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Synthesis of Methadone

WillD

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Crystal partially evaporates and dissolves
 

Hank Schrader

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There are a lot of errors in the synthesis here.
You write that you need 2,2-Diphenyl-3-methyl-4-dimethylambutyronitrile,
this is not the correct nitrile isomer and you can obtained from it only isomethadone.

2,2-Diphenyl-3-methyl-4-dimethylamino butyronitrile does not have a crystalline form.
You write: "It was then recrystallized from petroleum ether to give 900 g of 2,2-Diphenyl-3-methyl-4-dimethylambutyronitrile."

Initially, you started correctly,
and said that you need 4-cyano-2-dimethylamino-4,4-diphenylbutane.
4-cyano-2-dimethylamino-4,4-diphenylbutane (Premethadone)
CAS: 125-79-1 is the correct nitrile. Only from it you can get methadone.

In the synthesis of a nitrile, you don't use a solvent...
Also, you don't use a Catalyst, which shifts the reaction in the right direction to increase the yield of the desired nitrile.
You are left with a lot of unreacted precursor, since the deprotonation must be done in the presence of a catalyst.

I'll disappoint you, but you can't get methadone in THF, you can get methadone only through ethyl ether.. The addition reaction does not work in THF.
In your synthesis there is no word about the purification of nitrile, therefore it is dirty and black under the conditions that you describe.
I don't know where you got this synthesis, but you won't get anything good - sorry.
 

adrenochrome

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There are a lot of errors in the synthesis here.
You write that you need 2,2-Diphenyl-3-methyl-4-dimethylambutyronitrile,
this is not the correct nitrile isomer and you can obtained from it only isomethadone.

2,2-Diphenyl-3-methyl-4-dimethylamino butyronitrile does not have a crystalline form.
You write: "It was then recrystallized from petroleum ether to give 900 g of 2,2-Diphenyl-3-methyl-4-dimethylambutyronitrile."

Initially, you started correctly,
and said that you need 4-cyano-2-dimethylamino-4,4-diphenylbutane.
4-cyano-2-dimethylamino-4,4-diphenylbutane (Premethadone)
CAS: 125-79-1 is the correct nitrile. Only from it you can get methadone.

In the synthesis of a nitrile, you don't use a solvent...
Also, you don't use a Catalyst, which shifts the reaction in the right direction to increase the yield of the desired nitrile.
You are left with a lot of unreacted precursor, since the deprotonation must be done in the presence of a catalyst.

I'll disappoint you, but you can't get methadone in THF, you can get methadone only through ethyl ether.. The addition reaction does not work in THF.
In your synthesis there is no word about the purification of nitrile, therefore it is dirty and black under the conditions that you describe.
I don't know where you got this synthesis, but you won't get anything good - sorry.
Hank Schrader1. firstly, he wrote that he received the correct nitrile by recrystallized from petroleum ether (here you can use hexane) 2. Without a solvent, nitrile also comes out, since alkali acts as a catalyst and why does the reaction in tetrahydrofuran not go?) you don’t know how the Grignard reaction adds a substance
 

Midget_Impinger

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Does anyone know how to synthesize any fun opiates _from_ methadone? I have a lot of liquid methadone on hand, and no use for it. Im just holding onto it until I find a use for it (ie: synthesis to something more fun)
 

Hank Schrader

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We produced methadone in different ways.
Methadone bases are not suitable for consumption!
The base has a beautiful crystal shape, but if you inject it into yourself... you can die, it crystallizes right into you.
You need to use only hydrochloride salt and well purified!
Trust me, I have been producing methadone since 2006!
DC9Wk7TQqB Qd57Rye98Y M20AI19so5 HvV3gPLK0x
 

reza

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We produced methadone in different ways.
Methadone bases are not suitable for consumption!
The base has a beautiful crystal shape, but if you inject it into yourself... you can die, it crystallizes right into you.
You need to use only hydrochloride salt and well purified!
Trust me, I have been producing methadone since 2006!
View attachment 9661 View attachment 9662 View attachment 9663 View attachment 9664
Hank SchraderWill you help me synthesize methadone hydrochloride? I want to produce methadone tablets of 20 mg.
I need help to find the right way to center methadone hydrochloride. please guide me
 

None

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OrganicChemis

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@Hank Schrader is absolutely right on most points.
However, it is actually possible to produce the methadone precursor without a solvent through a reaction of diphenylacetonitrile,
dimethylamino-2-chloropropane HCl and sodium hydroxide. The reaction partners involved should be ground very finely and
mixed well. After the reaction has taken place, extraction can be carried out with diethyl ethe

What seems very strange to me, however, is the ethylmagenesium bromide. I have already prepared EMB countless times (for methadone
synthesis, but also for other syntheses). EMB does not have a yellowish color and is not a clear reagent. EMB that I have made so far always
had a brown-grey color and had always a slight cloudiness.

to THF: All I can say is that I have never used THF to make EMB. Therefore I can't say whether methadone synthesis is possible with it (it is
definitely usable for Grignard). I don't use it as a Grignard solvent because it has unlimited miscibility with H2O.

You were also right about the name of the methadone precursor. The correct IUPAC name is (4S)-4-(dimethylamino)-2,2-diphenylpentanenitrile.
(3S)-4-(dimethylamino)-3-methyl-2,2-diphenylbutanenitrile
is the IUPAC name for the Isomethadone precursor.

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and here is Levomathadone & Dexromethadone
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Last edited:
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