Megapumps1234
New Member
Ok bros, there has been a lot of debate over the years about whether the estradiol benzoate can be removed from Synovex (discontinued) and Component EH (currently in production). I have taken it upon myself as a theoretical exercise to prove that this does work. My work is all theoretical, but I believe that it holds quite well. I am not a chem major, but I do have a degree in Applied Mathematics (i.e. a degree in thinking). I do not endorse this experiment nor do I assume any liability should you violate the laws of your country to perform such an experiment.
Let's start with the NaOH + estradiol benzoate reaction:
Ok, so if estrogen forms a water-soluble salt, why does every fanboy talk about testosterone base forming with enough NaOH (as opposed to a water-soluble testosterone salt)? The answer lies in the fact that the propionate ester attaches to the C-17 position on the testosterone molecule.
Let's start with the NaOH + estradiol benzoate reaction:
- Estradiol benzoate is 17B estradiol with the oxygen on the C-3 position attached to a benzoate ester instead of hydrogen. The C-3 position is a part of a phenol group (i.e. aromatic ring), which is resonance stabilized
- Resonance stabilization simply means that the structure will be more likely to donate a proton than it would otherwise (i.e. its more acidic than say, an alcohol group). This would help explain why the C-17 position on 17B estradiol isn't where the ester attaches.
- Furthermore, the Benzoate ester itself is resonance stabilized around the COO bond.
- When we dissolve NaOH, it dissociates in Na+ and OH-. The OH- will attack the COO bond on the Benzoate ester because the carbon has a partial positive charge from the two oxygens pulling the electron clouds toward themselves. When this happens, the Oxygen-Estrogen bond falls off the benzoate ester, which I'll call OE-.
- OE- is the conjugate base of 17B estradiol.
- The benzoate ester has become benzoic acid from the addition of OH-. The Hydrogen will dissociate, leaving a benzoate ion (i.e. conjugate base).
- The sodium ions from the NaOH will pair with the benzoic ion and estradiol ions, forming benzoic salt and estradiol salt. The remaining hydrogens will form water with the extra oxygens.
- Balanced equations imply that we need 2x the moles of NaOH as we do estradiol benzoate.
- 2(NaOH) + 1(Estradiol benzoate) = Estradiol salt + sodium benzoate + H20. You can write out all the hydrogens and carbons to check my work, but I'm 99.9% sure this balances based on my findings.
Ok, so if estrogen forms a water-soluble salt, why does every fanboy talk about testosterone base forming with enough NaOH (as opposed to a water-soluble testosterone salt)? The answer lies in the fact that the propionate ester attaches to the C-17 position on the testosterone molecule.
- Testosterone propionate is testosterone base with the hydrogen at the C-17 position replaced by the propionate ester.
- Unlike the C-3 position on estrogen, the carbon ring composing the C-17 is not a phenol group and thus follows reactivity of a secondary alcohol. This means that the testosterone base molecule is going to work harder to keep the hydroxyl group attached. In other words, it doesn't want to dissociate in water and is therefore a very weak acid and thus a very strong conjugate base.
- So, this explains why NaOH goes after the estradiol benzoate ester before the testosterone propionate ester.
- With enough NaOH (and potentially only with a lot of heat), the propionate ester will eventually be stripped as well.
- The OH- ions will attack the COO position on the propionate ester just like it would the benzoate ester, which means that the oxygen-testosterone bond will be broken, which I'll call OT-
- The propionic ester is now propionic acid from the addition of OH-, which will dissociate into hydrogen ions and propionate ions.
- The OT- is very basic compared to OE-, so it will pull those Hydrogens right back into its orbit, forming testosterone base! The Na+ ions will form with the propionic ion to form sodium propionate.
- At this point, only testosterone will be water-insoluble.
- QED
- How much time or heat is required to make sure this all actually happens like we want?
- How much lye is required? Using 2x molar equivalents may not be enough because some may attack the prop before reaching all the estradiol benzoate. My guess is 4x molar equivalents of NaOH will get the job done, leaving some testosterone base + testosterone propionate.