Methods of synthesizing cannabigergol, cannabigerolic acid, and analogs thereof

Abstract

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 high 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 an acid catalyst and optionally a solvent, 
         wherein the acid catalyst is iron (III) perchlorate hydrate. 
       
     
     
         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 the acid catalyst is in an amount of between about 0.001 and about 0.5 molar equivalents with respect to the compound (I). 
     
     
         6 . The method of  claim 1 , wherein R 1  is C 1 -C 12  alkyl. 
     
     
         7 . The method of  claim 1 , wherein R 1  is C 5 H 11 . 
     
     
         8 . The method of  claim 1 , wherein R 1  is C 3 H 7 . 
     
     
         9 . The method of  claim 1 , wherein R 1  is C 7 H 15 . 
     
     
         10 . A method for preparing a cannabigerol (CBG) analog, comprising:
 reacting geraniol with a compound (I) of the following structure:   
       
         
           
           
               
               
           
         
         wherein R 1  is C 3 H 7  or C 7 H 15 ; 
         in the presence of an acid catalyst and optionally a solvent, 
         wherein the acid catalyst is camphorsulfonic acid, acidic alumina, montmorillonite K10, iron (III) perchlorate hydrate, or any combination thereof. 
       
     
     
         11 . The method of  claim 10 , wherein the acid catalyst is camphorsulfonic acid. 
     
     
         12 . The method of  claim 10 , wherein the acid catalyst is acidic alumina. 
     
     
         13 . The method of  claim 10 , wherein the acid catalyst is montmorillonite K10. 
     
     
         14 . The method of  claim 10 , wherein the acid catalyst is iron (III) perchlorate hydrate. 
     
     
         15 . The method of  claim 10 , wherein the method includes the solvent. 
     
     
         16 . The method of  claim 15 , wherein the solvent is chloroform, heptane, tert-butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof. 
     
     
         17 . The method of  claim 10 , 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. 
     
     
         18 . 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. 
     
     
         19 . The method of  claim 1 , wherein the acid catalyst is in an amount of between about and about 1 molar equivalents with respect to the compound (I). 
     
     
         20 . The method of  claim 1 , wherein the reacting step is performed with heating.