Whenever I did acetylation we did the reaction using a basic solvent (usually pyridine) and used 4-dimethylpyridine as an acetylation catalyst. Monitor the reaction using thin layer chromatography if you can. Once the reaction is complete, quench the acetic anhydride by adding methanol (converts to methyl acetate). Poor onto diethyl ether (ethyl acetate will work as well) and wash twice with 1M HCL, once with 5% NaHCO3, once with brine. Dry with MgSO4 and evaporate the solvent. You should not require further purification.
Acetic anhyride is restricted because it is used to convert morphine into heroin.
Did you use this method for thc acetate or just acetylations in other chemical reactions? Was this done at room temp or did use use heat? If so what temp and for how long? Pyridine looks to be toxic even in small quantities. I dont know if that is safe to consume without distilling to completely remove trace amounts of pyridine and diethyl ether. I like how this method allows for TLC plates. My method doesnt have any initial solvent besides the AA (which is refluxing while the reaction takes place) so TLC is not practical.
AA can also be used on other regulated drugs to increase potency/effects not just morphine. Its also used in the synthesis of asprin as well as a chemical reagent for plastic manufactures. Im guessing its widespread use is what makes it so available despite the regulation/restriction.
qma: Not that much heat but good excuse to bring out new toy
FrankVon: I looked back on my notes and found that I did do a few reactions with triethylamine or N,N-diisopropylethylamine as the base. The HCl will remove those as well in the workup.
On the acetic anhydride, I worked about 8 months in drug lab (police), at the time chemical suppliers sent details for suspicious chemical purchases. Acetic anhydride almost inevitably lead to heroin bust. I am not sure the criteria they used to screen customers but I am guessing delivering to a residential address set off a few alarm bells.
You guys… it’s way easier than you think. Dissolve THC distillate into heptane or pentane. Calculate the molar amount. Let’s say one mole. Add .99 mole of triethylamine and .99 of acetic anhydride. Easy. I have confirmed this with a chemist and my mass spec. Just don’t know why anyone would want to make it. It’s a prodrug and is not 3x as potent as THC, it’s actually pretty worthless in my opinion. If it was good why wouldn’t everyone make it and increase their weight mass by 25%?
its implications are fascinating. its the pallatability enhancer of vaporized extracts, a good depressant/ sedative, and in very limited anecdotal evidence, ive heard it has brought sensation back to limbs that had lost their sense of touch…
its a new drug obviously, and as its not native to the cannabis plant we need exhaustive toxicology studies. but its implications add insight to a very large wall… Acetylation of isolated cannabinoids may be very interesting, or it may not…
THC: 46 reactions as a reagent, mostly esterifications, phosphorylation, a tosylation, and a trifluoromethylation.
CBD: 75 reactions as a reagent, methylation, hydrogenation, halogenation, oxidation to quinone, esterifications, nosylation, surprisingly a reported acetylation, substitutions, and phosphorylation.
Hi CER, why did you use triethylamine as a catalyst? I understand it drives the reaction forward at room temperature but it does require a low pH (as @budchemist said HCL would remove it) to be water soluble and looks to be quite toxic if not removed entirely. How did you remove it?
That is awesome you have a mass spec or have access to one.
Yes it is possible and from what I have read has great benefits but I cant find a ton of published articles about it online.
I briefly spoke to Robert August (if anyone knows his username for this forum please let me know) about cannabinoid acetylations when I started this project. This is from his instagram, " The acetylation of cbd to yield O-acetyl-cbd. The acetylation of cbd forms an carboxylic ester. This acetylation/esterification forms a very clean product with increased bioavailability and potency while also increasing the mass of the starting compound (highly pure cbd isolate) by almost twice the starting mass of the cbd precursor. After refinement and work up, one is left with an extremely safe & potent form of medicinal cbd that’s ideal for both medical patients (seizure control in younger patients especially)… As well as various other beneficial non medicinal uses." (link with picture: https://www.instagram.com/p/BUfGJEOheft/ )
Ive had someone that was battling cancer regain feeling in their toes after many years from a dab of ringos gift (cbd dominant) definitely wasnt acetate
Hi Stone, the method above where thc distillate was dissolved in excess AA and then was refluxed in a nitrogen atmosphere for 3 hours worked (successful with 87% theoretical yield) but I am still working on making a method that is easier and safer. This is the list of the disadvantages the method above has and the errors I had:
Fire Safety: The reflux had to be done under a nitrogen atmosphere because AA vapors will react with water vapors in the air. This is an exothermic reaction that could generate enough heat to hit the flash point. A catalyst like p-tosic (@Photon_noir recommendation) or triethylamine (@SES recommendation) would lower the temperature the reaction would happen at.
Transferring/Human error: The reflux was performed in a one neck rbf and had to be transferred to a two neck rbf for fractional distillation. I used ethanol as a transfer solvent which could of reacted with trace AA and produced small amounts (at room temp) of ethyl ethanoate and ethanoic acid which is not desired at all. So if I did it again I would just start with a 2 neck flask or use pentane/hexane as a transfer solvent when needed.
Purity/Storage: Liquid liquid extraction with pentane/hexane and saline solution should of been performed before fractional distillation to react trace amounts of AA with water to form acetic acid and be removed with multiple water washes. Pentane/hexane should be dried and removed before fractional distillation step. This will help with the storage of thc acetate.
To answer your second question, I did not notice any formations of crystals at any point. The end product was light yellow (probably the same pigment impurity the thc distillate had) and sappy (starting distillate was hard at room temp). Do you have any source that says it crystallizes?
Move over sauce carts, we got coughless carts™
