Guys, this is good convo, fascinating to hear both sides.
Really seems the tough end for you guys is accuracy of method, I see the struggle to have standards and proper identification and measure, amazing to me that some of the oldest “tried and true” methods being implemented.
It seems there is always more development necessary in order to both refine extraction processes and testing methods. Oh the rabbit holes to go down.
I guess my next question (if not too lame man) how would one go about identifying the unidentified compounds? And where about is the measure of accuracy if measuring said compounds? Would MS methods give you a more defined picture of the unidentified?
Guess these are nagging questions for people like me in the back.
Like the man said IR and NMR… Problem is that you have isomer soup and you need to separate them at decent amounts (ie via flash and not uhplc) to get a pure isomer to identify on IR/nmr… But you can’t just IR isomer soup.
Aka the need for in-line IR on the end of a uhplc…o. or maybe gc? I think there is decent gc-ir but not working at a university here
And I have done all the digging an ms or ms/ms can do on these isomers. They don’t fragment differentlyaand they all weight the same.
thats what I mean though, it seems as though these techniques are old tried and trues, as even you have stated there needs to be a new standard test to determine what makes up the soup. Extractors are trying to do the same thing as testing agents (essentially), decifer what qualities and properties they want out of their extract, and testing agents are trying to decipher the compounds left over, by implementing similar method no? Refining it further into what are hopefully basic constituents to quantize amounts.
I apologize for the youthful rant and excitement. The deep breath data is intriguing to correlate and consider.
Basically there needs to be better fractionizing of compounds, to have a more defined and accurate profile, that standard practice and method just either A.) Hasn’t been figured out, or B.) Is in development, but not en mass usage.
Err I think it’s just a problem because they are isomers with very close RTs man. If you don’t know what that means, that’s fine. Not a lot of folk would in the outdoors… But if you want to learn… Chem classes are the start and focus on the analytical methods I guess. If you can get all it down, can make some decent money doing honest work
I know it’s an avenue worth pursuing 100% I have a cursory knowledge from a few Chem courses, and having the bigger brains describe things to me, I still have much to learn, and grasp fundamentals of.
There are certainly manufacturers that are leaving HHCs in their final product, but that’s the tip of the iceberg as I see it. In the first Waters PDF I linked up top, one of the unknowns they describe sounds like 8-OH-iso-HHC or 9α-OH-HHC:
The acid degradation product eluting at approximately 2.9 minutes, was identified as an unknown with a m/z of 333 Da, rather than CBG (m/z 317 Da) which shares the same retention time.
They can also be seen as far back as Mechoulam’s earliest work. It’s clear to me that those are at least two byproducts that form in appreciable amounts in unrefined samples ie I would say they are worth testing for in any given sample.
For the unknowns @ 314.5 I doubt they are ∆6a,7 or ∆6a,10a THC. I am still pretty young and new to chemistry relative to a lot of the minds here, but intuitively, if they’re not ∆7 or ∆10 THC, at least one of those peaks may be exo THC as it seems to be more stable. I could see small quantities of ∆7 and ∆10 THC perhaps forming appreciably only in the right conditions (eg a less reactive acid), whereas exo THC may be more like ∆9 THC where it is relatively stable but the reaction prefers to move the double bond to the 8 position.
That still leaves a few other peaks. I would be curious to see what happens in a similar reaction with CBC. I think one paper mentions CBC degrades into 8-OH-iso-HHC for example. I agree with your thoughts on NMR which is why I’m thinking what can we do to intentionally try to create these byproducts to make their identification easier? If they are just less stable forms of THC, that’s probably too tall of an order.
There are some other strange configurations like ABN-CBD and ABN-THC but I don’t see how those would be forming. There are also CBD isomers that could be forming maybe as intermediates but I doubt that as well (not necessarily that they form at all although I have no reason to believe that, but I particularly doubt that they are among the culprits). My thoughts are everywhere, I’ll need to revisit this later.
Im definitely out of my element when it comes to thinking up unknowns. Better minds on this forum have suggested exo-THC and ABN-THC, possible both of those could exist as d8 and d9… so that is four candidates that would be 315 on MS. Iso-THCs? maybe some of that too. I am not sure what the differences are truthfully, would be nice to see a pic of them all together if that is around.
I have not seen much at 333 (or 337, which is another HHC) in these conversions, and the only significant impurities are those byproducts at 315 in the picture. Actually, other than these THC isomer byproducts, the stuff is usually very clean… no significant CBD left over, just a little CBN, just a little THCv. But still +2% THC isomer soup, in all samples. Really the only problem I see are these isomers.
exo-THC already represents a shift of the double bond, there’s no exo-∆9-THC etc, but there are multiple ABN THCs with ABN-∆8-THC being the most stable. If ABN-THC was forming, small amounts of ABN-∆9-THC would probably form as well as ABN-exo-THC assuming exo-THC is in fact appearing. That would be convenient. Hopefully someone with more background can chime in but I don’t see a mechanism for this reaction to produce those compounds. I would expect to see more olivetol and other breakdown products if that were the case. As for iso THC / HHCs, they’re all much heavier than 315 that I know of. I’ll post pictures of some or all of these tomorrow. Based on what you’re saying though, it sounds like whatever these THC-like unknowns are, they are forming from the CBD and not side reactions with impurities.
Right these are definitely side reactions from cbd itself. Seems like there is some freedom when the cbd rings are closing… Not very good at predictions on that level. But there are definitely other things forming from cbd, not coming from impurities in starting material.
That is why I’m thinking it my be impossible to JUST make d8 from cbd… Too much freedom during ring closure. Not enough direction, just chemical chance it will make mostly d8.
We agree it is very difficult, if not impossible, to only create d8-THC through isomerization of CBD. This is why it was called the “Pegasus Challenge.”
This is common with many other reactions where there is a particular preferred structure which is most stable, in this case ∆8 THC, but there are other stable structures that exist and produced as well in smaller quantities. There are ways around this but probably not something that can be employed at scale.
I feel very dumb about the iso THCs. I couldn’t find many references to these after Mechoulam and assumed they were misidentified HHCs. Not a great assumption since Mechoulam clearly reveals the structure for 9α-OH-HHC as well as the two mentioned iso THCs. I would add those to the top of the list no question.
The only references I can find to ABN THC by the way is with synthesis from olivetol so I still doubt those are forming here. I’m still pretty sure it would take an entirely different sort of reaction.
@Kingofthekush420 Speculating but HHC (dihydrocannabinol) seems to be an intermediate before the regular THCs and Δ8 iso THC seems to be a separate pathway that then further forms Δ4,8 iso THC. It probably forms before the ring has a chance to close so maybe less of it is produced by more strongly reactive acids.
I’ll do the first big update to the list tomorrow. I’ll try to better organize it as well as note how likely each unknown is to appear in a particular sample. @mitokid’s suggestion to use two decimals for MWs is a great idea. I rounded certain MWs that I pulled from Kiselak partly because I was being lazy and partly because the main goal was to give a ballpark where they are found.
Higher temperatures should lead to less stability so if you can mitigate other side reactions then I could see this helping push the reaction to form only the most stable compounds.
THC stereoisomers are usually formed through various olivetol or terpene syntheses. I’ll double check but (-)-∆6-iso-THC is likely the same thing as “∆8-iso-THC” or “iso-THC” eg the main iso-THC byproduct.
– I just checked and I think I’m wrong about this. Maybe it’s formed from an olivetol synthesis. The iso-THCs are most certainly worth exploring more.
thats what I mean though, it seems as though these techniques are old tried and trues, as even you have stated there needs to be a new standard test to determine what makes up the soup. Extractors are trying to do the same thing as testing agents (essentially), decifer what qualities and properties they want out of their extract, and testing agents are trying to decipher the compounds left over, by implementing similar method no? Refining it further into what are hopefully basic constituents to quantize amounts.
for the brain.