I am currently working on a flow synthesis process based on the following paper:
One-flow synthesis of tetrahydrocannabinol and cannabidiol using homo- and heterogeneous Lewis acids
Victor R. L. J. Bloemendal1 & Bram Spierenburg1 & Thomas J. Boltje1 & Jan C. M. van Hest2 &
Floris P. J. T. Rutjes1*
Received: 5 November 2020 /Accepted: 30 November 2020
The flow synthesis apparatus was designed by a consultant and runs a homogeneous bf3 etherate catalyst with olivetol and pmenth as tje resorcinols. the goal is to produce a D8/D9 THC blend with a maximum ratio of 1:1, but the more D9 the better.
the problem we are having is yield. the consultant indicated we would easily achieve 90% yield of cannabinoids on the starting reactants, yet the best Ive been able to do is 40%, the paper indicates the best they ever did in the lab was around that number and older papers doing one pot batch synthesis seem to be achieving around the 40-45% yield range as well.
so im hoping to hear from somebody here who has worked in this field to shed some light on this for me.
I’m curious to hear why this process is profitable in your market. Nearly everywhere CBD is a cheaper and more readily available precursor then olivetol.
CBD and THC are both regulated medicines in my country and cost about $100 per gram legally or $60 per gram on the black market for THC, CBD is not available on the black market. olivetol costs me about $1.50 per gram.
well to be fair it does work. ive been working on it for 9 months, and the best result Ive had is 40% yield of mostly D9 and a bit of D8 THC by weight of resorcinols, and Ive had the result confirmed by an analytical lab. legitimate peer reviewed scientific papers indicate possible yields up to 60% by going to a heterogeneous solid bed catalyst and im using a homogeneous catalyst, and the consultant is telling me 90% plus is possible which is why Im reaching out to talk to people who have done it.
you might perhaps be assuming every other country classifies everything the same way your country does.
in my country CBD is a regulated medicine covered explicitly by legislation, any CBD product must go through a lengthy, costly, onerous process of being approved for medical use and then requires a doctors prescription and a person cannot import medicines so it must be purchased from a pharmacy and only comes in a weak ethanol suspension. olivetol does not appear anywhere in my countrys legislation or regulation, it is not controlled like it is in the USA. I can simply import kilograms from Chinese suppliers with literally no import documentation other than ensuring the product is accurately labelled.
pmenth is not a resorcinol, its a terpene. You will always need 1 part resorcinol (olivetol) and 1 part terpene (pmenth or verbenol) to make these cannabinoids.
But also, no kidding a consultant said 90% and then never got there - thats classic consultant speak. I would tend to believe the experts who wrote that paper are more insightful than some fly by night consultant - there may very will be a good reason why those yields are what they are in the paper, there is some chance you will not be able to improve upon them.
That all said, to optimize this procedure yourself you probably just need to screen a bunch of conditions - different solvents, catalysts, dilutions, temperatures, etc. Going straight to a flow reactor is going to ultimately obfuscate your results because its a more complicated system than a simple batch reactor (vial) - you might consider doing some amount of optimization in a vial/batch reactor and then consider how to translate what youve learned there into a flow reactor.
I dont much see the point of the flow reactor if you run homogenous - strong acids like BF3 are going to react the moment they see reagents well below room temperature. By the time the reagents enter the heated section of the system, they’ve already done some amount of reacting and it will be difficult to assess if the heat youre applying is doing anything helpful. Not saying a flow reactor is a bad idea eventually, but if your goal is to understand the reaction dynamic and optimize youre making it really difficult on yourself by going directly into a flow reactor without an appreciation of how each of the reaction conditions affects reactivity.
Of course. I think even acetone is technically a ‘watched chemical.’ My post was more about how even in places like Russia people make their nasty synthetic THC from CBD, not olivetol. It’s not a synthesis that really makes sense to do, with I guess New Zealand being an exception. But olivetol is useful if you’re making CBN or (I think) CBC, like you are
thanks for your insights there. we did take samples from post flow synthesis pre reflux and found our best result to be 40% CBD with trace amounts of other cannabinoids after a 15 minute residence time at 20C. post reflux that CBD had successfully converted to the roughly 1:1 blend of D8 to D9 we were expecting. after re-reading the 2021 paper it seems the researchers managed 60% total cannabinoids with the PBR Bf3 catalyst, so my guess is thats going to be the maximum we can achieve unlesw there is some secret im missing here
Easiest way to make CBN is from the CBD equivalent. I’ve never made any CBN homolog from anything but the corresponding CBD (although THC is also a convenient enough starting material).
I never had much luck with those procedures either, altho presumably someone somewhere has considering there’s been a bunch of CBDP and THCP on the market. Unless it’s literally all been made in China and submitted to chromatography. Running chromatography in the states pretty much instantly increases the cost beyond what anyone is willing to pay, but if the chromatography step is ran in China it’s way cheaper. My bet has been that a lot of the CBDP and THCP on the market is just Chinese import that someone distills in the US and passes off as their own “proprietary technology” a la Hau Processing.
