Org Prep Daily

March 16, 2008

Tetrabutylammonium Permanganate

Filed under: procedures — milkshake @ 9:52 pm

purple.gif

In a 0.5L beaker, a slurry of tetrabutylammonium hydrogensulfate 34.0g (100 mmol) in ice cold water 50 mL was treated with 1M NaOH 101 mL and the mix was stirred until complete dissolution. (The pH of the solution was about 11-12, on indicator paper strip). While stirring with a large stainless steel spatula,  aqueous 40% sodium permanganate solution 29mL (=39g, 110 mmol, Aldrich) diluted with cold water 50 mL was gradually added to the beaker and the obtained thick sludge was hand-stirred on ice bath for 20 min. During this time the produced blackberry-colored congealed mass became fine-grained and purple supernatants separated. The solids were collected on a large glass Buchner funnel (350mL, medium porosity), the cake was thoroughly compressed on the funnel, washed with ice-cold water (8x20mL) then fluffed up with a spatula again and washed with more ice-cold water (100mL). In the final washing stage, the produced washings were only light-purple. The solids were dried by air suction and then on highvac.
Y=35.78g (99%) of a bright violet powder.

Note 1: Drying this quantity of material on highvac took one full day. The product is best stored in a dark bottle in the fridge.
Note 2: I just put a small heap of the dried product to torch and it burned wickedly fast like gunpowder – with a puff.
Note 3: People inhaling manganese oxide dust or injecting themself with permanganate solution can develop a Parkinson-like irreversible CNS damage.

26 Comments »

  1. Awesome!
    What did you use it for?

    Comment by N — March 17, 2008 @ 12:28 am

  2. Oxidation of N-aryl pyrrolidine to N-aryl pyrrolidinone (0.1M substrate solution in DCM, 2 equivs of permanganate added in one portion as a 0.2M MeCN solution, RT, 45 min stirring, workup with aqueous bisulfite, extraction with ether)

    Comment by milkshake — March 17, 2008 @ 1:10 am

  3. Alternatively, you could just mix aqueous solutions of KMnO4 and Bu4NBr, filter, rinse the precipitate with water and ether, and dry o/n on hi vac (JACS 109, 5703). It worked perfectly fine for me w/o further purification when I was doing some manganese complexation chemistry. Beats hand stirring for 20 min :-)

    Comment by Course 5 UROP — March 17, 2008 @ 2:43 am

  4. Thank you for the reference – I was not aware of it; I am probably making things more complicated than they have to be. I just needed some organic-soluble permanganate last night so I looked up what kind of quat salts we had in house and I improvised the procedure.

    The reason why I stirred it by hand was that the mix was quite thick initially and my rod-shaped stirbar got stuck. (It probably does not need to be stirred that long, I just wanted to make sure all trapped solution get mixed up properly). I am glad not to have Br- around (traces of Br- can probably affect the long-term storability) but ether washing is a good trick; it should shorten the drying time.

    Comment by milkshake — March 17, 2008 @ 3:10 am

  5. I suppose you could generate TBA manganate in situ using TBAB and KMnO4, right? I remember doing something like this way back in grad school. For what oxidation or how well it worked escapes my memory :)

    Comment by moody blue — March 17, 2008 @ 10:39 pm

  6. there is a paper in J Het Chem using BnNEt3Cl and KMnO4 (3+3 equivs) in refluxing DCM to oxidize dialkyl anilines which was the inspiration for me. They mentioned the pre-formed isolated permanganate salt was explosive but it gave them a somewhat improved yield than the in situ – formed reagent. I did not have BnNEt3Cl and did not want to wait for it. Instead of doing quaternisation of NEt3 I thought I might as well try to isolate the Bu4N salt which should be much less risky to handle as a dry solid (because it has no benzylic and aromatic protons) and see how it works. It turns out the oxidation is pretty fast in DCM at RT and it seems that two equivs of permanganate are needed (with 1.5 eq. the oxidation did not complete)

    Comment by milkshake — March 17, 2008 @ 11:17 pm

  7. Detonation of benzyl(triethyl)ammonium permanganate during drying at 40°C under vaccuum are reported
    See : Graefe, J.; Rienaecker R.; Angewandte Chemie (1983), 95(8), 634 et cited literature
    I avoid to dry this product
    I use it ‘in situ’ or as a solution

    Comment by J-Paul Dej — March 20, 2008 @ 1:13 pm

  8. Then it’s “Org Prep Deadly”. Harr, harr harr…

    Comment by Heinz — March 20, 2008 @ 2:55 pm

  9. The first trial of L-DOPA in the treatment of Parkinson’s disease was done in Chilean manganese miners, so elemental manganese (and perhaps oxidized manganese) can cause the disorder. My patients were in their debt. But do people really inject themselves with permangante, and if so why?

    I did take care of a soldier who injected himself with peanut butter having heard that it produced a good trip. He died from small embolic peanut butter occlusions of his vessels.

    Another historical note — synthetic chemists also got into the act, trying to make demerol (a narcotic) analogues and came up with MPTP which produced severe Parkinsonism after 1 or 2 injections. It’s led to a lot of experimental work (on monkeys), but no useful therapy has come from it despite over two decades of trying. MPTP is metabolized to MPP+ which is thought to be a mitochondrial poison — but just why it affects dopamine containing neurons while leaving everything else in the body pretty much alone isn’t known — theories abound.

    Comment by Retread — March 20, 2008 @ 10:12 pm

  10. They do some work with MPTP here at the institute and it is not that selective neurotoxin actually. From what I heard it is rather easy to overdose the mice with MPTP and kill them. Also the produced effect is fickle – the mice end up with a variable dopaminergic neuron depletion (which is a big problem if you need as uniform group of animals as possible, when developing a drug to halt the PD progression..) If I remember correctly MPTP is taken up by dopamine transport system, MPP+ in cell decouples respirative chain and produces oxygen radical species. (And I would expect also that the production of dopamine by the dopaminergic neurons by itself puts them under increased oxidative damage pressure so perhaps they naturally need lesser insult, to keel over.)

    The permanganate injecting – there is a link – was done by Latvian drug users who mixed ephedrine (or pseudoephedrine) with permanganate to produce methcatinone in situ – and they would inject themself with the whole goddamned mix.

    Comment by milkshake — March 20, 2008 @ 10:28 pm

  11. We’re saying the same thing about MPTP, as the respirative chain is found in mitochondria. There are also neurons in the brainstem which produce norepinephrine (which can be regarded as slightly oxidized dopamine), but they are unaffected by MPTP as are the neurons in the brainstem producing serotonin. The selectivity of MPTP is incredible (all cells in the body have mitochondria except red blood cells) and such selectivity and the hope of finding similarly selective compounds for other problems keeps legions of pharmaceutical chemists busy.

    Thanks for the note about methcathinone. I Googled it, and there is all sorts of rogue chemistry out there for making it. The Latvians definitely skinned the Khat.

    The notion that oxidative products product can be equated with physiological badness is certainly the dominant Zeitgeist, but it might be wrong. Have a look at the post “We had to destroy the village in order to save it” in Chemiotics in The Skeptical Chemist. Confirmatory data on the points raised is coming out and I may do another post on the subject. If the work cited there is correct (and true in general) it would be a major paradigm shift, an always exciting event.

    Comment by Retread — March 21, 2008 @ 8:02 am

  12. For those (including me) who don’t know about MPTP and related compounds: http://en.wikipedia.org/wiki/MPTP

    Hey guys, your knowledge impressed me!

    Comment by Vasili — March 21, 2008 @ 4:27 pm

  13. we write these know-it-all comments mostly to show off. I am very impressed that I made you fall for it.

    By the way, the Wikipedia article you linked contains two bits of useful info that I was unaware of, so I mentioned it to the competent people here.

    Comment by milkshake — March 21, 2008 @ 7:39 pm

  14. Just incorporate those “bits” into your next showing…

    I just don’t mind if you like to show off, providing there is some truth there. These facts are useful to my next off-line showings too…

    Comment by vasili — March 22, 2008 @ 5:05 am

  15. Yup, no question. We do it for the fame and glory it brings. That’s why we use pseudonyms.

    Comment by retread — March 22, 2008 @ 9:43 am

  16. Detonation risk rule of thumb?? Somewhere I heard a general rule to guesstimate when you need to worry, that involved a simple carbon:heteroatom ratio. Anyone know it?

    Comment by Jose — March 24, 2008 @ 1:23 pm

  17. PROTIP: Using terms like ‘guesstimate’ and ‘proactive’ will make you appear to lack creativity and reflect an inability to think for yourself. This is why such terms are the favored vernacular of most postdocs.

    As a general rule of thumb, the more heteroatoms you have in pi-systems with carbon or bonded to each other (O-O, N-N, N=N, N=O, etc) the more chance of detonation you will get. There comes a point when you start to get a pretty good eye for what will be explosive and what won’t be.

    Also, base sensitizes aliphatic nitro and azido compounds.

    Comment by Azulene — March 27, 2008 @ 11:32 am

  18. Uncle Al, is that you?!

    Comment by Jose — March 27, 2008 @ 12:29 pm

  19. No. Most certainly not. No sage here, but the advice is valid.

    Comment by Azulene — March 27, 2008 @ 11:49 pm

  20. I used to work with bis-pyridine silver permanganate AgPy2MnO4, which is soluble in organic solvents. It is readily prepared from potassium permanganate, silver nitrate, and pyridine. The salt could be stored for weeks in the fridge, and was insensitive to hammer blow.

    Comment by horks — March 29, 2008 @ 5:05 am

  21. Pyridine and KMnO4 are great conditions to oxidize benzylic carbons. I have experienced Mono, Di, and Tri oxidations of benzylic methylenes to give the corresponding mono, di, and tri ketones.

    Comment by MRLchemist — November 1, 2008 @ 6:13 pm

  22. Hi MS,

    I am having problems in the oxidation secondary alchol with benzimidazole substiutent. This convesrion is known with Potassium dichromate but I got the product with low yield. I also tried Mno2, CrO3 but did not get the desired product. Please suggest me any oxidants which oxidize secondary alcohols with heterocyclic substiutents.

    Thanks for the help.

    Marto

    Comment by marto — August 23, 2011 @ 1:33 pm

  23. Thanks very much for this.

    Comment by marto — August 23, 2011 @ 11:54 pm

  24. Hi MS,

    Please suggest some oxidation agents for substiuted toluene to the carboxylic acid derivative on higher scale (kg scale)
    or any other way I can prepare

    Thanks

    Marto

    Comment by marto — November 22, 2011 @ 9:36 am

    • I have seen actually this ArMe to ArCO2H oxidation done with potassium chromate K2CrO4 (not the dichromate), in water, in a pressure flask at something like 120C if I remember correctly. CrO3 in acetic acid as a solvent with heating should work too but you need to be very cautious because that system can be prone to exothermic runaway

      Comment by milkshake — November 22, 2011 @ 11:23 am


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