Decarboxylation of Δ9-tetrahydrocannabinol: Kinetics and molecular modeling

Helene Perrotin-Brunel*, Wim Buijs, Jaap Van Spronsen, Maaike J.E.Van Roosmalen, Cor J. Peters, Rob Verpoorte, Geert-Jan Witkamp

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Efficient tetrahydrocannabinol (Δ9-THC) production from cannabis is important for its medical application and as basis for the development of production routes of other drugs from plants. This work presents one of the steps of Δ9-THC production from cannabis plant material, the decarboxylation reaction, transforming the Δ9- THC-acid naturally present in the plant into the psychoactive Δ9-THC. Results of experiments showed pseudo-first order reaction kinetics, with an activation barrier of 85 kJ mol-1 and a pre-exponential factor of 3.7 × 108 s-1. Using molecular modeling, two options were identified for an acid catalyzed β-keto acid type mechanism for the decarboxylation of Δ9- THC-acid. Each of these mechanisms might play a role, depending on the actual process conditions. Formic acid proved to be a good model for a catalyst of such a reaction. Also, the computational idea of catalysis by water to catalysis by an acid, put forward by Li and Brill, and Churchev and Belbruno was extended, and a new direct keto-enol route was found. A direct keto-enol mechanism catalyzed by formic acid seems to be the best explanation for the observed activation barrier and the pre-exponential factor of the decarboxylation of Δ9-THC-acid. Evidence for this was found by performing an extraction experiment with Cannabis Flos. It revealed the presence of short chain carboxylic acids supporting this hypothesis. The presented approach is important for the development of a sustainable production of Δ9-THC from the plant.

Original languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalJournal of Molecular Structure
Volume987
Issue number1-3
DOIs
StatePublished - Feb 22 2011

Keywords

  • Cannabis
  • Decarboxylation
  • Kinetics
  • Molecular modeling
  • Tetrahydrocannabinol

ASJC Scopus subject areas

  • Analytical Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Decarboxylation of Δ<sup>9</sup>-tetrahydrocannabinol: Kinetics and molecular modeling'. Together they form a unique fingerprint.

Cite this