Continuous isolation of cannabidiol and cannabinoids and conversion of cannabidiol to delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol
In alternative embodiments, provided are processes for obtaining or purifying a substantially pure Δ 8 tetrahydrocannabinol (Δ 8 THC) and/or Δ 9 tetrahydrocannabinol (Δ 9 THC) and optionally a plurality of cannabinoids or terpenes from a natural or a synthetic source, wherein the natural or the synthetic source comprises a cannabidiol (CBD) and optionally a plurality of cannabinoids or terpenes. Also provided are processes comprising the continuous isolation and purification of cannabinoids or terpenes, and further isomerization of the purified cannabidiol to Δ 8 tetrahydrocannabinol (Δ 8 THC) and Δ 9 tetrahydrocannabinol (Δ 9 THC). In alternative embodiments, provided are processes for converting Δ8-THC into Δ 9 -THC. In alternative embodiments, provided are processes for the industrial scale continuous isolation and purification of cannabinoids and further isomerization of the purified cannabidiol to Δ 9 -THC.
1. A method or process for obtaining or purifying a composition comprising a substantially pure Δ 8 -THC and a substantially pure Δ 9 -THC from a natural or a synthetic source, wherein the natural or the synthetic source comprises Δ 8 -THC and Δ 9 -THC,
the method comprising:
(a) obtaining or being provided a first extract, aliquot or sample of the natural or synthetic source, wherein the first extract, aliquot or sample comprises a cannabidiol (CBD) from the natural or the synthetic source;
(b) dissolving the first extract, aliquot or sample in a first reaction solvent;
(c) adding a catalyst to the first extract, aliquot or sample and the first reaction solvent to generate a first reaction mixture, wherein the catalyst includes p-toluenesulfonic acid and the catalyst is free of boron trifluoride and free of boron trifluoride diethyl etherate;
(d) reacting the first extract, aliquot or sample, with the catalyst and the first reaction solvent, under reaction conditions at a temperature of about 5° C. for between about 1 to 30 hours;
(e) adding a neutralizing agent to the first reaction mixture;
(f) removing or substantially removing most or all of the catalyst and the neutralizing agent from the first reaction mixture to generate a first reaction product;
(g) dissolving the first reaction product in a second solvent;
(h) loading the dissolved first reaction product onto a first chromatography column, wherein the Δ 8 -THC and Δ 9 -THC are reversibly bound to the first chromatography column; and
(i) eluting the dissolved first reaction product from the first column with an or at least one elution solution,
thereby obtaining or purifying the composition comprising the substantially pure Δ 9 -THC and the substantially pure Δ 8 -THC.
2. The method or process of claim 1 , further comprising dissolving ormixing in or adding the composition in a solvent to make a mixture of solvent and Δ 9 THC and Δ 8 THC, and loading the mixture onto a second chromatography column, and
eluting the dissolved composition from the second column with an elution solution,
thereby obtaining or purifying a substantially pure Δ 9 THC and Δ 8 THC.
3. The method or process of claim 2 , wherein the second chromatography column is the same column or the same type of column as the first chromatography column.
4. The method or process of claim 1 , wherein the natural source comprises a plant, algal, yeast, lichen or a microbial material, or a material derived from a plant source or plant, algal, yeast, lichen or microbial material.
5. The method or process of claim 1 , wherein the catalyst is added before, simultaneous with, or after addition of the first reaction solvent to the first extract, aliquot, or sample.
6. The method or process of claim 1 , wherein the reaction conditions comprise about 4to 24 hours.
7. The method or process of claim 1 , wherein the reaction conditions comprise about 6 to 15 hours.
8. The method or process of claim 1 , wherein the reacting converts the CBD to a mixture comprising (unreacted) CBD, Δ 8 -THC, and Δ 9 -THC.
9. The method or process of claim 1 , further comprising removing all or substantially most of the first reaction solvent, thereby leaving a first reaction product comprising (unreacted) CBD, Δ 8 -THC, and Δ 9 -THC.
10. The method or process of claim 1 , wherein the second solvent is the same as the first reaction solvent.
11. The method or process of claim 1 , wherein the first chromatography column is a normal phase chromatography column or a reverse phase chromatography column.
12. The method or process of claim 1 , wherein the eluting comprises use of a gradient elution process and the substantially pure Δ 9 -THC and the substantially pure Δ 8 -THC are separately collected in different or separate gradient elution fractions.
13. The method or process of claim 1 , wherein the eluting comprises use of an isocratic simulated moving bed (SMB) elution process and the substantially pure Δ 9 -THC and the substantially pure Δ 8 -THC are separately collected in different or separate elution fractions.
14. The method or process of claim 1 , wherein the natural or the synthetic source further comprises at least one terpene.
15. The method or process of claim 14 , wherein the CBD is reversibly bound to the first chromatography column in (h).
16. The method or process of claim 15 , wherein the CBD is eluted before the Δ 8 -THC and Δ 9 -THC.
17. The method or process of claim 1 , further comprising removing the first reaction solvent after (f) and before (g).