ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
0/0

Why Is THCA Decarboxylation Faster than CBDA? an in Silico Perspective

preprint
submitted on 03.09.2020 and posted on 03.09.2020 by Weiying He, Paul J. Foth, Markus Roggen, Glenn M. Sammis, Pierre Kennepohl
Tetrahydrocannabinol acid (THCA) and cannabidiol acid (CBDA), the two crucial organic components in cannabis and hemp, decarboxylate at different rates to their more active neutral forms. Theoretical calculations are used herein to analyze how the remote annulated ring or pendant substituent influences the rate determining steps of the decarboxylation processes. The uncatalyzed keto-enol tautomerization that precedes decarboxylation is found to be extremely slow in both cases albeit with a ten-fold preference for CBDA. A single molecule of methanol dramatically enhances the reaction rates by allowing for tautomerization through a more favorable six-membered ring transition state. Methanol-catalyzed tautomerization is found to be faster in THCA than in CBDA. This difference results from both the larger dipole moment of the THCA scaffold as well as its greater rigidity relative to CBDA. The greater dipole moment leads to a somewhat better binding of methanol. The lower entropic penalty in THCA towards tautomerization leads to faster decarboxylation.

Funding

NSERC Discovery 2015-RGPIN-05856

NSERC Discovery 2016-RGPIN-05453

History

Email Address of Submitting Author

pierre.kennepohl@ucalgary.ca

Institution

University of Calgary

Country

Canada

ORCID For Submitting Author

0000-0003-3408-9157

Declaration of Conflict of Interest

No conflict of interest

Version Notes

Version 1.0

Exports