Created: January 22, 2022
Modified: January 22, 2022
Modified: January 22, 2022
free base
This page is from my personal notes, and has not been specifically reviewed for public consumption. It might be incomplete, wrong, outdated, or stupid. Caveat lector.- Some drugs, like cocaine, or DMT, come in multiple forms: as some sort of salt or as a 'free base'. What's the difference between these forms?
- The drug molecule itself is an amine, meaning that we can view it as ammonia with some fancy groups substituting for the hydrogen atoms. Put differently, it has a nitrogen atom somewhere, and that nitrogen atom has (as per usual) a lone pair of electrons. This setup is inherently a base or a nucleophile, since it can accept a proton to form a positive ion (the conjugate acid) in which the lone pair becomes a bonded hydrogen atom. (in the simple case, this converts ammonia, NH3, to ammonium, NH4+).
- Amines with psychoactive properties seem to often be called alkaloids, though I can't find a scientific definition of the term anywhere so it may just be convention.
- When the molecule is in the 'pure' form with just the lone pair, we call this the "free base". Because it is a base, this substance may be reactive and not very stable.
- Alternately, we can combine the conjugate acid, which will in general be a cation with a positive charge, and with some anion in an ionic bond. This yields a salt, which is typically much more stable, and is water-soluble due to the ionic bond.
- For example, cocaine is most often found as the hydrochloride salt, cocaine hydrochloride, in which free base cocaine is ionically bonded to HCl molecules. (each of which we can think of as a proton plus a Cl- ion). But there are other possible salt forms, e.g., sulfate and nitrate salts.
- We want drugs to be reactive in the body (that's the whole point), but stable forms are easier to store.
- When taking the drug:
- The freebase is generally better to smoke, because it's less stable so it vaporizes at a lower temperature. Freebase cocaine vaporizes around 80C, below the boiling point of water, while cocaine hydrochloride must get much hotter, around 180C, which would also break down the cocaine itself and/or release hydrochloric acid.
- Salt forms are generally better to ingest, snort, or inject, because they dissolve in water and are less caustic.
- How to convert a salt to a freebase? It seems like a general recipe involves trituration: we find some substance in which the salt dissolves but the freebase doesn't. Often this is just water, since the salt is typically polar whereas the freebase may be nonpolar. Then we:
- Dissolve the salt in the solvent (e.g., hot water).
- Add a base, e.g., a solution of sodium carbonate or bicarbonate. This must be a preferred bonding partner: the counterion must prefer to bond to the 'new' base than to the original freebase. In doing so, it forms a new salt and leaves the freebase on its own.
- The freebase will precipitate out of the mixture, since we've assumed it's not soluble in the solvent. Hopefully it forms crystals or similar, so we can isolate it by just filtering them out.
- To convert back, you can just dissolve the freebase in an acidic solution (it generally won't dissolve in water). For example, to inject crack cocaine, one can dissolve it in ascorbic acid (vitamin C) or citric acid solutions, effectively converting it back into an ascorbate or citrate salt.