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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.