06-19-04 10:10
No 514291
I decided to combine 2 methods for the reductive amination of our favorite ketone, namely the AL/Hg amalgam a la RoundBottom and the Barium procedure of pre-forming the imine.
108 grams ketone or 0.61 mol
82.5 grams of MeAM*HCl or 1.22 mol in about 90 ml water
48.8 grams of NaOH in 100 ml water.
The ketone is dissolved in 200ml xylene. It is then added to the MeAm solution under vigorous stirring to mix the 2 phases. The NaOH is dripped in over a period of about 10-15 minutes on a ice-bath. The solution turns from yellow to orange as the NaOH is dripped in.
After addition, the solution is left to stir at room temp for 2 hours. The xylene layer is seperated and both layers are kept(water and xylene layers).
About 45 grams of aluminium in about 700 ml MeOH with 200 mg HGCl2 is activated in a 2L RB flask. With an addition funnel, the imine/xylene layer is added dropwise over an hour. The temp of the methanol rises up to a good reflux.
The solution is left to stir an extra 3 hours.
*** Here for some reason, I felt maybe some of the imine was still in the water solution since it was still orange. I dedcide to drip this in at this point to see what would happen. In felt confident enough that the amination was terminated, so i wasnt scared of the water present. When the water phase was dripped in, the temp started rising again, Imine still present in the water layer? I dont know, but I guess so, by seen it reacting.
Then the usual work-up, basification, extracting, A/B then distilling the freebase.
Once work-up was complete, I was left with 96 grams of beautiful raw freebase thats being gassed by now.
The theoritical yield is 82%.
I think the procedure is as easy as the RB one except that the smell is cut down drastically as well as the amount of MeAM used. The MeAM gas is forced out of the solution but doesnt escape at all. I use an addition funnel(not pressure equalizing) and I see no bubbles coming up the NaOH solution as it is dripped in.
Also it seems some imine stays in the water layer since the reduction started again as I dropped it on the activated aluminium. This would oppose Barium's method using NaBH4.???
Maybe a little extra yield could be obtained by also reducing the water layer??
Im confused about this part here
(Stranger)
08-31-04 07:39
No 528504
I did 2 50g MDP2P batches to try your method, the first as you wrote, the second a little bit different (NOTE: don't smoke cannabis before entering the lab), because i dropped in both layers at once. Luckily there was NO difference...
greetings
DF
(Stranger)
09-01-04 16:32
No 528973
This method works very good, i think it was a very good idea to do the amine formation first, then reduce it as usual.
NaOH dripping in
turned orange after addition
normal reduction with al
i prefer to vacuumfilter the sludge, which is allways a timeconsuming job for me, because the filterpaper is clogged by the fine aluparticles very fast. Then i distill off the meamloaded methanol, which is used in further reductions, to save meam.
then normal workup, basify, extract, A/B, extract freebase with DCM, then vacuumdictill freebase.
i took the fraction between 150-158C with an water aspirator vacuum and got about 40g of waterwhite freebase out of 50g MDP2P - this is a good result for me. Sure there is some extra stuff in it, but i was alittle bit in a hurry, and a little bit high...
greetings & thanx,
DF