Introduction
In the following topic, 3-chloromethcathinone (3-CMC) synthesis from 2-Bromo-3'-chloropropiophenone precursor is represented in details and complete description of procedures. This method is similar with 4-MMC synthesis. Nevertheless I decided to make this topic due to pretty numerous questions about this synthesis in my DM. All questions concerning this product may be discussed in comment section, welcome to share your synthetic experience.
Difficulty rating: 4/10
Difficulty rating: 4/10
Equipment and glassware:
- Round bottom flask 2 L (preferably with two necks);
- Reflux condenser;
- Magnetic stirrer with heating plate;
- Funnel;
- Spatula;
- Laboratory scale (0.1 g-200 g is suitable);
- Measuring cylinders 100 ml and 20 ml;
- Beakers 2 L; 500 ml x2; 100 ml x4; 50 ml x3;
- Pipette;
- Drip funnel 100 ml;
- Laboratory grade thermometer (0 °C to 100 °C) with flask adapter;
- Retort stand and clamp for securing apparatus;
- Separating funnel 2000 ml;
- pH indicator papers;
- Pyrex dish or similar;
- Buchner flask and funnel;
- Vacuum pump;
Reagents:
- 2-Bromo-3'-chloropropiophenone CAS 34911-51-8 100 g;
- Ethyl acetate 350 ml;
- Methylamine 40% aq 122.5 ml;
- Sodium bicarbonate solution (NaHCO3) 5% or sodium hydroxide (NaOH) 10% solution;
- Distilled water;
- Hydrochloric acid (HCl 35%) solution ~30 ml;
- Dry acetone ~50-100 ml;
3-Chloromethcathinone (3-CMC) Synthesis From 2-Bromo-3'-chloropropiophenone Scheme
3-Chloromethcathinone (3-CMC) Synthesis From 2-Bromo-3'-chloropropiophenone
1. Ethyl acetate 350 ml is poured into a 2 L round bottom flask with magnetic stirrer bar.
2. Reaction mixture is stirred and the reaction flask is heated up to 30 °C. Reflux condenser is installed.
3. The mixture is stirred until 100 g of 2-Bromo-3'-chloropropiophenone CAS 34911-51-8 is dissolved.
4. Methylamine 40% aq 122.5 ml is added in portions to avoid overheating (exothermic reaction) with a constant stirring. It’s worth to use drip funnel (optional).
5. The mixture is stirred for ~3.5-4 h, temperature is maintained 55-65°C.
6. The stirring is stopped. The reaction mixture is transferred into the separatory funnel, left for layer separations. A bottom layer is drained.
7. After synthesis, the mixture is rinses three times: once with 5% sodium bicarbonate solution or a 10% sodium hydroxide solution (prepared in advance). Then twice with water. The volume of washing solution is equal to volume of reaction solution.
8. 3-CMC free base in ethyl acetate is separated into a reaction flask. Water is added in a ratio of 1/2 of the 2-bromo-3'-chloropropiophenone mass (~50 ml).
9. The HCl 35% solution ~30 ml is dissolved in 50 ml of water. Then, HCl solution is added dropwise to pH 5-6 with a constant stirring. The mixture is stirred well for 15-20 min after complete HCl adding and let settled. pH checked after 2-3h settling.
10. Next, the mixture is poured into a 2 L beaker and the beaker is put into a freezer for 12 h.
11. A vacuum filtration system (Buchner flask and funnel, vacuum pump) is assembled.
12. The vacuum pump is turned on.
13. The crystalline beaker content from freezer is poured onto the Buchner filter.
14. The cold 3-CMC solution is filtered and pressed until the funnel content is become solid.
15. A cold dry acetone is poured onto the solid product in the funnel in several small portions during filtration.
16. Acetone is filtered. Step 15 is repeated, if the solid is not white.
17. White solid 3-CMC hydrochloride product is moved onto a Pyrex dish for drying after the filtration procedure.
18. Pyrex dish with 3-CMC is placed into a dry well ventilated warm room or vacuum desiccator.
19. 3-CMC product is dried to a constant mass at cold place. Product is mixed and shredded periodically in order to increase drying speed.
The mother liquor after 3-CMC hydrochloride filtration (Step 13) can be additionally acidified to pH 4 and check. If there is a crystalline precipitation is formed (most likely), warm ~40°C distilled water is added. If the precipitate is dissolved, separate layer with water and crystallize it again. Separate water and evaporate it. If there is no precipitate, throw this out.
2. Reaction mixture is stirred and the reaction flask is heated up to 30 °C. Reflux condenser is installed.
3. The mixture is stirred until 100 g of 2-Bromo-3'-chloropropiophenone CAS 34911-51-8 is dissolved.
4. Methylamine 40% aq 122.5 ml is added in portions to avoid overheating (exothermic reaction) with a constant stirring. It’s worth to use drip funnel (optional).
5. The mixture is stirred for ~3.5-4 h, temperature is maintained 55-65°C.
6. The stirring is stopped. The reaction mixture is transferred into the separatory funnel, left for layer separations. A bottom layer is drained.
7. After synthesis, the mixture is rinses three times: once with 5% sodium bicarbonate solution or a 10% sodium hydroxide solution (prepared in advance). Then twice with water. The volume of washing solution is equal to volume of reaction solution.
8. 3-CMC free base in ethyl acetate is separated into a reaction flask. Water is added in a ratio of 1/2 of the 2-bromo-3'-chloropropiophenone mass (~50 ml).
9. The HCl 35% solution ~30 ml is dissolved in 50 ml of water. Then, HCl solution is added dropwise to pH 5-6 with a constant stirring. The mixture is stirred well for 15-20 min after complete HCl adding and let settled. pH checked after 2-3h settling.
10. Next, the mixture is poured into a 2 L beaker and the beaker is put into a freezer for 12 h.
11. A vacuum filtration system (Buchner flask and funnel, vacuum pump) is assembled.
12. The vacuum pump is turned on.
13. The crystalline beaker content from freezer is poured onto the Buchner filter.
14. The cold 3-CMC solution is filtered and pressed until the funnel content is become solid.
15. A cold dry acetone is poured onto the solid product in the funnel in several small portions during filtration.
16. Acetone is filtered. Step 15 is repeated, if the solid is not white.
17. White solid 3-CMC hydrochloride product is moved onto a Pyrex dish for drying after the filtration procedure.
18. Pyrex dish with 3-CMC is placed into a dry well ventilated warm room or vacuum desiccator.
19. 3-CMC product is dried to a constant mass at cold place. Product is mixed and shredded periodically in order to increase drying speed.
The mother liquor after 3-CMC hydrochloride filtration (Step 13) can be additionally acidified to pH 4 and check. If there is a crystalline precipitation is formed (most likely), warm ~40°C distilled water is added. If the precipitate is dissolved, separate layer with water and crystallize it again. Separate water and evaporate it. If there is no precipitate, throw this out.
