carry out another recrystallization. they repeat this operation several times. then alkali is added to the combined water phases to raise the pH to 11. two phases are formed. one is oil. I understood the original patent well. will the actions carried out in this way give the appropriate effect?https://patents.google.com/patent/US2276508A/en
Two mols, for example, 2'70 grams, of racemic e-methylphenethylamine base are reacted with one mol (1'50 grams) of d-tartaric acid, thereby forming d1-a-methylphenethylamine d-tartrate. a neutral salt. The neutral salt thus obtained is fully dissolved by the addition of sufficient, say about one liter, of absolute ethanol, and heating to about the boiling point. The solution is then allowed towel to room temperature with occasional stirring to eiiect crystallization. The crystals are filtered oil and will be found to contain a preponderance of the laevo enantiomorph. On recrystallization the preponderance of the lenantiomorph is increased and the process is repeated until no further change in optical rotation is effected and a reading of is obtained in a concentration of 8 grams per 100 cc. of aqueous solution. The product thus obtained is Liz-methylphenethylamine d-tartrate. The residual solid in the mother liquors is repeatedly and systematically crystallized, yielding a further fraction of biz-methylphenethylamine d-tartrate which may be purified by recrystallization. d-a-methylphenethylamine may be readily recovered from the mother liquors by the addition of tartaric acid thereto for the formation of acid tartrates and separation of d-a-methylphenethylamine d-bitartrate by crystallization.
The free base'of either optical isomer may be obtained by addition to the d-tartrate in the case of the laevo isomer and the d-bitartrate in the case of the dextro isomer of alkali in excess, as, for example, by the addition of an aqueous solution of caustic soda, which will cause the base to separate as an oil which may be recovered and purified by any well known procedure.
Two mols, for example, 2'70 grams, of racemic e-methylphenethylamine base are reacted with one mol (1'50 grams) of d-tartaric acid, thereby forming d1-a-methylphenethylamine d-tartrate. a neutral salt. The neutral salt thus obtained is fully dissolved by the addition of sufficient, say about one liter, of absolute ethanol, and heating to about the boiling point. The solution is then allowed towel to room temperature with occasional stirring to eiiect crystallization. The crystals are filtered oil and will be found to contain a preponderance of the laevo enantiomorph. On recrystallization the preponderance of the lenantiomorph is increased and the process is repeated until no further change in optical rotation is effected and a reading of is obtained in a concentration of 8 grams per 100 cc. of aqueous solution. The product thus obtained is Liz-methylphenethylamine d-tartrate. The residual solid in the mother liquors is repeatedly and systematically crystallized, yielding a further fraction of biz-methylphenethylamine d-tartrate which may be purified by recrystallization. d-a-methylphenethylamine may be readily recovered from the mother liquors by the addition of tartaric acid thereto for the formation of acid tartrates and separation of d-a-methylphenethylamine d-bitartrate by crystallization.
The free base'of either optical isomer may be obtained by addition to the d-tartrate in the case of the laevo isomer and the d-bitartrate in the case of the dextro isomer of alkali in excess, as, for example, by the addition of an aqueous solution of caustic soda, which will cause the base to separate as an oil which may be recovered and purified by any well known procedure.
Hi, I need some help! I have tried the Rusznak method for resolving racemic amphetamine. Here is the only information from Erowid, I tried to search for the paper, but could not find anything:
I used half amounts compared to the description. Everything went fine, I got the Amphetamine disolved then base extracted with 30ml of Toluene (I didn`t have benzene - could this be the problem?), then added the other ingredients and kept for about 4 hours. There was some precipitate forming, but nothing some shaking in the separatory funnel would not help. Aqueous phase separated, and alkali given to PH 13. A nice layer of base formed on top of the water, so at this point I thought everything is fine. The base was extracted with 30ml of Toluene, however, when the acetone-sulphuric acid was added there was only a moderate precipitation, which did not increase, rather it started to disappear when a small layer of sulphuric acid - water was formed at the bottom of the beaker.
How can I save the hopefully D-Amphetamine extracted? I have also saved all the phases, so if someone points out a blunder earlier on, I can reverse. This is a very nice and easy method and I think it went fine, I just probably made some horrible mistakes in the simple extraction at the end. Actually wanted to re-read Patton`s extraction topic before starting with the final extraction, but was too excited and just went for it.
Any herlp would be appreciated.
My tips are:
- my acetone was not anhydrous - I distilled the acetone on NaSO4 yesterday and it was kept in a closed flask, but not in the freezer
- sulphuric acid contained water (it is pretty concentrated but not sure exactly - between 90-95%)
- I should have dried the Toluene before adding the acid - or perhaps just evaporate it a bit?
- Toluene is not the right solvent for this extraction for some reason (unknown to me).
- Should I reverse buy adding some alkali, then drying the Toluene, then let it evaporate?
A mixture of 0.1 mole (13.52 g.) phenylisopropylamine (or 14.92 g. methamphetamine base) in 60 ml benzene, 0.05 mole d-tartaric acid (7.50 g.) in 30 ml water, and 2 g sodium hydroxide (reagent grade or titrated equivalent) in 3 ml water was kept 4 hours with intermittent shaking, and the organic phase evaporated to give 98% L-phenylisopropylamine. The aqueous phase was extracted with benzene at pH 13 and evaporated to give 96% D-enantiomer.
I used half amounts compared to the description. Everything went fine, I got the Amphetamine disolved then base extracted with 30ml of Toluene (I didn`t have benzene - could this be the problem?), then added the other ingredients and kept for about 4 hours. There was some precipitate forming, but nothing some shaking in the separatory funnel would not help. Aqueous phase separated, and alkali given to PH 13. A nice layer of base formed on top of the water, so at this point I thought everything is fine. The base was extracted with 30ml of Toluene, however, when the acetone-sulphuric acid was added there was only a moderate precipitation, which did not increase, rather it started to disappear when a small layer of sulphuric acid - water was formed at the bottom of the beaker.
How can I save the hopefully D-Amphetamine extracted? I have also saved all the phases, so if someone points out a blunder earlier on, I can reverse. This is a very nice and easy method and I think it went fine, I just probably made some horrible mistakes in the simple extraction at the end. Actually wanted to re-read Patton`s extraction topic before starting with the final extraction, but was too excited and just went for it.
Any herlp would be appreciated.
My tips are:
- my acetone was not anhydrous - I distilled the acetone on NaSO4 yesterday and it was kept in a closed flask, but not in the freezer
- sulphuric acid contained water (it is pretty concentrated but not sure exactly - between 90-95%)
- I should have dried the Toluene before adding the acid - or perhaps just evaporate it a bit?
- Toluene is not the right solvent for this extraction for some reason (unknown to me).
- Should I reverse buy adding some alkali, then drying the Toluene, then let it evaporate?
I have just realized that I omitted the last instruction which may be the solution to the problem.
Still, even if evaporation works, what is the next thing to do to obtain D-Amphetamine sulphate? Just simply precipitate (acetone - sulphuric acid) but after evaporation? Why does it need to be evaporated? Is the reason that Toluene does not mix with Sulphuric acid, unlike IPA?
The aqueous phase was extracted with benzene at pH 13 and evaporated to give 96% D-enantiomer.
Still, even if evaporation works, what is the next thing to do to obtain D-Amphetamine sulphate? Just simply precipitate (acetone - sulphuric acid) but after evaporation? Why does it need to be evaporated? Is the reason that Toluene does not mix with Sulphuric acid, unlike IPA?
Yes, you can filter L-amph D-tartaric acid after precipitation. Why are you reinventing the wheel? The method in this topic.
sorry ;maybe i read too much for my little brain 
you clearly explain it in the method..
Thanks for your works !
you clearly explain it in the method..
Thanks for your works !
Hi Patton, when you used 6g of the Amphetamine sulphate in the above extraction and then added half of the amount of D-Tartaric acid (in terms of mol). I think 3.3g is too much because when calculating the molar amount the freebase needs to be taken into account. 6g of Amphetamine sulphate is 4.4g freebase, which is 0.0326 Mol of base (1 Mol is 135g). We need 0.0326/2 Mol D-Tartaric acid which is roughly 2.446g. Let me know if my thinking is on the right track. If yes, then it is thanks to you for your Amphetamine salt topic. I was trying this extraction and tried to calculate how much L-Amphetamine-D-Tartaric acid precipitate I should get.
By the way first I got way too little precipitate, just above 1g after drying. I guess this is why the author of the patent says to continue the crystalisation until we get a solution with the right rotation? I`m thinking of trying to put the solution into the freezer so that more L-Amphetamine-D-Tartaric acid can precipitate? It would be much more comfortable not having to do the crystallisation so many times.
By the way first I got way too little precipitate, just above 1g after drying. I guess this is why the author of the patent says to continue the crystalisation until we get a solution with the right rotation? I`m thinking of trying to put the solution into the freezer so that more L-Amphetamine-D-Tartaric acid can precipitate? It would be much more comfortable not having to do the crystallisation so many times.
You absolutely right. I'll fix my mistake.
Let us know your result, please.
Let us know your result, please.
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You can racemize the 50% lisomer you are left with and repeat as many times as possible.You do 3 of them bam 90% ish theoretical yield of the wanted isomer.
Here you go, good sir, from the horse's mouth.Kind of dangerous to have the stuff laying around, so probably not worth it for the chemist producing for himself.This article talks about methyl-amp. but I am 100% sure you can do this with the unmethylated variant.
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