I recently discovered an interesting posting/discussion between LabTop and tBoc. Since I am probably still wearing sunglasses, I need some advice. I made some edits to the step by step process, will you just verify that for me before I begin.
Also, for future reference, on the final step od reductive amination of the keytone: I read MethylMan and Ritters interpretation of the process, as well as BrightStars.
What is the best way to scale up that procedure a bit.
27-55g seems really time consuming.
Anyway, let me not get ahead of myself. Here goes the post for discussion.
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Experiments with and discussions of the above procedure
by tBOC
Note by Rhodium:
This document is a collection of several postings from the Hive by tBOC, but I have cut out unnecessary text from most of them. Thus I have inserted five dashes (- - - - -) between the different posts to make reading easier.
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tBOC reads chem_wannabe's ammonium nitrate oxidation procedure, and thinks that it is rather incredible... almost unbelievable. It just so happens that tBOC
loves to grow flowers, and uses NH4NO3 as fertilizer, and tBOC is also into photography and just happens to have glacial acetic acid around. Also tBOC was trying to use glacial acetic acid to get his pennies their brightest and fucked up, accidentally turning his beautiful penny collection into a nice blue powder.
Well, tBOC happens to be a freak of nature (but we love him so/he's a freak of nature but we let him go) who likes to take alkenes, make ketones and then reductively aminate them (with legal ones, of course) so he decides to try this.
Preliminary Literature:
- The Organic Chemistry Lab Survival Manual' by James W. Zubrick.
- Philkal #109
- Organic Chemistry, Marie Anne Fox/Whitesell
- Organic Synthesis, Collective Edition
Equipment: ------------------
1 fractional distillation set up (safrol), magnetic stirrer, boiling stones, vacuum pump, tubing, support stand
1 reflux condenser - Vigreaux 400mm
3 addition funnels - 250, 500, 1000ml
1 filtering flask - 2000ml
1 buchner funnel, Hirsch funnel
2 separotary funnels - 1000, 2000ml
1 reaction flask - 3000ml
2L flat bottom flask - flat stir bar
hot plate/srirrer, compatible lab jack
submersible water pump, tubing - home depot
water bath, ice
misc. PYREX glass containers 250-2000ml
glass storage bottles 250 - 2000ml
TLC analysis kit, (Thin Layer Chromatography)
vacuum pump, tubing - mcmaster.com
high vac joint grease
1 active coal filter, fan, tubing - home depot
co2 fire extinguisher
good rubber or chem resistant apron, gloves, face mask/gogles, respirator
strong magnet - for retaining stirbars in containers when dumping out reaction contents
hygroscopic packets - put in p-benzoquinone after opening it up to keep it from oxidizing
coffee grinder
---- digital hotplate/stirrer - Fischer 11-496-80 - $595 - and get Thermocouple Immersion probe 11-496-94 @ $120
---- need hot plate at least 500 w for distillations
---- teflon tape wrapped around outside of joint seams
---- always use an egg-shapped stir bar
---- don't distill to dryness - BLACK CRAP WILL NOT COME OUT !!!! - use high-oleic safflower oil as a distillation buffer
---- When sassafras oil is distilled, if any tar is left in the original distillation flask acetone and a baby bottle brush gets the tar (burnt) out nicely.
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Procedure: (see distis proceedure of safrole in the Distis file)
1. Safrole --> MDP2Pol -----------------
20g safrole
20 ml H2SO4
80 ml H2O
?(distilled h2o?)
? see note
tBOC takes all of his safr... er... alkene, and distills it off and puts it into
his refrigerator. He then takes some H2SO4, 97%, and makes it into a 80% --------(should be no more than %80)-
solution and puts that in the 'fridge as well. Now tBOC likes to do things right the first time so he doesn't have to do them again, so tBOC reads, asks questions, reads again, and comes to the conclusion that one should hydrate
alkenes AS COLD AS POSSIBLE to ensure that the reaction occurs through an SN2 pathway, and not an SN1 pathway (i.e. cold, so one obtains the kinetic product, no carbocation rearrangements.)
So tBOC takes his (not)safrole, puts 20g in a RBF with a magnetic stirrer and puts the whole thing in an ice/salt/H2O bath. He then loads up a dropping flask
with 20mL of his chilled 80% H2SO4 solution and begins to add it to the alkene at the rate of 1 drop per second. Once all the acid is added, he lets it stir for another five minutes or so, then he loads up that dropping flask with 80 mL cold water (about 3C) and adds this to the H2SO4/alkene at the rate of 1 drop per second.
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notes for the paragraph above:
In the not-safrole--> not-MDP2Pol stage, the H2SO4 is added at 80% concentration direct from the freezer at the rate of about 3 drops/sec to the not-safrole which is being magnetically stirred in a ice-water/salt bath chilled to -5C or less. Then chilled dH2O is added dropwise at the same or a slightly faster rate to the sulfate as soon as the H2SO4 is all in. Normally I just use a sep funnel
and as soon as the H2SO4 is all added just pour my water in the top then go smoke a cigarette or two. Once all the dH2O is added, some salt is then stirred in to help break up the emulsion. Yields are consistently 100%.
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When all the water was added, tBOC throws the whole thing in a separatory funnel and waits until it's separated. tBOC then pours out the water into a beaker, and pours the top layer into a RBF with a magnetic stirrer, then weighs it. Minus the tare weight, tBOC has _22g_ of his alcohol. Now, theoretical yield on this process should have been 22.222g. Goddamn it, tBOC is pissed that he didn't get that last 0.222g out of the reaction. Result 20g MDP2Pol.
2. Oxydation procedure: -------
20g MDP2Pol
1.2 molar equivalents of ammonium nitrate fertilizer +(NH4NO3)+
4 mL glacial acetic acid (aldrich, guaranteed 99+%) AcOH
1 mL H2O
a dash of cupric acetate - Cu(AcO)2
60mL of %50 NaOH
some silica sand
Oh well. To 20 grams of this alcohol tBOC adds 1.2 molar equivalents of ammonium nitrate fertilizer +(NH4NO3)+, 4 mL glacial acetic acid (aldrich, guaranteed 99+%), 1 mL H2O and a dash of cupric acetate for flavoring. tBOC then heats gently on his heating mantle (about 25 out of 120) with a reflux apparatus in place, and takes 60mL water and adds 60mL NaOH to it. Once this solution is made and cooled to room temperature, tBOC removes the heat from the now yellow reaction mixture and cools this by first running cold water over the outside of the flask and then by setting
it in an ice bath for about five minutes. - (I found the original reference to this procedure: JACS Vol 70, page 3666 (1948).
At this point tBOC notices A LOT of white solid at the bottom. tBOC wonders about this, wondering if perhaps he had added too much NH4NO3 to the reaction. Oh well, he thinks, and filters it off, takes the remaining reddish-yellow liquid, and puts it into a sep funnel and adds a total of 9.3mL of his NaOH - (Sodium Hydroxide (NaOH) (Drain Cleaner Crystals) (Read these labels, Get the stuff that is JUST NaOH.)(Red Devil Lye, Lye - Hardware Store)
solution to the yellow stuff dropwise. Two layers are clearly evident: a bottom black yucky layer and a top yellow layer with just the slightest tinge of red.
tBOC pours off the bottom layer, then pours the top layer onto some silica sand in a Hirsch funnel (carefully) and pulls it through with his aspirator. The shit
that comes out is nice yellow beautiful and smells like cardamon. tBOC hates vac distillation, so he checks the solution with a TLC analysis using an 80/20 Et2O/hexanes mixture with 3 spots made on the same plate, a product spot, a rxn mixture spot, and a product/rxn mixture co-spot. The rxn mixture spot is homogenous, and the co-spot reveals that it is definitely not the starting material. tBOC is happy now that he knows he can make a ketone from a terminal alkene in a little less than an hour.
But the final score isn't in. tBOC weighs his product and sees that he has 19g. Goddamn it. tBOC didn't get 100% theoretical yield-- again. tBOC is pissed. tBOC consoles himself with the knowledge that he doesn't have to vac distill and that 20g of his alkene becomes 19g of his ketone in about an hour. tBOC guesses it isn't all THAT bad. Result 19g MDP2P.
------- Notes on to the oxidation ---------------
tBOC, once he FINALLY got some alcohol made, weighs out
10g (not bothering to wash or purify in any way) and weighs out 10g of NH4NO3 (a rather large molar excess, about 2 mol NH4NO3/mol alcohol) and combines these two in a RBF in an ice bath. tBOC adds a pinch of Cu(AcO)2 and 30ml glacial
acetic acid (aldrich, guaranteed 99+%) and 5mL water straight from the sink. The alcohol is now sitting on top of the acid and not much is happening, so tBOC starts with the gentle heating. After about 10 minutes there is a definite yellow tint to the top layer and acid phase which had initially turned slightly brown is now entirely bluish-green. tBOC decides to let it run for an hour or so and see what happens while he goes off to get laid.
When he comes back 1.5h later, tBOC cuts the power, cools down the mixture and throws it into a sep funnel. After the layers have been sitting for a while (two bong bowls and a cigarette) tBOC separates the two and does TLC analysis on the top layer. THE SHIT COMES OUT AS ONE SPOT ON THE TLC. tBOC weighs it (10g, qualitative... nice!!!) chucks it into the freezer (set to -10C, and it DID NOT FREEZE, btw) and takes the acid layer, which is now the color of dirty pennies, and tries to use it on a second batch of alcohol (bad idea).
3. Reductive amination ---------------
5g of ketone MDP2P - (you can go up to 10g keeping the other quantities the same, see notes below)
21g 35%nitromethane content racing fuel
amalgamated aluminum
75mL 50/50 MeOH/nBuOH (nBuOH is n-butanol, MeOH is methanol)
600mL 50% NaOH
filter
-some 30% HCl
~ethanol*
tBOC starts amalgamating aluminum, puts his 5g of ketone in a sep funnel with 21g 35%nitromethane content racing fuel (as is, straight from package, no purification of any kind) and shakes the two.
Once the aluminum had amalgamated well, tBOC pours off water, rinses the sizzzling aluminum with some distilled water, and reaches for some ethanol to put it in. Unfortunately tBOC doesn't have any. The only alcohol tBOC has is n-BuOH (n-butyl alcohol, 1 butanol)(with the alcohol called for being 50/50 MeOH/nBuOH to keep the temp down)
so tBOC pour 75mL of this over the aluminum in a 1L beaker and adds the racing fuel/ketone mix over the course of about 35 seconds. The reaction starts going crazy, so tBOC throws a wet rag over the top of it and sets it in a spare bedroom an takes off to work.
----------- Keep the reaction below 60C!....see notes
!Best to keep between 40C - 50C!
tBOC comes back, finds the aluminum all dissolved, and throws in 300mL 50%NaOH and dumps the whole thing in a sep funnel. Next morning tBOC pours out the bottom layer and pours in another 300mL 50%NaOH solution and goes off to work.
tBOC comes back, pours out the bottom again, and filters the top layer (about 70mL of liquid) on a buchner funnel. tBOC then figures he'll do an acid base extraction on it then crystallize so he checks pH (slightly alkaline: ~9-10) and starts to add 30% HCl. A white solid started to crash out of solution almost immediately, but tBOC keeps adding HCl until the pH is about 4, then filters off the white crap and puts it in the oven to dry while tBOC separates off the bottom layer of water from the n-BuOH and then smokes a cigarette.
tBOC comes back to find one solid chunk of white crystal in the oven, so he weighs it. 4.1g. "Damn, that sucks. Should've been a whole hell of a lot more, especially since I was soooo careful with monitoring this process," thinks tBOC.
Now tBOC has no way of taking a melting point, so he figures he'll just see what a dab tastes like. tBOC puts a little on his finger and tastes it. Hmmmmm.... salty. BUT tBOC's fingers ALWAYS taste salty to him for some odd reason (don't ask...please...) so he tastes it again. Yup, definitely salty. But it's not all that salty tasting and it doesn't look like any salt he's ever seen. So tBOC
takes a decent chunk (about 50mg, maybe 70-80... not sure) and pops it on his tongue. Yup, definitely tastes rather salty.
tBOC sets it aside, looks up properties of his amine-HCl salt and finds that it is supposedly soluble in alcohol. Ahhhhhhh, maybe it's in the n-BuOH still, thinks tBOC. Or it could be in the aqueous phase he just separated. tBOC pours the water phase on a plate and sets it on top of his oven, which is cooking up some po... er... brownies and tBOC smokes another cigarette while pondering what to do and decides to distill off some nitromethane for next time while he tests a small aliquot of the alcohol for the presence of amine by adding some CH2Cl2 and seeing if anything falls out.
So tBOC sets up his distillation apparatus, which for some reason is a lot more difficult than he remembers it to be. He puts the distillation head on backwards, plugs his mantle directly into the wall socket (without a variable
transformer in place) and wonders how that little elf on his coffee table got into his house.
By the time tBOC gets the distillation apparatus set up he realizes he is actually quite intoxicated and decides that playing with nitromethane wouldn't be a good idea, so tBOC closes up shop and takes off for a very wonderful stroll
in the middle of the night, making it back to his place just in time to crawl onto his roof and watch the most beautiful sunrise of his life.
tBOC goes inside and sees the plate has been sitting on his warm oven for a long time, and has completely dried out, leaving behind a bunch of crap that looks like table salt, laced with some kind of white powder. tBOC smiles to himself, thinking that as soon as tBOC gets some more absolute EtOH he can dissolve the white stuff in it, leaving behind the (supposed) table salt then add some Et2O
or CH2Cl2 or maybe even some n-hexanes to the alcohol to get out some more of that wonderful little elf dust.
Success, thinks tBOC. And it's all OTC. Result >4.1g MDMA.
- - Notes - Reductive amination with Al/Hg + MeOH/BuOH + MDP2P + Nitromethane -
Now on to the fuckups with reductive aminations. tBOC sets up two simultaneous reactions, both with n-BuOH as the solvent using nitromethane reduced as the in-situ amine source. Same scales with both, 0.25mol ketone with 0.40mol
nitromethane added to 40gAl/Hg in 650mL n-BuOH, only one is with 5g ketone, the other with 15g. (tBOC forgets the actual weight amounts but knows he calculated and weighed out these same proportions in each batch.)
The 5g batch runs smooth and clean, no problems. Adding 300ml 50%NaOH and washing with water results in a nice clear top layer that spits out 4.6g white crystals when acidified to pH 4 with 30% HCl. The 15g batch, however, instead of having the yellow color of the ketone disappearing as the reaction proceeds, starts to turn red and when the 50%NaOH is added after it cools, turns into a
black mess. No amount of washing, A/B extractions, etc, yields any product at all. tBOC thinks for a minute, reads Shulgin's add-the-amine-in-yourself method and notices one little phrase: Keep the reaction below 60C....
Well, goddamn. Maybe the 15g batch got a tad too toasty, thinks tBOC. So tBOC takes another 10g ketone and instead of using straight nBuOH, he mixes it 50/50 with MeOH (with a much lower boiling point, should keep it cool enough, thinks tBOC....)
+++++++++++++++++++++++
And he was right. 10g ketone, same proportions of other reagants (with the alcohol called for being 50/50 MeOH/nBuOH), dumped in shitloads 50% NaOH after +
the reaction was done and it had returned to room temperature, washed with water, titrated to pH 4 with 30%HCl and out drops 8.2g product.
So, tBOC has learned that once he has his safrole pure, he can put in about 3h of work and get out up at least 8.2g (likely more) sweet honey crystals as long as he keeps the following in mind:
At least 1.2 mol NH4NO3/mol alcohol and as much as an equal w/w amount. This oxidation is actually a catalytic dehydrogenation with CuO as the active reagant being generated in situ on demand by the NH4NO3.
+
Excess of AcOH: about 35mL of around 80% AcOH works great for 10g not-MDP2Pol.Ya just gotta love the generosity of this reaction towards lazy people who hate measuring shit out .
Keep final reaction cool. Use 50/50 mix MeOH/nBuOH and you should be fine. tBOC SHOULD have known this, it's been repeated over and over again on this board. But tBOC has a tendency to make the same stupid mistakes over and over again without learning from them. +++++++++++++++++++++++++++++++++++++++++++++++
Misc. Notes:
- - - - -
I separate the not-MDP2P directly from the 80% AcOH. If I dilute with water,
?
I find that it tends to diminish the top layer, making separation a bitch,
requiring extraction, filtration, distillation, etc.
