Continuous isolation of cannabidiol and conversion of cannabidiol to delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol
In alternative embodiments, provided are processes comprising the continuous isolation and purification of cannabinoids 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 for catalytic modification of cannabidiol (CBD) into a resulting final reaction product composition comprised substantially of Δ 9 -THC and Δ 8 -THC, the method comprising the steps of:
providing a first extract, aliquot or sample of CBD;
mixing the CBD with a first reaction solvent;
adding a catalyst to the CBD and the first reaction solvent to generate a first reaction mixture containing primarily CBD;
reacting the CBD with the catalyst and the first reaction solvent, under reaction conditions of about 0° C., to prepare a modified portion and an unmodified CBD portion of the reaction mixture together comprising CBD, Δ9-THC and Δ8-THC;
adding a neutralizing agent to the first reaction mixture when about 70% of the CBD remains and about 30% of the CBD in the first reaction mixture has been modified to Δ9-THC and Δ8-THC creating the modified portion;
removing substantially all of the catalyst and the neutralizing agent from the first reaction mixture to generate a first reaction product comprising CBD, Δ9-THC and Δ8-THC, wherein the modified portion of the first reaction product is 75% or more Δ9-THC and Δ8-THC;
removing the first reaction solvent;
dissolving the first reaction product in elution solution;
loading the dissolved first reaction product onto a first chromatography column;
eluting the dissolved first reaction product from the first column with an or at least one elution solution;
collecting, in a first elution fraction, the CBD in the first reaction product from the elution solution;
collecting, in a second elution fraction, the Δ9-THC and Δ8-THC in the first reaction product from the elution solution;
removing all or substantially most of the elution solvent from the first and second elution fractions, thereby obtaining a final reaction product composition comprising Δ9-THC and Δ8-THC; and
discarding or recycling through the first reaction mixture any fraction of the elution which is not THC,
wherein the catalyst includes p-toluenesulfonic acid and the catalyst is free of boron trifluoride and free of boron trifluoride diethyl etherate.
2. The method of claim 1 wherein the catalyst is added before, simultaneous with or after addition of the first reaction solvent to the CBD.
3. The method of claim 1 wherein the reaction conditions comprise a time of between about 1 to 30 hours.
4. The method of claim 1 wherein the removing the catalyst step further comprises adding a neutralizing agent and water whereby the neutralizing agent and water in the reaction mixture create a salt of the catalyst that reports to a water phase and is decanted off.
5. The method of claim 1 wherein the first chromatography column is a normal phase chromatography column or a reverse phase chromatography column.
6. The method of claim 1 wherein eluting from the column comprises use of a gradient or isocratic elution process.
7. The method of claim 1 wherein in the first chromatography column the Δ9-THC and Δ8-THC are reversibly bound.
8. The method of claim 3 , wherein the reaction conditions comprise a time of about 4 to 24 hours.
9. The method of claim 3 , wherein the reaction conditions comprise a time of about 6 to 15 hours.
10. The method of claim 3 , wherein the reaction conditions comprise a time of about 8 hours.