US 12,435,053 B2
Process for preparing caryophyllene oxide
Michael Backes, Holzminden (DE); Nadine Heinemeier, Bevern (DE); Stefan Brennecke, Halle (DE); Martin Heinemeier, Höxter (DE); Dietmar Schatkowski, Einbeck (DE); and Artur Dueck, Stadtoldendorf (DE)
Assigned to SYMRISE AG, Holzminden (DE)
Appl. No. 17/282,436
Filed by SYMRISE AG, Holzminden (DE)
PCT Filed Oct. 5, 2018, PCT No. PCT/EP2018/077140
§ 371(c)(1), (2) Date Apr. 2, 2021,
PCT Pub. No. WO2020/069754, PCT Pub. Date Apr. 9, 2020.
Prior Publication US 2021/0387959 A1, Dec. 16, 2021
Int. Cl. C07D 303/06 (2006.01); A61K 9/00 (2006.01); C07D 301/06 (2006.01); C07D 301/32 (2006.01)
CPC C07D 303/06 (2013.01) [A61K 9/0053 (2013.01); C07D 301/06 (2013.01); C07D 301/32 (2013.01); C07B 2200/13 (2013.01)] 19 Claims
 
1. A method for oxidizing beta-caryophyllene comprising:
(i) reacting 60 to 95 wt. % of beta-caryophyllene and 2 to 20 wt. % of alpha-humulene with oxygen at a temperature of 80 to 150° C. without a catalyst, without an enzyme, and without a solvent for 10 to 60 hours, and forming a reaction mixture comprising compounds (1), (2), and (3),

OG Complex Work Unit Chemistry
wherein the reaction is carried out until a ratio of unreacted beta-caryophyllene to a sum of the compounds (1), (2), and (3) in the reaction mixture is 4:1 to 1:4 (unreacted beta-caryophyllene:sum of compounds (1), (2), and (3));
(ii) after carrying out the reaction of (i) and reaching the ratio of 4:1 to 1:4, heating the reaction mixture to a temperature of 110 to 150° C. until the reaction mixture has a peroxide value of less than 30 meq O/kg;
(iii) distilling the reaction mixture to obtain a fraction comprising the compounds (1), (2), and (3); and
(iv) optionally, crystalizing the fraction comprising the compounds (1), (2), and (3).