Introduction
The BB Forum team is pleased to publish the simple synthesis of JWH-018, which does not require rare or elaborate equipment or reagents. There is a step-by-step video guide and a clearly written explanation of each step to obtain the cannabinoid JWH-018 with a fairly high yield. The synthesis can be repeated even by chemistry beginners.
Equipment and glassware:
Step 1. Synthesis of 3-(1-(1-Naphthoyl)indole from Indole
Step 2 (Optional). Recrystallization of 3-(1-naphthoyl)indole 13. The crude 3-(1-naphthoyl)indole should be diluted in 10 L of IPA (or ethanol).
19. 100 g of the previously purified 3-(1-naphthoyl)indole are poured into a flask.
20. 50 g of sodium hydroxide is added.
21. Next, 25 g of TBAB (tetrabutylammonium bromide) is added.
22. 200 ml of water are poured into the flask.
23. 75 g of 1-bromopentane are added.
24. A stirrer is switched on.
25. The reaction mixture in the flask is self-heated. An external heater is switched on until the mixture starts to boil. The boiling point is maintained for 15-30 min, depending on the boiling intensity.
26. An excess of 1-bromopentane will evaporate to the atmosphere (use adequate ventilation). A reflux condenser is installed.
27. After a while, the mixture is poured into a beaker. The mixture is left for a layer separation.
28. The desired upper layer is collected. The collected upper layer is transferred to a separate vessel.
29. The oil is cooled to room temperature (this procedure also helps to evaporate excess 1-bromopentane if it still remains).
The yield of JWH-018 is ~125 g as oil from 3-(1-naphthoyl)indole 100 g. Thus, ~200 g (69 % indole) of JWH-018 is obtained from 100 g indole.
The BB Forum team is pleased to publish the simple synthesis of JWH-018, which does not require rare or elaborate equipment or reagents. There is a step-by-step video guide and a clearly written explanation of each step to obtain the cannabinoid JWH-018 with a fairly high yield. The synthesis can be repeated even by chemistry beginners.
Equipment and glassware:
- 2 L and 1 L flat bottom flasks.
- Ice water bath (ice water or cold brine).
- Hot water bath
- 500 mL beakers x3; 1 L x2; 3 L x1; 5 L x1
- Funnel
- Glass rod
- Büchner flask (~5 L) and funnel
- Vacuum pump
- Magnetic stirrer with heating plate
- Pyrex dishes x2
- Reflux condenser
- 20 cm3 syringe
- Plastic spoon
- Indole 100 g;
- Dichloromethane (DCM) 500 mL
- Aluminum chloride 114 g
- 1-naphthoyl chloride 163 g
- Distilled water 3.2 L
- Isopropyl alcohol 10 L or ethanol
- Sodium hydroxide 50 g
- TBAB (tetrabutylammonium bromide) 25 g
- 1-Bromopentane 75 g
Step 1. Synthesis of 3-(1-(1-Naphthoyl)indole from Indole
- 100 g of indole are poured into a 2 L flask.
- 300 mL of dichloromethane (DCM) is added to the same flask.
- The reaction mixture is stirred until complete dissolution of the indole.
- The mixture is cooled in an ice bath (ice water or cold brine) to 0-10 °C.
- Aluminum chloride 114 g is gradually added while stirring.
- The mixture is stirred until complete dissolution of the aluminum chloride.
- Weigh 163 g of 1-naphthoyl chloride into a beaker and add 200 mL of DCM there. Note: 1-naphthoyl chloride has a solid state, but it can easily melt if you place its container in a hot water bath.
- The DCM solution of 1-naphthoyl chloride is added gradually from the beaker to the flask. The temperature of the reaction mixture is maintained at 0-10 °C.
- After this addition, the flask is left with constant stirring overnight (or for a shorter time until crystallization is finished).
- After a while, a solid precipitate crystallizes in the mixture. The crystals should be crushed with a glass rod.
- Pour the reaction mixture in small portions with constant stirring into a vessel containing 3 L of cold water. The crude 3-(1-naphthoyl)indole precipitates and settles to the bottom of the vessel.
- The 3-(1-naphthoyl)indole precipitate separates from the water. Note: You can dry and use the crude 3-(1-naphthoyl)indole in this form, but further purification by recrystallization is recommended.
Step 2 (Optional). Recrystallization of 3-(1-naphthoyl)indole 13. The crude 3-(1-naphthoyl)indole should be diluted in 10 L of IPA (or ethanol).
- The mixture is shaken well and poured into a large beaker to simplify loading into a 10 L flask.
- After making the 3-(1-naphthoyl)indole solution more liquid, the mixture is poured into a 10 L flask and ethanol is added to fill the total volume of the 10 L flask.
- The mixture is heated until complete dissolution of the 3-(1-naphthoyl)indole.
- The mixture is then cooled, and the flask is placed in a freezer for two days until the end of precipitation.
- The recrystallized product is filtered as precipitate and dried to constant weight. After drying, 160 g of pure 3-(1-naphthoyl)indole are obtained.
19. 100 g of the previously purified 3-(1-naphthoyl)indole are poured into a flask.
20. 50 g of sodium hydroxide is added.
21. Next, 25 g of TBAB (tetrabutylammonium bromide) is added.
22. 200 ml of water are poured into the flask.
23. 75 g of 1-bromopentane are added.
24. A stirrer is switched on.
25. The reaction mixture in the flask is self-heated. An external heater is switched on until the mixture starts to boil. The boiling point is maintained for 15-30 min, depending on the boiling intensity.
26. An excess of 1-bromopentane will evaporate to the atmosphere (use adequate ventilation). A reflux condenser is installed.
27. After a while, the mixture is poured into a beaker. The mixture is left for a layer separation.
28. The desired upper layer is collected. The collected upper layer is transferred to a separate vessel.
29. The oil is cooled to room temperature (this procedure also helps to evaporate excess 1-bromopentane if it still remains).
The yield of JWH-018 is ~125 g as oil from 3-(1-naphthoyl)indole 100 g. Thus, ~200 g (69 % indole) of JWH-018 is obtained from 100 g indole.
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