Methods of synthesizing cannabigergol, cannabigerolic acid, and analogs thereof
Disclosed are methods for preparing cannabigerol (CBG) or a CBG analog, embodiments of the method comprising providing a compound (I); combining the compound (I) with geraniol and a solvent to form a reaction mixture; and combining the reaction mixture with an acid catalyst to form a product mixture comprising the CBG or the CBG homolog. The method may further comprise separating the CBG or the CBG analog from the product mixture and may further comprise purifying the CBG or CBG analog. Methods for preparing cannabigerolic acid (CBGA) or a cannabigerolic acid analog are also disclosed. The present disclosure also provides highly purity CBG, CBGA, and analogs thereof.
1. A method for preparing cannabigerol (CBG) or a CBG analog, comprising:
reacting geraniol with a compound (I) of the following structure:
wherein R 1 is hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, (OCH 2 CH 2 ) 0-6 O(C 1 -C 8 alkyl), (C 0 -C 4 alkyl)-NR 2a R 2b , (C 0 -C 4 alkyl)-aryl, (C 0 -C 4 alkyl)-heteroaryl, (C 0 -C 4 alkyl)-cycloalkyl, or (C 0 -C 4 alkyl)-heterocycloalkyl, wherein R 2a and R 2b are each independently hydrogen or C 1 -C 6 alkyl;
in the presence of acidic alumina and optionally a solvent.
2. The method of claim 1 , wherein the method includes the solvent.
3. The method of claim 2 , wherein the solvent is chloroform, heptane, tert-butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof.
4. The method of claim 1 , wherein the compound (I) and geraniol are present in a compound (I):geraniol molar ratio of between about 1:1.5 and about 1:3.5.
5. The method of claim 1 , wherein R 1 is C 1 -C 12 alkyl.
6. The method of claim 1 , wherein R 1 is C 5 H 11 .
7. The method of claim 1 , wherein R 1 is C 3 H 7 .
8. The method of claim 1 , wherein R 1 is C 7 H 15 .
9. The method of claim 1 , wherein the compound (I) and geraniol are present in a compound (I):geraniol molar ratio of between about 10:1 and about 1:10.
10. The method of claim 1 , wherein the compound (I) and geraniol are present in a compound (I):geraniol molar ratio of between 10:1 and 1:1.
11. The method of claim 1 , wherein the acid alumina is in an amount of between about 0.001 and about 10 molar equivalents with respect to the compound (I).
12. The method of claim 1 , wherein the acid alumina is in an amount of between about 0.001 and about 1 molar equivalents with respect to the compound (I).
13. The method of claim 1 , wherein the reacting step is performed with heating.
14. A method for preparing cannabigerol (CBG) or a CBG analog, comprising:
reacting geraniol with a compound (I) of the following structure:
wherein R 1 is C 1 -C 12 alkyl;
in the presence of acidic alumina an acid catalyst and a solvent.
15. The method of claim 14 , wherein the solvent is chloroform, heptane, tert-butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof.
16. The method of claim 14 , wherein the compound (I) and geraniol are present in a compound (I):geraniol molar ratio of between about 10:1 and about 1:10.
17. The method of claim 14 , wherein the reacting step is performed with heating.
18. A method for preparing cannabigerol (CBG) or a CBG analog, comprising:
reacting geraniol with a compound (I) of the following structure:
wherein R 1 is hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, (OCH 2 CH 2 ) 0-6 O(C 1 -C 8 alkyl), (C 0 -C 4 alkyl)-NR 2a R 2b , (C 0 -C 4 alkyl)-aryl, (C 0 -C 4 alkyl)-heteroaryl, (C 0 -C 4 alkyl)-cycloalkyl, or (C 0 -C 4 alkyl)-heterocycloalkyl, wherein R 2a and R 2b are each independently hydrogen or C 1 -C 6 alkyl;
under heating in the presence of acidic alumina and a solvent,
wherein the compound (I) and geraniol are present in a compound (I):geraniol molar ratio of between about 10:1 and about 1:10.
19. The method of claim 18 , wherein the solvent is chloroform, heptane, tert-butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof.
20. The method of claim 18 , wherein R 1 is C 1 -C 12 alkyl.