Fig. 2: Mid-IR Spectra: Example spectra of cannabis extract throughout the course of decarboxylation by the application of heat.
Fig. 3: Fit of IR spectra, based on PCR model, to HPLC reference data: Cannabinoid concentration plots over the course of decarboxylation for three separate decarboxylation reactions.
While the decarboxylation reaction has been studied [1a, 1b], [2a, 2b], [3a], and a mechanism has been proposed [3b], most of this work has been based on basic THCA analogs. Our calculations  for decarboxylation of THCA and CBDA show that:
- The rate determining step is the intramolecular protonation process from the carboxylic group to benzene ring.
- The rate difference is due to steric effects caused by meta substitute rather than electronic effect from para substitute.
- The steric effect was achieved by blocking the occurrence of an orthogonal carboxylic group conformation of the transition state (forthcoming research).
For the in-process analytics we developed a Fourier transform infrared attenuated total reflectance (FT-IR-ATR) method in collaboration with PerkinElmer. We utilized cannabis extracts of different cannabinoid concentrations and decarboxylation ratios in the reaction setup. The extracts were heated in an oil bath equipped with an overhead stirrer.
During an 80-minute reaction time we recorded extract temperature in regular intervals, measured mid-IR spectra every five minutes and collected aliquots for high-performance liquid chromatography (HPLC) analysis. For the IR spectra (Figure 2) principal component regression (PCR) was used to generate quantitative models for THCA and THC.
Over the course of the decarboxylation reaction, the change in THCA and THC concentration can be observed (Figure 3). Cannabinoid concentrations predicted from IR spectra are overlaid with the HPLC reference values.
The excellent fit between our IR model and the reference data demonstrates the utility and power of a low-cost, in-process analytical tool for real-time reaction analysis and control.
In conclusion, we showed our multi-level approach to reaction analysis and process development to support the cannabis industry in their production challenges.
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 Unpublished work together with Weiying He and Paul Foth.