US2023097854A1PendingUtilityA1

Methods for converting thc-rich cannabinoid mixtures into cbn-rich cannabinoid mixtures

Assignee: CANOPY GROWTH CORPPriority: Aug 23, 2019Filed: Sep 28, 2022Published: Mar 30, 2023
Est. expiryAug 23, 2039(~13.1 yrs left)· nominal 20-yr term from priority
A61K 36/3482A61K 31/658C07C 50/24C07D 311/80C07C 50/04
62
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Claims

Abstract

Disclosed herein is a method of converting a THC-rich cannabinoid mixture that comprises at least about 20% THC into a CBN-rich cannabinoid mixture that comprises at least about 2.0% CBN. The method comprises contacting the cannabinoid mixture with a benzoquinone reagent under reaction conditions comprising: (i) a reaction temperature that is within a target reaction-temperature range; and (ii) a reaction time that is within a target reaction-time range, such that at least a portion of the of the THC in the THC-rich cannabinoid mixture is converted into CBN.

Claims

exact text as granted — not AI-modified
1 . A method of converting a tetrahydrocannabinol (THC)-rich cannabinoid mixture that comprises at least 20 wt. % THC into a cannabinol (CBN)-rich cannabinoid mixture that comprises at least 2.0 wt. % CBN, the method comprising reacting the cannabinoid mixture with a benzoquinone reagent, wherein the benzoquinone reagent comprises a compound as defined in formula (I): 
       
         
           
           
               
               
           
         
         wherein X 1 , X 2 , X 3 , and X 4  are each independently: H; a halide; a C 1-12 -hydrocarbyl; a C 3-12 -heteroaryl; a C 3-12 -heteroaralkyl; a C 3-12 -heteroaralkenyl; hydroxyl; a C 1-12 -alkoxy; a C 0-12 -amino; a C 1-12 -acyl; a C 1-12 -amide; a C 2-12 -ester; or a C 2-12 -ketone, provided that the benzoquinone reagent is not chloranil. 
       
     
     
         2 . The method of  claim 1 , wherein the THC-rich cannabinoid mixture comprises at least about 80 wt. % THC. 
     
     
         3 . The method of  claim 1 , wherein the THC-rich cannabinoid mixture comprises at least about 95 wt. % THC. 
     
     
         4 . The method of  claim 1 , wherein the THC-rich cannabinoid mixture is derived from a marijuana biomass. 
     
     
         5 . The method of  claim 1 , wherein the THC-rich cannabinoid mixture is a cannabis distillate, a cannabis resin, a cannabis extract, or a combination thereof. 
     
     
         6 . The method of  claim 1 , wherein the benzoquinone reagent comprises: 
       
         
           
           
               
               
           
         
       
       or a combination thereof. 
     
     
         7 . The method of  claim 1 , wherein the reacting of the THC-rich cannabinoid mixture with the benzoquinone reagent is at a benzoquinone:THC ratio of between 1.0:1.0 and 10.0:1.0 on a molar basis. 
     
     
         8 . The method of  claim 1 , wherein the reacting of the THC-rich cannabinoid mixture with the benzoquinone reagent is at a benzoquinone:THC ratio of between 2.0:1.0 and 7.0:1.0 on a molar basis. 
     
     
         9 . The method of  claim 1 , wherein the reacting of the THC-rich cannabinoid mixture with the benzoquinone reagent is at a temperature of between about 20° C. and about 190° C. 
     
     
         10 . The method of  claim 1 , wherein the reacting of the THC-rich cannabinoid mixture with the benzoquinone reagent is at a temperature of between about 80° C. and about 120° C. 
     
     
         11 . The method of  claim 1 , wherein the reacting of the THC-rich cannabinoid mixture with the benzoquinone reagent is in the presence of a solvent. 
     
     
         12 . The method of  claim 11 , wherein the solvent is pentane, hexane, heptane, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisole, 1-butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methylethyl ketone, 2-methyl-1-propanol, 1-pentanol, 1-propanol, propane, propyl acetate, trimethylamine, or a combination thereof. 
     
     
         13 . The method of  claim 1 , wherein the CBN-rich cannabinoid mixture comprises at least about 60 wt. % CBN. 
     
     
         14 . The method of  claim 1 , wherein the CBN-rich cannabinoid mixture comprises at least about 90 wt. % CBN. 
     
     
         15 . The method of  claim 1 , wherein the benzoquinone reagent comprises:
 a compound as defined in formula (I) where X 1 =H, X 2 =H, X 3 =H, and X 4 =H,   a compound as defined in formula (I) where X 1 =CN, X 2 =CN, X 3 =Cl, and X 4 =Cl, or   a compound as defined in formula (I) where X 1 =H, X 2 =OH, X 3 =H, and X 4 =H.   
     
     
         16 . A method of converting tetrahydrocannabinol (THC) into cannabinol (CBN), the method comprising:
 reacting the THC with a benzoquinone reagent that is a compound as defined in formula (I):   
       
         
           
           
               
               
           
         
         where X 1 , X 2 , X 3  and X 4  are as defined as in any one of 1 to 133: 
       
       
         
           
                 
                 
                 
                 
                 
               
                     
                 
                     
                   X 1   
                   X 2   
                   X 3   
                   X 4   
                 
                     
                 
                     
                 
                 
                 
                 
                 
                 
               
                   1 
                   H 
                   H 
                   H 
                   H 
                 
                   2 
                   C 6 H 5   
                   H 
                   H 
                   H 
                 
                   3 
                   CH 3   
                   H 
                   H 
                   H 
                 
                   4  
                   C(CH 3 ) 3   
                   H 
                   H 
                   H 
                 
                   5 
                   OCH 3   
                   H 
                   H 
                   H 
                 
                   6  
                   N(CH 3 ) 2   
                   H 
                   H 
                   H 
                 
                   7 
                   NH 2   
                   H 
                   H 
                   H 
                 
                   8 
                   CH 2 CH 3   
                   H 
                   H 
                   H 
                 
                   9 
                   OH 
                   H 
                   H 
                   H 
                 
                   10 
                   OCH 2 CH 3   
                   H 
                   H 
                   H 
                 
                   11 
                   F 
                   H 
                   H 
                   H 
                 
                   12 
                   Cl 
                   H 
                   H 
                   H 
                 
                   13 
                   Br 
                   H 
                   H 
                   H 
                 
                   14 
                   SH 
                   H 
                   H 
                   H 
                 
                   15 
                   SiH 3   
                   H 
                   H 
                   H 
                 
                   16 
                   CHO 
                   H 
                   H 
                   H 
                 
                   17 
                   COOCH 3   
                   H 
                   H 
                   H 
                 
                   18 
                   CF 3   
                   H 
                   H 
                   H 
                 
                   19 
                   CN 
                   H 
                   H 
                   H 
                 
                   20 
                   COOH 
                   H 
                   H 
                   H 
                 
                   21 
                   SO 3   −   
                   H 
                   H 
                   H 
                 
                   22 
                   NO 2   
                   H 
                   H 
                   H 
                 
                   23 
                   COCH 3   
                   H 
                   H 
                   H 
                 
                   24 
                   C 6 H 5   
                   C 6 H 5   
                   H 
                   H 
                 
                   25 
                   CH 3   
                   CH 3   
                   H 
                   H 
                 
                   26  
                   C(CH 3 ) 3   
                   C(CH 3 ) 3   
                   H 
                   H 
                 
                   27 
                   OCH 3   
                   OCH 3   
                   H 
                   H 
                 
                   28 
                   N(CH 3 ) 2   
                   N(CH 3 ) 2   
                   H 
                   H 
                 
                   29 
                   NH 2   
                   NH 2   
                   H 
                   H 
                 
                   30 
                   CH 2 CH 3   
                   CH 2 CH 3   
                   H 
                   H 
                 
                   31 
                   OH 
                   OH 
                   H 
                   H 
                 
                   32 
                   OCH 2 CH 3   
                   OCH 2 CH 3   
                   H 
                   H 
                 
                   33 
                   F 
                   F 
                   H 
                   H 
                 
                   34 
                   Cl 
                   Cl 
                   H 
                   H 
                 
                   35 
                   Br 
                   Br 
                   H 
                   H 
                 
                   36 
                   SH 
                   SH 
                   H 
                   H 
                 
                   37 
                   SiH 3   
                   SiH 3   
                   H 
                   H 
                 
                   38 
                   CHO 
                   CHO 
                   H 
                   H 
                 
                   39 
                   COOCH 3   
                   COOCH 3   
                   H 
                   H 
                 
                   40 
                   CF 3   
                   CF 3   
                   H 
                   H 
                 
                   41 
                   CN 
                   CN 
                   H 
                   H 
                 
                   42 
                   COOH 
                   COOH 
                   H 
                   H 
                 
                   43 
                   SO 3   −   
                   SO 3   −   
                   H 
                   H 
                 
                   44 
                   NO 2   
                   NO 2   
                   H 
                   H 
                 
                   45 
                   COCH 3   
                   COCH 3   
                   H 
                   H 
                 
                   46 
                   C 6 H 5   
                   H 
                   C 6 H 5   
                   H 
                 
                   47 
                   CH 3   
                   H 
                   CH 3   
                   H 
                 
                   48 
                   C(CH 3 ) 3   
                   H 
                   C(CH 3 ) 3   
                   H 
                 
                   49 
                   OCH 3   
                   H 
                   OCH 3   
                   H 
                 
                   50 
                   N(CH 3 ) 2   
                   H 
                   N(CH 3 ) 2   
                   H 
                 
                   51 
                   NH 2   
                   H 
                   NH 2   
                   H 
                 
                   52 
                   CH 2 CH 3   
                   H 
                   CH 2 CH 3   
                   H 
                 
                   53 
                   OH 
                   H 
                   OH 
                   H 
                 
                   54 
                   OCH 2 CH 3   
                   H 
                   OCH 2 CH 3   
                   H 
                 
                   55 
                   F 
                   H 
                   F 
                   H 
                 
                   56 
                   Cl 
                   H 
                   Cl 
                   H 
                 
                   57 
                   Br 
                   H 
                   Br 
                   H 
                 
                   58 
                   SH 
                   H 
                   SH 
                   H 
                 
                   59 
                   SiH 3   
                   H 
                   SiH 3   
                   H 
                 
                   60 
                   CHO 
                   H 
                   CHO 
                   H 
                 
                   61 
                   COOCH 3   
                   H 
                   COOCH 3   
                   H 
                 
                   62 
                   CF 3   
                   H 
                   CF 3   
                   H 
                 
                   63 
                   CN 
                   H 
                   CN 
                   H 
                 
                   64 
                   COOH 
                   H 
                   COOH 
                   H 
                 
                   65 
                   SO 3   −   
                   H 
                   SO 3   −   
                   H 
                 
                   66 
                   NO 2   
                   H 
                   NO 2   
                   H 
                 
                   67 
                   COCH 3   
                   H 
                   COCH 3   
                   H 
                 
                   68 
                   C 6 H 5   
                   H 
                   H 
                   C 6 H 5   
                 
                   69 
                   CH 3   
                   H 
                   H 
                   CH 3   
                 
                   70 
                   C(CH 3 ) 3   
                   H 
                   H 
                   C(CH 3 ) 3   
                 
                   71 
                   OCH 3   
                   H 
                   H 
                   OCH 3   
                 
                   72 
                   N(CH 3 ) 2   
                   H 
                   H 
                   N(CH 3 ) 2   
                 
                   73 
                   NH 2   
                   H 
                   H 
                   NH 2   
                 
                   74 
                   CH 2 CH 3   
                   H 
                   H 
                   CH 2 CH 3   
                 
                   75 
                   OH 
                   H 
                   H 
                   OH 
                 
                   76 
                   OCH 2 CH 3   
                   H 
                   H 
                   OCH 2 CH 3   
                 
                   77 
                   F 
                   H 
                   H 
                   F 
                 
                   78 
                   Cl 
                   H 
                   H 
                   Cl 
                 
                   79 
                   Br 
                   H 
                   H 
                   Br 
                 
                   80 
                   SH 
                   H 
                   H 
                   SH 
                 
                   81 
                   SiH 3   
                   H 
                   H 
                   SiH 3   
                 
                   82 
                   CHO 
                   H 
                   H 
                   CHO 
                 
                   83 
                   COOCH 3   
                   H 
                   H 
                   COOCH 3   
                 
                   84 
                   CF 3   
                   H 
                   H 
                   CF 3   
                 
                   85 
                   CN 
                   H 
                   H 
                   CN 
                 
                   86 
                   COOH 
                   H 
                   H 
                   COOH 
                 
                   87 
                   SO 3   −   
                   H 
                   H 
                   SO 3   −   
                 
                   88 
                   NO 2   
                   H 
                   H 
                   NO 2   
                 
                   89 
                   COCH 3   
                   H 
                   H 
                   COCH 3   
                 
                   90 
                   C 6 H 5   
                   C 6 H 5   
                   C 6 H 5   
                   H 
                 
                   91 
                   CH 3   
                   CH 3   
                   CH 3   
                   H 
                 
                   92 
                   C(CH 3 ) 3   
                   C(CH 3 ) 3   
                   C(CH 3 ) 3   
                   H 
                 
                   93 
                   OCH 3   
                   OCH 3   
                   OCH 3   
                   H 
                 
                   94 
                   N(CH 3 ) 2   
                   N(CH 3 ) 2   
                   N(CH 3 ) 2   
                   H 
                 
                   95 
                   NH 2   
                   NH 2   
                   NH 2   
                   H 
                 
                   96 
                   CH 2 CH 3   
                   CH 2 CH 3   
                   CH 2 CH 3   
                   H 
                 
                   97 
                   OH 
                   OH 
                   OH 
                   H 
                 
                   98 
                   OCH 2 CH 3   
                   OCH 2 CH 3   
                   OCH 2 CH 3   
                   H 
                 
                   99 
                   F 
                   F 
                   F 
                   H 
                 
                   100 
                   Cl 
                   Cl 
                   Cl 
                   H 
                 
                   101 
                   Br 
                   Br 
                   Br 
                   H 
                 
                   102 
                   SH 
                   SH 
                   SH 
                   H 
                 
                   103 
                   SiH 3   
                   SiH 3   
                   SiH 3   
                   H 
                 
                   104 
                   CHO 
                   CHO 
                   CHO 
                   H 
                 
                   105 
                   COOCH 3   
                   COOCH 3   
                   COOCH 3   
                   H 
                 
                   106 
                   CF 3   
                   CF 3   
                   CF 3   
                   H 
                 
                   107 
                   CN 
                   CN 
                   CN 
                   H 
                 
                   108 
                   COOH 
                   COOH 
                   COOH 
                   H 
                 
                   109 
                   SO 3   −   
                   SO 3   −   
                   SO 3   −   
                   H 
                 
                   110 
                   NO 2   
                   NO 2   
                   NO 2   
                   H 
                 
                   111 
                   COCH 3   
                   COCH 3   
                   COCH 3   
                   H 
                 
                   112 
                   C 6 H 5   
                   C 6 H 5   
                   C 6 H 5   
                   C 6 H 5   
                 
                   113 
                   CH 3   
                   CH 3   
                   CH 3   
                   CH 3   
                 
                   114 
                   C(CH 3 ) 3   
                   C(CH 3 ) 3   
                   C(CH 3 ) 3   
                   C(CH 3 ) 3   
                 
                   115 
                   OCH 3   
                   OCH 3   
                   OCH 3   
                   OCH 3   
                 
                   116 
                   N(CH 3 ) 2   
                   N(CH 3 ) 2   
                   N(CH 3 ) 2   
                   N(CH 3 ) 2   
                 
                   117 
                   NH 2   
                   NH 2   
                   NH 2   
                   NH 2   
                 
                   118 
                   CH 2 CH 3   
                   CH 2 CH 3   
                   CH 2 CH 3   
                   CH 2 CH 3   
                 
                   119 
                   OH 
                   OH 
                   OH 
                   OH 
                 
                   120 
                   OCH 2 CH 3   
                   OCH 2 CH 3   
                   OCH 2 CH 3   
                   OCH 2 CH 3   
                 
                   121 
                   F 
                   F 
                   F 
                   F 
                 
                   122 
                   Br 
                   Br 
                   Br 
                   Br 
                 
                   123 
                   SH 
                   SH 
                   SH 
                   SH 
                 
                   124 
                   SiH 3   
                   SiH 3   
                   SiH 3   
                   SiH 3   
                 
                   125 
                   CHO 
                   CHO 
                   CHO 
                   CHO 
                 
                   126 
                   COOCH 3   
                   COOCH 3   
                   COOCH 3   
                   COOCH 3   
                 
                   127 
                   CF 3   
                   CF 3   
                   CF 3   
                   CF 3   
                 
                   128 
                   CN 
                   CN 
                   CN 
                   CN 
                 
                   129 
                   COOH 
                   COOH 
                   COOH 
                   COOH 
                 
                   130 
                   SO 3   −   
                   SO 3   −   
                   SO 3   −   
                   SO 3   −   
                 
                   131 
                   NO 2   
                   NO 2   
                   NO 2   
                   NO 2   
                 
                   132 
                   COCH 3   
                   COCH 3   
                   COCH 3   
                   COCH 3   
                 
                   133 
                   CN 
                   CN 
                   Cl 
                   Cl 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         17 . A method of converting tetrahydrocannabinol (THC) into cannabinol (CBN), the method comprising:
 reacting the THC with a benzoquinone reagent that is a compound as defined in formula (I):   
       
         
           
           
               
               
           
         
         wherein X 1 , X 2 , X 3 , and X 4  are each independently: H; a halide; a C 1-12 -hydrocarbyl; a C 3-12 -heteroaryl; a C 3-12 -heteroaralkyl; a C 3-12 -heteroaralkenyl; hydroxyl; a C 1-12 -alkoxy; a C 0-12 -amino; a C 1-12 -acyl; a C 1-12 -amide; a C 2-12 -ester; or a C 2-12 -ketone, 
       
       provided that the benzoquinone reagent is not chloranil. 
     
     
         18 . The method of  claim 17 , wherein the benzoquinone reagent comprises: 
       
         
           
           
               
               
           
         
       
       or a combination thereof. 
     
     
         19 . The method of  claim 17 , wherein the reacting of the THC with the benzoquinone reagent is in the presence of a solvent. 
     
     
         20 . The method of  claim 19 , wherein the solvent is pentane, hexane, heptane, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, ethyl acetate, diethyl ether, tert-butyl methyl ether, water, acetic acid, anisole, 1-butanol, 2-butanol, butane, butyl acetate, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methylethyl ketone, 2-methyl-1-propanol, 1-pentanol, 1-propanol, propane, propyl acetate, trimethylamine, or a combination thereof.

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