My first try in converting CBDP to THCP

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First of all I would like to say that I am not located in the US. The THCP is in the greyzone in my country. I happen to have 500gr of CBDP, which I would like to convert to d8-THCP.

Here is my short plan for this synthesis, please feel free to ask questions/critisise :slight_smile:

This is one of the suggested routes from CBDP to d8-THCP. I would like to try it, but would like to know what you guys think:

Conditions from the article: CBDP, PtSA (0.1eq), DCM, r.t, 48h

CBDP:
CAS: 55824-13-0
Molar mass: 342.523 g·mol−1
Producer: —
Form: Isolate

pTSA

CAS: 6192-52-5
Molar Mass: 190.22
Producer: Sigma-Aldrich™

DCM:
CAS: 75-09-2
Molar mass: 84.93
Water content: 0.02%
Producer: Thomas Baker

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List of Equipment:

In-house HPLC/UV (c18 150*4.7 2.7um)

6l jacketed reactor

5l rotary evaporator

10l dual SPD with a cold trap

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500gr CBDP = 1.46 Moles of CBDP

500ml Dry Methylyne Chloride

0.1 eq PTSa of that would be 0.146 moles of PTSA or 25.14 gramms

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Melt the CBDP in the oven, dissolve in DCM. 1:1 w/v

Add PTSA and start vigorous stirring.

(Atmosphere has to be made inert? Nitrogen/Argon + vaccuum)

After a complete conversion (determined by HPLC tests every 8 hours):

t0 = 0hours

t1 = 8 hours in

t2 = 16 hours in

t3 = 24 hours in

t4 = 32 hours in

t5 = 40 hours in

t5 = 48 hours in

(If CBDP peak is still there)

t6 = 54hrs in

Wavelengths (dual-band): 220 CBDP, 230 THCP

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Quench ass oon as the tangent of the reactant generation = 0

Washing steps:

Wash 1: x2

1000ml of Distilled water. Stir for 5 minutes

Allow the solution to separate

After 30 minutes discard the aqueous phase

Wash 2: x2

50gr of sodium bicarbonate to 3.7liters of water.

Shake/homogenize

100rpm for 5 minutes

15minutes leave to separate

Discard aqueous phase

Wash 3: x2

50gr of Sodium Chloride to 3.7 litres of water

Shake/homogenize

100rpm for 5 minutes

15minutes leave to separate

Discard aqueous phase

Wash 4: x2

1000ml of Distilled water. Stir for 5 minutes
Allow the solution to separate
After 30 (full separation) minutes discard the aqueous phase

***Discard a bit of oil at the very end, so the water doesn’t get through with DCM

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PH Check:
Take a small amount of heptane/delta crude into a 100ml beaker
Test the pH of the solution with basic pH test strips. Target pH is 5.5-6.5 pH.
If the solution is far off from the targeted pH, repeat steps above one or two more times to help neutralize the pH.

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Dry the organic phase using Calcium Chloride/Magnisium Sulphate/Molecular Sieves.
(which one is prefferable for DCM/Heptane?)

Remove solvent in a Rotevap.

Test using HPLC.

Use SPD

Test again

Questions:

  1. I have both DCM and Heptane, I don’t mind using either, but the original recipe clearly stated DCM
    Although working with a reactor having an organic layer on top is easier for washups. But the RT/cold method working with DCM is very appealing. What would the temperature has to be when using heptane/toluene? Reflux? How long for?
  2. If I use an HPLC to monitor the reaction - would distilling still be a must? Also could someone point out to me the boiling/melting points of CBDp and THCp (none factsheets I found)

Thx for reading guys. I have learned so much by reading, rereading the forum for the last week.

Will post the results/chromatograms here.

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Dcm ptsa doesn’t sound like a good idea BUT I never did this synthesis
Instinct would be hexane heptane or tolueen if I would have to chose

Inert is best but if it s like normal ptsa
Isomerization should not make a lot of diffrance

Solvent cbd-p ratio is low so the exotherm will be big Catch it in time

Doubt it s gooing to take so long with ptsa but might be right

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Thank you @Roguelab , I would never have dreamed of getting a reply from such a respectable forum member :slight_smile:

I have had previous small-batch experiments with CBD-THC conversion.
Toluene/PTSA also worked well (70%+) prior to distillation , but 36hrs of cold DCM/PtSA gave a better yield (86%) , without having to worry about heating.

Could you elaborate a bit on the inert gas part? One of the reasons I believe is the humidity = water content = dipoles the pTSA. What other drawbacks of having air/vacuum only are there?

Would you suggest using a higher solvent to cbd-p ratio? 2:1?

Would molecular sieves be appropriate to add to get rid of the water (DCM has 0.02%)?
Could they stay in the RM, or that would not make any sense

Also the so called exotherm - is there a chance that it doesn’t start immediatly after adding PTSA into the vessel?

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if you’re using pTSA you only need like 1 mol% (0.01 eq). Switch from DCM to heptane. 1mL/g is too little solvent for ANY solvent, if you try this in DCM you’ll almost certainly blow up. If size doesnt matter, do like 4mL/g heptane or toluene (heptane is better). Charge 1% pTSA at like 40-50C, it will exotherm by like 20-30C, when exotherm stops maintain >80C for 60 minutes and work up. Workup looks ok - if it were me I would cool <50C and do bicarb>water>brine…add bicarb kinda slowly because it’ll generate heat/gas as it quenches pTSA. You should not be running this reaction for 48 hours, including the workup this should all be easily completed in a single 8 hour shift - from clean to reactor to clean reactor.

DCM is the wrong solvent for a million reasons…low boiling, and heavier than water. You shouldnt even be touching DCM if youre tryna make D8. Dry with whatever you want, you really can’t go wrong as long as you filter it out…so maybe pick whatever is easiest to filter (sodium sulfate)

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I have quite a bit of extra room in my RV, so 4:1 ratio should be fine.

Why is heptane better than toluene? I thought pTSA + Toluene is the wombo combo :slight_smile:

So 4:1 ratio, bicarbing first would make sense.

I have read a few posts on here, which suggested using TiBAL - I am defo not touching it, but out of curiousity, does anyone know where does this come from?

Any differences in from CBD->THC? I doubt that the length would take any affect on the reaction flow.
Apart from having a higher boiling point. Which I seriously am having troubles finding the digits of.

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There’s just not much benefit to using toluene. Heptane has lower toxicity, and is a little better for supressing byproducts. Reaction will go cleaner in heptane, but toluene will be very similar.

Aluminum stuff is for attempting to make d9THC instead of d8THC

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But wouldnt Chlorinating delta 8 THCP to -trans- HCL-THCP and then pure delta 9 an option?
I heard this everywhere but sourcing this potassium tert amylate seems not an easy task

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Fool in a shed in real life :stuck_out_tongue_winking_eye:

Thank you @eyeworm for clearing the path

@xdubr I would not be suprised if @eyeworm is one of the most knowledgeable chemists on this platform no I would take his advise by heart. Since they make sense

As for thc D9 starting material is cbd NOT cbd-p

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Lucky for you, pTSA and TiBAl aren’t going to chlorinate anything. AlCl3 maybe.

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Alcl3 will sure clorinate the thc as @roguelab can confirm

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Welcome to the Future!

Your post should receive the gold standard for excellence in question-asking. Tons of info, a basic understanding of the process at hand, and very clear questions. Only thing missing is offers of HJs for the assistance

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If I remember correctly in the original paper its Zinc chloride and HCL in 1.4 dioxane.

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Could you please tell me what an HJ is? :slight_smile: I would do my best to fill in the GAP

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Distillation is not always necessary - you could also run chromatography and then evaporate. Depending on how much, this might be easier. Its how I handle all my R&D work - that way I’m collecting fractions without exposing to additional heat than necessary and causing any potential degradation.

If watching on the HPLC - you probably have enough stuff to do small batch chromatography, then test those fractions, then collect the fractions that have your desired compound.

The others recommended Heptane - I use just about anything before using DCM, since it is so nasty. Anything I can do to not use halogens is a good thing in my book, as long as things still work. I will say thought, for sure, that many things worked really well in DCM that didn’t work at all or terribly inefficient in other solvents.

I feel like this starts right away. That’s my personal experience - so preparing for it - making sure there is enough solvent to not all boil away, planning for what to do with the heat, making sure there is space/safety, all important.

One of my very first lab explosions was a runaway aluminum chloride reaction because there was too much moisture in what I was working with. So controlled starting materials and environment can be super important. :slight_smile:

Good luck and please share your HPLC results with us as it goes. I love adventures like this - especially when I can watch from afar. <3

I’m pretty sure this means hand jobs - and probably you don’t actually need to fill in that gap. :wink:

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I thought handies were the preferred form of payment around these parts

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I have seen those timings. 15min RT in DCM. AlCL3

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Can t recal this route any chance to share the paper ? Thx

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Sure, here you go :slight_smile:
Δ 9 -THCP(10.1038@s41598-019-56785-1).pdf (4.4 MB)

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Btw, I have asked the CBDP factory, for their suggested route (not naming the country its from, but its kinda obvious to those skilled in Art):

They suggest using CBD-C8, AlCL3 and DCM in 1.0, 0.03, 10.4 molar equivalents. I cant judge if this route is correct - do not have access to Aluminium Chloride unfortunately.

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How would you deal with too much moisture nowadays? Flame pretreat vessel? Vacuum + inert gas purging? Drying out the starting material?

I generally live in a very humid area. 60%+ easily