This is where you are getting it wrong. Cyclization of CBD is by Nature’s definition the most stoichiometric reaction one can envision.
Both the nucleophile (one of the two phenolic hydroxyls) AND the electrophile (the tertiary carbocation) are located within the same carbon skeletal framework. The catalyst is only there to help form the carbocation.
Both the nucleophile and electrophile are present (by structure) in a perfect 1:1 stoichometry. Although there are two phenolic hydroxyls in each molecule of CBD, once it has cyclized using one of the hydroxyls, the other one ceases to function as an nucleophile. Unless you want to form a fourth ring with the trisubstituted 9-10 double bond, of course.
It is an intramolecular ring-formation and all that rotational freedom (entropy) that is now locked up in a tricyclic ring structure must go somewhere, thus the pronounced exotherm. It is the TΔS term in the Gibbs equation.
If this is true, why is the cyclization only carried out in the presence of a catalyst?
A stoichiometric reaction requires a stoichiometric amount of reagents, in which reagents are consumed in order to form product. The very consumption of the reagents is what makes the reaction stoichiometric by nature.
If the reaction doesn’t occur when lacking the presence of a catalyst, it is not a stoichiometric reaction…?
Edit: in the case of these acid-catalyzed reactions we are talking about catalysis and not stoichometrics—so I really cannot concede that point. The fact that the nucleo and electro philes are generated (in the presence of a catalyst) on the CBD molecule does NOT make the reaction stoichiometric.
Again, I disagree. As someone who has tried very hard to halogenate a d8 just to transition it back to d9, i can tell you that strongly shifted is bullshit.
You have to impart a metric fuckload of energy to a d8 molecule to make it into a d9.
Thus, as stated previously, the reversibility is negligible.
I know you didn’t but I opted to use this as opportunity to try to educate. Any reasonable person interprets the catch it before the shift as in before too much d8 has formed.
I am just saying that that is not how it works. Once a molecule of d9 has been formed it is not waiting around for all the CBD to cyclize before “deciding” whether to isomerize to d8 or not.
Each d9 molecule has “its own mind”, if you will. It is simply “looking around” checking if there’s enough energy present to go to d8 in which case it will.
There are two equilibrium constants from CBD to D8.
The first is dictated by concentration of CBD, the second dictated by concentration of D9.
Both extremely irreversible.
As far as D9 “looking around” I disagree. There is enough energy present to shift the reaction to AT LEAST 75-80% D8 especially as the concentration of D9 increases as a result of rxn 1.
Like you mentioned earlier, there is a great deal of entropy resulting from the initial cyclization. That change imparts energy to the reaction continuum and increases the rate of rxn 2.
Edit: I just want to mention, @mitokid you seem to know your stuff quite well, but I’m really not following your logic here nor do I agree. If I’m fundamentally misunderstanding chemistry this hard maybe I’m in the wrong field.
It is quite evident how much more stable d8 than d9 is. The energy required to go back up the hill from the right side is far greater than the energy to go up from the left side.
Edit:
If you have the thermo chemical data, maybe you should be the first in the world to publish it. Otherwise this baseless.
What I’m saying is coming from hundreds of CBD isomerizations with real-time HPLC analysis at several time points. Conducted with several protic and aprotic acids in several solvents.
My data suggests that you are very, VERY wrong.
Maybe you try halogenating a d8 and turning it in to a d9 then get back to me if you don’t melt your face off with gaseous halogen or hydrogen chloride.
This is incorrect. Cyclization of CBD is most certainly first order in concentration of catalyst. It is an intramolecular reaction and not governed by a “concentration” of the atomic centers forming a new bond.
I am starting to get confused. Are you aiming for d8 or d9? I assumed the latter since you talked about stopping the reaction before the shift.
Reaction rate one is pseudo first order, not actual first order.
The only thing catalyst changes is k1 and k2. Catalysts have an effect on Activation energy, not the reaction rate equation. Kinetics fuckin 101
Edit: can @roiplek, @rocksteady, or some other chemist Please come help me out here?
Edit 2: my mistake here was that catalysts have an effect on the activation energy “one time” as in the Activation Energy is not a function of the catalyst’s relative molar concentration
That is a little drastic but another quite common trait among cannabis chemists, inability to change ones mind when presented with a different way of interpreting the World around us, and overreacting.
Hold my beer while I go check my stack of cannabis papers…
I came from Pharma, I don’t mind going back if I have to.
But I am 1,000% sure that I’m right when it comes to kinetics because we have established data and have correctly predicted the outcome of such reactions many, many times both at bench and process scale.
There are two activation energies to be considered: The first is the activation energy of protonation of the propenyl double bond. The second is the activation energy to actually form the carbon-oxygen bond, that barrier is negligible due to the intramolecular nature of the reaction.
The conversion from d8 to d9 is typically carried out below room temp, otherwise you can create other cannabinoids when de-halogenating your halogenated cannabinoid.
I am fundamentally disagreeing with your (mis)interpretation of chemistry fundamentals.
I am confident in my knowledge here because I have applied the chemistry fundamentals and successfully carried out reactions at both bench and process scales—
If im speaking with someone who hasn’t applied their misunderstanding of chemistry to see how incorrect they are, then why am I spending time discussing any more?
First you say that the reaction rate equation is based on the concentration of catalyst, then you say the rate limiting step is the cyclization.
Both of those things are red flags to me.
The rate limiting step is the formation of a catalytic complex—I.e. a transition state molecular complex—the cyclization is essentially apontaneous following the formation of such a complex.
And you saying “so common for cannabis chemists” like you know what you’re talking about.
You haven’t put out one decent piece of information in this exchange.
Just because you can correctly identify phenolic hydroxyls and tertiary carbocations doesn’t mean a goddamned thing.
Your specific interpretation of thermochemistry is way incorrect and you clearly have not attempted the chemistry yourself in any meaningful way or you’d provide data and resources that validate the claims you’re making.
I’m good on refuting the chemistry equivalent of poo-poo that you’re spewing over the forum.
Good luck with the applied chemistry, you’re going to need it unless you decide to pore through your textbooks again.
Maybe your decade in the Arrhenius facility was a decade too short.
Conversion occuring in a coated column at vacuum below 0.01 micron at temperatures around 200-250C is (in my opinion) an extenuating circumstance.
I won’t deign to know exactly what’s happening there (nor would any other chemist without formulating a hypothesis and gathering the data to corroborate it).
I said the rate-limiting step is formation of the carbocation. It is basically downhill from there. You gotta apply the breaks so you don’t end up on d8.
I think this is where this exchange is unclear…
If you want to get to d8 there’s really no “shift” to be waiting for and perfectly time.
The reaction kinetics of cyclization is governed by the ratio of catalyst:CBD and concentration of catalyst. The concentration of CBD can be expressed in terms of those two values.
I found the 97:3 paper, BTW. It is Razdan’s “Hashish - Part 26” from 1981.