4-MMC (mephedrone) synthesis. Bromination in dichlormethane.

[Marvin "Popcorn" Sutton]

We'll consider mephedrone (4MMC) synthesis in this article. Dichloromethane (DCM) is used as a solvent. It has a low boiling point (~40 °C) and synthesis procedures take a little time.​

Work conditions:

• Air temperature 20-24 ºC;
• Relative humidity <60%;
• Well-ventilated room (with air intake/exhaust hood);
• Access to water and electricity;

Main stages:

1. Bromination;​

2. Methylamination;​

3. Separation/cleaning of the free base;​

4. Acidification;​

Bromination

1. 4'-Methylpropiophenone (cas 5337-93-9) 1000g and DCM 3000 ml is placed into a 10 l flask, stirred until a homogeneous solution is obtained.
2. A portion of bromine (Br2) 1000 g, 330 ml is poured into a drip funnel.​

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It is important to know: Work with bromine takes special safety measures because the substance is very corrosive and toxic. Every surface, which has contact with bromine, will be completely spoiled. It is better to use long graduated pipette or graduated cylinder in order to measure volume of this substance. Bromination have to be carried out outside or in a well-ventilated room by reason that bromine is very volatile. The procedure isn't tricky but takes an attention. All glassware, which will be used for manipulations with bromine, must be cooled and absolutely dried.

3. Hydrochloric acid (HCl 36% aq) 50 mL is added into the reaction mixture. It is the catalyst of bromination reaction. A weak stirring is turned on and bromine addition is started.
4. The first portion of bromine ~50 ml is added. The solution is turned brown and eventually is discolored. It means that the bromination reaction is taken place. You have to wait this moment, and not pour out all bromine in a one portion to avoid a violent exothermic reaction with a subsequent boiling off of the solution.
5. Bromine is added from the drip funnel to the solution dropwise, when the first Br2 portion is discolored, in order to a smooth reaction course. If the solution begins to boil, the addition of bromine have to be stopped until the solution is cooled to 30-35 ºC.
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It is important to know: Hydrogen bromide is released during bromination. It is the caustic white gas (acid). It takes respiratory organs and eyes protection (full face mask) and well ventilated exhaust fumes hood.​

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6. It is necessary to make sure that the reaction has been completed after all the bromine has been poured in: reaction temperature is stopped to rising, the solution is stopped to discoloring. Then, the reaction mixture is stirred for 30-60 min.

7. Obtained solution is washed from remaining bromine, it positively influence on the final product quality. The reaction mixture is washed with an equal volume of sodium thiosulfate (Na2S2O3) 10% solution or sodium bicarbonate (NaHCO3) 10% solution. The solutions is stirred well for 10 min, layers are clearly separated. The lower organic layer is taken for further manipulations. The top layer is disposed.

8. Next, the reaction mixture is washed with an equal volume of water to neutral pH. The washing procedure of the organic layer can be repeated several times, if it is necessary. The reaction 2-Bromo-4'-methylpropiophenone (cas 1451-82-7) yield is ~1400g, which is already dissolved in DCM.​

Methylamination

9. Methylamine 40% aqueous solution is added to the solution from previous reaction. This reaction is also exothermic, so that methyl amine is added at slow rate in order to avoid the solution boiling. This influences on the reaction yield. Methylamine is taken in excess by reason that it is partially evaporated during the reaction. The average proportion is 2 ml per 1g of 2-Bromo-4'-methylpropiophenone. Methylamine 40% aqueous solution 2800 ml is added to 2-Bromo-4'-methylpropiophenone 1400 g. Methylamine is added via drip funnel in a thin flow or It is divided to 2-3 portions and poured in equal portions with a moderate stirring without splashing.

10. The reaction mixture is stirred for 2 h at 40 ºC.​

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Free base separation and purification
11. After the mixture from the previous part is processed, the free base is washed and separated. The lower organic layer is separated from the upper aqueous layer. The organic layer is washed as described in step 7 (same procedures), the upper layer is scrapped. The organic layer washing is repeated several times until methylamine smell is disappeared.​

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12. The mephedrone (4-MMC) free base DCM solution yield is ~3000 ml. If the organic layer is too small after methylamination, pour DCM 1-2 L. This will help to extract 4-MMC free base better. Then, layers are separated and an aqueous layer is disposed.

13. It is very important to separate the organic layer from the water. To be sure, you can put the DCM solution in the freezer, the remaining water will freeze and easy to separate. Also, you can dry your solution by anhydrous magnesium sulphate (MgSO4). If the water is left, problems with precipitation in the next step can happen during acidification.​

Acidification

14. The resulting mephedrone free base in the DСM is treated with hydrochloric acid. The best way salt production is HCl gasification. A 35-38% HCl hydrochloric acid water solution in acetone or isopropanol is also used in the ratio of 1 ml of hydrochloric acid per 10 ml of solvent (1:10).

The acid is added in small portions with a constant stirring. If the reaction mass become to thick, it is diluted with acetone. The mixture should be liquid enough in order to acidify 4-MMC free base evenly. White gas (HCl) is actively released during this procedure. Respiratory organs and eyes protection have to be used. In order to minimize the release of gas, it is recommended to cool the solution. During the acidification process, it is important to control the pH. At 5.5-6 pH, the acidification is stopped. The mixture is put into a freezer for several hours. After that, the product is filtered and dried. pH is controlled with pH indicator paper.​

Purification and crystallization instructions:

Mephedrone (4-MMC) powder purification

Introduction Mephedrone (4-MMC) synthesis reaction is carried out with production of some amount by-products. Also, some amount of unredacted precursor is left in the reaction mixture after reaction. It takes to purify a 4-MMC product with insufficient purity to reduce health risks. Manual As...

bbgate.com

https://bbgate.com/index.php?threads/crystallization-of-mefedrone-4mmc.72/​

 

[Hans-Dietrich]

Bromination would be easier to do in a flask with a side neck, from which gaseous acid must enter the container with the absorber. For methylamination, you can use a HDPE canister with a tight-fitting stopper. Methylamine can be safely added in a trickle, the main thing is that the reaction mass does not start to boil. After adding all the methylamine, it is necessary to close the stopper and stir until the reaction mixture cools down. Then the synthesis can be considered complete. The emerald green color in the third picture indicates that there is too much unreacted 2-bromo-4-methilpropiophenone. In this case, it is necessary to distill the reaction mass with steam and separate the unreacted 2-bromo-4-methilpropiophenone, if this is not done, the product will acquire a color that will be difficult to wash. This will also get rid of the remaining methylamine. When laying 1.4 kg 2-bromo-4-methilpropiophenone you will not be able to simply take a glass rod and stir the acid in the base. A top drive agitator or similar device must be used. It is desirable to cool the reaction mass. A separatory funnel can then be used to supply the acid.

 

[Hans-Dietrich]

There is no doubt that this is a real synthesis )) I just expressed my comments on the process based on my experience. Welcome )))

 

[Marvin "Popcorn" Sutton]

Thank you for your comment, your additions are very important. I'm glad that there are interested persons who contribute to the topic.
This synthesis is described directly by the chemist who performed it, I communicated with him online during the whole process and recorded. This is a first-person report of how everything happened in the lab.
This is one of the many syntheses the two of us have put together. It is a classic technique that has been worked out many times with different solvents.
For a 10L flask, this is the perfect calculated reagents charge. It is better not to distill the free base, but just to warm it at a boiling point solvent (watch the boiling point of the solvent in which the reaction takes place), although there may be different opinions here. Acidification was done in a PP bucket, adding acid from a chemical cup, and stirred with a Teflon stirrer attached to a electric screwdriver.
This is 100% real synthesis, which was carried out by me including))))

 

[Hans-Dietrich]

Distilling the reaction mass with steam and distilling the freebase are two different processes. For steam distillation, additional water or steam is used. It looks like this: Water is added to the flask with the reaction mixture, about half of the volume of the reaction mixture and brought to a boil. The steam takes particles of the reaction mass with it and carries a receiver into the flask. The unreacted ketone will be transferred to the vapor receiver first. Green particles will be visible in the condenser. At some point, the freebase will go with steam. Then you need to change the receiver or stop the process altogether and start the salt release. Water will need to be added as it evaporates. By the way, the resulting ketone can be reused ))) You do not need to distill the entire content of the source. Something in the flask must come off. There it will be seen when the process needs to be completed. By the way, I also mixed the substance with a screwdriver and a Teflon stirrer. The screwdriver eventually burned out )))

 

[Marvin "Popcorn" Sutton]

I decided that distilling halogen ketone with water vapor is not the end of the matter. Thanks for the explanation. But I still do it differently, I just heat the reaction mixture at the level of boiling solvent. Some of the solvent escapes with the remaining ketone and methylamine, the reaction mixture changes color and smell(DANGER! Do not inhale!).
Especially useful for those who make large volumes, so as not to look for bulky containers, you can do with enameled buckets and an electric stove and pick up the desired level of heating. But it is necessary to observe safety precautions and to carry out this procedure under a good hood or in the open air.
In order not to break the electric mixer, you need to keep the mixture liquid enough, adding acetone when it thickens. It is not necessary to acidify the entire volume, you can do it in portions.

 

[Hans-Dietrich]

Yes, there is logic in your words. Is that making large syntheses in a buckets is not entirely professional )). I think if the drug chemist has grown up to the production of industrial batches of the substance, then the equipment must correspond to the level )))

And I almost forgot ... When the reaction mixture boils after synthesis, the solvent will partially fly away, yes, and completely fly away methylamine, and the color will change unconditionally, but the ketone will not go anywhere. In any case, something more serious than banal evaporation must be done. Alternatively, add IPA and evaporate the reaction mixture 1-2 times. Maybe something else ...

 

[MadHatter]

I'm sorry ... which article? Do I miss something?

 

[Marvin "Popcorn" Sutton]

You didn't miss anything, it's just beginning

 

[rickyrick]

What is in your opinion best bromine synthesis method?(cost effective,medium scale)

 

[Hans-Dietrich]

There is no better thing. There is more or less smelly.

 

[rickyrick]

thought so.thanks.

 

[MadHatter]

Ah ok. Then I'll just patiently wait foor the good stuff

 

[hlebsladky2]

Hello! How will adding DCM during methylamination help the freebase extract from the water? btw will it even work if bromination was done in a different way(peroxide, hydrobromide acid) ?

 

[Marvin "Popcorn" Sutton]

DCM does not need to be added during methylamination. It is used during bromination as a solvent for 4-methylpropiophenone. Then it also dissolves the resulting brominated bromo ketone. And at the end of the methylamination, it is the extractor of the mephedrone base. If a lot of DCM evaporates during the reactions and the free base does not form an organic layer after the methylamination, a portion of DCM is added to extract the free base.

 

[Venom2021]

you can see that an error has been made, the flask should be closed immediately after adding methylamine so that the gas does not escape and the solution does not overheat immediately. The color of the mephedrone freebase should be amber or yellow like morning urine. Here is red, this phenomenon is well known to me, so here we get a small quantity of 4mmc and very poor quality. This synthesis can be done in a water bath in a jar or vodka bottle. Pour methylamine all at once and mix it for 10 minutes until the solution starts to heat up to 35 ° then put the bottle in the water bath and shake the bottle every 10 minutes vigorously for 30 seconds and so for 2 hours every 10 minutes each time, thank you

 

[rafael1985]

How much you put HCl for one kg ketone or You only check with pH papers

 

[Venom2021]

On 1kg bk4 you use about 550ml to 600ml acid 37%

 

[rafael1985]

Ok but how is with 2 bromo 3 chloro one liter is 1,5 kg is the same for 1 kg like for 2 bromo 4 methylo?

 

[KWasd]

I have a question from a different point of view. Suppose you have a completely airtight room, where fresh air is forced in on one side and a high-powered fan pulls it out of the centre of the room on the other.

How do you deal with the filtration of the odour in the air? Do you use any purifiers, if so, what kind and with what kind of cartridge, or is it enough to give a high-capacity carbon filter with activated carbon on the exhaust as is used in cannabis cultivation. If such a filter would do the job, which activated carbon is best, CTC or ordinary carbon?

How is the air and odours filtered in the laboratories? Regards