Below is a bit of research into a problem I’ve seen from several labs while working on the analytical side of the industry. I haven’t attempted any of the below myself, but have performed enough chroma, LLE, and other remediation techniques to have a feel for how to manipulate compounds to end up where you want them to. I tried to make the tek below as translatable as possible to a broader audience.
The XLogP of Etoxazole (5.4) is similar to cannabinoids (THC XLogP: 7). This hinders the ability to separate the compounds via chromatography, as the most common schema in our industry, reverse phase flash chromatography, relies on differential binding of the compounds of interest to modified silica beads relative to your solvent system. Plainly, both Etoxazole and delta 9 THC would bind to hydrophobic silicas in a similar manner relative to commonly used solvent systems, making their separation difficult and/or expensive at scale. The miscibility of some of these solvents (water, MeOH, EtOH, acetone, heptane) as well as the massive amount of solvent utilized, just doesn’t make sense economically anymore.
The molecular weight of Etoxazole is 359.4. Again, this property of the compound is similar to delta 9 THC (314.46ish). Whereas some pesticides such as Abamectin (MW: 1732.1) can be easily remediated from cannabinoids via fractional distillation due to the vast difference between the boiling points of the compounds of interest (aba stays in the boiling flask/residue), molecules with similar molecular weights and properties become exceedingly difficult to fractionally distill. Interestingly, both the molecular structure as well as the literature suggest that decomposition should occur before the liquid → vapor phase change. However, given that Etoxazole has become increasingly abundant in distillates, the parameters of cannabinoid distillation must create an environment more suitable for vaporization and condensation of Etoxazole than for decomposition due to heat.
Given the above, exploiting the solubilities of these compounds via an LLE seems to be the most feasible remediation tactic. The following is a theoretical experimental approach for the remediation of Etoxazole, given the following:
- The solubility (g/L; 20C; PubChem) of Etoxazole in the following solvents:
- Acetone: 300
- Methanol: 90
- Ethanol: 90
- n-Heptane: 13
- The miscibility/immiscibility of solvents is vital for an LLE:
- n-heptane/methanol immiscibility
- n-heptane/acetone miscibility
Taken together, the best solvent system for the LLE would be:
- n-Heptane and MeOH
- Etoxazole solubility 6.92x in MeOH relative to n-heptane
Unfortunately, I wouldn’t begin to know where to look for pesticide solubility in cannabinoid distillates, and so the theoretical approach would be reliant on superior Etoxazole solubility in MeOH relative to n-heptane/distillate mixture.
If I were to approach a project like this, I would utilize a 1:1 v/v heptane/distillate mixture. For sake of example, in a 20L reactor, 5L heptane:5L distillate. Given how cheap MeOH is relative to overall COGS of this process, I would utilize 7.5L MeOH. This would leave enough space in a 20L reactor to insert variables such as temperature control, or leaving the last 500mL of MeOH in the reactor between washes rather than remove all MeOH and inevitably waste material via heptane/distillate elution.
The procedure could be:
- 3x MeOH wash on 5L distillate, dissolved in heptane
- 3x wash with water. 1x 5% brine at first to pull out any residual polar compounds in the distillate, followed by 2x pure distilled water.
- Dry what’s left in the reactor via eluting into a column containing 3A sieves before heading to the rotary evaporator to remove hydrocarbon and recover distillate
Let me know what you all think, and thanks always to this community for providing a platform to discuss ideas like this!