Cannibinol -->d-6-THC -->d-6-THC Acetatete synth

[superhybrid]

Here is a process developed for producing THC acetate and Hash oil using simple methods.

1.) The cannabis was selected and had to have no crushed seeds in which the oil from the seeds would leak into the cannabis.
2.) The cannabis was dried in an oven at 115 deg. C till dry and crunchy.
3.) At this point using your hands proceed to crush the pot into a powder being careful not to crush seeds in which the seed oil could enter the extract.
4.) Put the crushed cannabis into a spaghetti strainer. This will remove most seeds.
5.)  Remove the last amount of seeds by using a cake pan and shift the cannabis from side to side on an angle. The cannabis should be at the top of the pan. The seeds should roll down the pan into the bottom.
6.) At this point it will be in your best interest to have all the seeds out that you can.
7.) Now you can extract the cannibinol and THC into acetone. When the cannabis is in the acetone small seeds will float to the top.  At this point it will be in your best interest to remove them. That is easy as they are floating to the top while the cannabis is at the bottom. Do enough extractions till you feel that all the cannibinol is removed from the plant matter.
8.) Once you have this you can evaporate the acetone from the plant matter but not with out boiling stones. If you have a roto evaporator even better yet. Do not allow the heat of the mixture to rise above 200 deg. C which is the boiling point of  THC/Cannibinol
9.) Once you have the pure extract you can dissolve it into toluene and prepare it for the next step.
10.) Here is where you will need a reflux apparatus and boiling stones. Add the toluene/extract solution into the reflux condensor and at that point also add about 7 grams of toluene sulphonic acid which can be made simply from toluene and fuming sulphuric acid in the reflux condenser.  This 7 grams of organic acid per 14 grams of cannabis extract. This will form delta-6 THC which is supposedly more of a psychedelic program than delta-9.
11.) Reflux the above for about 4 hours at around 150 deg. C with most importantly boiling stones(quartz rocks from the yard).
12.) Basify mix with Na2HCO3 and do a wash with two volumes water in a sep funnel.
13.) Now boil off (roto vap)the toluene and you will have your product, It should be a reddish brown oil that smells a lot like opium if you have ever smelt it.

You now have delta-6 THC theoretically. It smells a lot different than the beginning product and the chlorophylls should have been extracted with the water extraction. Mind you though that cannabis contains muscimol, hordenine and piperidine. What refluxing the cannabis extract does with these compounds is beyond me at the moment.

Now for the THC Acetate formation.(Also known as Fisher Esterification)

1.) Now take the above THC and add glacial acetic acid to it in which it should dissolve the THC like acetone would.
2.) Add this back to your reflux condensor with say 10mL of H2SO4 per 200mL of glacial acetic acid. The glacial acetic acid will be your solvent for this reflux so add enough for the amount of THC you have which accordingly would be 14 grams. Remember boiling stones with this specifically as acetic acid has a higher rate of cohesion/adhesion than toluene and your whole product could bump and end up on the ceiling or you.
3.) Reflux this for say 2 hours at 120 deg. C.
4.) Now basify as above only this time add toluene on top of the acid and water. The water is so the Na2HCO3 has something to dissolve in and improves the coversion of the acetic acid to Sodium acetate. The basification takes along time and you do not want to use NaOH as this will break your ester apart. As you basify this mix it will produce a lot of bubbles and these bubbles will rise to the top of your vessle and overflow your product all over the table or you. What will stop this from happening will be the toluene on top of the acidic solution as the foam stops when it meets the toluene. It will not take long and all the ester will be in the toluene before the acid is completely basified. Leave the toluene in the mix until the basification is done unless you are tricky(the basification is done when it stops fizzing). Three toluene extractions were done anyway just to keep some on top of the basification vessle so the water solution would not overflow. The ester is water soluble in pure water but if it is a salt solution(as this is) it is not and has a high affinity for the toluene layer.
5.) Once you are confident with the amount extracted you can boil off(roto vap) the toluene to acquire the ester. This ester forms a hygroscopic solid which is how it was found that it is soluble in water. Under low heat it would be best to leave the ester in a beaker/bowl of slightly boiling water for a time as to remove the residual toluene also. 


Making the Hash Oil.

1.) This ester once formed was then dissolved in about a equal volume of hot water to form a thick oily compound in which one would assume would be the Hash oil one hears about from time to time.
2.) To make hash from this it was assumed one would take and powderize the scraps from the first cannabis extraction and add the appropriate amount of THC acetate to it.


For the reflux a electric griddle was used and salt was layered on it to produce a firm foundation for the reflux apparatus. If this would not have been done a large amount of heat would not have been transfered to the reflux vessle.

[lugh]

Acetone isn't a very selective solvent, low molecular weight hydrocarbons such as heptane, hexane, pentane or butane work better. Petroleum ether aka naptha is a mixture of these hydrocarbons, that's why it's the preferred solvent.

[obituary]

how would DCM work?

[superhybrid]

Acetone is the best otherwise toluene would have been used and the acetone part would have been skipped altogether. Acetone will dissolve everything which is fine. Even after drying for two hours you will still have some water in the dope which will inhibit the extraction with a non polar solvent such as toluene. After the reflux the chlorophylls will be taken out anyway as they are by the presence of yellowish greenish wash water. It is best to use acetone as it is the best solvent and at this point selectivity is not needed as was thought you would have gathered. DCM would work but acetone would still be best for the first initial extraction. Who is to say you do not want some of the other goodies in the reaction such as hordenine and piperidine. It would seem the best dope is going to have these in them.

Yiels was about 16 grams of the acetate which yielded about 30 grams of the oil. It has a smell all its own similar to a fruit smell which most fruit smells are esters similar to THC acetate. Bananna oil is isopentyl acetate while there are some aromatic acetates such as peach.

[lugh]

For small scale work acetone can work, but it's so flammable that it's a very bad choice for anything larger. It's not very selective, like alcohols, it will extract most of the chlorophyll and sugars. Using petroleum ether/hexane in a continuous percolation apparatus



One can extract the cannaboids (90% with one half hour of shaking) in a reasonably short period of time, and then isomerize the other cannaboids to THC using para-toluenesulfonic acid in a one pot shot (attach a reflux condenser directly to the receiver flask). For best results, you want about 1 gram of CBD in 100 ml solvent that is about 0.05% acid (.0.005 molar). Another way to figure the parameters is to use 5 ml of oil per 100 ml of solvent. Refluxing for an hour will isomerize over 90% of the THC's to delta six
As far as preparation, SWIM who has made hash oil for over 30 years states that it's best to decarboxylate the cannabis using aluminum foil covered cookie sheets at 250 degrees Fahrenheit in an electric oven until for ten to fifteen minutes, use the foil to load a blender, and grind to a fine powder. Packing a percolator is an art, a small amount of cotton is inserted, then a thin layer of clean sand is then leveled off. Using a sawn off broomstick handle, the dampened cannabis is added in small portions at a time, each sucessive portion pressed down in the same manner, but more firmly than the preceding portion. If the percolator is badly packed the solvent will form channels through the cannabis, greatly reducing the efficiency of the process:

If one wishes, one can fractionally distill the oil in high vacuum to obtain 90% THC oil, or one can decolorize using Norit, a thin layer of the extracted cannabis in the percolator can be used as a filter medium    

[superhybrid]

If one had a soxtlet yeah, but most don't! It has been said above that the hexanes would be the most selective, why would not the toluene? It would seem to be that if one wanted this done and to eliminate as many steps as possible one could extract with the toluene instead of acetone or as you say hexane. Once again as has been stated it was wanted to have all extracts in the relux, not just the cannibinoids. If one wanted the acetone extract could have been then been washed with water and toluene to purify the cannabinoids from chlorophylls and others including piperidine and hordenine to some extant but as was stated again and again it was not wanted.

Unfortunatly the para-toluene sulfonic acid produced by the above methods will only be around 90% while the ortho and meta isomers will make up the rest of the 10%. It has been concluded that the other 10% of the isomers are not going to hurt the reaction.

Activted charcoal is what has been used in the past to decolorize oils and what nots. It can be bought from Wal-Mart if needed from the fish tank section. As was stated it needs a very good filter as such the finely powdered cannabiis and as has been used in the past to filter out the fine charcoal is something called celite or possibly talc could be used.

[lugh]

If one doesn't have a percolator and other useful glassware, SWIM says he once bored a hole into the end of glass soda bottle using the following method and used that!

From the Chemical Formulary

By taking a good steel drill and wetting it with a saturated solution of camphor in oil of turpentine, holes may be rapidly and easily drilled through the thickest plate glass

Toluene works well, but it requires much more electricity to boil it compared to naptha, which can be heated conveniently with hot water heated by a coffee immersion heater. The most selective solvents for terpenes (THC's) and terpene ethers (safrole) are low molecular weight hydrocarbons.

[terbium]

and the chlorophylls should have been extracted with the water extraction.

The chlorophylls will neutralize your toluenesulphonic acid; perhaps this is why you need such a large amount. Better to remove the chlorophylls before attempting the acid catalyzed condensation/isomerization.

[lugh]

There are many ways to do this (and maybe Adams didn't know all of them , but could you point out a reference stating that glacial acetic acid/sulfuric acid produces THC acetate? It seems unlikely that the researchers in this field would have used acetic anhydride if an estrification was facile. DCM and toluene work well also, but aren't as selective as the low weight hydrocarbons (though much better than alcohols or ketones). This leads to much more chlorophyll being extracted, that's why petroleum ether is considered to be the best solvent, one can isomerize directly with the minimal amount of acid, the chlorophyll content is low enough not to interfere. Filter paper on top of the cannabis is the easiest way to prevent channelling from the solvent, though it's not the only way.

[superhybrid]

There are many ways to do this (and maybe Adams didn't know all of them , but could you point out a reference stating that glacial acetic acid/sulfuric acid produces THC acetate?

No but as being a chemistry major for the last two years you may just have to take my word for it. I have also done plenty of research for my school in the organic lab since that is a sort of specialty. I would say look up Fisher esterification on the web you may learn something.

Terbium, the chlorophylls are taken' out with the water wash after the protonation reaction with the organic acid in the first step. There is no need to take out the chlorophylls in the first extraction. If you want to take them out then do it as you say. The final product will be the same. The product was cleaned before the esterification from all water solubles.

At the present this pretty oil has a nice reddish amber color and [sniff] mmmmmmm[/sniff] has a real nice smell.

[superhybrid]

Here you go I did your work for you. Next time it will be up to you to find it though. Here they use HCl to do it, you can use H2SO4 though also for the catalyzation as was done in the above procedure.

http://www.chemhelper.com/fischester.html

It seems you are all concerned with the amount of acid being used for this reaction. Toluene is cheap, H2SO4 is cheap also what more do you need, sheesh. If you want to use hexane to do it then do it. Seems you need your dope to be real anhydrous for it though with out a soxlet extracter.

[lugh]

No need to explain Fischer estrification to this bee (that's first semester O-Chem), though perhaps some others could benefit. While anything is possible, it just seems that the previous sponsored researchers in this field would have found and published this route, instead of the reported procedure using acetic anhydride. Also, SWIM reports the one attempt using aquarium charcoal instead of Norit was a disaster, the product was captured. SWIM reports that he never had any problems with the product being retained in the cannabis powder when using percolation, it's critical to move the solvent through the material being extracted, as opposed to merely refluxing or shaking it. According to Starks (who is quoting Adams et al), chloroform is the most effective solvent in terms of extraction speed, it just isn't as selective as low molecular weight hydrocarbons. Read the various reports posted by gyro et al on the Hive, no chlorophyll or sugars are extracted by butane, it's just not so convenient if there is a significant percentage of CBD present, since isomerization requires reflux.

[superhybrid]

Yeah, one does this and another does that. He likes cheetos you like tostados. Activated charcoal is activated charcoal by the way, no matter what ye want to think. Norit is just a brand name for activated charcoal  What is next here; my dad can beat up your dad?

[lugh]

Yes, but different types of charcoal have different adsorption properties, why do you think they make more than one kind! It seems that most bees would like to know of potential pitfalls, science isn't easy. Skepticism is the backbone of science, this isn't a personal attack. As far as dads, he's too old to be capable of anything but gunplay, and violence is the last refuge of the incompetent (of which there are enough in the world already). It would be great if Emil Fischer's idea works with THC acetate, the proof is in the pudding.  Any bees interested in pursuing experiments with this process should bear in mind that Fischer estrification is a reversible reaction, one must push the equilibrium toward the ester by using a large excess of acetic acid. Another feature of this reaction is that hydrolysis is likely, unless one uses a Dean-Stark trap to remove the water produced. No characterization data was submitted, that would be helpful.

[foxy2]

Sphybrid
If your head gets any bigger its going to explode.

I wonder what causing all that pressure?
Its surely not brain cells

Do Your Part To Win The War

[b159510]

I have also done plenty of research for my school in the organic lab since that is a sort of specialty. I'm a senior and a chem major at one of the top 10 science programs in the US. NO WAY is a sophomore doing research for a university. The very idea is laughable. Did you post references for this reaction, or is this all your own work?
Back to the Primitive

[Lilienthal]

> This ester forms a hygroscopic solid which is how it was found that it is soluble in water.

This seems to be some toluene dissolved acetate salt. It's highly unlikely that acetylation would make the extremely lipophilic cannabinoid more water soluble.

[Dope_Amine]

I didn't read this whole thread, but goddamnit when are people gonna learn that using anything but a HIGHLY non-polar solvent is gonna bring all kinds of junk into the mix.  I've used both DCM and acetone and gotten crap.  So this means using a hydrocarbon like hexane, but considering the fact that you'd never get that solvent completely out except by azeotroping, it would make sense to use something a bit more volatile like hmmmmm......BUTANE or ISOBUTANE.

I have THC acetate in my refrigerator right now.  Made it by doing a butane extraction, isomerizing, and then reacting with acetic anhydride.  It's cool, but if you like getting really high, straight up butane extracted golden oil is better.  The plateau with how far you can take the acetate is lower.  Party on dudes.....

Oh, and btw I do research in an inorganic lab so that makes me way cooler than all of you guys (j/k).
something for your mind.......

[foxy2]

Hexane shouldn't be much harder to get out of the oil than butane.  I highly doubt it forms an azeotrope.

A little heating under vacuum should do the trick nicely.
Do Your Part To Win The War

[superhybrid]

This seems to be some toluene dissolved acetate salt. It's highly unlikely that acetylation would make the extremely lipophilic cannabinoid more water soluble.

Without chromatography one is not going to produce a pure compound even with butane or hexane. It was not the point to make a pure compound also. If one wanted to make a purer compound then indeed it seems the ever consistent lughs method would be adhered too but it wasn’t but not without knowing of this method mind you. One can believe that a alcohol such as THC is responsible for the entire high from cannabis but as is known cannabis and related plants contain more than the alkaloids hordenine and piperidine which if you don’t know are moieties of morphine which some find in hops plants ironically,  a marijuana relative. Maybe you will understand now why the cyclo alcoholic ethers were not specifically extracted from the cannabis; it just wasn’t pertinent to the agenda you see. Your intelligence and thoughtfulness is appreciated though mind you. With chromatography one could achieve a pure compound from the first effort. The compound/s was/were brought through a TLC plate to find a small amount of dark impurity but as for the largest amount being the lighter colored oil compound/solution. The burn test revealed a small amount of charcoalic residue but alas there was no NaOAc residue. Seems a DCM/hexane on silica jel column chromatography would have been ideal but kitchen chemistry wasn’t for it.   

I have also done plenty of research for my school in the organic lab since that is a sort of specialty. I'm a senior and a chem major at one of the top 10 science programs in the US. NO WAY is a sophomore doing research for a university. The very idea is laughable. Did you post references for this reaction, or is this all your own work?

 

Well indeed research had been done all through Organic Chemistry II in which aminic lipids were formed that were meant to be tested as synthetic glucose passage ways for diabetes patients. Apparently what the lipids would do is form a channel into the cell in which glucose could bind to in order to transport across the lipid bilayer. If you do not know, some diabetes patients do not have the amount of glucose channels necessary for proper glucose transport into the cell that is where these lipids came into play.

Some time ago a book was read called Cannabis alchemy in which they formed the ester by reaction with acetic acid. Apparently they thought the acetic acid was enough of a catalyst to form the ester but alas it was figured that a small amount of ACS reagent grade H2SO4 would suffice to shorten the reaction time. The book was read but having been a long time since that time, memory was all there was to go by you see. That could be one reason why the amounts of reagents and reflux times were a little off. No mas’ don’t beat em’ It won’t happen again.

As for laughing at this presence, it wouldn’t be the first time. References aren’t needed all the time asshole.

[lugh]

Actually, Cannabis Alchemy uses the acetic anhydride method, and gives no reference to the originator. The author is certainly no highly trained chemist, since he insists one build a nitrogen filled glove box to handle acetic anhydride. It's a good box for doing more dangerous work, just overkill with the very obnoxious acetic anhydride. So if you actually obtained THC acetate by this "mistake in memory" you'll have repeated the same process that has led to many other great discoveries in chemistry that were made by a similar mistake. Nobody should be laughing, this may very well be a great advance in THC chemistry. We'll know when someone is able to duplicate your results. Advances in science are sometimes improbable.

[superhybrid]

It has been three years since Cannabis Alchemy was read and it was thought for sure they used glacial acetic acid. A fischer reaction has been done before using the acetic acid route and if memory serves me right the yields were above 80%. H2SO4 was used and if it was wondered that was the reason for using it again. Must go with what one knows as also available. Acetic anhydride is a little harder to come by than glacial acetic acid.  

With equimolar amounts of acetyl chloride and NaOAc one can form acetic anhydride which I am sure was already known. One only needs thionyl chloride and acetic acid to form acetyl chloride if memory is correct.

[lugh]

Those that think Cannabis Alchemy's acetylation procedure using acetic anhydride is the only course should read Journal of the Chemical Society 75, 20 (1899), in it cannabinol is acetylated by refluxing with either acetic anhydride or acetyl chloride. While this isn't definitive support for Fischer esterification of cannaboids, it does show that the author of Cannabis Alchemy didn't fully research the matter. In the same vein, in support of Dope Amine's post, Raphael Mechoulam's structure activity table shows that THC has the same physiological effect as THC acetate with only half the dose. What we can learn from this is something that many of us already knew, that books of this type are very often filled with misinformation.

[Rhodium]

Could you direct me to that SAR by Raphael Mechoulam? I cannot find it with a websearch.

https://www.rhodium.ws

[terbium]

I find it in a table in the book Marijuana - Chemistry, Pharmacology, Metabolism and Clinical Effects, Edited by Raphael Mechoulam, Academic Press, Publ. 1973, Library of Congress Catalog #72-77349

Chapter 2 - Structure Activity Relationships, Table V - Activity of delta-1 and delta-6-THC Derivatives and Related Materials. This table gives the dosage necessary to produce certain observable effects in rhesus monkeys: - indicates no change; +-, tranquility; +, drowsiness,decreased motor activity,occasional partial ptosis,occasional head drop; ++, stupor, ataxia, full ptosis, suppresion of motor activity, typical crouched position ("thinker position") for up to three hours, presence of reaction to external sensorial stimuli; +++, severe stupor and ataxia, full ptosis, immobility, "thinker position" lasting for more than 3 hours and absence of reaction to external stimuli.

From the table:

Compound        Dose (mg/kg)     Activity

(-)-delta1-THC            0.05                     +
                                0.1                      ++
                                0.25                     ++
                                0.5                      +++

delta1-THC acetate        0.2                      +-
                                  0.5                      +
                                  1.0                      ++

(-)-delta6-THC            0.1                      +-
                                0.25                     +
                                0.5-0.9                  ++
                                1.0-2.0                  +++

delta6-THC acetate        0.2                      -
                                  0.5                      +
                                  1.0                      ++
                                  5.0                      +++

[superhybrid]

The above table makes it seem that the acetate was possibly not worth acquiring. It was thought that potency doubled by adjoining the acetyl group.

[goiterjoe]

I seriously doubt the guy did enough experimentations with different monkeys and different dosing times for any of his statistics to be valid.  Monkeys build up tolerances just like us, and not all monkeys have the same mental capacities and reactions to diferent chemicals.  and who's to say that his chart shows the acetates are less active?  he tests to see how much it takes to make the monkeys immobile, but maybe the acetates produce a speedy high?  My experiences with THC acetate have been that it takes a long time to kick in, it lasts a lot longer than regular THC, and I'm productive when I'm on it.  Mexican dirt weed puts me in the fetal position, but that damn sure doesn't mean it's the bomb shit. 
If pacman influenced us, we'd glide around dark rooms eating pills and listen to repetitive music.

[Osmium]

As far as I know Mechoulam is THE pimp daddy of THC chemistry, I even seem to remember he was the one determining the structure. I wouldn't be so fast in arguing his findings.
Mokeys aren't cheap, they aren't wasted for experimentation like rats. It's very well possible that he used the same group of monkeys for lots of his research, so these lucky creatures really could have been VERY used to THC and the like.

[b159510]

As far as I know Mechoulam is THE pimp daddy of THC chemistry, I even seem to remember he was the one determining the structure..Interesting info. Two other chemists were (also?) key in determining the structure of THC; Sir Alexander Todd ( Nobel Prize for work on nucleotides) and Roger Adams Ph.D., clarified the structure of THC, and showed that the test used by the FBI to detect THC actually was detecting an inactive companion chemical found in marijuana. Gotta luv those old-school guys.
Back to the Primitive

[lugh]

All three of these gentlemen played instrumental roles in the clarification of cannaboid chemistry, Adams was the first to isolate pure d6-THC, Mechoulam and Shvo determined the stereochemistry in 1963. Many others played important roles as well. THC acetate may very well affect different people in a different manner, individual body chemistry's differ. What's important about this discussion is that we probably have a simple new method for producing the acetate, for those that enjoy it, and the best methods for extraction have been discussed. The pharmaceutical percolator is the preferred tool, it is designed expressly for this purpose. High vacuum distillation will produce 90% THC oil very easily.

[superhybrid]

It is possible that somehow the acetate has to be deacetylated before it is active; same or similar to diacetyl morphine. Chemgrrl gave a reference to the deacetylation of morphine in the brain and it was learned in class to counter the affects of cocaine they are forming compounds/enzymes to de-esterize the cocaine molecule since it is a diester. We all have these enzymes but some more than others as possibly hyperactive people do. Cocaine never did much for some subjects known personally and here at the hive.

 The explanation given for the above water solublity is that the alkaloids present formed amides which may or may not increase solubility. If one wanted to break these amides I believe the extract could be refluxed gently with HCl.

[Lilienthal]

I seriously doubt that amides ar formed from amines under that conditions. And even if so they wouldn't be much more hydrophilic.

[superhybrid]

Lil, amides are formed by this process under reflux. It is a simple dehydration reaction in which H2O leaves the reaction but at the same time it is also reversible. I am sure there is a equilibrium point and most likely the product only went to 30 to 70% completion for the formation of the amides but as is known amides are quite water soluble so indeed if there was only a small amount of amide it may be enough to dissolve alot of the acetate and THC non ester since this reaction/'s is reversible.

Anything else?

[Lilienthal]

[goiterjoe]

I'm not doubting his ability as a chemist by any means, but he might not have used the best techniques to study chemical activity.  I guess you can't expect every researher to be like Shulgin though.  Hell, I downright loathe the THC high, so I would probably experiment with rats and monkeys as well.
Drunk driving, that's what I like to do,
I like drunk driving with you.