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

[WillD]

Reaction scheme:

​

Reagents:
1. 4'-Methylpropiophenone (cas 5337-93-9) 1 kg;
2. Hydrobromic acid 48% 1300 ml;
3. Hydrogen peroxide 35% 750 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 1000 g is added into a 10 L reactor flask.​

2. Hydrobromic (HBr) acid 1300 g 48% is poured into the flask and stirred for 5 min.
3. Hydrogen peroxide 750 g 35% is added into a drip funnel 1 l.
4. Hydrogen peroxide is added dropwise to the stirred reaction mixture.
5. Bromine is released during hydrogen peroxide addition to the mixture, dissolved in solution and reacted.
6. Hydrogen peroxide must be added at an appropriate rate so that the reaction mixture becomes colorless.
7. 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.
8. The second part of discoloration reaction can be conducted for longer time. Hydrogen peroxide is added according with reaction temperature.
9. Reaction mixture is left for a 12 h with a constant stirring at room temperature as soon as all hydrogen peroxide is added.
10. After 12 h precipitate is formed.
11. Sodium bicarbonate aq solution is added to the reaction mixture to reach neutral pH 6-7, stir it well. The mixture with 2-bromo-4'-methylpropiophenone is filtered through a Buchner funnel. Product is washed with small amount of distilled water.
12. Crude 2-bromo-4'-methylpropiophenone (cas 1451-82-7) is used for further reactions. Theoretical yield up to 1530 g. Practice yield is almost quantitative (video yield 94%).

13. 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

 

[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?

 

[yin-yang]

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

 

[G.Patton]

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

 

[yin-yang]

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.

 

[DavidNichols]

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.

wannabeechemist

I read your post about stereochemistry of 4-MMC how S and R enantiomers form different looking crystals

Can you please link me that post?

 

[G.Patton]

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

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

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.

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 =)

 

[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 °.

 

[G.Patton]

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.

 

[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?

 

[little-flower]

Can we perform this reaction with 12% H202? I think maybe it's good""

 

[StarWars]

U can do

 

[Rush-Benzo]

Using ready-made BK4 how much should I give it for a 2L m40?

 

[G.Patton]

Using ready-made BK4 how much should I give it for a 2L m40?

Rush-BenzoHello, you can increase amount of reagents proportionally. Read Moles, grams, litres and chemical calculations topic.

 

[xoxo2.0]

Hello, you can increase amount of reagents proportionally. Read Moles, grams, litres and chemical calculations topic.

G.Pattonthis is @G.Patton s 1000th reaction score

 

[Rush-Benzo]

Hello, you can increase amount of reagents proportionally. Read Moles, grams, litres and chemical calculations topic.

G.PattonI was referring to something completely different. I don't know how much final BK4 you came out with after completing stage 1. I want to start from stage 2 and I don't know how much BK4 to use. How much did you final come out of stage 1.

 

[G.Patton]

I was referring to something completely different. I don't know how much final BK4 you came out with after completing stage 1. I want to start from stage 2 and I don't know how much BK4 to use. How much did you final come out of stage 1.

Rush-Benzo

I don't know how much final BK4 you came out with after completing stage 1.

Around 1350-1450 g 2-bromo-4'-methylpropiophenone from the first stage.

 

[Rush-Benzo]

Around 1350-1450 g 2-bromo-4'-methylpropiophenone from the first stage.

G.PattonThank you very much.

If it is not a problem I will ask one more question. In step 2 point 9 you tell to distil at least half of the ethyl acetate, what is this supposed to do? In the instructional video it is said that this step is optional. By omitting it will I lose efficiency, quality or will it just make it easier for me to work with a smaller volume of liquids?

I am in the process of buying a powerful vacuum pump, out of curiosity I will ask how long does it take to distil these 6L of ethyl acetate heating to 55 degrees?

 

[StarWars]

Thank you very much.

If it is not a problem I will ask one more question. In step 2 point 9 you tell to distil at least half of the ethyl acetate, what is this supposed to do? In the instructional video it is said that this step is optional. By omitting it will I lose efficiency, quality or will it just make it easier for me to work with a smaller volume of liquids?

I am in the process of buying a powerful vacuum pump, out of curiosity I will ask how long does it take to distil these 6L of ethyl acetate heating to 55 degrees?

Rush-BenzoLook on video if u use 1kg bk4 u need 2l ethyl acetate and 2l methyloamine.
There they sell 6 l on the video haha

 

[G.Patton]

Thank you very much.

If it is not a problem I will ask one more question. In step 2 point 9 you tell to distil at least half of the ethyl acetate, what is this supposed to do? In the instructional video it is said that this step is optional. By omitting it will I lose efficiency, quality or will it just make it easier for me to work with a smaller volume of liquids?

I am in the process of buying a powerful vacuum pump, out of curiosity I will ask how long does it take to distil these 6L of ethyl acetate heating to 55 degrees?

Rush-Benzo>>>In step 2 point 9 you tell to distill at least half of the ethyl acetate, what is this supposed to do?
It is need to crystallize your mephedrone.
>>>By omitting it will I lose efficiency, quality or will it just make it easier for me to work with a smaller volume of liquids?
You will distill it in any case, it is better to do at this stage to get bigger yield during HCl addition.

 

[StarWars]

>>>In step 2 point 9 you tell to distill at least half of the ethyl acetate, what is this supposed to do?
It is need to crystallize your mephedrone.
>>>By omitting it will I lose efficiency, quality or will it just make it easier for me to work with a smaller volume of liquids?
You will distill it in any case, it is better to do at this stage to get bigger yield during HCl addition.

G.Pattonyou put it on an electric stove and it evaporates with 50% of the solvent after washing but there are still a lot of mistakes in this video. you cleanse 1x water + soda then 3 times water then you evaporate 50% then you add magnesium solfate so as not to lose the product and acidify and that's it. I have a similar video on an old laptop where they use dcm instead of ethyl acetate. In my opinion, it makes no sense to evaporate, I did without it and there were no problems in the synthesis

 

[G.Patton]

you put it on an electric stove and it evaporates with 50% of the solvent after washing but there are still a lot of mistakes in this video. you cleanse 1x water + soda then 3 times water then you evaporate 50% then you add magnesium solfate so as not to lose the product and acidify and that's it. I have a similar video on an old laptop where they use dcm instead of ethyl acetate. In my opinion, it makes no sense to evaporate, I did without it and there were no problems in the synthesis

StarWarsWhat yield did you get? Same?