WO2020248062A1

WO2020248062A1 - Improved methods for cannabinoid isomerization

Info

Publication number: WO2020248062A1
Application number: PCT/CA2020/050808
Authority: WO
Inventors: Christopher Adair; Ben GEILING; Mohammadmehdi HAGHDOOST MANJILI
Original assignee: Canopy Growth Corporation
Priority date: 2019-06-11
Filing date: 2020-06-11
Publication date: 2020-12-17

Abstract

Disclosed herein is a method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid, in which the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid. The composition has a second cannabinoid:third cannabinoid ratio of greater than 1.0:1.0. The method comprises contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) a protic-solvent environment, an aprotic-solvent environment, or a solvent-free environment; (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis- acidic heterogeneous reagent and the solvent/solvent free environment; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent, the solvent/solvent-free environment, and the reaction temperature.

Description

IMPROVED METHODS FOR CANNABINOID ISOMERIZATION

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to and benefit of United States Provisional

Patent Application Serial Number 62/860, 140 filed on June 1 1 , 2019, which is hereby incorporated by reference.

TECHNICAL FIELD

[0002] The present disclosure generally relates to methods for isomerizing cannabinoids. In particular, the present disclosure relates to methods for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid, or into a mixture of a second cannabinoid and a third cannabinoid in which the second cannabinoid and the third cannabinoid are isomers of the first cannabinoid.

BACKGROUND

[0003] Cannabinoids are often defined in pharmacological terms as a class of compounds that exceed threshold-binding activities for specific receptors found in central-nervous-system and/or peripheral tissues. Such pharmacological definitions are functional in nature, and they encompass a wide range of compounds with, for example: various structural forms ( e.g . different fused-ring systems); various functional-group locants (e.g. different arene-substitution patterns); and/or various alkyl-substituent chain lengths (e.g. C₃H₇ vs C₅H_{1 1}). Accordingly, cannabinoids are also often defined based on chemical structure and, in this context, many cannabinoids are characterized as isomeric

cannabinoids. Isomeric cannabinoids are those which share the same atomic composition but different structural or spatial atomic arrangements. For example, D¹-cannabidiol ( D¹-CBD), D⁹-tetrahydrocannabinol ( D⁹-THC) and D⁸-tetrahydrocannabinol ( D⁸-THC) are all isomeric cannabinoids in that they each have an atomic composition of C₂₁H₃₀O₂, but different structural arrangements as shown in SCHEME 1 :

SCHEME 1

[0004] The structural and/or spatial differences associated with isomeric cannabinoids often correlate with notable differences in pharmacological properties and/or cannabinoid binding affinities. Moreover, isomeric cannabinoids often vary greatly with respect to natural abundance. Accordingly, methods for converting cannabinoids into their isomeric analogs are desirable. However, known methods for isomerizing cannabinoids typically employ chemicals that are dangerous, and/or toxic. Moreover, such methods typically rely on protocols that are generally considered hazardous and/or not suitable for industrial scale reactions ( e.g . reagent-addition, quenching, and/or work-up steps that are highly exothermic). Several known methods for isomerizing cannabinoids also require special care to eliminate oxygen and moisture from the reaction vessel for optimal reactivity and safety. Accordingly, improved methods of isomerizing cannabinoids are desirable.

SUMMARY

[0005] The present disclosure provides improved methods of converting a first cannabinoid into primarily a second cannabinoid or mixtures of a second cannabinoid and a third cannabinoid. The methods of the present disclosure are suitable for use at industrial scale in that they do not require: (i) complicated and/or dangerous reagent-addition, quenching, and/or work-up steps; and (ii) dangerous and/or toxic solvents and/or reagents. Importantly, the methods of the present disclosure provide access to compositions with wide-ranging second cannabinoid:third cannabinoid ratios as evidenced by the wide- ranging second cannabinoid:third cannabinoid ratios disclosed herein. Because the second cannabinoid:third cannabinoid ratios disclosed herein can be correlated to particular reaction conditions and reagents, the methods of the present disclosure can be tuned towards particular second cannabinoid/third cannabinoid selectivity outcomes. [0006] The present disclosure asserts that the ability to form primarily a second cannabinoid and/or compositions of various second cannabinoid:third cannabinoid ratios which are greater than 1.0:1 .0 as demonstrated herein is associated with the utilization of Lewis-acidic heterogeneous reagents. Results disclosed herein indicate that slight changes to reaction conditions involving Lewis-acidic heterogeneous reagents can be leveraged to provide particular second cannabinoid/third cannabinoid selectivities. The utilization of Lewis-acidic heterogeneous reagents for the present transformations also appears to be compatible with the use of class III solvents (or neat reaction conditions) which may obviate the need for the dangerous and/or hazardous solvents that are typical of the prior art. The utilization of Lewis-acidic heterogeneous reagents may also allow product mixtures to be isolated by simple solid/liquid separations ( e.g . filtration and/or decantation). As such, the utilization of Lewis-acidic heterogeneous reagents appears to underlie one more of the advantages of the present disclosure.

[0007] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid. The second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and the composition has a second cannabinoid :third cannabinoid ratio of greater than 1 .0: 1.0 In such embodiments, the method may comprise contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) a protic-solvent system; (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the protic- solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the protic-solvent system.

[0008] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid. The second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and the composition has a second cannabinoid :third cannabinoid ratio of greater than 1 .0: 1.0. In such embodiments, the method may comprise contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) an aprotic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system.

[0009] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid. The second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and the composition has a second cannabinoid :third cannabinoid ratio that is greater than 1.0: 1.0. In such embodiments, the method may comprise contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under neat reaction conditions comprising: (i) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent; and (ii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the reaction temperature.

[0010] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid. In such embodiments, the method may comprise contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) a protic-solvent system; (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the protic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the protic-solvent system.

[0011] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid. In such embodiments, the method may comprise contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) an aprotic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system.

[0012] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid. In such embodiments, the method may comprise contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under neat reaction conditions comprising: (i) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent; and (ii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the reaction temperature.

[0013] Other aspects and features of the present disclosure will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG. 1 shows a high-performance liquid chromatogram for EXAMPLE 1. [0015] FIG. 2 shows a high-performance liquid chromatogram for EXAMPLE 2. [0016] FIG. 3 shows a high-performance liquid chromatogram for EXAMPLE 3. [0017] FIG. 4 shows a high-performance liquid chromatogram for EXAMPLE 4. [0018] FIG. 5 shows a high-performance liquid chromatogram for EXAMPLE 5.

[0019] FIG. 6 shows a high-performance liquid chromatogram for EXAMPLE 6. [0020] FIG. 7 shows a high-performance liquid chromatogram for EXAMPLE 7. [0021] FIG. 8 shows a high-performance liquid chromatogram for EXAMPLE 8. [0022] FIG. 9 shows a high-performance liquid chromatogram for EXAMPLE 9. [0023] FIG. 10 shows a high-performance liquid chromatogram for EXAMPLE 10

[0024] FIG. 11 shows a high-performance liquid chromatogram for EXAMPLE 11 [0025] FIG. 12 shows a high-performance liquid chromatogram for EXAMPLE 12 [0026] FIG. 13 shows a high-performance liquid chromatogram for EXAMPLE 13 [0027] FIG. 14 shows a high-performance liquid chromatogram for EXAMPLE 14.

[0028] FIG. 15 shows a high-performance liquid chromatogram for EXAMPLE 15.

[0029] FIG. 16 shows a high-performance liquid chromatogram for EXAMPLE 16.

[0030] FIG. 17 shows a high-performance liquid chromatogram for EXAMPLE 17.

[0031] FIG. 18 shows a high-performance liquid chromatogram for EXAMPLE 18.

[0032] FIG. 19A shows the effect of ZSM-5 silica/alumina ratio for EXAMPLE 19.

[0033] FIG. 19B shows the effect of ZSM-5 silica/alumina ratio for EXAMPLE 19.

[0034] FIG. 20A shows the effect of water and isopropyl alcohol (IPA) as additives for EXAMPLE 21.

[0035] FIG. 20B shows the effect of butylated hydroxyanisole (BHA) as an additive for EXAMPLE 21.

[0036] FIG. 21 shows a high-performance liquid chromatogram for EXAMPLE 22.

DETAILED DESCRIPTION

[0037] As noted above, the present disclosure provides improved methods for converting a first cannabinoid into primarily a second cannabinoid or mixtures of a second cannabinoid and a third cannabinoid in which the second cannabinoid:third cannabinoid ratio is greater than 1.0: 1.0. The methods of the present disclosure are suitable for use at industrial scale in that they do not require: (i) complicated and/or dangerous reagent- addition, quenching, and/or work-up steps; and (ii) dangerous and/or toxic solvents and/or reagents. Importantly, the methods of the present disclosure provide access to compositions having wide-ranging second cannabinoid:third cannabinoid ratios as evidenced by the wide-ranging second cannabinoid/third cannabinoid selectivity disclosed herein. For example, a first set of reaction conditions disclosed herein provides a second cannabinoid :third cannabinoid ratio of about 1.5:1.0, and a second set of reaction conditions disclosed herein provides a second cannabinoid:third cannabinoid ratio of about 19.2: 1.0. Because the reagents and reaction conditions disclosed herein can be correlated to particular second cannabinoid:third cannabinoid ratios, the methods of the present disclosure may be tuned towards particular second cannabinoid/third cannabinoid selectivity outcomes. While there may be little information available in the current research literature on pharmacokinetic interactions between mixtures of isomeric cannabinoids having defined ratios, the present disclosure asserts that access to an array of

compositions of wide-ranging isomeric ratios is desirable in both medicinal and recreational contexts. Moreover, the present disclosure asserts that access to an array of compositions of varying isomeric ratios is desirable to synthetic chemists.

[0038] Without being bound to any particular theory, the present disclosure asserts that the ability to convert a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid or into a composition comprising isomeric cannabinoids in various ratios as demonstrated herein is associated with the utilization of Lewis-acidic heterogeneous reagents. Results disclosed herein indicate that slight changes to reaction conditions involving Lewis-acidic heterogeneous reagents can be leveraged to provide particular isomeric selectivities. The utilization of Lewis-acidic heterogeneous reagents also appears to be compatible with the use of class III solvents (or neat reaction conditions) which may obviate the need for the dangerous and/or hazardous solvents that are typical of the prior art. The utilization of Lewis-acidic heterogeneous reagents may also allow product mixtures to be isolated by simple solid/liquid separations (e.g. filtration and/or decantation). As such, the utilization of Lewis-acidic heterogeneous reagents appears to underlie one more of the advantages of the present disclosure.

[0039] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second

cannabinoid:third cannabinoid ratio of greater than 1.0: 1.0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) a protic-solvent system; (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the protic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the protic-solvent system. [0040] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second

cannabinoid:third cannabinoid ratio of greater than 1.0: 1.0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) an aprotic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system.

[0041] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid, wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second

cannabinoid:third cannabinoid ratio that is greater than 1.0: 1.0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under neat reaction conditions comprising: (i) a reaction temperature that is within a target

reaction-temperature range for the Lewis-acidic heterogeneous reagent; and (ii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the reaction temperature.

[0042] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid, the method comprising contacting the first cannabinoid with a

Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) a

protic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the protic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the protic-solvent system.

[0043] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) an aprotic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the

Lewis-acidic heterogeneous reagent and the aprotic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system.

[0044] In select embodiments, the present disclosure relates to a method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid, the method comprising contacting the first cannabinoid with a

Lewis-acidic heterogeneous reagent under neat reaction conditions comprising: (i) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent; and (ii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the reaction temperature.

[0045] In the context of the present disclosure, the term“contacting” and its derivatives is intended to refer to bringing the first cannabinoid and the Lewis-acidic heterogeneous reagent as disclosed herein into proximity such that a chemical reaction can occur. In some embodiments of the present disclosure, the contacting may be by adding the heterogeneous catalyst to the first cannabinoid. In some embodiments, the contacting may be by combining, mixing, or both.

[0046] As used herein, the term“cannabinoid” refers to: (i) a chemical compound belonging to a class of secondary compounds commonly found in plants of genus cannabis, (ii) synthetic cannabinoids and any enantiomers thereof; and/or (iii) one of a class of diverse chemical compounds that may act on cannabinoid receptors such as CB1 and CB2.

[0047] In select embodiments of the present disclosure, the cannabinoid is a compound found in a plant, e.g., a plant of genus cannabis, and is sometimes referred to as a phytocannabinoid. One of the most notable cannabinoids of the phytocannabinoids is tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is another cannabinoid that is a major constituent of the phytocannabinoids. There are at least 1 13 different cannabinoids isolated from cannabis, exhibiting varied effects.

[0048] In select embodiments of the present disclosure, the cannabinoid is a compound found in a mammal, sometimes called an endocannabinoid. [0049] In select embodiments of the present disclosure, the cannabinoid is made in a laboratory setting, sometimes called a synthetic cannabinoid. In one embodiment, the cannabinoid is derived or obtained from a natural source (e.g. plant) but is subsequently modified or derivatized in one or more different ways in a laboratory setting, sometimes called a semi-synthetic cannabinoid.

[0050] In many cases, a cannabinoid can be identified because its chemical name will include the text string“^*cannabi^*”. However, there are a number of cannabinoids that do not use this nomenclature, such as for example those described herein.

[0051] As well, any and all isomeric, enantiomeric, or optically active derivatives are also encompassed. In particular, where appropriate, reference to a particular cannabinoid includes both the“A Form” and the“B Form”. For example, it is known that THCA has two isomers, THCA-A in which the carboxylic acid group is in the 1 position between the hydroxyl group and the carbon chain (A Form) and THCA-B in which the carboxylic acid group is in the 3 position following the carbon chain (B Form). As will be appreciated by those skilled in the art who have benefitted from the teachings of the present disclosure, the terms“first cannabinoid” and/or“second cannabinoid” may refer to: (ii) salts of acid forms, such as Na⁺ or Ca²⁺ salts of such acid forms; and/or (iii) ester forms, such as formed by hydroxyl-group esterification to form traditional esters, sulphonate esters, and/or phosphate esters.

[0052] Examples of cannabinoids include, but are not limited to, Cannabigerolic

Acid (CBGA), Cannabigerolic Acid monomethylether (CBGAM), Cannabigerol (CBG), Cannabigerol monomethylether (CBGM), Cannabigerovarinic Acid (CBGVA),

Cannabigerovarin (CBGV), Cannabichromenic Acid (CBCA), Cannabichromene (CBC), Cannabichromevarinic Acid (CBCVA), Cannabichromevarin (CBCV), Cannabidiolic Acid (CBDA), Cannabidiol (CBD), D6-Cannabidiol ( D6-CBD), Cannabidiol monomethylether (CBDM), Cannabidiol-C4 (CBD-C4), Cannabidivarinic Acid (CBDVA), Cannabidivarin (CBDV), Cannabidiorcol (CBD-C1 ), Tetrahydrocannabinolic acid A (THCA-A),

Tetrahydrocannabinolic acid B (THCA-B), Tetrahydrocannabinol (THC or D9-THC),D8-tetrahydrocannabinol (D8-THC), trans-D10-tetrahydrocannabinol (trans-D10-THC), cis-D10-tetrahydrocannabinol (cis-D10-THC), Tetrahydrocannabinolic acid C4 (THCA-C4), Tetrahydrocannabinol C4 (THC-C4), Tetrahydrocannabivarinic acid (THCVA), Tetrahydrocannabivarin (THCV), D8-Tetrahydrocannabivarin (D8-THCV),

D9-Tetrahydrocannabivarin (D9-THCV), Tetrahydrocannabiorcolic acid (THCA-C1 ), Tetrahydrocannabiorcol (THC-C1 ), D7-cis-iso-tetrahydrocannabivarin,

D8-tetrahydrocannabinolic acid (D8-THCA), D9-tetrahydrocannabinolic acid (D9-THCA), Cannabicyclolic acid (CBLA), Cannabicyclol (CBL), Cannabicyclovarin (CBLV),

Cannabielsoic acid A (CBEA-A), Cannabielsoic acid B (CBEA-B), Cannabielsoin (CBE), Cannabinolic acid (CBNA), Cannabinol (CBN), Cannabinol methylether (CBNM),

Cannabinol-C4 (CBN-C4), Cannabivarin (CBV), Cannabino-C2 (CBN-C2), Cannabiorcol (CBN-C1 ), Cannabinodiol (CBND), Cannabinodivarin (CBDV), Cannabitriol (CBT),

1 1 -hydroxy-D9-tetrahydrocannabinol (1 1 -OH-THC), 1 1 nor 9-carboxy-D9- tetrahydrocannabinol, Ethoxy-cannabitriolvarin (CBTVE), 10-Ethoxy-9-hydroxy-D6a- tetrahydrocannabinol, Cannabitriolvarin (CBTV), 8,9 Dihydroxy-D6a(10a)- tetrahydrocannabinol (8,9-Di-OH-CBT-C5), Dehydrocannabifuran (DCBF), Cannbifuran (CBF), Cannabichromanon (CBCN), Cannabicitran, 10-Oxo-D6a(10a)-tetrahydrocannabinol (OTHC), D9-cis-tetrahydrocannabinol (cis-THC), Cannabiripsol (CBR), 3,4,5,6-tetrahydro-7- hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH- iso-HHCV), Trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC), Yangonin,

Epigallocatechin gallate, Dodeca-2E, 4E, 8Z, 10Z-tetraenoic acid isobutylamide, hexahydrocannibinol, and Dodeca-2E,4E-dienoic acid isobutylamide.

[0053] Within the context of this disclosure, where reference is made to a particular cannabinoid without specifying if it is acidic or neutral, each of the acid and/or

decarboxylated forms are contemplated as both single molecules and mixtures.

[0054] As used herein, the term“THC” refers to tetrahydrocannabinol.“THC” is used interchangeably herein with“D9-THC”.

[0055] In select embodiments of the present disclosure, a“first cannabinoid” and/or a“second cannabinoid” may comprise THC (D9-THC), D8-THC, trans-D10-THC, c/s-D10-THC, THCV, D8-THCV, D9-THCV, CBD, CBDA, CBDV, CBDVA, CBC, CBCA, CBCV, CBG, CBGV, CBN, CBNV, CBND, CBNDV, CBE, CBEV, CBL, CBLV, CBT, or cannabicitran [0056] Structural formulae of cannabinoids of the present disclosure may include the following:

[0057] In select embodiments of the present disclosure, the“first cannabinoid”, the“second cannabinoid”, or the third cannabinoid may comprise CBD, CBDV, CBC, CBCV, CBG, CBGV, THC, or THCV. [0058] In select embodiments of the present disclosure, the fist cannabinoid is D⁹-THC or D¹⁰-THC.

[0059] In select embodiments of the present disclosure, the first cannabinoid may be a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof. [0060] In the context of the present disclosure,“isomeric cannabinoids” are those which share the same atomic composition but different structural or spatial atomic arrangements. As such, the statement“the second cannabinoid is an isomer of the first isomer” means that the first cannabinoid and the second cannabinoid share the same atomic composition but different structural or spatial atomic arrangements. Likewise, the statement“the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid” means that the first cannabinoid, the second cannabinoid, and the third cannabinoid share the same atomic composition but different structural or spatial atomic arrangements.

[0061] In the context of the present disclosure, the relative quantities of product cannabinoids may be expressed as a ratio such as - second cannabinoid:third

cannabinoid. Those skilled in the art will recognize that a variety of analytical methods may be used to determine such ratios, and the protocols required to implement any such method are within the purview of those skilled in the art. By way of non-limiting example, such ratios may be determined by diode-array-detector high pressure liquid chromatography,

UV-detector high pressure liquid chromatography, nuclear magnetic resonance

spectroscopy, mass spectroscopy, flame-ionization gas chromatography, gas

chromatograph-mass spectroscopy, or combinations thereof. In select embodiments of the present disclosure, the compositions provided by the methods of the present disclosure have second cannabinoid:third cannabinoid ratios of greater than 1 .0: 1.0, meaning the quantity of the second cannabinoid in the composition is greater than the quantity of the third cannabinoid in the composition. For example, the compositions provided by the methods of the present disclosure may have second cannabinoid:third cannabinoid ratios of: (i) greater than about 2.0: 1.0; (ii) greater than about 3.0: 10; (iii) greater than about 5.0: 10; (iv) greater than about 10.0: 1.0; (v) greater than about 15.0: 1.0; (vi) greater than about 20.0: 1.0; (vii) greater than about 50.0:1.0; and (viii) greater than about 100.0: 1.0.

[0062] In the context of the present disclosure, converting a first cannabinoid into

“primarily” a second cannabinoid refers to converting the first cannabinoid into exclusively the second cannabinoid or into a composition in which the second cannabinoid is present to a greater extent than any other reaction product. In select embodiments of the present disclosure, converting the first cannabinoid into“primarily” the second cannabinoid may yield a product mixture which is at least: (i) 50 % second cannabinoid on a molar basis; (ii) 60 % second cannabinoid on a molar basis; (iii) 70 % second cannabinoid on a molar basis; (iv) 80 % second cannabinoid on a molar basis; (v) 90 % second cannabinoid on a molar basis; or (vi) 95 % D⁹-THC on a molar basis. Importantly converting a first cannabinoid into a composition in which a second cannabinoid is the primary product does not necessarily imply that the second cannabinoid is the most prevalent component of a reaction composition, as other constituents derived from the starting material may be more prevalent. For example, the first cannabinoid may be the major product in a reaction mixture that includes primarily unreacted first cannabinoid. [0063] In the context of the present disclosure, converting a first cannabinoid into primarily a second cannabinoid or into a mixture of a second cannabinoid and a third cannabinoid may involve the formation of additional cannabinoids which may or may not be isomers of the first cannabinoid ( i.e . a fourth cannabinoid, a fifth cannabinoid, etc.). In select embodiments, the additional cannabinoid is exo-tetrahydrocannabinol (exo-THC). In select embodiments, the amount of exo-THC is detectable by HPLC. In select embodiments, the formation of the additional cannabinoid exo-THC may be directly related to the

Brønsted-acidity of the Lewis-acid heterogeneous reagent. In the context of the present disclosure, exo-THC may have the following structure:

[0064] In the context of the present disclosure, a Lewis-acid heterogeneous reagent is one which: (i) comprises one or more sites that are capable of accepting an electron pair from an electron pair donor; and (ii) is substantially not mono-phasic with the reagent. Likewise, in the context of the present disclosure, a Brønsted-acid heterogeneous reagent is one which: (i) comprises one or more sites that are capable of donating a proton to a proton-acceptor; and (ii) is substantially not mono-phasic with the starting material and/or provides an interface where one or more chemical reaction takes place. Importantly, the term“reagent” is used in the present disclosure to encompass both reactant-type reactivity (i.e. wherein the reagent is at least partly consumed as reactant is converted to product) and catalyst-type reactivity (i.e. wherein the reagent is not substantially consumed as reactant is converted to product).

[0065] In the context of the present disclosure, the acidity of a Lewis-acid heterogeneous reagent and/or a Brønsted-acid heterogeneous reagent may be characterized by a variety of parameters, non-limiting examples of which are summarized in the following paragraphs.

[0066] As will be appreciated by those skilled in the art who have benefitted from the teachings of the present disclosure, determining the acidity of heterogeneous solid acids may be significantly more challenging than measuring the acidity of homogenous acids due to the complex molecular structure of heterogeneous solid acids. The Hammett acidity function (Ho) has been applied over the last 60 years to characterize the acidity of solid acids in non-aqueous solutions. This method utilizes organic indicator bases, known as Hammett indicators, which coordinate to the accessible acidic sites of the solid acid upon protonation. Typically, a color change is observed during titration with an additional organic base ( e.g . n-butylamine), which is measured by UV-visible spectroscopy to quantify acidity. Multiple Hammett indicators with pKa values ranging from +6.8 (e.g. neutral red) to -8.2 (e.g. anthraquinone) are tested with a given solid acid to determine the quantity and strength of acidic sites, which is typically expressed in mmol per gram of solid acid for each indicator. Hammett acidity values may not provide a complete characterization of acidity.

For example, accurate measurement of acidity may rely on the ability of the Hammett indicator to access the interior acidic sites within the solid acid. Some solid acids may have pore sizes that permit the passage of small molecules but prevent larger molecules from accessing the interior of the acid. H-ZSM-5 may be a representative example, wherein larger Hammett indicators such as anthraquinone may not be able to access interior acidic sites, which may lead to an incomplete measure of its total acidity.

[0067] Temperature-Programmed Desorption (TPD) is an alternate technique for characterizing the acidity of heterogeneous solid acids. This technique typically utilizes an organic base with small molecular size (e.g. ammonia, pyridine, n-propylamine), which may react with the acid sites on the exterior and interior of the solid acid in a closed system.

After the solid acid is substantially saturated with organic base, the temperature is increased and the change in organic base concentration is monitored gravimetrically, volumetrically, by gas chromatography, or by mass spectrometry. The amount of organic base desorbing from the solid acid above some characteristic temperature may be interpreted as the acid-site concentration. TPD is often considered more representative of total acidity for solid acids compared to the Hammett acidity function, because the selected organic base is small enough to bind to acidic sites on the interior of the solid acid. [0068] In select embodiments of the present disclosure, TPD values are reported with respect to ammonia. Those skilled in the art who have benefited from the teachings of the present disclosure will appreciate that ammonia may have the potential disadvantage of overestimating acidity, because its small molecular size enables access to acidic sites on the interior of the solid acid that are not accessible to typical organic substrates being employed for chemical reactions ( i. e . ammonia may fit into pores that a cannabinoid may not). Despite this disadvantage, TPD with ammonia is still considered a useful technique to compare total acidity of heterogeneous solid acids (larger NH₃ absorption values correlate with stronger acidity).

[0069] Another commonly used method for characterizing the acidity of

heterogeneous solid acids is microcalorimetry. In this technique, the heat of adsorption is measured when acidic sites on the solid acid are neutralized by addition of a base. The measured heat of adsorption is used to characterize the strength of Brønsted-acid sites (the larger the heat of adsorption, the stronger the acidic site, such that more negative values correlate with stronger acidity).

[0070] Microcalorimetry may provide the advantage of being a more direct method for the determination of acid strength when compared to TPD. However, the nature of the acidic sites cannot be determined by calorimetry alone, because adsorption may occur at Brønsted sites, Lewis sites, or a combination thereof. Further, experimentally determined heats of adsorption may be inconsistent in the literature for a given heterogeneous acid. For example, AH_0ads NH₃ values between about 100 kJ/mol and about 200 kJ/mol have been reported for H-ZSM-5. Thus, heats of adsorption determined by microcalorimetry may be best interpreted in combination with other acidity characterization methods such as TPD to properly characterize the acidity of solid heterogeneous acids.

[0071] Non-limiting examples of: (i) Hammett acidity values; (ii) TPD values with reference to ammonia; and (iii) microcalorimetry values with reference to ammonia, for a selection of Lewis-acidic heterogeneous reagents in accordance with the present disclosure are set out in TABLE 1. TABLE 1 : Non-limiting examples of: (i) Hammett acidity values; (ii) TPD values with reference to ammonia; and (iii) microcalorimetry values with reference to ammonia.

[0072] In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may have a Hammett-acidity value (H_o) of between about -8.0 and about 0.0. For example, the Lewis-acidic heterogeneous reagent may have a

Hammett-acidity value (H_o) of between: (i) about -8.0 and about -7.0; (ii) about -7.0 and about -6.0; (iii) about -6.0 and about -5.0; (iv) about -5.0 and about -4.0; (v) about -4.0 and about -3.0; (vi) about -3.0 and about -2.0; (vii) about -2.0 and about -1.0; or (viii) about -1.0 and about 0.

[0073] In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may have a temperature-programmed desorption value of between about 7.5 and about 0.0 as determined with reference to ammonia (TPD_NH3). For example, the Lewis-acidic heterogeneous reagent may have a temperature-programmed desorption value of between: (i) about 7.5 and about 6.5 as determined with reference to ammonia (TPD_NH3); (ii) about 6.5 and about 5.5 as determined with reference to ammonia (TPD_NH3); (iii) about 5.5 and about 4.5 as determined with reference to ammonia (TPD_NH3); (iv) about 4.5 and about 3.5 as determined with reference to ammonia (TPD_NH3); (V) about 3.5 and about 2.5 as determined with reference to ammonia (TPD_NH3); (vi) about 2.5 and about 1.5 as determined with reference to ammonia (TPD_NH3); (vii) about 1.5 and about 0.5 as determined with reference to ammonia (TPD_NH3); or (viii) about 0.5 and about 0.0 as determined with reference to ammonia (TPD_NH3).

[0074] In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may have a heat of absorption value of between about -165 and about -100 as determined with reference to ammonia (DH°_{ads NH3}). For example, the Lewis-acidic heterogeneous reagent may have a heat of absorption value of between: (i) about -165 and about -150 as determined with reference to ammonia (DH°_{ads NH3}); (ii) about -150 and about -135 as determined with reference to ammonia (DH°_{ads NH3}); (iii) about -135 and about -120 as determined with reference to ammonia (DH°_{ads NH3}); (iv) about -120 and about -105 as determined with reference to ammonia (DH°_{ads NH3}); or (v) about -105 and about -100 as determined with reference to ammonia (DH°_{ads NH3}).

[0075] In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may comprise an ion-exchange resin, a microporous silicate such as a zeolite (natural or synthetic), a mesoporous silicate (natural or synthetic) and/or a phyllosilicate (such as montmorillonite).

[0076] Lewis-acidic heterogeneous reagents that comprise an ion-exchange resin may comprise acidic functional groups linked to a backbone of the polymer. Lewis-acidic heterogeneous reagents that comprise an ion-exchange resin may comprise, for example, Amberlyst polymeric resins (also commonly referred to as“Amberlite” resins). Amberlyst polymeric resins include but are not limited to Amberlyst-15, 16, 31 , 33, 35, 36, 39, 46, 70, CH10, CH28, CH43, M-31 , wet forms, dry forms, macroreticular forms, gel forms, H⁺ forms, Na⁺ forms, or combinations thereof). In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may comprise an Amberlyst resin that has a surface area of between about 20 m²/g and about 80 m²/g. In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may comprise an Amberlyst resin that has an average pore diameter of between about 100 Å and about 500 Å. In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may comprise Amberlyst-15. Amberlyst-15 is a styrene-divinylbenzene-based polymer with sulfonic acid functional groups linked to the polymer backbone. Amberlyst-15 may have the following structural formula:

[0077] Lewis-acidic heterogeneous reagents that comprise an ion-exchange resin may comprise, for example, Nafion polymeric resins. Nafion polymeric resins may include but are not limited to Nafion-NR50, N 1 15, N1 17, N324, N424, N1 1 10, SAC-13, powder forms, resin forms, membrane forms, aqueous forms, dispersion forms, composite forms, H⁺ forms, Na⁺ forms, or combinations thereof.

[0078] Lewis-acidic heterogeneous reagents that comprise microporous silicates

(e.g. zeolites) may comprise, for example, natural and synthetic zeolites. Lewis-acidic heterogeneous reagents that comprise mesoporous silicates may comprise, for example, AI-MCM-41 and/or MCM-41 . Lewis-acidic heterogeneous reagents that comprise phyllosilicates may comprise, for example, montmorillonite. A commonality amongst these materials is that they are all silicates. Silicates may include but are not limited to AI-MCM- 41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, USY, Mordenite, Ferrierite,

Montmorillonite K10, K30, KSF, Clayzic, bentonite, H⁺ forms, Na⁺ forms, or combinations thereof. Zeolites are commonly used as adsorbents and catalysts (e.g. in fluid catalytic cracking and hydrocracking in the petrochemical industry). Although zeolites are abundant in nature, the zeolites used for commercial and industrial processes are often made synthetically. Their structural framework consists of SiO₄ and AIO₄- tetrahedra, which are combined in specific ratios with an amine or tetraalkylammonium salt“template” to give a zeolite with unique acidity, shape and pore size. The Lewis and/or Brønsted-Lowry acidity of zeolites can typically be modified using two approaches. One approach involves adjusting the Si/AI ratio. Since an AIO₄- moiety is unstable when attached to another AIO₄- unit, it is necessary for them to be separated by at least one SiO₄ unit. The strength of the individual acidic sites may increase as the AIO₄- units are further separated. Another approach involves cation exchange. Since zeolites contain charged AIO₄- species, an extraframework cation such as Na⁺ is required to maintain electroneutrality. The extra-framework cations can be replaced with protons to generate the“H-form” zeolite, which has stronger Brønsted acidity than its metal cation counterpart.

[0079] In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may comprise“H⁺-form” zeolites "Na⁺-form" zeolites, and/or a suitable mesoporous material. By way of non-limiting example, the acidic heterogeneous reagent may comprise AI-MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite,

USY, Mordenite, Ferrierite, Montmorillonite, Bentonite, or combinations thereof. Suitable mesoporous materials and zeolites may have a pore diameter ranging from about 0.1 nm to about 100 nm, particle sizes ranging from about 0.1 mm to about 50 mm, Si/AI ratio ranging from 5-1500, and any of the following cations: H⁺, Li⁺, Na⁺, K⁺, NH₄ ⁺ , Rb⁺, Cs⁺, Ag⁺.

Furthermore, suitable zeolites may have frameworks that are substituted with or coordinated to other atoms including, for example, titanium, copper, iron, cobalt, manganese, chromium, zinc, tin, zirconium, and gallium.

[0080] In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent is H-ZSM-5 (P-38 (Si/AI = 38), H⁺ form, ~5 angstrom pore size,

2 mm particle size), Na-ZSM-5 (P-38 (Si/AI = 38), Na⁺ form, ~5 angstrom pore size, 2 mm particle size), AI-MCM-41 (aluminum-doped Mobil Composition of Matter No. 41 ; e.g., P-25 (Si/AI = 25), 2.7 nm pore diameter), or combinations thereof.

[0081] In select embodiments of the present disclosure, the ZSM-5 has a silica to alumina ratio (molecular ratio, MR) that may be selected to control the second

cannabinoid:third cannabinoid ratio, the percent CBD conversion, or both.

[0082] In select embodiments of the present disclosure, the Lewis-acidic heterogeneous reagent may be acidic alumina. Acidic alumina is also known as activated alumina and is a highly porous aluminum oxide often used in chromatography separation of, for example, phenols, sulphonic acids, carboxylic acids and amino acids.

[0083] In embodiments where the Lewis-acidic heterogeneous reagent is acidic alumina, the method may further comprise adding an additive in an amount of about 1 % w/w to about 5% w/w. In some embodiments, the additive is added in an amount of about 3% w/w. In select embodiments, the additive is water, isopropanol, or a combination thereof. Without being bound by a particular theory, the addition of an additive may influence the second cannabinoid:third cannabinoid ratio.

[0084] In select embodiments of the present disclosure, a first cannabinoid is contacted with a Lewis-acidic reagent in a protic-solvent system. By way of non-limiting example a protic-solvent system may comprise methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, water, acetic acid, formic acid, 3-methyl-1-butanol, 2-methyl-1 - propanol, 1-pentanol, nitromethane, or a combination thereof.

[0085] In select embodiments of the present disclosure, a first cannabinoid is contacted with a Lewis-acidic reagent in an aprotic-solvent system. By way of non-limiting example an aprotic-solvent system may comprise dimethyl sulfoxide, ethyl acetate, dichloromethane, chloroform, toluene, pentane, heptane, hexane, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide,

N-methylpyrrolidone, anisole, butyl acetate, cumene, ethyl formate, isobutyl acetate, isopropyl acetate, methyl acetate, methylethylketone, methylisobutylketone, propyl acetate, cyclohexane, para-xylene, meta-xylene, ortho-xylene, 1 ,2-dichloroethane, or a combination thereof. As will be appreciated by those skilled in the art who have benefitted from the present disclosure, aprotic solvent systems may comprise small amounts of protic species, the quantities of which may be influenced by the extent to which drying and/or degassing procedures are employed.

[0086] In select embodiments, the methods of the present disclosure may be conducted in the presence of a class III solvent. Heptane, ethanol, and combinations thereof are non-limiting examples of class III solvents.

[0087] In select embodiments of the present disclosure, a first cannabinoid is contacted with a Lewis-acidic reagent under neat reaction conditions. As will be appreciated by those skilled in the art who have benefitted from the present disclosure, neat reaction conditions are substantially free of exogenous solvent.

[0088] In select embodiments of the present disclosure, a first cannabinoid is contacted with a Lewis-acidic reagent under reaction conditions characterized by: (i) a reaction temperature that is within a target reaction-temperature range for the particular Lewis-acidic heterogeneous reagent (and the particular solvent system where appropriate); and (ii) a reaction time that is within a target reaction-time range for the particular Lewis- acidic heterogeneous reagent, (the particular solvent system where appropriate) and the particular reaction temperature. As evidenced by the examples of the present disclosure, the acidity of the Lewis-acidic heterogeneous reagent (and the characteristics of the solvent system where appropriate) impact the target reaction-temperature range and the target reaction-time range. Without being bound to any particular theory, the examples of the present disclosure appear to indicate that protic-solvent systems, mild reaction

temperatures, and short reaction times tend to favour the formation of kinetic products, while aprotic solvent-systems or neat reaction conditions, increased reaction temperatures, and/or increased reaction times tend to favor thermodynamic product formation.

Importantly, these reaction parameters appear to be dependent variables in that altering one may impact the others. As such, each reaction temperature may be considered in reference to a target reaction-temperature range for the particular Lewis-acidic

heterogeneous reagent, (the particular solvent system where appropriate) and the particular reaction time associated with the reaction. Likewise, each reaction time in the present disclosure may be considered in reference to a target reaction-time range for the particular Lewis-acidic heterogeneous reagent, (the particular solvent system where appropriate) and the particular reaction temperature. With respect to reaction temperatures, by way of non-limiting example, methods of the present disclosure may involve reaction temperatures ranging from about 0 °C to about 200 °C. For example, methods of the present disclosure may involve reaction temperatures between: (i) about 5 °C and about 15 °C; (ii) about 15 °C and about 25 °C; (iii) about 25 °C and about 35 °C; (iv) about 35 °C and about 45 °C; (v) about 45 °C and about 55 °C; (vi) about 55 °C and about 65 °C; (vii) about 65 °C and about 75 °C; (viii) about 75 °C and about 85 °C; (ix) about 85 °C and about 95 °C; (x) about 95 °C and about 105 °C; (xi) about 105 °C and about 1 15 °C; or a combination thereof. Of course, the reaction temperature may be varied over the course of the reaction while still being characterized the one or more of the foregoing reaction temperatures. With respect to reaction times, by way of non-limiting example, methods of the present disclosure may involve reaction temperatures ranging from about 30 minutes to about 85 hours. For example, methods of the present disclosure may involve reaction times between: (i)

30 minutes and about 1 hour; (ii) about 1 hour and about 5 hours; (iii) about 5 hours and about 10 hours; (iv) about 10 hours and 25 hours; (v) about 25 hours and about 40 hours; (vi) about 40 hours and about 55 hours; (vii) about 55 hours and about 70 hours; or (viii) about 70 hours and about 85 hours.

[0089] In select embodiments, methods of the present disclosure may involve reactant concentrations ranging from about 0.001 M to about 2 M. For example methods of the present disclosure may involve reactant concentrations of: (i) between about 0.01 M and about 0.1 M; (ii) between about 0.1 M and about 0.5 M; (iii) between about 0.5 M and about 1.0 M; (iv) between about 1 .0 M and about 1 .5 M; or (v) between about 1.5 M and about 2.0 M.

[0090] In select embodiments, methods of the present disclosure may involve

Lewis-acidic heterogeneous reagent loadings ranges from about 0.1 molar equivalents to about 100 molar equivalents relative to the reactant. For example methods of the present disclosure may involve Lewis-acidic heterogeneous reagent loadings of: (i) between about 0.1 molar equivalents to about 1.0 molar equivalents, relative to the reactant; (ii) 1.0 molar equivalents to about 5.0 molar equivalents, relative to the reactant; (iii) 5.0 molar equivalents to about 10.0 molar equivalents, relative to the reactant; (iv) 10.0 molar equivalents to about 50.0 molar equivalents, relative to the reactant; or (v) 50.0 molar equivalents to about 100.0 molar equivalents, relative to the reactant.

[0091] In select embodiments, the methods of the present disclosure may further comprise a filtering step. By way of non-limiting example the filtering step may employ a fritted Buchner filtering funnel. Suitable filtering apparatus and protocols are within the purview of those skilled in the art.

[0092] In select embodiments, the methods of the present disclosure may further comprise a solvent evaporation step, and the solvent evaporation step may be executed under reduced pressure ( i.e . in vacuo) for example with a rotary evaporator. Suitable evaporating apparatus and protocols are within the purview of those skilled in the art.

[0093] In select embodiments, the methods of the present disclosure may further comprise a step of distillation. Without being bound by any particular theory, distillation may remove impurities and result in a composition comprising a total cannabinoid content about equal to the total cannabinoid content prior to undergoing one of the methods disclosed herein. Suitable distillation apparatus and protocols are within the purview of those skilled in the art.

EXEMPLARY EMBODIMENTS

[0094] (1 ) A method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second cannabinoid:third cannabinoid ratio of greater than 1.0: 1.0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) a protic-solvent system; (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the protic solvent; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the protic-solvent system.

[0095] (2) The method of (1 ), wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent.

[0096] (3) The method of (1 ) or (2), wherein the Lewis-acidic heterogeneous reagent has a Hammett-acidity value (Ho) of between about -8.0 and about 0.0.

[0097] (4) The method of any one of (1 ) to (3), wherein the Lewis-acidic heterogeneous reagent has a temperature-programmed desorption value of between about 7.5 and about 0.0 as determined with reference to ammonia (TPDNH3).

[0098] (5) The method of any one of (1 ) to (4), wherein the Lewis-acidic heterogeneous reagent has a heat of absorption value of between about -165 and about -100 as determined with reference to ammonia (DHoads NH3).

[0099] (6) The method of (1 ), wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

[00100] (7) The method of (6), wherein the ion-exchange resin is an Amberlyst polymeric resin. [00101 ] (8) The method of (7), wherein the Amberlyst polymeric resin has a surface area of between about 20 m2/g and about 80 m2/g and an average pore diameter of between about 100 Å and about 500 Å.

[00102] (9) The method of (7) or (8), wherein the Amberlyst polymeric resin comprises Amberlyst 15.

[00103] (10) The method of (6), wherein the ion-exchange resin is a Nafion polymeric resin.

[00104] (1 1 ) The method of (10), wherein the Nafion polymeric resin comprises

NR50, N1 15, N1 17, N324, N424, N1 1 10, SAC-13, or a combination thereof.

[00105] (12) The method of (6), wherein the Lewis-acidic heterogeneous reagent is Al MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof.

[00106] (13) The method of (12), wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about 0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof.

[00107] (14) The method of (12) or (13), wherein the Lewis-acidic heterogeneous reagent is H-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00108] (15) The method of (12) or (13), wherein the Lewis-acidic heterogeneous reagent is Na-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00109] (16) The method of (12) or (13), wherein the Lewis-acidic heterogeneous reagent is AI-MCM-41 with a Si/AI ratio of about 25, and a pore diameter of about 2.7 nm. [00110] (17) The method of any one of (1 ) to (16), wherein the protic-solvent system comprises a class III solvent.

[00111 ] (18) The method of (17), wherein the class III solvent is ethanol.

[00112] (19) The method of any one of (1 ) to (18), wherein prior to being converted to the composition comprising the second cannabinoid and the third cannabinoid, the first cannabinoid is dissolved in the protic-solvent system at a concentration between about 0.001 M and about 2 M.

[00113] (20) The method of any one of (1 ) to (19), wherein the target

reaction-temperature range is between about 20 °C and about 100 °C. [00114] (21 ) The method of any one of (1 ) to (20), wherein the target reaction-time range is between about 10 minutes and about 72 hours.

[00115] (22) The method of any one of (1 ) to (21 ), wherein the Lewis-acidic heterogeneous reagent has a reagent loading between about 0.1 molar equivalents and about 100 molar equivalents relative to the first cannabinoid. [00116] (23) The method of any one of (1 ) to (22), further comprising isolating the composition from the Lewis-acidic heterogeneous reagent by a solid-liquid separation technique.

[00117] (24) The method of (23), wherein the solid-liquid separation technique comprises filtration, decantation, centrifugation, or a combination thereof. [00118] (25) The method of any one of (1 ) to (24), wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof.

[00119] (26) The method of (25), wherein the extract is a crude extract from hemp.

[00120] (27) The method of any one of (1 ) to (26), wherein the second

cannabinoid:third cannabinoid ratio of the composition is greater than about 3.0: 1.0. [00121 ] (28) The method of any one of (1 ) to (26), wherein the second

cannabinoid:third cannabinoid ratio of the composition is greater than about 6.0: 1.0. [00122] (29) The method of any one of (1 ) to (26), wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 20.0: 1.0.

[00123] (30) A method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second cannabinoid:third cannabinoid ratio of greater than 1.0: 1.0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) an aprotic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system.

[00124] (31 ) The method of (30), wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent.

[00125] (32) The method of (30) or (31 ), wherein the Lewis-acidic heterogeneous reagent has a Hammett-acidity value (Ho) of between about -8.0 and about 0.0.

[00126] (33) The method of any one of (30) to (32), wherein the Lewis-acidic heterogeneous reagent has a temperature-programmed desorption value of between about 7.5 and about 0.0 as determined with reference to ammonia (TPDNH3).

[00127] (34) The method of any one of (30) to (33), wherein the Lewis-acidic heterogeneous reagent has a heat of absorption value of between about -165 and about -100 as determined with reference to ammonia (DHoads NH3).

[00128] (35) The method of (30), wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

[00129] (36) The method of (35), wherein the ion-exchange resin is an Amberlyst polymeric resin. [00130] (37) The method of (36), wherein the Amberlyst polymeric resin has a surface area of between about 20 m2/g and about 80 m2/g and an average pore diameter of between about 100 Å and about 500 Å.

[00131 ] (38) The method of (36) or (37), wherein the Amberlyst polymeric resin comprises Amberlyst 15.

[00132] (39) The method of (35), wherein the ion-exchange resin is a Nafion polymeric resin.

[00133] (40) The method of (39), wherein the Nafion polymeric resin comprises

NR50, N1 15, N1 17, N324, N424, N1 1 10, SAC-13, or a combination thereof.

[00134] (41 ) The method of (35), wherein the Lewis-acidic heterogeneous reagent is Al MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof.

[00135] (42) The method of (41 ), wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about 0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof.

[00136] (43) The method of (41 ) or (42), wherein the Lewis-acidic heterogeneous reagent is H-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00137] (44) The method of (41 ) or (42), wherein the Lewis-acidic heterogeneous reagent is Na-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00138] (45) The method of (41 ) or (42), wherein the Lewis-acidic heterogeneous reagent is AI-MCM-41 with a Si/AI ratio of about 25, and a pore diameter of about 2.7 nm. [00139] (46) The method of any one of (30) to (45), wherein the aprotic-solvent system comprises a class III solvent.

[00140] (47) The method of (46), wherein the class III solvent is heptane.

[00141 ] (48) The method of any one of (30) to (47), wherein prior to being converted to the composition comprising the second cannabinoid and the third cannabinoid, the first cannabinoid is dissolved in the aprotic-solvent system at a concentration between about 0.001 M and about 2 M.

[00142] (49) The method of any one of (30) to (48), wherein the target reaction-temperature range is between about 20 °C and about 100 °C. [00143] (50) The method of any one of (30) to (49), wherein the target reaction-time range is between about 10 minutes and about 72 hours.

[00144] (51 ) The method of any one of (30) to (50), wherein the Lewis-acidic heterogeneous reagent has a reagent loading between about 0.1 molar equivalents and about 100 molar equivalents relative to the first cannabinoid. [00145] (52) The method of any one of (30) to (51 ), further comprising isolating the composition from the Lewis-acidic heterogeneous reagent by a solid-liquid separation technique.

[00146] (53) The method of (52), wherein the solid-liquid separation technique comprises filtration, decantation, centrifugation, or a combination thereof. [00147] (54) The method of any one of (30) to (53), wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof.

[00148] (55) The method of (54), wherein the extract is a crude extract from hemp.

[00149] (56) The method of any one of (30) to (55), wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 3.0: 1.0. [00150] (57) The method of any one of (30) to (55), wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 6.0: 1.0.

[00151 ] (58) The method of any one of (30) to (55), wherein the second cannabinoid :third cannabinoid of the composition is greater than about 20.0: 1.0. [00152] (59) A method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid, wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second cannabinoid:third cannabinoid ratio that is greater than 1.0: 1.0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under neat reaction conditions comprising: (i) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent; and (ii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the reaction temperature.

[00153] (60) The method of (59), wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent.

[00154] (61 ) The method of (59) or (60), wherein the Lewis-acidic heterogeneous reagent has a Hammett-acidity value (Ho) of between about -8.0 and about 0.0.

[00155] (62) The method of any one of (59) to (61 ), wherein the Lewis-acidic heterogeneous reagent has a temperature-programmed desorption value of between about 7.5 and about 0.0 as determined with reference to ammonia (TPDNH3).

[00156] (63) The method of any one of (59) to (62), wherein the Lewis-acidic heterogeneous reagent has a heat of absorption value of between about -165 and about -100 as determined with reference to ammonia (DHoads NH3).

[00157] (64) The method of (59), wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

[00158] (65) The method of (64), wherein the ion-exchange resin is an Amberlyst polymeric resin. [00159] (66) The method of (65), wherein the Amberlyst polymeric resin has a surface area of between about 20 m2/g and about 80 m2/g and an average pore diameter of between about 100 Å and about 500 Å.

[00160] (67) The method of (65) or (66), wherein the Amberlyst polymeric resin comprises Amberlyst 15.

[00161 ] (68) The method of (64), wherein the ion-exchange resin is a Nafion polymeric resin.

[00162] (69) The method of (68), wherein the Nafion polymeric resin comprises

NR50, N1 15, N1 17, N324, N424, N1 1 10, SAC-13, or a combination thereof.

[00163] (70) The method of (64), wherein the Lewis-acidic heterogeneous reagent is Al MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof.

[00164] (71 ) The method of (70), wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about 0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof.

[00165] (72) The method of (70) or (71 ), wherein the Lewis-acidic heterogeneous reagent is H-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00166] (73) The method of (70) or (71 ), wherein the Lewis-acidic heterogeneous reagent is Na-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00167] (74) The method of (70) or (71 ), wherein the Lewis-acidic heterogeneous reagent is AI-MCM-41 with a Si/AI ratio of about 25, and a pore diameter of about 2.7 nm. [00168] (75) The method of any one of (59) to (74), wherein the target reaction-temperature range is between about 20 °C and about 100 °C.

[00169] (76) The method of any one of (59) to (75), wherein the target reaction-time range is between about 10 minutes and about 72 hours.

[00170] (77) The method of any one of (59) to (76), wherein the Lewis-acidic heterogeneous reagent has a reagent loading between about 0.1 molar equivalents and about 100 molar equivalents relative to the first cannabinoid.

[00171 ] (78) The method of any one of (59) to (77), wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof.

[00172] (79) The method of (78), wherein the extract is a crude extract from hemp.

[00173] (80) The method of any one of (59) to (79), wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 3.0: 1.0.

[00174] (81 ) The method of any one of (59) to (79), wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 6.0: 1.0.

[00175] (82) The method of any one of (59) to (79), wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 20.0: 1.0.

[00176] (83) A method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) a protic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the protic- solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the protic-solvent system.

[00177] (84) The method of (83), wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent. [00178] (85) The method of (83) or (84), wherein the Lewis-acidic heterogeneous reagent has a Hammett-acidity value (Ho) of between about -8.0 and about 0.0.

[00179] (86) The method of any one of (83) to (85), wherein the Lewis-acidic heterogeneous reagent has a temperature-programmed desorption value of between about 7.5 and about 0.0 as determined with reference to ammonia (TPDNH3).

[00180] (87) The method of any one of (83) to (86), wherein the Lewis-acidic heterogeneous reagent has a heat of absorption value of between about -165 and about -100 as determined with reference to ammonia (DHoads NH3).

[00181 ] (88) The method of (83), wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

[00182] (89) The method of (88), wherein the ion-exchange resin is an Amberlyst polymeric resin.

[00183] (90) The method of (89), wherein the Amberlyst polymeric resin has a surface area of between about 20 m2/g and about 80 m2/g and an average pore diameter of between about 100 Å and about 500 Å.

[00184] (91 ) The method of (89) or (90), wherein the Amberlyst ion-exchange resin comprises Amberlyst 15.

[00185] (92) The method of (88), wherein the ion-exchange resin is a Nafion polymeric resin.

[00186] (93) The method of (92), wherein the Nafion polymeric resin comprises

NR50, N1 15, N1 17, N324, N424, N1 1 10, SAC-13, or a combination thereof.

[00187] (94) The method of (88), wherein the Lewis-acidic heterogeneous reagent is Al MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof. [00188] (95) The method of (94), wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about 0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof. [00189] (96) The method of (94) or (95), wherein the Lewis-acidic heterogeneous reagent is H-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00190] (97) The method of (94) or (95), wherein the Lewis-acidic heterogeneous reagent is Na-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00191 ] (98) The method of 94 or 95, wherein the Lewis-acidic heterogeneous reagent is AI-MCM-41 with a Si/AI ratio of about 25, and a pore diameter of about 2.7 nm.

[00192] (99) The method of any one of (83) to (98), wherein the protic-solvent system comprises a class III solvent. [00193] (100) The method of (99), wherein the class III solvent is ethanol.

[00194] (101 ) The method of any one of (83) to (100), wherein prior to being converted to the second cannabinoid, the first cannabinoid is dissolved in the protic-solvent system at a concentration between about 0.001 M and about 2 M.

[00195] (102) The method of any one of (83) to (101 ), wherein the target reaction-temperature range is between about 20 °C and about 100 °C.

[00196] (103) The method of any one of (83) to (102), wherein the target reaction-time range is between about 10 minutes and about 72 hours.

[00197] (104) The method of any one of (83) to (103), wherein the Lewis-acidic heterogeneous reagent has a reagent loading between about 0.1 molar equivalents and about 100 molar equivalents relative to the first cannabinoid. [00198] (105) The method of any one of (83) to (104), further comprising isolating the second cannabinoid from the Lewis-acidic heterogeneous reagent by a solid-liquid separation technique.

[00199] (106) The method of (105), wherein the solid-liquid separation technique comprises filtration, decantation, centrifugation, or a combination thereof.

[00200] (107) The method of any one of (83) to (106), wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof.

[00201 ] (108) The method of (107), wherein the extract is a crude extract from hemp.

[00202] (109) A method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) an aprotic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system.

[00203] (1 10) The method of (109), wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent.

[00204] (1 1 1 ) The method of (109) or (1 10), wherein the Lewis-acidic

heterogeneous reagent has a Hammett-acidity value (Ho) of between about -8.0 and about 0.0.

[00205] (1 12) The method of any one of (109) to (1 1 1 ), wherein the Lewis-acidic heterogeneous reagent has a temperature-programmed desorption value of between about 7.5 and about 0.0 as determined with reference to ammonia (TPDNH3).

[00206] (1 13) The method of any one of (109) to (1 12), wherein the Lewis-acidic heterogeneous reagent has a heat of absorption value of between about -165 and about -100 as determined with reference to ammonia (DHoads NH3). [00207] (1 14) The method of (109), wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

[00208] (1 15) The method of (1 14), wherein the ion-exchange resin is an Amberlyst polymeric resin.

[00209] (1 16) The method of (1 15), wherein the Amberlyst polymeric resin has a surface area of between about 20 m2/g and about 80 m2/g and an average pore diameter of between about 100 Å and about 500 Å.

[00210] (1 17) The method of (1 15) or (1 16), wherein the Amberlyst polymeric resin comprises Amberlyst 15.

[00211 ] (1 18) The method of (1 14), wherein the ion-exchange resin is a Nafion polymeric resin.

[00212] (1 19) The method of (1 18), wherein the Nafion polymeric resin comprises

NR50, N1 15, N1 17, N324, N424, N1 1 10, SAC-13, or a combination thereof.

[00213] (120) The method of (1 14), wherein the Lewis-acidic heterogeneous reagent is Al MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof.

[00214] (121 ) The method of (120), wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about 0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof.

[00215] (122) The method of (120) or (121 ), wherein the Lewis-acidic

heterogeneous reagent is H-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm. [00216] (123) The method of (120) or (121 ), wherein the Lewis-acidic

heterogeneous reagent is Na-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00217] (124) The method of (120) or (121 ), wherein the Lewis-acidic

heterogeneous reagent is AI-MCM-41 with a Si/AI ratio of about 25, and a pore diameter of about 2.7 nm.

[00218] (125) The method of any one of (109) to (124), wherein the aprotic-solvent system comprises a class III solvent.

[00219] (126) The method of (125), wherein the class I II solvent is heptane.

[00220] (127) The method of any one of (109) to (126), wherein prior to being converted to the second cannabinoid, the first cannabinoid is dissolved in the

aprotic-solvent system at a concentration between about 0.001 M and about 2 M.

[00221 ] (128) The method of any one of (109) to (127), wherein the target reaction-temperature range is between about 20 °C and about 100 °C.

[00222] (129) The method of any one of (109) to (128), wherein the target reaction-time range is between about 10 minutes and about 72 hours.

[00223] (130) The method of any one of (109) to (129), wherein the Lewis-acidic heterogeneous reagent has a reagent loading between about 0.1 molar equivalents and about 100 molar equivalents relative to the first cannabinoid.

[00224] (131 ) The method of any one of (109) to (130), further comprising isolating the second cannabinoid from the Lewis-acidic heterogeneous reagent by a solid-liquid separation technique.

[00225] (132) The method of (131 ), wherein the solid-liquid separation technique comprises filtration, decantation, centrifugation, or a combination thereof.

[00226] (133) The method of any one of (109) to (132), wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof. [00227] (134) The method of (133), wherein the extract is a crude extract from hemp.

[00228] (135) A method for converting a first cannabinoid into primarily a second cannabinoid that is an isomer of the first cannabinoid, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under neat reaction conditions comprising: (i) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent; and (ii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the reaction temperature. [00229] (136) The method of (135), wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent.

[00230] (137) The method of (135) or (136), wherein the Lewis-acidic

heterogeneous reagent has a Hammett-acidity value (Ho) of between about -8.0 and about 0.0. [00231 ] (138) The method of any one of (135) to (137), wherein the Lewis-acidic heterogeneous reagent has a temperature-programmed desorption value of between about 7.5 and about 0.0 as determined with reference to ammonia (TPDNH3).

[00232] (139) The method of any one of (135) to (138), wherein the Lewis-acidic heterogeneous reagent has a heat of absorption value of between about -165 and about -100 as determined with reference to ammonia (DHoads NH3).

[00233] (140) The method of (135), wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

[00234] (141 ) The method of (140), wherein the ion-exchange resin is an Amberlyst polymeric resin.

[00235] (142) The method of (141 ), wherein the Amberlyst polymeric resin has a surface area of between about 20 m2/g and about 80 m2/g and an average pore diameter of between about 100 Å and about 500 Å. [00236] (143) The method of (141 ) or (142), wherein the Amberlyst polymeric resin comprises Amberlyst 15.

[00237] (144) The method of (140), wherein the ion-exchange resin is a Nafion polymeric resin.

[00238] (145) The method of (144), wherein the Nafion polymeric resin comprises

NR50, N1 15, N1 17, N324, N424, N1 1 10, SAC-13, or a combination thereof.

[00239] (146) The method of (140), wherein the Lewis-acidic heterogeneous reagent is Al MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof.

[00240] (147) The method of (146), wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about 0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof.

[00241 ] (148) The method of (146) or (147), wherein the Lewis-acidic

heterogeneous reagent is H-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

[00242] (149) The method of (146) or (147), wherein the Lewis-acidic

[00243] (150) The method of (146) or (147), wherein the Lewis-acidic

[00244] (151 ) The method of any one of (135) to (150), wherein the target reaction-temperature range is between about 20 °C and about 100 °C. [00245] (152) The method of any one of (135) to (151 ), wherein the target reaction-time range is between about 10 minutes and about 72 hours.

[00246] (153) The method of any one of (135) to (152), wherein the Lewis-acidic heterogeneous reagent has a reagent loading between about 0.1 molar equivalents and about 100 molar equivalents relative to the first cannabinoid.

[00247] (154) The method of any one of (135) to (153), wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof.

[00248] (155) The method of (154), wherein the extract is a crude extract from hemp.

EXAMPLES

[00249] EXAMPLE 1 : For this reaction, the first cannabinoid is CBD and the second cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added Amberlyst-15 (100 mg). The reaction was stirred at room temperature for 24 hours. The reaction was filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed near complete consumption of the first cannabinoid (<1 % remained) with the second cannabinoid as the major product (see, TABLE 2 and FIG. 1 ).

[00250] EXAMPLE 2: For this reaction, the first cannabinoid is CBD and the second cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added Amberlyst-15 (500 mg). The reaction was stirred at 60°C for 2 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed near complete consumption of the first cannabinoid (<0.2% remained) with the second cannabinoid as the major product (see, TABLE 2 and FIG. 2).

[00251] EXAMPLE 3: For this reaction, the first cannabinoid is CBD and the second cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added Amberlyst-15 (500 mg). The reaction was stirred at reflux for 2 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed complete consumption of the first cannabinoid with the second cannabinoid as the major product (see, TABLE 2 and FIG. 3).

[00252] EXAMPLE 4: For this reaction, the first cannabinoid is CBD and the second cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added Amberlyst-15 (500 mg). The reaction was stirred at 80°C for 2 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed near complete consumption of CBD (<2% remained) with the second cannabinoid as the major product (see, TABLE 2 and FIG. 4).

[00253] EXAMPLE 5: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁸-THC, and the third cannabinoid is D⁹-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added Amberlyst-15 (500 mg). The reaction was stirred at room temperature for 2 hours. The reaction was filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed near complete consumption of the first cannabinoid (<1% remained) with the second cannabinoid as the major product and the third cannabinoid as a minor product (see, TABLE 2 and FIG. 5).

[00254] EXAMPLE 6: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁸-THC, and the third cannabinoid is D⁹-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added Amberlyst-15 (50 mg).

The reaction was stirred at room temperature for 24 hours. The reaction was filtered using a fritted Buchner filtering funnel and the reaction solvent was evaporated in vacuo. Analysis by HPLC showed unreacted first cannabinoid (<12% remained) with the second cannabinoid as the major product and the third cannabinoid as a minor product (see, TABLE 2 and FIG. 6).

[00255] EXAMPLE 7: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁹-THC, and the third cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in ethanol (10 mL) was added Amberlyst-15 (500 mg). The reaction was stirred at reflux for 2 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed unreacted first cannabinoid (>35% remained) with the second cannabinoid as the major product and the third cannabinoid as a minor product. (see, TABLE 2 and FIG. 7).

[00256] EXAMPLE 8: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added AI-MCM-41 (1 g, ACS Material). The reaction was stirred at reflux for 18 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed complete consumption of the first cannabinoid with the second cannabinoid as the major product (see, TABLE 2 and FIG. 8).

[00257] EXAMPLE 9: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁸-THC, the third cannabinoid is D⁹-THC, and the fourth cannabinoid is cannabinol (CBN). A mixture of the first cannabinoid (500 mg, 1 .59 mmol) and ZSM-5 (1g, ACS Material, P-38, H+) were heated without solvent at 100°C for 18 hours. The reaction was cooled to room temperature and then diluted with 30mL of TBME. The resulting suspension was filtered using a fritted Buchner filtering funnel. The solvent from the filtrate was evaporated in vacuo. Analysis by HPLC showed complete consumption of the first cannabinoid with the second cannabinoid as the major product and the third cannabinoid and the fourth cannabinoid as minor products. (see, TABLE 2 and FIG. 9).

[00258] EXAMPLE 10: For this reaction, the first cannabinoid is CBD and the second cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added ZSM-5 (1g, ACS Material, P-38, Na+). The reaction was stirred at reflux for 18 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed complete consumption of the first cannabinoid with the second cannabinoid as the major product (see, TABLE 2 and FIG. 10).

[00259] EXAMPLE 11 : For this reaction, the first cannabinoid is CBD and the second cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL ) was added ZSM-5 (1g, ACS Material, P-38, H+). The reaction was stirred at reflux for 2 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed complete consumption of the first cannabinoid with the second cannabinoid as the major product. (see, TABLE 2 and FIG. 11 ).

[00260] EXAMPLE 12: For this reaction, the first cannabinoid is CBD and the second cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added ZSM-5 (1g, ACS Material, P-38, H+). The reaction was stirred at reflux for 18 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed complete consumption of the first cannabinoid with the second cannabinoid as the major product. (see, TABLE 2 and FIG. 12).

[00261 ] EXAMPLE 13: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁸-THC, and the third cannabinoid is D⁹-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added ZSM-5 (1 g, ACS Material, P-38, H+). The reaction was stirred at 80°C for 18 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed near complete consumption of the first cannabinoid (<2% remained) with a mixture of the second cannabinoid and the third cannabinoid as the major products (see, TABLE 2 and FIG. 13).

[00262] EXAMPLE 14: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁸-THC, and the third cannabinoid is D⁹-THC. A mixture of the first cannabinoid (500 mg, 1.59 mmol) and ZSM-5 (1g, ACS Material, P-38, H+) were heated without solvent at 100°C for 30 minutes. The reaction was cooled to room temperature and then diluted with 30mL of TBME. The resulting suspension was filtered using a fritted Buchner filtering funnel. The solvent from the filtrate was evaporated in vacuo. Analysis by HPLC showed unreacted first cannabinoid (>45% remained) with the second cannabinoid and the third cannabinoid as the major products (see, TABLE 2 and FIG. 14).

[00263] EXAMPLE 15: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁸-THC, and the third cannabinoid is D⁹-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in ethanol (10 mL) was added ZSM-5 (1g, ACS Material, P-38, H+). The reaction was stirred at reflux for 18 hours. The reaction was cooled to room temperature and then filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed unreacted first cannabinoid (>50% remained) with the second cannabinoid and the third cannabinoid as the major products (see, TABLE 2 and FIG. 15).

[00264] EXAMPLE 16: For this reaction, the first cannabinoid is CBD, the second cannabinoid is D⁹-THC, and the third cannabinoid is D⁸-THC. To a solution of the first cannabinoid (500 mg, 1.59 mmol) in heptane (10 mL) was added ZSM-5 (1 g, ACS Material, P-38, H+). The reaction was stirred at 60°C for 18 hours. The reaction was cooled to room temperature and was filtered using a fritted Buchner filtering funnel. The reaction solvent was evaporated in vacuo. Analysis by HPLC showed unreacted first cannabinoid (>49% remained) with the second cannabinoid and the third cannabinoid as the major products (see, TABLE 2 and FIG. 16)

[00265] EXAMPLE 17: For this reaction, the first cannabinoid is D⁹-THC, and the second cannabinoid is D⁸-THC. To a solution of first cannabinoid-rich cannabis extract (500 mg, -80% w/w first cannabinoid, 0% w/w second cannabinoid) in heptane (10 mL) was added Amberlyst-15 (500 mg). The reaction was stirred at reflux for 18 hours. The reaction was filtered using a fritted Buchner filtering funnel and then the reaction solvent was evaporated in vacuo. Analysis by HPLC showed near complete consumption of the first cannabinoid (<3% remaining) with the second cannabinoid as the major product (see, TABLE 2 and FIG. 17).

[00266] EXAMPLE 18: For this reaction, the first cannabinoid is D⁹-THC, and the second cannabinoid is D⁸-THC. To a solution of first cannabinoid-rich cannabis extract (500 mg, -80% w/w first cannabinoid, 0% w/w second cannabinoid) in heptane (10 mL) was added Amberlyst-15 (500 mg). The reaction was stirred at room temperature for 18 hours. The reaction was filtered using a fritted Buchner filtering funnel and then the reaction solvent was evaporated in vacuo. Analysis by HPLC showed near complete consumption of the first cannabinoid (<3% remaining) with the second cannabinoid as the major product (see, TABLE 2 and FIG. 17). TABLE 2: HPLC results from EXAMPLES 1 -18. Percentage values for CBD, D⁸-THC and D⁹-THC were determined by HPLC-DAD (215 nm).

[00267] EXAMPLE 19: For this Example, the first cannabinoid is CBD, the second cannabinoid is D⁹-THC, and the third cannabinoid is D⁸-THC. The effect of the silica to alumina ratio (molecular ratio, MR). in the ZSM-5 catalyst on the D⁹-THC:D⁸-THC ratio was studied.

[00268] To a solution of CBD isolate (500 mg, 1.59 mmol) in heptane (10 mL) was added ZSM-5 (500 mg; 100% mass equivalent; MeQ). The reaction was stirred at 100 °C for 2 hours. The reaction was cooled to room temperature, filtered , and the reaction solvent was evaporated in vacuo. As shown in FIG. 19, increasing the alumina sites provided a higher CBD conversion (FIG. 19A) but lower D⁹-THC:D⁸-THC ratio under the reaction conditions used (FIG. 19B).

[00269] Example 20: For this Example, the first cannabinoid is CBD, the second cannabinoid is D⁹-THC, and the third cannabinoid is D⁸-THC. A mixture of CBD isolate (500 mg, 1.59 mmol) and acidic alumina (500 mg; 100% MeQ) in heptane (10 mL) was stirred at 110 °C for 24 h. The reaction was cooled to room temperature, diluted with of TBME, filtered and the reaction solvent was evaporated in vacuo. Analysis by HPLC showed D⁹-THC as the major product.

[00270] Example 21 : For this Example, the first cannabinoid is CBD, the second cannabinoid is D⁹-THC, and the third cannabinoid is D⁸-THC. Experiments were performed to study the effect of additives on CBD conversion. The reactions were performed using the procedure described in Example 20, with the inclusion of an additive in the reaction mixture and using a reaction temperature of 100 °C. Water, isopropyl alcohol and butylated hydroxyanisole (BHA) were each studied as additives at 3 w/w%. As shown in FIG. 20A, the addition of water resulted in a small amount of CBD remaining while isopropyl alcohol moderately reduced conversion and BHA completed prevented the conversion under the reaction conditions tested (FIG 20B).

[00271] Example 22: For this reaction, the first cannabinoid is CBD and the second cannabinoid is D⁸-THC. To a solution of CBD distillate (1.030 g) in heptane (20 mL) was added AI-MCM-41 (1.004 g). The reaction was heated in an oil bath at 65 °C with stirring. After 24 h, the reaction was removed from the oil bath and centrifuged. The catalyst was washed and supernatant was added to the washing. The combined solution was concentered, filtered and evaporated to dryness. Analysis by HPLC showed near complete conversion (<1% remaining) with the major product being D⁸-THC (see Table 3 and

FIG. 21 ). It is believed that the 3% difference between starting and final cannabinoid content can be attributed to tetrahydrocannabivarin (THCV). [00272] TABLE 3: HPLC results from EXAMPLE 22. Percentage values for CBD, D⁸-THC and D⁹-THC were determined by HPLC-DAD (215 nm).

[00273] In the present disclosure, all terms referred to in singular form are meant to encompass plural forms of the same. Likewise, all terms referred to in plural form are meant to encompass singular forms of the same. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[00274] As used herein, the term“about” refers to an approximately +/-10 % variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to.

[00275] It should be understood that the compositions and methods are described in terms of "comprising," "containing," or "including" various components or steps, the compositions and methods can also "consist essentially of or "consist of the various components and steps. Moreover, the indefinite articles "a" or "an," as used in the claims, are defined herein to mean one or more than one of the element that it introduces. [00276] For the sake of brevity, only certain ranges are explicitly disclosed herein. However, ranges from any lower limit may be combined with any upper limit to recite a range not explicitly recited, as well as, ranges from any lower limit may be combined with any other lower limit to recite a range not explicitly recited, in the same way, ranges from any upper limit may be combined with any other upper limit to recite a range not explicitly recited. Additionally, whenever a numerical range with a lower limit and an upper limit is disclosed, any number and any included range falling within the range are specifically disclosed. In particular, every range of values (of the form, "from about a to about b," or, equivalently, "from approximately a to b," or, equivalently, "from approximately a-b") disclosed herein is to be understood to set forth every number and range encompassed within the broader range of values even if not explicitly recited. Thus, every point or individual value may serve as its own lower or upper limit combined with any other point or individual value or any other lower or upper limit, to recite a range not explicitly recited.

[00277] Therefore, the present disclosure is well adapted to attain the ends and advantages mentioned as well as those that are inherent therein. The particular embodiments disclosed above are illustrative only, as the present disclosure may be modified and practiced in different but equivalent manners apparent to those skilled in the art having the benefit of the teachings herein. Although individual embodiments are dis-cussed, the disclosure covers all combinations of all those embodiments. Furthermore, no limitations are intended to the details of construction or design herein shown, other than as described in the claims below. Also, the terms in the claims have their plain, ordinary meaning unless otherwise explicitly and clearly defined by the patentee. It is therefore evident that the particular illustrative embodiments disclosed above may be altered or modified and all such variations are considered within the scope and spirit of the present disclosure. If there is any conflict in the usages of a word or term in this specification and one or more patent(s) or other documents that may be incorporated herein by reference, the definitions that are consistent with this specification should be adopted.

[00278] Many obvious variations of the embodiments set out herein will suggest themselves to those skilled in the art in light of the present disclosure. Such obvious variations are within the full intended scope of the appended claims.

Claims

Claims:

1. A method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second cannabinoid :third cannabinoid ratio of greater than 1.0: 1 .0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) a protic-solvent system; (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the protic solvent; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the protic-solvent system.

2. The method of claim 1 , wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent.

3. The method of claim 1 or 2, wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

4. The method of claim 3, wherein the ion-exchange resin is an Amberlyst polymeric resin.

5. The method of claim 4, wherein the Amberlyst polymeric resin has a surface area of between about 20 m²/g and about 80 m²/g and an average pore diameter of between about 100 Å and about 500 Å.

6. The method of claim 4 or 5, wherein the Amberlyst polymeric resin comprises Amberlyst 15.

7. The method of claim 3, wherein the Lewis-acidic heterogeneous reagent is AI-MCM- 41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof.

8. The method of claim 7, wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about

0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof.

9. The method of claim 7 or 8, wherein the Lewis-acidic heterogeneous reagent is H- ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

10. The method of claim 7 or 8, wherein the Lewis-acidic heterogeneous reagent is Na- ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

1 1 . The method of claim 7 or 8, wherein the Lewis-acidic heterogeneous reagent is Al- MCM-41 with a Si/AI ratio of about 25, and a pore diameter of about 2.7 nm.

12. The method of claim 1 , wherein the Lewis-acidic heterogeneous reagent is acidic alumina.

13. The method of claim 12, further comprising contacting the first cannabinoid and the acidic alumina with an additive.

14. The method of claim 13, wherein the additive is water, isopropyl alcohol, or a combination thereof.

15. The method of any one of claims 1 to 14, wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof.

16. The method of claim 14, wherein the extract is a crude extract from hemp.

17. The method of any one of claims 1 to 16, wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 6.0:1 .0.

18. The method of any one of claims 1 to 16, wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 20.0: 1.0.

19. The method of any one of claims 1 to 16, wherein the composition comprises primarily the second cannabinoid.

20. A method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second cannabinoid :third cannabinoid ratio of greater than 1.0: 1 .0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under reaction conditions comprising: (i) an aprotic-solvent system (ii) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system; and (iii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the aprotic-solvent system.

21 . The method of claim 20, wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent.

22. The method of claim 20 or 21 , wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

23. The method of claim 22, wherein the ion-exchange resin is an Amberlyst polymeric resin.

24. The method of claim 23, wherein the Amberlyst polymeric resin has a surface area of between about 20 m²/g and about 80 m²/g and an average pore diameter of between about 100 Å and about 500 Å.

25. The method of claim 23 or 24, wherein the Amberlyst polymeric resin comprises Amberlyst 15.

26. The method of claim 22, wherein the Lewis-acidic heterogeneous reagent is AI-MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof.

27. The method of claim 26, wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about 0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof.

28. The method of claim 26 or 27, wherein the Lewis-acidic heterogeneous reagent is H-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

29. The method of claim 26 or 27, wherein the Lewis-acidic heterogeneous reagent is Na-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

30. The method of claim 26 or 27, wherein the Lewis-acidic heterogeneous reagent is AI-MCM-41 with a Si/AI ratio of about 25, and a pore diameter of about 2.7 nm.

31 . The method of claim 20, wherein the Lewis-acidic heterogeneous reagent is acidic alumina.

32. The method of claim 31 , further comprising contacting the first cannabinoid and the acidic alumina with an additive.

33. The method of claim 32, wherein the additive is water, isopropyl alcohol, or a combination thereof.

34. The method of any one of claims 20 to 33, wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof.

35. The method of claim 34, wherein the extract is a crude extract from hemp.

36. The method of any one of claims 20 to 35, wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 6.0:1 .0.

37. The method of any one of claims 20 to 35, wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 20.0: 1.0.

38. The method of any one of claims 20 to 35, wherein the composition comprises primarily the second cannabinoid.

39. A method for converting a first cannabinoid into a composition comprising a second cannabinoid and a third cannabinoid, wherein the second cannabinoid and the third cannabinoid are each isomers of the first cannabinoid, and wherein the composition has a second cannabinoid:third cannabinoid ratio that is greater than 1.0: 1.0, the method comprising contacting the first cannabinoid with a Lewis-acidic heterogeneous reagent under neat reaction conditions comprising: (i) a reaction temperature that is within a target reaction-temperature range for the Lewis-acidic heterogeneous reagent; and (ii) a reaction time that is within a target reaction-time range for the Lewis-acidic heterogeneous reagent and the reaction temperature.

40. The method of claim 39, wherein the Lewis-acidic heterogeneous reagent is a Brønsted-acidic heterogeneous reagent.

41 . The method of claim 39 or 40, wherein the Lewis-acidic heterogeneous reagent comprises an ion-exchange resin, a microporous silicate, a mesoporous silicate, a phyllosilicate, or a combination thereof.

42. The method of claim 41 , wherein the ion-exchange resin is an Amberlyst polymeric resin.

43. The method of claim 42, wherein the Amberlyst polymeric resin has a surface area of between about 20 m²/g and about 80 m²/g and an average pore diameter of between about 100 Å and about 500 Å.

44. The method of claim 42 or 43, wherein the Amberlyst polymeric resin comprises Amberlyst 15.

45. The method of claim 41 , wherein the Lewis-acidic heterogeneous reagent is AI-MCM-41 , MCM-41 , MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-1 1 , ZSM-22, ZSM-23, ZSM-35, SAPO-1 1 , SAPO-34, SSZ-13, TS-1 , KIT-5, KIT-6, FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF, Clayzic, bentonite, or a combination thereof.

46. The method of claim 45, wherein the Lewis-acidic heterogeneous reagent has a pore diameter of between about 0.1 nm and about 100 nm, a particle size of between about 0.1 mm and about 50 mm, a Si/AI ratio of between about 5 and about 1500, or a combination thereof.

47. The method of claim 45 or 46, wherein the Lewis-acidic heterogeneous reagent is H-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

48. The method of claim 45 or 46, wherein the Lewis-acidic heterogeneous reagent is Na-ZSM-5, with a Si/AI ratio of about 38, a pore size of about 5 Å, and a particle size of about 2 mm.

49. The method of claim 45 or 46, wherein the Lewis-acidic heterogeneous reagent is AI-MCM-41 with a Si/AI ratio of about 25, and a pore diameter of about 2.7 nm.

50. The method of claim 39, wherein the Lewis-acidic heterogeneous reagent is acidic alumina.

51 . The method of claim 50, further comprising contacting the first cannabinoid and the acidic alumina with an additive.

52. The method of claim 51 , wherein the additive is water, isopropyl alcohol, or a combination thereof.

53. The method of any one of claims 39 to 52, wherein the first cannabinoid is a component of a distillate, an isolate, a concentrate, an extract, or a combination thereof.

54. The method of claim 53, wherein the extract is a crude extract from hemp.

55. The method of any one of claims 39 to 54, wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 6.0:1 .0.

56. The method of any one of claims 39 to 54, wherein the second cannabinoid:third cannabinoid ratio of the composition is greater than about 20.0: 1.0.

57. The method of any one of claims 39 to 54, wherein the composition comprises primarily the second cannabinoid.