Hi Bees!
Recently my buddy (called SWIA for simplicity) decided to do a CTH reductive amination with ammonium formate, like posted by
Post 335851
(Sunlight: "MDA and MDMA from CTH reductive amination", Novel Discourse)- but as he hadn't other ketones to work with at the moment, he tried it on plain P2P (which was of course homemade, but vac distilled and rather pure), and got decent yields...
Said shortly: CTH reductive amination of 75mmol P2P in 165 ml MeOH/water 9:1 solvent using 36g ammonium formate and 5g Pd/C 10% and 13 hours reaction time yielded ~8.2g amphetamine freebase (molar 80% yield)
Here is what he did:
First, 165ml of 9:1 methanol/water solution were prepared (10% H2O). This was put in a 300ml Erlenmayer together with 36 grams ammonium formate, 10.2ml P2P (which he had put out of the fridge 1 hour ago to warm it to 20°C - density of P2P is 1.0144 g/cm
3 at 20°C) and a medium sized stirbar.
This was stirred ~10 minutes at 30°C, until almost all of the salt had dissolved. Then, 4.9 grams of 10% Pd/C were added (before addition SWIA made sure there wasn't much gaseous MeOH in the flask, because he was paranoid about autoignition of >150ml warm methanol
) and the mixture was stirred violently for a few seconds to mix it thoroughly. The erlenmayer was then plugged with a tissue paper and rxn was stirred for 13 hours at room temp.
After this time, the rxn had become a viscous mud of carbonates, Pd/C and solvent (with a stinging ammonia odor
).
Now the workup (it surely can be shortened):
First, SWIA added diluted HCl to the rxn (lots of CO
2) until acidic. Then, he vacuum filtered the mixture twice through same filtercake (second time it came through crystal clear) and washed the filtercake three times each with methanol and dil. HCl. The solution+washings were then basified with NaOH(s) and methanol and ammonia were removed by distillation under reduced pressure. After ~40% of the solution had distilled over, SWIA disconnected vacuum, checked the smell of distillation flask and couldn't detect any ammoniacal smell anymore, so he acidified again with HCl and continued distillation (later he neutralized the first ammoniacal fraction with HCOOH and removed the MeOH by distillation, and tiny droplets appeared in the residual water/ammoniumformate mix - probably the unreacted ketone). When residual soln. became slightly milky (lots of salt in there), he stopped distilling.
Everything was cooled, and there were not even traces of unreacted ketone visible, so aequ. NaOH was added until pH 12 was reached - no extraction of acidic soln. was done before. At this point, a slightly pink coloration of the aequous phase was noticed.
When having basified, SWIA extracted with 100, 75 and finally 50ml toluene and gave the last xtraction one night time for separation. The combined toluene extracts were washed with brine, then water, then dried over Na
2SO
4 and the toluene was removed on a water bath under hard vac to yield 9.1ml of a yellow oil, which was dissolved in 40ml dry iPrOH, acidified with ethanolic H2SO4 and the resulting amorph crystals precipitated with dry acetone.
After cooling the mother liquor to below 0°C, the slurry was vacuum filtered, crystals washed with more dry acetone and dried in a dessicator at 50°C to yield 10.9 grams of slightly pink amphetamine sulfate (the pink color is probably amphetamine-p2p-imine. Or maybe just traces of ketone being fucked up by the anhydrous sulfuric, becoming reddish?)
I conclusion I would say, the CTH procedure described by Sunlight works equally good with plain phenylacetone, at least with amm.formate as hydrogen/ammonia donor. Maybe the catalyst load used is an excess (50% w/w catalyst/ketone??), but I'm sure that with lower catalyst amounts (30% w/w) and longer rxn times (like described by Sunlight) it will work equally well. SWIA's catalyst wasn't the best (reused 1x), but still pretty reactive, and gas evolution (which if it ceases is a nice indicator for the end of reduction, too) started 2-3 minutes after addition of Pd/C..
Greetz A
