Conversion of CBD to THC

Conversion of cannabidiol (CBD) to tetrahydrocannabinol (THC) can occur through a ring-closing reaction.^[1]^[2]^[3] This cyclization can be acid-catalyzed^[4] or brought about by heating.^[5]^[6]^[7]^[8]^[9]^[10]^[11]

^ Adams R, Baker BR (September 1940). "Structure of Cannabidiol. VII. A Method of Synthesis of a Tetrahydrocannabinol which Possesses Marihuana Activity". Journal of the American Chemical Society. 62 (9): 2405–2408. doi:10.1021/ja01866a041.
^ Adams R, Pease DC, Cain CK, Clark JH (September 1940). "Structure of cannabidiol. VI. Isomerization of cannabidiol to tetrahydrocannabinol, a physiologically active product. Conversion of cannabidiol to cannabinol". Journal of the American Chemical Society. 62 (9): 2402–2405. doi:10.1021/ja01866a040.
^ Adams R, Pease DC, Cain CK, Baker BR, Clark JH, Wolff H, et al. (August 1940). "Conversion of cannabidiol to a product with marihuana activity. A type reaction for synthesis of analogous substances. Conversion of cannabidiol to cannabinol". Journal of the American Chemical Society. 62 (8): 2245–2246. doi:10.1021/ja01865a508.
^ Nivorozhkin A, Palfreyman MG (2025-06-01). "Acid-Catalyzed Conversion of Cannabidiol to Tetrahydrocannabinols: En Route to Demystifying Manufacturing Processes and Controlling the Reaction Outcomes". Cannabis and Cannabinoid Research. 10 (3): 377–388. doi:10.1089/can.2025.0015. ISSN 2578-5125.
^ Razdan RK (January 1981). "The Total Synthesis of Cannabinoids.". In ApSimon J (ed.). Total Synthesis of Natural Products. Vol. 4. John Wiley & Sons. pp. 185–262. doi:10.1002/9780470129678.ch2. ISBN 978-0-470-12953-1.
^ Bloemendal VR, van Hest JC, Rutjes FP (2020). "Synthetic pathways to tetrahydrocannabinol (THC): an overview". Organic & Biomolecular Chemistry. 18 (3203–3215): 3203–3215. doi:10.1039/D0OB00464B. hdl:2066/218829. PMID 32259175.
^ Bloemendal VR, Spierenburg B, Boltje TJ, van Hest JC, Rutjes FP (June 2021). "One-flow synthesis of tetrahydrocannabinol and cannabidiol using homo-and heterogeneous Lewis acids". Journal of Flow Chemistry. 11 (2): 99–105. doi:10.1007/s41981-020-00133-2. hdl:2066/235956.
^ Hurrle T, Gläser F, Bröhmer MC, Nieger M, Bräse S (May 2021). "The Diels-Alder Approach towards Cannabinoid Derivatives and Formal Synthesis of Tetrahydrocannabinol (THC)". ChemistryOpen. 10 (5): 587–592. doi:10.1002/open.202000343. PMC 8121136. PMID 33988908.
^ Bassetti B, Hone CA, Kappe CO (May 2023). "Continuous-Flow Synthesis of Δ9-Tetrahydrocannabinol and Δ8-Tetrahydrocannabinol from Cannabidiol". The Journal of Organic Chemistry. 88 (9): 6227–6231. doi:10.1021/acs.joc.3c00300. PMC 10167683. PMID 37014222.
^ Ujváry I (February 2024). "Hexahydrocannabinol and closely related semi-synthetic cannabinoids: A comprehensive review". Drug Testing and Analysis. 16 (2): 127–161. doi:10.1002/dta.3519. PMID 37269160.
^ Capucciati A, Casali E, Bini A, Doria F, Merli D, Porta A (April 2024). "Easy and Accessible Synthesis of Cannabinoids from CBD". Journal of Natural Products. 87 (4): 869–875. doi:10.1021/acs.jnatprod.3c01117. PMID 38427968.

[1] Adams R, Baker BR (September 1940). "Structure of Cannabidiol. VII. A Method of Synthesis of a Tetrahydrocannabinol which Possesses Marihuana Activity". Journal of the American Chemical Society. 62 (9): 2405–2408. doi:10.1021/ja01866a041.

[2] Adams R, Pease DC, Cain CK, Clark JH (September 1940). "Structure of cannabidiol. VI. Isomerization of cannabidiol to tetrahydrocannabinol, a physiologically active product. Conversion of cannabidiol to cannabinol". Journal of the American Chemical Society. 62 (9): 2402–2405. doi:10.1021/ja01866a040.

[3] Adams R, Pease DC, Cain CK, Baker BR, Clark JH, Wolff H, et al. (August 1940). "Conversion of cannabidiol to a product with marihuana activity. A type reaction for synthesis of analogous substances. Conversion of cannabidiol to cannabinol". Journal of the American Chemical Society. 62 (8): 2245–2246. doi:10.1021/ja01865a508.

[4] Nivorozhkin A, Palfreyman MG (2025-06-01). "Acid-Catalyzed Conversion of Cannabidiol to Tetrahydrocannabinols: En Route to Demystifying Manufacturing Processes and Controlling the Reaction Outcomes". Cannabis and Cannabinoid Research. 10 (3): 377–388. doi:10.1089/can.2025.0015. ISSN 2578-5125.

[5] Razdan RK (January 1981). "The Total Synthesis of Cannabinoids.". In ApSimon J (ed.). Total Synthesis of Natural Products. Vol. 4. John Wiley & Sons. pp. 185–262. doi:10.1002/9780470129678.ch2. ISBN 978-0-470-12953-1.

[6] Bloemendal VR, van Hest JC, Rutjes FP (2020). "Synthetic pathways to tetrahydrocannabinol (THC): an overview". Organic & Biomolecular Chemistry. 18 (3203–3215): 3203–3215. doi:10.1039/D0OB00464B. hdl:2066/218829. PMID 32259175.

[7] Bloemendal VR, Spierenburg B, Boltje TJ, van Hest JC, Rutjes FP (June 2021). "One-flow synthesis of tetrahydrocannabinol and cannabidiol using homo-and heterogeneous Lewis acids". Journal of Flow Chemistry. 11 (2): 99–105. doi:10.1007/s41981-020-00133-2. hdl:2066/235956.

[8] Hurrle T, Gläser F, Bröhmer MC, Nieger M, Bräse S (May 2021). "The Diels-Alder Approach towards Cannabinoid Derivatives and Formal Synthesis of Tetrahydrocannabinol (THC)". ChemistryOpen. 10 (5): 587–592. doi:10.1002/open.202000343. PMC 8121136. PMID 33988908.

[Bassetti_2023-9] Bassetti B, Hone CA, Kappe CO (May 2023). "Continuous-Flow Synthesis of Δ9-Tetrahydrocannabinol and Δ8-Tetrahydrocannabinol from Cannabidiol". The Journal of Organic Chemistry. 88 (9): 6227–6231. doi:10.1021/acs.joc.3c00300. PMC 10167683. PMID 37014222.

[10] Ujváry I (February 2024). "Hexahydrocannabinol and closely related semi-synthetic cannabinoids: A comprehensive review". Drug Testing and Analysis. 16 (2): 127–161. doi:10.1002/dta.3519. PMID 37269160.

[11] Capucciati A, Casali E, Bini A, Doria F, Merli D, Porta A (April 2024). "Easy and Accessible Synthesis of Cannabinoids from CBD". Journal of Natural Products. 87 (4): 869–875. doi:10.1021/acs.jnatprod.3c01117. PMID 38427968.

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