CATALYTIC CONVERSATION OF CANNABIDIOL AND METHODS THEREOF

Abstract

A method of converting cannabidiol (CBD) into Δ9-Tetrahydrocannabinol (Δ9-THC) and Δ8-Tetrahydrocannabinol (Δ8-THC). The method provides a polar aprotic solvent such as Tert-Butyl Methyl Ether, Tetrahydrofuran, dicloromethane, or chloroform. Cannabidiol starting material mixes into the polar aprotic solvent in a chemical reactor to make a cannabinoid solution. Adding a metallic catalyst capable of performing intramolecular hydroalkoxylation to the cannabinoid solution and mixing it converts the cannabidiol starting material into Δ9-Tetrahydrocannabinol (Δ9-THC) and Δ8-Tetrahydrocannabinol (Δ8-THC) in a ratio of at least 6:1. The catalyst is a metal such as a transition metal or is selected from the group consisting of ruthenium, aluminum, iron, gold, silver, copper, platinum, and combinations thereof. In one embodiment a co-catalyst is used such as a triflate salt. Regulating the temperature of the reaction to less than 20° C. yields a predominance of Δ9-THC, i.e. Δ9-THC is more than 75% of the cannabinoid mix.

Claims

1. A method for converting cannabidiol (CBD) into Δ9-Tetrahydrocannabinol (Δ9-THC) and Δ8-Tetrahydrocannabinol (Δ8-THC), the method comprising: providing a solvent; mixing cannabidiol starting material and the solvent in a chemical reactor to make a cannabinoid solution; adding a catalyst to the cannabinoid solution and mixing to convert the cannabidiol starting material into Δ9-Tetrahydrocannabinol (Δ9-THC) and Δ8-Tetrahydrocannabinol (Δ8-THC), wherein the temperature at which the catalyst is mixed with the cannabinoid solution determines the ratio of Δ9-Tetrahydrocannabinol (Δ9-THC) conversion and Δ8-Tetrahydrocannabinol (Δ8-THC) conversion.

2. The method as set forth in claim 1, wherein the cannabidiol starting material is cannabidiol isolate with at least a 95% purity.

3. The method as set forth in claim 2, wherein the cannabidiol starting material includes cannabidiol and at least one other cannabinoid and having less than 95% purity.

4. The method as set forth in claim 2, wherein the catalyst is anhydrous iron (III) chloride.

5. The method as set forth in claim 2, wherein preferably the catalyst is anhydrous iron (III) chloride and the method stirs the catalyst and the cannabinoid solution for between 20-40 minutes, preferably 30 minutes.

6. The method as set forth in claim 5, wherein the step of adding a catalyst repeats in preferably 30 minutes increments until virtually all of the cannabidiol starting material has been converted.

7. The method as set forth in claim 6, wherein progress of the conversion reaction is observed via utilizing high pressure liquid chromatography.

8. The method as set forth in claim 6, wherein the amount of catalyst used is between 1% and 99% on a molecular percentage basis.

9. The method as set forth in claim 6, wherein the amount of catalyst used is 15% on a molecular percentage basis.

10. The method as set forth in claim 5, wherein the process yields a product having at least 95% cannabinoid content.

11. The method as set forth in claim 5, wherein the process yields a product having at least 80% Δ9-Tetrahydrocannabinol (Δ9-THC).

12. The method as set forth in claim 5, wherein the catalyst converts a portion of the cannabidiol starting material into tetrahydrocannabinol to yield a product having at least 95% cannabinoid content including detectable amounts of tetrahydrocannabinol.

13. The method as set forth in claim 1, wherein the temperature at which the catalyst is mixed with the cannabinoid solution remains above 20° C. to favor conversion of the cannabidiol starting material into Δ8-Tetrahydrocannabinol (Δ8-THC) conversion compared to conversion of the cannabidiol starting material into Δ9-Tetrahydrocannabinol (Δ9-THC).

14. The method as set forth in claim 1, wherein the temperature at which the catalyst is mixed with the cannabinoid solution remains below 20° C. to favor conversion of the cannabidiol starting material into Δ9-Tetrahydrocannabinol (Δ9-THC) conversion compared to conversion of the cannabidiol starting material into Δ8-Tetrahydrocannabinol (Δ8-THC).

15. The method as set forth in claim 1, wherein the temperature at which the catalyst is mixed with the cannabinoid solution remains below 20° C. to favor conversion of cannabidiol starting material into Δ9-Tetrahydrocannabinol (Δ9-THC) and the method yields a product having a cannabinoid mix with at least 75%, typically greater than 80%, Δ9-Tetrahydrocannabinol (Δ9-THC).

16. The method as set forth in claim 1, wherein the temperature at which the catalyst is mixed with the cannabinoid solution remains below 20° C. to favor conversion of cannabidiol starting material into Δ9-Tetrahydrocannabinol (Δ9-THC) and the method yields a product having a cannabinoid mix with at least 80% Δ9-Tetrahydrocannabinol (Δ9-THC).

17. (canceled)

18. A method of converting cannabidiol (CBD) into Δ9-Tetrahydrocannabinol (Δ9-THC) and Δ8-Tetrahydrocannabinol (Δ8-THC), the method comprising: providing a polar aprotic solvent selected from the group consisting essentially of Tert-Butyl Methyl Ether, Tetrahydrofuran, dicloromethane, chloroform, and combinations thereof; mixing cannabidiol starting material and the polar aprotic solvent in a chemical reactor to make a cannabinoid solution; adding a metallic catalyst capable of performing intramolecular hydroalkoxylation to the cannabinoid solution and mixing to convert the cannabidiolstarting material into Δ9-Tetrahydrocannabinol (Δ9-THC) and Δ8-Tetrahydrocannabinol (Δ8-THC) in a Δ9-THC:Δ8-THC ratio of at least 6:1.

19. The method as set forth in claim 18, wherein the catalyst is selected from the group consisting essentially of ruthenium, aluminum, iron, gold, silver, copper, or platinum.

20. The method as set forth in claim 18, wherein the catalyst is a transition metal catalyst.

21. The method as set forth in claim 18, wherein the catalyst further comprises a triflate salt co-catalyst.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG. 1 is a chemical reaction converting CBD to Tetrahydrocannabinol (THC) with the FeCl, catalyst.

[0023] FIG. 2 is a flow chart of a method in accordance with the present invention.

DETAILED DESCRIPTION

[0024] FIG. 1 shows a chemical reaction converting CBD to Δ9 Tetrahydrocannabinol (THC) with the FeCl.sub.3 catalyst. Preferably, the reaction converts cannabidiol (CBD) into Δ9-Tetrahydrocannabinol (Δ9-THC) and detectable amounts of Δ8-Tetrahydrocannabinol (Δ8-THC).

[0025] A method of the invention provides a polar aprotic solvent such as Tert-Butyl Methyl Ether, Tetrahydrofuran, dicloromethane, or chloroform. Cannabidiol starting material mixes into the polar aprotic solvent in a chemical reactor to make a cannabinoid solution. Adding a metallic catalyst capable of performing intramolecular hydroalkoxylation to the cannabinoid solution and mixing it converts the cannabidiol into Δ9-Tetrahydrocannabinol (Δ9-THC) and Δ8-Tetrahydrocannabinol (Δ8-THC) in a ratio of at least 6:1. The catalyst is a metal such as a transition metal or is selected from the group consisting of ruthenium, aluminum, iron, gold, silver, copper, platinum, and combinations thereof: In one embodiment a co-catalyst is used such as a triflate salt. Regulating the temperature of the reaction to less than 20° C. yields a predominance of Δ9-THC, i.e. Δ9-THC is more than 75% of the cannabinoid mix.

[0026] FIG. 2 shows a method of the present invention generally designated with the reference numeral 10. The method 10 converts CBD isolate to Δ9 THC using a FeCl.sub.3 catalyst and a saturated hydrocarbon solvent. Preferably this process yields at least 80% Δ9 THC in the cannabinoid mix, and a product having a greater than 95% cannabinoid content. The ratio of Δ9 THC:Δ8 THC is greater than 6:1.

[0027] The term THC as used herein includes the combination of acid form and non-acid forms of Tetrahydrocannabinol, as well as isoforms thereof unless the isoforms are particularly specified such as Δ9-Tetrahydrocannabinol (Δ9-THC) or Δ8-Tetrahydrocannabinol (Δ8-THC).

[0028] The term “cannabinoid mix” is the mixture of cannabinoids in a sample of biomass, distillate, isolate, formulation, or other cannabinoid rich product. The term “cannabinoid” encompasses hundreds of bioactive compounds and molecules commonly found in Cannabis saliva L that are proven to influence or impact the CB1, CB2, 5-HT1A, TRPV1, GPR55, PPARs or other receptors in the human endocannabinoid system.

[0029] Influence can be up regulation, down regulation or modulation of the particular cannabinoid receptor, including allosteric modulation. Cannabinoids can act as a receptor antagonist, agonist or combination thereof depending on many factors including the presence of other cannabinoids.

[0030] The method 10 includes the step 12 of providing dry Tert-Butyl Methyl Ether (TBME) in a chemical reactor. The step 12 can utilize any solvent that can be used with cannabidiol (CBD). Alternatively, various aprotic solvents with a low polarity can be used. For example Tetrahydrofuran (THF), DCM, chloroform, and analogs thereto can be used in accordance with the present invention. Step 12 simply sets forth a preferred solvent.

[0031] In an alternate embodiment of step 12, a polar solvent can be used. For example, polar solvents such as nitromethane and acetonitrile may be used.

[0032] It can be appreciated that various hydrocarbon solvents including Pentane and Hexane Hydrocarbon analogues of TBME can be used in accord with the present invention. For example, an alternative to TBME can be the Hexane Tert-Butyl Ethyl Ether C.sub.6H.sub.14O under varied circumstances.

[0033] The amount of solvent used can vary from 1 to 100 molecular volumes per weight of the starting material. Preferably, the amount of solvent used it is about 5 volumes. Preferably, the starting material is cannabidiol (CBD) isolate having a purity of at least 95% in a dry powdered form.

[0034] The step 14 mixes the TBME Mixing the TBME under an argon atmosphere and cooling to 18° C. to create a TBME solution, the step 16 of adding cannabidiol (CBD) isolate to the TBME solution and mixing, the step 18 of adding a catalyst such as anhydrous iron (III) chloride and mix until the catalyzed reaction is deemed to be complete to yield an organic phase, the method 10 includes the step 20 of washing the organic phase of excess iron with aqueous citric acid and washing the organic phase with saturated sodium chloride to remove excess water. The step 20 further includes drying the organic phase over anhydrous magnesium sulfate to yield a dried product. Filtering, concentrating and distilling the dried product to yield a tetrahydrocannabinol (THC) product.

[0035] The step 12 includes providing a clean 20 L chemical reactor. The step 14 adds 10 L of a dry saturated hydrocarbon such as a pentanol hydrocarbon.

[0036] Preferably the saturated hydrocarbon is Tert-Butyl Methyl Ether (TBME) having the chemical formula C.sub.5H.sub.12O and a molecular weight (MW) of 88.15 g/mol. The step 14 mixes the TBME under a non-reactive atmosphere, such as an inert gas atmosphere. Preferably the atmosphere is an argon atmosphere.

[0037] One advantage of using TBME is the boiling point of approximately 131.4° F. (55° C.), which makes utilization in liquid phase viable across a broad working temperature range.

[0038] The step 14 cools the TBME in the argon atmosphere to 18° C., which is below its' boiling point.

[0039] The step 16 adds 2.0 kg (6.36 mol, 1.0 Eq) of cannabidiol isolate to the cooled TBME. Mix until dissolution is complete. Next, in step 18, the method adds a catalyst.

[0040] In step 18, preferably the catalyst is 30 g (0.18 mol, 0.0283 equivalent weight (Eq)) of anhydrous iron (III) chloride having the chemical formula FeCl.sub.3 to the reactor and stirs the catalyst and the cannabinoid solution for between 20 minutes to 40 minutes, preferably for 30 minutes. FeCl.sub.3 has a molecular weight of 162.204 g/mol. In an alternate embodiment the catalyst range of 0.1 mol to 3 mol is utilized.

[0041] During the step 18, progress of the reaction is observed via utilizing high pressure liquid chromatography (HPLC) (Restek Raptor ARC-18 HPLC column). The step 18 adds additional 30 g (0.184952282311164 mol) charges of the iron catalyst in 30 minute increments until virtually all of the cannabidiol starting material has been converted i.e. until the reaction is deemed to be complete by the disappearance of starting material. In practice, this typically takes about 120 g (0.739809129244656 mol) of catalyst (0.12 Eq total equivalents) and at least two hours of time. Eq=MW/n wherein “Eq” is the equivalent weight, which is the molecular weight (MW) divided by the number of equivalents (n).

[0042] Once the reaction is deemed to be complete, excess iron is removed via washing the organic phase with aqueous citric acid. The organic phase is also washed with saturated sodium chloride to remove excess water. The organic phase is dried over anhydrous magnesium sulfate, is filtered, and is concentrated under reduced pressure to yield the product in the form of a brown oil. This oil is then further purified via distillation, to yield 1.8 kg in the form of a pale yellow oil with a purity of at least 95% delta 9 THC.

[0043] Benefits of the FeCl.sub.3 catalyst is that the cost is low compared to other catalysts available. The reaction is predictably efficient, consistent even with temperature variations and low toxicity in any final product.