Copper‐Catalyzed Decarboxylation

Hey all, I’m not sure this is something that would work in application for the cannabis world, but I wanted to get some opinions or hear if anyone has already considered attempting this reaction with THCA or other cannabinoic acids.

The paper describes the use of copper salts and an aliphatic amine (TMEDA and HMTA seemed to work best as they are good σ-donors and are not sterically hindered) to catalyze the decarboxylation of aromatic compounds.

I was thinking that if done correctly this reaction might allow for the decarboxylation of THCA, CBDA or other cannabinoic acids in less time and at lower temperatures than traditional heating methods. This could potentially allow for increased production rates and higher quality product as heating can result in some degridation.

Let me know what y’all think.

-Maxwell

cahiez2013.pdf (457.2 KB)

You’d be giving yourself a hell of a lot of extra work having to do additional workup to wash out the cupric salts and the stinky amine. It’s much easier to cook cannabinoids to decarb, some substances do not decarboxylate from thermodynamic control as easily and that’s where you have to employ these other methods.

HMTA is great stuff tho :wink:

edit: look at all the extra work they had to do

“An oven-dried, nitrogen-flushed, 500-mL four-necked flask
equipped with a mechanical stirrer, a thermometer and
a condenser was charged with potassium 2-nitrobenzoic acid
(26.7 g, 130.00 mmol), bromobenzene (15.7 g, 100.00 mmol),
copper(I) bromide (144 mg, 1.00 mmol), TMEDA (116 mg,
1.00 mmol), Pd(acac)2 (30.5 mg, 0.1 mmol) and NMP
(130 mL). The resulting mixture was stirred at 170 8C for
20 h. When the reaction was complete, the mixture was
cooled to room temperature and filtered through celite. The
solid was rinsed with ethyl acetate (3 50 mL)
and the resulting filtrate was concentrated under vacuum,.
The residue was purified by column chromatography on silica gel
(eluent: petroleum ether/ethyl acetate, gradient 98:2 to
95:5) furnishing 2-nitrobiphenyl as a yellow oil; yield: 17.1 g
(86%)”

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Yeah, you make a good point. Regardless, the paper does cover some neat chemistry and I at least enjoyed the read :grin:

Thank you for your thoughts!

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I believe @Photon_noir has said before that magnesium oxide will cause decarboxylation and it definitely seemed to work when I tried

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Welcome back, @Montanadabman! Yes, MgO and other alkali metal, alkaline earth metal, and even transition metal oxides do this, too. MgO just happens to be less hygroscopic than several others, and it is one of the most innocuous when it does contact water… that is, the Mg(OH)2 base is not as likely to have undesirable side reactions at decarboxylation temperatures. It’s also pretty easy to procure.
The other one I would say is worth trying is the transition metal oxide of zinc, ZnO. CaO is just too hygroscopic, and NaO and KO are harder to find, hygroscopic, and make dangerously strong bases with water.

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