# US 12,371,412 B2 · Methods of preparing cannabinoids or derivatives thereof

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- Number: US 12,371,412 B2
- Document ID: US12371412B2
- Status: Granted
- Kind: B2
- Application number: 18/403,509
- Filed: 2024-01-03
- Published: 2025-07-03
- Granted: 2025-07-29
- Earliest claimed: 2024-01-03
- Assignees: FloraScience Inc.
- Applicants: FloraScience Inc.
- Inventors: Robert Paul Jensen; Vaughn Hartung
- Web page: https://patentgrep.com/patent/US12371412B2

## CPC

- C07D 311/80: Dibenzopyrans; Hydrogenated dibenzopyrans
- B01J 27/06: Halogens; Compounds thereof
- C07D 307/91: Dibenzofurans; Hydrogenated dibenzofurans
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

Provided are methods of preparing cannabinoids and cannabinoid derivatives and compositions containing the cannabinoids and derivatives.

## Claims

### Claim 1

A method of preparing cannabinol, or a pharmaceutically acceptable salt thereof, the method comprising:
admixing a catalyst, cannabidiol, and an oxidizing agent to form cannabinol, or a pharmaceutically acceptable salt thereof, wherein the catalyst is I2, Br2, or C12; and
wherein the oxidizing agent is selected from one or more of O2, S8, benzoquinone, chloranil, hydrogen peroxide, peracetic acid, diacetyl peroxide, ditertbutyl peroxide, dicumyl peroxide, peroxybenzoic acid, benzoyl peroxide, and dimethyl sulfoxide.

### Claim 2 (depends on 1)

The method of claim 1, wherein the admixing comprises:
(a) reacting the catalyst and the cannabidiol to form tetrahydrocannabinol; and
(b) reacting the tetrahydrocannabinol, the catalyst, and the oxidizing agent to form the cannabinol, or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the catalyst is I2.

### Claim 4 (depends on 2)

The method of claim 2, wherein reacting the catalyst and the cannabidiol is performed at a temperature of about 35° C. to about 200° C., about 50° C. to about 150° C., about 50° C. to about 100° C., or less than about 100° C.

### Claim 5 (depends on 1)

The method of claim 1, wherein the admixing is done in the presence of an organic solvent, wherein the organic solvent is one or more of benzene, toluene, xylenes, mesitylene, anisole, acetonitrile, acetic acid, acetic anhydride, heptane, cyclohexane, pyridine, chloroform, isopropyl acetate, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, and chlorobenzene.

### Claim 6 (depends on 1)

The method of claim 1, wherein the catalyst is present in an amount of about 10 mol % or less, about 5 mol % or less, or about 1 mol % or less, based on the total mols of cannabidiol.

### Claim 7 (depends on 2)

The method of claim 2, wherein the reacting the tetrahydrocannabinol, the catalyst, and the oxidizing agent is performed at a temperature in a range of about 50° C. to about 250° C., about 75°° C. to about 200° C., about 120° C. to about 170° C., or less than about 150° C.

### Claim 8 (depends on 1)

The method of claim 1, wherein the oxidizing agent comprises O2, wherein the O2 is present in a gaseous mixture that comprises N2.

### Claim 9 (depends on 1)

The method of claim 1, wherein the oxidizing agent comprises O2 and the O2 is present in an amount of less than about 25 wt %, less than about 20 wt %, less than about 15 wt %, about 10 wt % to about 20 wt %, or about 1 wt % to about 10 wt %, based on the total weight of the oxidizing agent.

### Claim 10 (depends on 2)

The method of claim 2, wherein step (a) and step (b) are performed in situ.

### Claim 11 (depends on 1)

The method of claim 1, wherein the method is performed in a single vessel.

### Claim 12 (depends on 1)

The method of claim 1, wherein the method further forms cannabifuran, and wherein the cannabifuran is formed in an amount of less than about 5 mol %, based on the total mols of cannabinol, or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The method of claim 1, comprising crystallizing the cannabinol, or a pharmaceutically acceptable salt thereof, wherein the crystallizing comprises:
dissolving the cannabinol, or a pharmaceutically acceptable salt thereof, in an organic solvent, wherein the organic solvent is hexane or heptane, to form a solution wherein the temperature is at least about 35° C.; and
cooling the solution to room temperature.

### Claim 14 (depends on 1)

The method of claim 1, wherein the cannabinol, or a pharmaceutically acceptable salt thereof, has a purity of about 90% or more, about 95% or more, or about 99% or more.

### Claim 15 (depends on 1)

The method of claim 1, wherein the cannabinol, or a pharmaceutically acceptable salt thereof, is substantially free of Δ(9,10)-tetrahydrocannabinol.

### Claim 16 (depends on 1)

The method of claim 1, wherein the cannabinol, or a pharmaceutically acceptable salt thereof, is substantially free of Δ(8,9)-tetrahydrocannabinol and Δ(9,10)-tetrahydrocannabinol.

### Claim 17 (depends on 1)

The method of claim 1, further comprising:
admixing the cannabinol, or a pharmaceutically acceptable salt thereof, with a dehydrating agent and acetic acid to form a mixture comprising acetylcannabinol, or a pharmaceutically acceptable salt thereof;
wherein the dehydrating agent is one or more of acetic anhydride, phosphoric acid, sulfuric acid, sodium bisulfite, phosphorus pentoxide, and polyphosphoric acid.

### Claim 18 (depends on 17)

The method of claim 17, wherein the mixture further forms acetylcannabifuran, or a pharmaceutically acceptable salt thereof, wherein the acetylcannabifuran, or a pharmaceutically acceptable salt thereof, is formed in an amount of less than about 5 mol %, based on the total mols of acetylcannabinol.

### Claim 19

A method of preparing cannabinol, or a pharmaceutically acceptable salt thereof, the method comprising:
admixing a catalyst, an oxidizing agent, and tetrahydrocannabinol to form cannabinol, or a pharmaceutically acceptable salt thereof,
wherein the catalyst is I2, Br2, or C2; and
wherein the oxidizing agent is selected from one or more of O2, S8, benzoquinone, chloranil, hydrogen peroxide, peracetic acid, diacetyl peroxide, ditertbutyl peroxide, dicumyl peroxide, peroxybenzoic acid, benzoyl peroxide, and dimethyl sulfoxide.

### Claim 20 (depends on 19)

The method of claim 19, wherein the tetrahydrocannabinol is prepared by a process comprising:
admixing the catalyst and cannabidiol to form the tetrahydrocannabinol.

### Claim 21

The method of 20, wherein admixing the catalyst and the cannabidiol is performed at a temperature of about 35° C. to about 200°° C., about 50° C. to about 150°° C., about 50° C. to about 100° C., or about less than about 100° C.

### Claim 22

A method of preparing cannabinol, or a pharmaceutically acceptable salt thereof, the method comprising:
(a) admixing cannabidiol and a catalyst to form a mixture of Δ(8,9)-tetrahydrocannabinol and Δ(9,10)-tetrahydrocannabinol; and
(b) admixing the mixture and an oxidizing agent to form the cannabinol, or a pharmaceutically acceptable thereof,
wherein the catalyst is I2 and the I2 is present in an amount of less than about 5 mol %, based on the total mols of the cannabidiol; and
wherein the oxidizing agent is selected from one or more of O2, S8, benzoquinone, chloranil, hydrogen peroxide, peracetic acid, diacetyl peroxide, ditertbutyl peroxide, dicumyl peroxide, peroxybenzoic acid, benzoyl peroxide, and dimethyl sulfoxide.

### Claim 23 (depends on 22)

The method of claim 22, wherein the catalyst is present in an amount of less than about 1 mol %, based on the total mols of the cannabidiol.

### Claim 24 (depends on 22)

The method of claim 22, wherein the cannabinol has a purity of about 90% or more, about 95% or more, or about 99% or more.

### Claim 25

A method of preparing acetylcannabinol, or a pharmaceutically acceptable salt thereof, the method comprising:
admixing cannabidiol, an oxidizing agent, I2, and acetic acid to form a mixture comprising cannabinol, or a pharmaceutically acceptable salt thereof, wherein the I2 is present in an amount of less than about 5 mol %, based on the total mols of cannabidiol; and
admixing the mixture with a dehydrating agent to form acetylcannabinol, or a pharmaceutically acceptable salt thereof;
wherein the dehydrating agent is one or more of acetic anhydride, phosphoric acid. sulfuric acid, sodium bisulfite, phosphorus pentoxide, and polyphosphoric acid.

### Claim 26 (depends on 25)

The method of claim 25, wherein the I2 is present in an amount of less than about 1 mol %, based on the total mols of cannabidiol.