JWH-018 synthesis via Grignard reagent

[G.Patton]

Mix 2.87 g (19 mmol) in a 50 ml flask of 1-bromopentane in 20 ml of diethyl ether, previously distilled over sodium, and 0.4 g (17 mmol) of magnesium powder. The flask is heated in a water bath until the ether begins to boil (use long Liebig reflux condenser), then the heating is removed because the reaction is exothermic. The reaction takes 15-20 minutes, after the Grignard reagent mixture is refluxed for 30 minutes. ​

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Then the reaction mixture is cooled to 0°С, transferred to a 250 ml flask, and 1.8 g (16 mmol; 1 eq.) of slightly yellowish indole in 20 ml of dichloromethane is added. Gas is released in the form of bubbles during this reaction, the mixture remains transparent, use a reflux condenser. ​

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To the same flask is added 1.63 g (15 mmol) of anhydrous ZnCl2 (in the form of a crushed powder). At the same time, gas and bubbles are actively released, the mixture becomes dull, the color changes to pink or greenish. The reaction mixture is stirred for 40 minutes. Next, a solution of 3.7 g (19 mmol) of 1-naphthoyl chloride dissolved in 30 ml of dichloromethane is added. The reaction mixture instantly changes color to red, the product immediately precipitates in the form of a thick paste. The mixture is stirred for an additional 1 hour at r.t., then diluted with an equal volume of 30% NH4Cl aq. and mixture is stirred few minutes.​

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Water and solvent are decanted, 10 ml of methanol is added to the precipitate and triturated with a glass rod, while small yellowish crystals are precipitated. The crystals are filtered, washed with 10 ml of methanol and 7 ml of diethyl ether. The mass of dry pale yellow dusty powder of JWH-018 is 2.93g (64%). An additional 200-400 mg of the product can be obtained from the filtered liquors.​

 

[beginner]

the diethyl ether could be replace by another solvant ?
cause of the law in europe

 

[Ortist]

the diethyl ether could be replace by another solvant ?
cause of the law in europe

beginnerfor some Gringard THF (dry) also works. Will it work with bromopentane or not i do not know. You need an etherial solvent to prepare Gringard reagent. All reagents MUST be dry, glass MUST be dry (died over the flame) etc.

 

[beginner]

for some Gringard THF (dry) also works. Will it work with bromopentane or not i do not know. You need an etherial solvent to prepare Gringard reagent. All reagents MUST be dry, glass MUST be dry (died over the flame) etc.

Ortistthanks

 

[Irving Langmuir]

the diethyl ether could be replace by another solvant ?
cause of the law in europe

beginnerNormally you can easily get diethyl ether by doing a fractional distillation of starting fluid. Lots of chemist youtubers have a video on it.

 

[Irving Langmuir]

Hi !
So I tried this synthesis. Everything was done according to the procedure, all the glassware was dry, all the color changes were the same as those described in the procedure.
There are only a few changes/errors I have made, I’ll list them here :

- I used one speck of iodine for the Grignard reaction to initiate it.

- Because there were only a few unreacted Mg left in the flask, I didn't bother decanting the grignard reagent. Having no other dry glassware, I didn't want to risk destroying it. This led to a slight contamination of the final product with Mg, but this does not explain the result obtained.

- After adding the indole in DCM, and then the ZnCl2, the mixture is supposed to be mixed for 40 min at 0°C. This was practically respected, except during 2 min when the temperature rose to 14°C, because the plate had not been properly turned off and was heating the ice bath. This was quickly corrected and doesn't seem to have greatly affected the reaction, as the rest of the procedure went according to plan (for example the change in red color upon addition of the 1-naphthoyl chloride)

- After adding the 1-naphthoyl chloride, the mixture was stirred for 2 hours, as I wanted to wait a little longer given that where I was working it was 12°C. For good measure, I heated the reaction mixture up to 25°C for the last 30 minutes. (We were supposed to mix it for 1 hour at room temperature)

So the real problem came at the crystallization stage (I've read that it's not easy to crysatlize and often forms an oil). When adding the MeOH and triturated with a glass rod, nothing crystallized out.

Only a pink precipitate resembling 3-(1-naphthoyl)indole was obtained after evaporation of the organic phase.
So I took all the residues of the evaporated organic phase, the pink powder, basically everything and mixed it in MeOH with activated carbon, filtered everything that didn't dissolve, evaporated some MeOH, and put it in the freezer. A brown precipitate was formed. It was not the product.

A sort of orange oil was obtained on evaporation of the MeOH (The MeOH that I had put into the reaction mixture, according to the procedure). Unfortunately, it had no psychoactive effect, according to someone who wanted to try it.

After talking to one of the experts, he told me that he found this synthesis strange, but that further experiences would be needed to confirm that this way of doing things is wrong. That was my report. Feel free to add your own, it would be interesting to know if this synthesis works!