# Mephedrone (4-MMC) synthesis from haloketone in ethyl acetate. 1-10 kg Scale.



## William Dampier (Aug 8, 2021)

*Reaction scheme:*



​
*Reagents:*
1. 4'-Methylpropiophenone (cas 5337-93-9) 1 kg;
2. Hydrobromic acid 48% 960 ml;
3. Hydrogen peroxide 35% 636 ml;
4. Sodium/potassium hydroxide 25% (NaOH/KOH) aqueous solution;
5. Distilled water;
6. Ethyl acetate 6 l;
7. Methylamine 40% aq - 2 l;
8. Acetone - 8 l;
9. Hydrochloric acid (HCl 38%) 500 ml;
10. Isopropyl alcohol;

*Equipment and* *glassware**:*
1. Scales;
2. Jacketed 10 L reactor equipped with reflux condenser, drip funnel, thermometer, top stirrer and temperature control system;
3. Heating pump;
3. Chiller pump;
4. Vacuum source;
5. Buckets;
6. Freezer;
7. Pyrex dishes;
8. Nutsche filter;
9. pH indicator papers;

*Stage 1. Halogenation.*


​*1. *4'-Methylpropiophenone (cas 5337-93-9) 1 kg is weighted and poured into a 10 L reactor; 
*2.* Hydrobromic acid (HBr 48%) 320 ml is added and stirred for 5 min.
*3.* Hydrogen Peroxide (H2O2 35% 212 ml) is poured into a drip funnel and installed onto the reactor neck.
*4.* Drip funnel tap is opened and hydrogen peroxide is added dropwise with a constant stirring.
*5.* Color of the mixture may vary from yellow to red. Hydrogen peroxide is added in order to discolor the mixture.
*6.* Reaction mixture temperature have to be kept less than 65 °C. An external cooling is applied in case of overheating. If reaction temperature is higher, hydrogen peroxide addition is stopped.
*7. Step 2-6* are repeated twice after hydrogen peroxide addition.
*8.* Crystallization can start during the reaction. Hydrobromic acid and hydrogen peroxide are added dropwise until the end of amount and stirred for 1.5-12 h.
*9.* Next, distilled water is added and stirred for 5 min.
*10.* Stirring is stopped. Reaction mixture is left until entire 2-bromo-4'-methylpropiophenone is fallen down in the reactor.
*11.* Water is removed with help of pump through the reactor neck.
*12.* Sodium/potassium hydroxide 25% (NaOH/KOH) aqueous solution is added to the reaction solution and stirred for 5 min.
*13.* Repeat *9, 10, 11 steps*.
*14.* The resulting product is left in the reactor.​
*Stage 2. Methamination.*


​*1.* Ethyl acetate 6 l is poured into the reactor.
*2. *Reaction mixture is stirred and heated in Jacketed reactor up to 30 °C with help of heating system.
*3.* The mixture is stirred until complete amount of 2-bromo-4'-methylpropiophenone (cas 1451-82-7) is dissolved.
*4.* The stirring is stopped. The reaction mixture is left for layer separations. A bottom layer is drained through a bottom reactor tap.
*5.* The stirrer is turned on and methylamine 40% aq 2 l is added at once.
*6.* The mixture is stirred for 20 min, temperature is kept below 65 °C.
*7.* Repeat *step 4*.
*8.* After that, the mixture is heated up to 55 °C and reactor vacuum pump is turned on. The reactor condenser chiller pump is turned on as well.
*9.* All amount of ethyl acetate or the biggest part of it is distilled off.
*10.* Vacuum pump is turned off. Acetone is added to the reactor with a constant stirring.
*11.* Hydrochloric acid (500 ml) is placed into the drip funnel and the funnel is installed onto the reactor neck.
*12.* Hydrochloric acid is added dropwise to reach pH 5 with constant stirring. A small amount (~2-5 ml) of reaction mixture is drained from the bottom reactor tap in order to check pH by pH indicator stripe. The sample is poured back into the reaction mixture.
*13.* After that, the mixture is poured into a bucket and the bucket is put into a freezer for 12 h.

*Stage 3. Filtration.*
*1.* A vacuum filtration system (Nutsche filter, filter cloth, vacuum pump) is assembled and installed.
*2.* The vacuum pump is turned on.
*3.* A bucket content from *step 13* *stage 2* is poured to the Nutsche filter.
*4.* The mixture is filtered and pressed until the funnel content is become solid.
*5.* A cold dry acetone is poured onto the solid product in the funnel in several small portions during filtration.
*6.* Acetone is filtered. *Step 5* is repeated, if the solid is not white.
*7.* White solid 4-MMC product is moved into a Pyrex dish for a drying after filtration procedure.
*8.* Pyrex dish with 4-MMC is placed into a dry well ventilated warm room. 
*9.* 4-MMC product is dried to a constant mass. Product is mixed and grinded periodically in order to increase drying speed.

*Stage 4. Recrystallisation.*
*Mephedrone (4MMC) crystallization*


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## woohoo

Didn't it should be separated from n-methylacetamide?
Seems its dirty reaction, how much it yields in comparison with nmp or aromatic solvent?


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## wannabeechemist

N-methylacetamide should be soluble in acetone, though I could not find how much. Freebase is indeed black and resulting powder turns green upon addition of crystalizing solvent mix (unreacted ketone?). Its safe to assume this isn't the cleanest procedure.

Some swear that any other reaction besides one using NMP as a solvent produces much, much inferior results in final product. More of the speedy high without any euphoria.

Did you run GC-MS to see if there are any impurities in resulting powder/ crystals?
@G.Patton
@Marvin "Popcorn" Sutton
@William Dampier


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## G.Patton

wannabeechemist said:


> Freebase is indeed black and resulting powder turns green upon addition of crystalizing solvent mix (unreacted ketone?). Its safe to assume this isn't the cleanest procedure.



wannabeechemistHi, probably you did something wrong or your reagents not so good. Yes, we did GC-MS. 96.4% 4-MMC


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## wannabeechemist

I didn't try this reaction yet. I watched video published here iodo-ketone amination. There I saw freebase is black and powder changed colour when preparing for crystalization. Maybe it was black cause of iodine being leaving group as opposed to bromine. 
Questions to comfirm:

1. Results above are from ethyl acetate as a solvent ?
2. Have you done this reaction with EA and bromoketone, does freebase look any different?
3. I noticed from video that crystals from EA look glass like, while NMP are lot whiter. I read your post about stereochemistry of 4-MMC how S and R enantiomers form different looking crystals, are both of these crystals equally racemic?
4. Did you notice any difference in subjective effect between EA and say NMP in final product?

Thank you for posting these results.


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## G.Patton

wannabeechemist said:


> 1. Results above are from ethyl acetate as a solvent ?



wannabeechemistActually I don't remember for sure. Probably yes.


wannabeechemist said:


> 3. I noticed from video that crystals from EA look glass like, while NMP are lot whiter. I read your post about stereochemistry of 4-MMC how S and R enantiomers form different looking crystals, are both of these crystals equally racemic?


Yes, these are racemic crystals.


wannabeechemist said:


> 4. Did you notice any difference in subjective effect between EA and say NMP in final product?


I haven't tasted the product as any good wine manufacturer =)


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## StarWars

*8.* After that, the mixture is heated up to 55
in the video it clearly says no need to heat up. and here someone wrote to then heat it up for what if the mixture reaches the temperature itself no higher than 65 °.


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## G.Patton

StarWars said:


> *8.* After that, the mixture is heated up to 55
> in the video it clearly says no need to heat up. and here someone wrote to then heat it up for what if the mixture reaches the temperature itself no higher than 65 °.



StarWarsHi, 55 deg *C is need to vacuum evaporation of solvents and methylamine excess. It is optional procedure.


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## Chemix-Express

I am very curious about this synthesis, in a few days I will have the opportunity to test it, so I have a few questions:
1. in step 2, point 10 instead of Acetone can I use IPA? When I use HCL 35-37% aq in combination with Acetone there is always a lot of colour, 1.4-Dioxane helped but is very expensive. Do you guys think IPA will work?
2. Stage 2, point 5 says to add all the m40 at once, while point 6 says to keep the temperature below 65 degrees C. Can I control the temperature by gradually adding the m40, or necessarily with an external refrigerator?
3. Should I count the reaction time (20 minutes) from the moment I finish adding the m40?
4. I am curious as to why there is so little information about the synthesis of 4MMC in ethyl acetate when neither at the beginning nor during the reaction does the mixture need to be heated, and ethyl acetate itself is very cheap. Is this followed by low yield/purity of the reaction?
5. To keep things short, would the ratio of 1kg bk4, 2L m40, 2L ethyl acetate be good, or is it better to give 1.5L m40 and 2.5L ethyl acetate for each kg bk4?


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