Ive summed all our proposals and i now rely upon two sources of information notwithstanding all the other patent info we have dumped into this thread (frankly you could take em conglomerate em into one big paper and feed it into Ai's theres so much info here)
Source 1: Patent:
https://patents.google.com/patent/US11851452B2/en
Methanol Acetone, HCl, EtOH, H2O, EtOAc (ethyl acetate buyer back there) all can produce the salt precip
Source 2: Crystallization of Organic Compounds, 2nd Edition O Reilly and other crystallization techniques (past org2 level stuff)
Going back to the "Psilocybin crystallization for beginners" in this thread
Whether simply evaping some HCl(aq) will precip psilocybin - WITH NO SEED CRYSTAL (once ya have the seed crystal then yes all ya need do is temp control for more nucleation seeding) but the other person (that "we" shit) we mentioned psilocybin HCl
US11851452B2 — Google Patents
Patent anchor
The key direct passage is that
psilocybin was slurried in 1:1 EtOH/EtOAc, HCl was added, and the resulting material was identified as crystalline psilocybin hydrochloride Form A. The patent therefore directly establishes the HCl/Form-A relationship, but it does
not establish that EtOAc itself is required.
Google Patents
Compound / solvent → temperature/history → crystal
- Psilocybin + HCl
→ HCl protonates the tertiary amine and supplies the Cl⁻ counterion
→ psilocybin hydrochloride
→ this is the fundamental salt-forming / ion-pairing step.
→ The subsequent crystal can be Form A, B, or C depending on the solid-state environment.
- Psilocybin·HCl + EtOH
→ patent used pre-existing non-crystalline hydrochloride
→ EtOH solution was cooled from 40 °C to room temperature
→ HCl Form A crystallized.
→ This is the strongest evidence that EtOAc is not inherently necessary for Form A.
- Psilocybin + HCl + EtOH/EtOAc
→ HCl establishes the hydrochloride
→ room-temperature crystallization
→ HCl Form A.
→ This is the patent's direct demonstration of forming the HCl salt and Form A from psilocybin itself.
- Psilocybin·HCl + EtOH/EtOAc
→ elevated-temperature slurry treatment
→ HCl Form A.
→ Again, EtOAc is a compatible crystallization medium, not proven to be part of the Form-A lattice.
- Psilocybin·HCl + acetone
→ room-temperature slurry
→ HCl Form A.
→ This is especially important because it demonstrates Form A in a completely different solvent environment.
- Psilocybin + HCl + EtOH/EtOAc + Form-B nucleation history
→ room-temperature slurry with Form B present
→ HCl Form B.
→ This demonstrates that nucleation history can redirect the crystallization outcome even within the same general solvent system.
- Psilocybin + HCl + EtOH
→ salt-screen slurry
→ HCl Form C was observed in the patent's screen.
→ Form C was subsequently characterized as approximately an ethanol solvate.
→ Therefore EtOH does not automatically mean Form A.
- Psilocybin·HCl + EtOH + toluene antisolvent
→ crystallization/antisolvent environment
→ HCl Form C, the ethanol-containing form.
→ This reinforces the importance of solvent environment.
- Psilocybin + MeOH/H₂O
→ fast evaporation
→ ordinary psilocybin Form B, characterized as the trihydrate.
→ This is not HCl Form A and is important evidence that water can strongly influence the solid form.
- Ordinary psilocybin Form A + water exposure
→ high relative humidity, 75–95% RH
→ water uptake
→ ordinary psilocybin Form B/hydrate.
→ Again, this demonstrates water's ability to redirect the solid-state structure.
The hierarchy we're left with
HCl = decisive salt-forming component (HERE I WAS RIGHT)
Psilocybin + HCl → R₃NH⁺ Cl⁻
EtOH / water / EtOAc / other solvents = crystallization environment
Temperature + solvent loss + supersaturation + nucleation history = solid-form selection
So the patent evidence supports:
HCl → hydrochloride identity → crystallization environment → Form A/B/C
rather than:
HCl + EtOAc → Form A
That is the key distinction.
And importantly, the patent gives us
Form A from EtOH alone and from acetone, so
EtOAc cannot be considered a necessary structural component of Form A.
What remains unproven is whether an
EtOH/H₂O/HCl environment specifically selects Form A rather than a hydrated/solvated competitor.
Google Patents
During the simultaneous evaping and dry gassing HCl into it (because tossing in muriatic wet HCl has water content that mucks up solubility for crystallization)
thats where im at, we proved the zwitterionic state allows us to form all kinds of forms
using the
patent's naming:
Zwitterionic psilocybin
- Form A — unsolvated
- Form B — trihydrate
- Form C — mono-ethanolate Google Patents
Psilocybin hydrochloride
- HCl Form A — essentially unsolvated crystalline HCl form
- HCl Form B — distinct HCl polymorph
- HCl Form C — ethanol-containing solvate/“ethanoate” form Google Patents
One caveat: the broader literature sometimes uses
different nomenclature for zwitterionic psilocybin (e.g. anhydrates/hydrates and A/A′ terminology), so the labels need to be tied to the particular paper/patent.
Lastly, the solvent used, the patents show little bit of solvent gets locked into the final crystal salt lattic (again solvent choice toxicity noted)
