Cannabinoids Acid Isomerization

bio · Working Bee

.
In trying to find a reliable subject procedure on the net a lot of conflicting information has been found.

Although I have never done this before SWIM has come into a large amount of weed that will be isomerized. The method presently preferred uses Hexane to extract and anhydrous MeOH or EtOH to isomerize at 1g oil to 10g alcohol. A preliminary procedure pieced together could be provided. Extraction went OK, it's the amount of acid required to isomerize that hasn't been figured out and ruining the oil or a failed reaction seems possible given the conflicting info that has been found. Re-inventing the wheel for something this simple doesn't turn me on either.

Most procedures that were found specify 1 drop
sulfuric acid (concentrated).per 1g oil but this is very ambiguous. Others say 1ml acid/g or even 4ml/ounce weed. The 1ml sulfuric acid/g oil comes out to about 790mm/l (millimole per liter) if using the 1g/10g proportions stated above and 98% acid. 4ml per ounce would be even a higher concentration.

Realizing that it is NOT really that critical as long as enough is used then why do some procedures say .05 to .005 molar acid solution? I just can't see a 5 or even 20mm solution as doing much good. Then again I don't claim to really know anything about this reaction either.

Even the large variations in oil content hardly explain the exponential differences in acid concentration from 800 millimole to 5 millimole.

I've seen anywhere from 2-10 hours, extraction reflux, stated on the little there is, on the net. At least what I was able to find.

Carbon boil sounds like a good idea for removing color. The isomerization reflux time (2-12hrs) is also highly variable depending on who you believe.

Now, is there some easier way to filter the sludge than a buchner whichs clogs or passes the fine shit? (BTW I have DE) Almost seems that a filter press would be needed if one was handling very much as half the solvent boils off before the sludge dries on the filter.

If the oil was mixed with 99% IPA and sprayed back on some already good weed I wonder what a good amount would be,not smoking the stuff myself anymore?

PS The carbon decolorization almost turned into a fiasco until I hit on the combination that worked. Also a cold soxhlet type extraction is being experimented with for large batches using minimal hexane. Three liter PET bottle (extractor) even takes boiling hexane just fine! Kimble sold out of the glass ones this size, lol.

bio · Working Bee

After spending a long time typing it all out
it got lost on the internet and dumb me hadn't put it into notepad as usual.

5.8% (226g/13.2g)isomerized dark amber very clean oil was returned from an 8hr reflux in MeOH with 2.1molar sulfuric acid solution.

bio · Working Bee

As long as I'm talking to myself I wonder what this bio guy thinks about this?

It took a little more than the stochiometric amount of bicarb to neutralize which puzzles me if acid is actually used up in this reaction or just acts as a catalyst which I suspect. If the isomerization is simply the migration of the double bond to the 1 or 6 position then acid would not actually be consumed. Obviously I don't really understand what's going on here but hell, never even heard of this until a couple weeks ago and just had to try it and man oh man it really works.

At any rate the testers say the product is fantastic , very trippy with no down to it at all.Also made some hash from the powder on the filter from the first extraction (5min only). This hair powder took 1/2 oil to get it all to stay together but is "out of this world" according to the testers and the best cannabis product they ever had.

Hey Synthetika, I posted some refs on the Psychotropica forum that may have the experimental (from other than a bunch of pot heads,lol) we are looking for on the original acid iso work from 1969-70. The Total synthesis of Cannabinoids" review article also has some interesting info on using UV light and also pyrolysis at low temp for different conversions. Perhaps some of the bees with library acess could dig this up!

Will post something once the procedure is optimized. The cold extraction method is definetly the way to go (as you suspected). Three fast extractions get almost all the oil and very little wax etc. The first water wash is pretty clean not the gummy, impossible to separate/filter mess that results from a Hexanes boil (3 hours was overkill).

IndoleAmine · Dreamreader Deluxe

The H2SO4 doesn't become used up AFAIK, it just acts as a catalyst. You can use excess, it won't hurt anything (at least I remember I read so), and as long as you neutralize it properly, it should be ok.

Did you use Et2O as solvent for the iso step?

And was your product also slightly orange coloured? (I attempted this many moons ago, and it was)

And an idea for saving solvent during xtraction: since the temp. obviously should kept low if one doesn't want to extract lots of wax, sugar and/or chlorophyll(?), the use of a soxhlet is not really cool - although it normally would be adviseable, because it just needs a whole heck of a lot less solvent.

Now what about soxhlet under moderate vacuum? Temp. is kept low, as well as solvent volume... (just an idea)

i_a

bio · Working Bee

.............H2SO4 doesn't become used up AFAIK, it just acts as a catalyst.I read so), and as long as you neutralize it properly, it should be ok.....

Yes, what I thought though this still hardly explains the .005 molar solutions etc. It didn't hurt anything for sure and I wonder if HCl gas could be of benefit as many procedures call for 100% H2SO4 and anhydrous solvent.

...................Did you use Et2O as solvent for the iso step?.............

Used 99.8% MeOH with .1% water 10g to 1g oil.

........... was your product also slightly orange coloured? (I attempted this many moons ago, and it was)................

Before the carbon treatment it had a reddish tint. For some reason RT dripping over the carbon worked much better than boiling regardless of the time. Of course it was done in the polar solvent but as a test also tried a sample with the hexanes and it worked but not nearly as well. Also took way more than the comonly accepted 1-2% to do anything at all. Spent carbon also goes into the recycle bin although no appreciable loss of product ocurred.

............ the use of a soxhlet is not really cool - although it normally would be adviseable, because it just needs a whole heck of a lot less solvent....

My modified soxhlet design takes condensed solvent directly from the condensor thru a dip tube to the bottom of the extractor up through a distributor plate then out a side overflow return to the boiler. This keeps it from packing/settling which tends to occur with a top feed. It's dried enough that flow is fast and the boil-up rate doesn't drip in. It pours in a continuos stream adjusted to have only a few minutes residence time. Vacuum is a good idea although hardly needed as near ambient solvent exits the vertical condensor. A subcooling stage would be more appropriate than vacuum if condensing temp was higher (closed loop air cooled heat exchanger) as the cooling water stays about the same here. Wish I still had my little chiller now!

Hey Indole, find some of those f....... articles will you. I have no acess to anything here other than the internet.

bio · Working Bee

I mentioned this recently and the results are in. The remainder can be read on Psychotropika.

"Not being a pot head I really can't say. If you mean compared to un-isomerized oil the verdict is out until the testers return in a couple days with a full report as they now have both types."

The testers did not know which oil was isoed and which was not. Both came from the same batch and looked, smelled and smoked the same.
Now if my understanding is correct the components being isomerized are not very active if at all yet some have an effect of a sedative type, sleepy, bombed, type of stone. This is more prvalent in the Indica strains as I recall.

One woman tester said she did not get high on the iso stuff but mentioned she still had a clear head and felt something unrecognized. A couple days later she tried the uniso stuff and low and behold she loved it and said it brought back old memories of other hash oil. Strange result as she thought that it was the same the second try and didn't expect any effect.

Another subject reported that the uniso completely bombed him out so that he had to lay down for some hoiurs. When told later what the difference was he said he prefers the other (isoed) as he gets real high but still has energy and can function. Most others have echoed this. It does certainly seem thou that some will prefer the unisoed mixed cannabinoids,

......................e only reason I ask is because butane exracted oil is very very clean, and very potent (because of no loss in potentcy by tempature or air/light exposure). It seems that people who know what they're doing with butane get the same end result in quality as others get in iso's. The only time afoaf seen dark oil was in an alcohol evap where the temps got too high, have seen dark-green too. Seems there higher the temps, the darker the oil. ..............................

I suspect that this is so mainly because the butane oil is more active ingredient due to less other shit like pigments, waxes etc. The dark color due to different things can be removd. or the oil distilled. I tried a very small test of a couple ml and it did distill (short path) from dark tarry oil to give irridescent, golden, shiny, clear, very small droplets. No vac or temp taken just a proof of concept to see what it looked like.

..............BTW, a long time ago rhodium told me that if you use rubbing alcohol intead of ethenol, you will become blinded after time from the iso alcohol evaporation when you smoke the oil and then collecting in your lungs otherwise injesting it. He said ethenol is fine and doesn't do anymore harm then drinking it. Afoaf doesn't even clean pipes with it now............

Well sure, I quess. The oral lethal dose of methanol is about 30ml. Anyone that smokes 2Propanol or methanol deserves whatever happens next if they put it on themselves w/o evaporating.

.............AFOAF normally dilutes the oil in ethanol because it is just too damn thick to work with and smoke. If smoking pure, just dilute it enough to be able to work it on whatever pipe you want to smoke it with.
If putting it on a joint/cannabis bud, dilute to consistenecy to take up in eyedropper then drop on desired product, evaporate in the freezer and you will have pure oil on your product...............

I like the IPA 99.5% as it dissolves the oil much better and a syringe to squirt it on works fine for dosing small batches. Evaporates in a couple hours spread thin on a plate. But certainly the 96% USP ethanol would be the only proper way to do it if one is in a hurry or doesn't know how to dry.

Also, IndoleAmine; if the cannabidiols are being converted to mono-ols then this should use some acid creating water, correct? I wonder then if this is so, why would all the alcohol groups not be reduced? Any thoughts on this?

IndoleAmine · Dreamreader Deluxe

I'm not sure what you mean with "it should use some acid-creating water".(?)

bio · Working Bee

Hey IndoleAmine; put this in your pipe and smoke it!

When I made this statement....."It took a little more than the stochiometric amount of bicarb to neutralize....." it was incorrect. In reviewing my notes just now for the next batch actually 58% of the acid was consumed based on the amount of bicarb utilized to neutralize, lol, rhymes. In my haste when posting I inadvertentley used 1:1 ratio.

So yes, acid is consumed, in the amount of about 1.6g H2SO4 to 1g finished oil. This comes out to .91ml/g which makes the info of 1ml/g
correct assuming a 10% excess which I am using for this batch.

...........I'm not sure what you mean with "it should use some acid-creating water".(?) ..................

It's what I've been wanting to find for a long time, lol, handy stuff.
Put an "ed" in there and then it makes more sense.

.......................Ok. Now lets assume it WOULD happen.

H2SO4 + 2 H2O --> SO4(2-) + 2 H30(1+)
R'R"CH-OH + H3O+ --> R'R"CH + H2O .......................

Yep, it did happen but am still a little confused on the stopping point of the reaction. At any rate now I know how much it takes and will do a more accurate determination this time using the same extract.

IndoleAmine · Dreamreader Deluxe

Interesting - and strange...

Fifty-eight percent of the H2SO4 were used up?
(If it woud've been 50%, I would've said "yes of course" - but 58%?)

Maybe using an exact equimolar amount (0.91ml/g) instead of slight excess (1ml/g) would give slightly better yields?

It sounds as if the sulfuric would shift between the equilibrium H2SO4 -> HSO4(-) -> SO4(2-), and if the right amount is used, the equilibrium is favored exactly to the middle, at the HSO4(-) stage. This way only every second OH would become neutralized, statistically speaking.

This would be an explanation why you only need to neutralize 42% of the remainder - the sulfuric reacts and gives off one hydrogen, and it is this rxn product "schweflige saeure" (HSO4) you are neutralizing; thus you need just approx. 50% of the bicarb you normally would need for H2SO4..

I think you "only" need to adjust the amount of H2O in such a way that approx. 50% of the sulfuric dissociates completely (or the dissociation is stopped at the "HSO4" middle stage due to equilibrium being reached, for that matter Wink

), and then exactly 50% of the available H+ ions will be used up - and hopefully this is the requirement for a superb yield (exactly 50% of the OH's are ISO'ed away)?

But I have no idea how to accomplish this..

..maybe use an amount of water equimolar to that of sulfuric - then only half of the available H(+) protons can form H3O(+) (and subsequently bind one OH(-)), and only every second OH will be "ISO'ed away", hopefully...

Or does the rxn maybe create water by itself? (I would guess so!?) Then the solution is simple, adding a tiny catalytic amnt. of H2O to get things going, and the rxn will eventually stop at the right point; because the increasing amnt. of H2O will prevent further dehydroxylation once ~50% of the OHs have been removed - at least according to the lechatelier principle:

A + B <-> C + D means that only half of the A reacts with B if you add an eqimolar amount of either C or D, and this is the reason why many reactions can be controlled by either removing or adding educts or products -> a dean-stark water trap to drive rxns forward is an example of practical application of this rule.

The same rule could be responsible for the fact that the isomerization stops automatically at the right point....

(enough ranting for now)

i_a

IndoleAmine · Dreamreader Deluxe

Since SWIA has just had some nice success with converting shitty weed into kick-ass, oily <dunnowhat> (too much oil on too little remaining weed Very Happy

), he is now pondering about maybe isomerizing his extract before juicing up the real awful crop of a friend's to make it worthwile smoking... Laughing

This is what he did so far:
Refluxed 10 grams of said shitty plant matter in 50ml Et2O for 30 minutes, decanted and filtered, repeated 2x with 20ml Et2O/10 min., combined ethereal extracts, evapped down to greenish oil. Dissolved in 30ml IPA, stirred with a few granules of decolorizing carbon (norite) and evapped again, to be left with a slightly more yellowish, but still green looking oil, which was redissolved in 5ml of Et2O and "applied" to ca. 1g(?) of dried, crushed but otherwise untreated plant matter and air dried with the help of a 60W light bulb (and aluminium foil cover).

The remainder was wetted with a few drops of dH2O, pressed and rolled between fingers with slight heating (lighter!) to keep it around body temp., to finally give something resembling the hash brand "scuff".. (for those who already did visit the netherlands.. Wink

), was bioassayed and found to be highly active, compared to the untreated stuff - unexpectedly active, to be more exact... Laughing

(immediately smashed a glass beaker onto the ground, and further shattered a 250ml duran flask with it Crying or Very sad

- testing while in lab is stooopid! Evil or Very Mad

)

Now my questions:

1) how can SWIA remove the chlorophyll and waxes completely? Et2O isn't as selective as SWIA thought it to be, I know you already mentioned how you deal with them; but honestly I don't remember how you did it exactly at the moment Very Happy

2) Do you think MeOH would be of advantage when attempting to isomerize - or can SWIA just isomerize with H2SO4 in Et2O, wash thoroughly with NaHCO3 soln. then dH2O, and then evap solvent to be left with sweet iso-honey?

thanks,

i_a

bio · Working Bee

The next door neighbor just finished another batch and he said that the results were confirmed.

.............Fifty-eight percent of the H2SO4 were used up?(If it woud've been 50%, I would've said "yes of course" - but 58%?)....

Using highly sophisticated multi colored pH strips in 3 ranges the best determination is about half a point. I ain't color blind but whoever designed those damn things must have better color perception than me I told the neighbor so he borrowed a few. Sure beats cabbage juice, lol.
Titration was carried out more carefully this time with an accuracy estimated to 5%+/-. Last time it overshot a little to pH 8-8.5 which looks like the same f........g color to me.

....................Maybe using an exact equimolar amount (0.91ml/g) instead of slight excess (1ml/g) would give slightly better yields?..........

In this 320g batch of the same weed 1ml/g was used and a little more than half the bicarb was required to neutralize. Specifically 33g 98% 338mm in 310ml MeOH (ca 1.1molar) was neutralized with bicarb 29.9g
356mm to pH 6.5-7.5 on all three different range strips (the $22 a pak kind). So it seems your theory of the HSO4 may be correct.

....................I think you "only" need to adjust the amount of H2O in such a way that approx. 50% of the sulfuric dissociates completely (or the dissociation is stopped at the "HSO4" middle stage due to equilibrium being reached, for that matter Wink ), and then exactly 50% of the available H+ ions will be used up - and hopefully this is the requirement for a superb yield (exactly 50% of the OH's are ISO'ed away)?.........................

The MeOH is .1% H2O which ain't much but it's there and no water was added. As far as 50% being converted this would statistically be correct I believe, however depending on the quality of the weed, the cannabinoid distribution could vary considerably. This WAS really good stuff but had over dried and partly disintegrated so was no longer desirable to most, therefore the conjecture is, it would be in the half/half isomer ratio.

.................But I have no idea how to accomplish this............

Happens by itself just like my acid creating water. Surprised that it's not available in your area yet. I've heard the housewives like it more than the chemists.

..................Or does the rxn maybe create water by itself? (I would guess so!?) Then the solution is simple, adding a tiny catalytic amnt. of H2O to get things going, and the rxn will eventually stop at the right point;...............

The neighbor said that according to his calculations it does create water and the trace of water in the alcohol may be all it takes although it seems to me that even this is not required. Of course we all know how difficult it is to achieve truly anhydrous conditions!

...........how can SWIA remove the chlorophyll and waxes completely? Et2O isn't as selective as SWIA thought it to be,..........

Actually ether is the best of both worlds in dissolving properties, gets everything the alcohols and alkanes do only Me2CO is better at this. Of course this is exactly what we DON'T want in this extraction. Alkanes are by far the best, The veg oil industry doesn't use hexane for no good reason.

Waxes, phospholipids etc. are hydrated by water. When washed they drop out instantly from the solute but don't shake that funnel or the "Emulsion from Hell" will welcome you with open arms as you spend 2 days trying to break the mess.

Squirt or spray in the water and the waxes precipitate, a little gentle swirling is OK and for tough cases very dilute (1-2%) NaOH helps by forming soaps which also love to form emulsions.
Do it 2 or 3 times till you get most then filter.

Quite a lot is trapped in the filters so after a rinse with your trusty pipette throw them into a bucket. When it's full next week add a gallon of your favorite solvent and throw it in with the next batch. Or if you do like the neighbor did in the beginning you can extract each filter paper individually until you go crazy. At least that's what he told me.

Hard to get it all here but more comes out after the iso, a lot more, so don't be fanatic about it like my neighbor is sometimes. But, why did you extract that crap in the first place, hehehe. I laugh when I read posts that proclaim IPA as the best ext. solvent because that and acetone are the only thing that takes the waxes and the rest of the crap off the equipment. Funny thing is although the hexane dissolved the shit in the first place, once it precipitates, it won't touch it. Even a soapy brush doesn't work. This is actually the stickiest shit that has ever been encountered so far, said Joe next door.

Activated carbon is another soliliquy (sp) for later. In a ambient polar solvent; use more for longer, then it works. Clays, like fullers earth, are better.

....................you think MeOH would be of advantage when attempting to isomerize - or can SWIA just isomerize with H2SO4 in Et2O, wash thoroughly with NaHCO3 soln. then dH2O, and then evap solvent to be left with sweet iso-honey?.......................

Yes, according to Joes research, a polar dry solvent is required and the temperature determines the time for conversion. MeOH is good because it's cheap in a dry state unlike EtOH or IPA. Eight hours at reflux seems to be a rule of thumb here, although as long as 12 has been seen.

Now, why don't you come on over and see if this stuff is any good! Damn they are beating old Joe's door down, even the cops like it. I only smoke Marlboros so have no idea what these potheads are up to.

IndoleAmine · Dreamreader Deluxe

Thx for the tips - I think SWIA will hit the residual green oil with 0.01N NaOH, then extract with hexane, evap down, dissolve in MeOH, decolorize at rt and then attempt an isomerization with 0.9ml H2SO4/gram at reflux for 8h - we'll see how it turns out.

About the acid-creating water: yep - I asked, and my local grocery said they already have ordered it, and its only a matter of time until they stock it - so this will be OTC soon, and all my problems will be solved (at least I hope so!?)... Very Happy

Another experiment involving 4 butane gas cans and a tube-shaped apparatus resembling a flash chromatography column produced 3 grams of a very nice, yellowish-brown oil, which will be isomerized too, using Et2O and 2.7ml H2SO4 at reflux for 24h, followed by neutralization, washing, drying and evaporation of solvent. Most surely the oil that will be used for this one is free from waxes and chlorophyll, alkanes are indeed a very pretty solvent for such extractions (alas, butane is one too; and with excellent evporating properties! Very Happy

)

BTW another example for the two-step dissociation of H2SO4 being responsible for a reaction equilibrium "favored to the middle" is making ether with Et2O/H2SO4..
A half molar amnt. of H2SO4 binds the OHs of half a mole of ethanol by becoming HSO4(-), and the remainder C2H5- is etherified with the other half mol of ethanol giving off one proton and becoming C2H5O(-).
Subsequently, one molecule of H2O is created per 2 molecules of ethanol condensing to one Et2O; and this is the reason why the reaction stops at the right point - as soon as x/2 moles H2O are formed from x moles C2H5OH, the H2SO4 is completely dissociated into HSO4(-) and can't accomplish anything anymore, and the rxn is finished.
At least when you use the right amount of acid - in this case it would be x/2 molar amount when x=amnt. of alc..

So I would say that my former statement "excess can't hurt" is irrational; using more than the required amnt. of H2SO4 normally would result in undesired side reactions...

..then again, as you said: your neighbor has shitty weed too - so the CBD content is probably more than 40% of the overall cannabinoids.

Now I am only puzzled as to about how sulfuric can differentiate between THC and CBD, and leave one untouched, while isomerizing the other to the former... Confused

(Since your neighbor titrated slightly more than half of the H2SO4 after rxn, it apparently works - nice enough, even without knowing why - not even half of the sulfuric reacted, so the single OH of THC apparently must be inert to such isomerization, in contrast to the diol, hm ... Question

)

i_a

bio · Working Bee

Damn, another bag showed up @ Joe's today. Guess he trusts me 'cause he waved it in the window and it wern't no big sandwich baggie either.

....................will hit the residual green oil with 0.01N NaOH, then extract with hexane, evap down, dissolve in MeOH, decolorize at rt ......

Ohh, it'll turn out don't worry about that. If the residual oil is neat you should add some Hx before hitting with base (.01N is only .04%) or it will most likely gel into a mess, The solvent also keeps the contact time to a minimum.

It's better to do say 2x base wash w/ a little than 1x with a lot. Just for the hell of it (thought it would be fun) to see the effect, last night a portion of isoed oil in Hx was treated with 1/3 volume 1% NaOH and then vigorously shaken for about a minute. Man, that was a mistake, turned into wierd looking jelly that had oily streaks thoughout. After a while it was obvious that this mess would never separate so sprinkled powdered salt on the surface in portions. A few hours later it mostly separated and a couple brine washes fixed it. Yea, I knew this was going to happen but old joe, he don't listen, just had to experience it for himself. Was reall funny 'cause it sure looked like it was all ruined!

..........its only a matter of time until they stock it - so this will be OTC soon
....
You are going to love this stuff. Maybe we better not post anymore on it before the word gets out and that Synthetika guy archives it for future generations. (ducking)

............. I would say that my former statement "excess can't hurt" is irrational; using more than the required amnt. of H2SO4 normally would result in undesired side reactions.............

Agree it "sounds" irrational but maybe not because the guy jb over at WD that helped me out on this said excess caused no harm which was apparently proven by Joe as last run twice the acid was used with no apparent detrimental effects. Take a look at jb's pics of the fantastic weed he iso's. I'm sure he ain't ruining it either.

...........Now I am only puzzled as to about how sulfuric can differentiate between THC and CBD, and leave one untouched, while isomerizing the other to the former....................

Yep, me too research does say that the delta 1(9) reverts to the unactive forms in time (heat,light,air etc) as they are the more stable positions. Maybe there is a clue in this??

Anyway keep up the good work and maybe ask the professor why!

IndoleAmine · Dreamreader Deluxe

I don't think my prof would be pleased to hear about SWIAs cannabidol isomerization attempts.. Laughing

bio · Working Bee

You might try spraying back on some good weed when you get enough but smoked straight (vaporized really) it's real smooth. Joe finally settled on 1.1g oil/oz weed diluted with 5-10ml IPA and sprayed on. This is calculated to be 3x potency assuming the iso doubles strenght at minimum using the 1.75% yield figure. Double, triple and 4X strenght was tested on unwitting subjects (very pleased to be they were) and Joe being the expert pothead that he is figured the 4x shit was just tooo strong. He is the one with the stuff they call "chronic" whatever the fuck that is. Everybody wants the chronic even at twice the price but now even that can't touch the triple wammy weed.

............
Not really hash-oil, but a nice product - resembles the famous and over-pricey "ice-o-lator" hash brands.....
(the black "glob" looks very nice indeed, thus I wanted to mention it)

Hash oil is really a misnomer and jb put it right describing the product as more like shoe polish. Yep, that black glob at room temp ain't goin nowhere even after 2 days on the bottom of a glass rod hanging in the stand. Adding some USP EtOH is the only way to make it "oil like" for those in a hurry that don't want to be poisoned.

Makes you wonder how much actual oil there is in some of these no work-up methods I've read.