Author Topic: Possible Peracetic Revision  (Read 17441 times)

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Semtexium

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Re: Possible Peracetic Revision
« Reply #20 on: October 04, 2001, 11:35:00 PM »
This is straight out of the peracid review that's on Rhod's site.  Simply omit the acetone, i.e. don't use any...  AFTER you successfully complete as written(minus the acetone)THEN modify it...  ;)

Peracetic acid Oxidation [5]
I became interested in the substitution of peracetic acid for performic acid for the oxidation of isosafrole to MDP2P because acetic acid is much more readily available than formic acid, and should be able to do the job just as good. It was inspired by a discussion in the Usenet newsgroup alt.drugs.chemistry in 1996 [6]. Improvements to the procedure outlined there was made by me, and it was tried out by Semtexium (aka Semtex Enigma), and the results follow here. An added improvement would be to neutralize the sulfuric acid used to catalyze the formation of the peracetic acid with 25 grams of sodium acetate before adding the isosafrole. Performic acid forms very easily just by mixing formic acid with hydrogen peroxide, but with acetic acid, it requires a strong acid catalyst and 12-16 hours standing[7].

Chemicals:

Peracid:
1500ml of Glacial Acetic Acid
325ml of 30% H2O2
5ml of H2SO4
Olefin:
500ml Acetone
325g of Isosafrole
Solvents:
7500ml of Water
1500ml of DCM
500ml of MeOH
H2SO4 (15%):
368g (200ml) of concentrated H2SO4
2300ml of Water
Wash(s):
1250ml of Water
1250ml of NaOH 5% solution
Drying:
50g of Anhydrous MgSO4
Distillation:
100ml of Cooking oil to prevent scorching
Procedure:

Mix the peracetic acid chemicals together in an appropriate sized flask (3L), swirl or stir solution until thouroughly mixed and let stand for 12 hours.
Combine the olefin chemicals and place into the freezer to chill.
Bring the peracid solution down to 5°C with the help of an ice/salt/water bath. While magnetically stirring this solution sitting in the ice bath, add the now chilled olefin solution to the peracid solution at such a rate that the mixture stays below 40°C. After all of the olefin has been added, let the solution stir for 16 hours, letting the ice bath melt away and the solution come to room temperature on it's own.
After the 16 hours of stirring has elapsed, pour the solution into 7500ml cold water, mix thouroughly, and extract this mixture with 3x500ml DCM. The extractions are combined and the solvent removed via distillation to yeild a thick, dark red syrup.
This syrup is taken up in 500ml methanol and added to the 2500ml 15% H2SO4 solution and lightly refluxed for two hours, after which time the flask is cooled under running water and/or the use of an ice bath, do not proceed until solution has reached room temperature or lower.
Using a large sepratory funnel or by simply pouring off the acid layer collect the dark bottom layer BEFORE extracting this mixture with 3x400ml DCM (you did reuse the DCM from the first extraction, didn't you?). Combine the extracts with the dark layer which was first collected and proceed.
Wash this dark mixture of ketone/solvent with 1250ml of water, then with the 1250ml of the 5% NaOH solution which was made previously. Please note that the separation with the second wash will be difficult to see, therefore the use of a flashlight is favorable to determine the different layers.
Dry organic phase over 50g of anhydrous MgSO4 (made by baking epsom salts at 300°C for a couple of hours, let cool, then grinding into a powder) making sure to filter off the MgSO4, and washing the filter cake with a small amount of DCM. The solvent is removed and kept for a later run, the resulting residue is combined with 100ml of vegetable cooking oil and distilled under vacuum to yield ketone (>200 grams) [That is a 56%+ yield].


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PoohBear4Ever

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Re: Possible Peracetic Revision
« Reply #21 on: October 04, 2001, 11:50:00 PM »
Thanks for the ref, and SWIP has reviewed said procedure prior to posting.  Going back to moles, it appears that the amount of H2O2 would produce 3mol peracetic acid for 2mol isostuffrole, leaving 1300ml GAA unreacted.  Is this for proper solvation of the isostufrole, for it would be a more dilute concentraion if, say, we used 800ml GAA.  Would higher concentraion peracetic give higher stuffrone yields,  or would that concentraion be too unstable? 


PB

Rhodium

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Re: Possible Peracetic Revision
« Reply #22 on: October 05, 2001, 12:10:00 AM »
The rest is for the solvation of the isosafrole and the formed glycol. For stability reasons, never make a peracetic acid solution stronger than around 30%. Below that, the amount of GAA can be changed at will, I believe, and only experimentation can tell how low you can go with the amount of solvent and still obtain the same yield.

I really encourage people to diddle with this, as the peracetic oxidation isn't at all perfected yet, as it is relatively new.

PoohBear4Ever

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Re: Possible Peracetic Revision
« Reply #23 on: October 05, 2001, 01:07:00 AM »
Thanks for the info.

If SWIP used 4mol H202, in 30% solution with 320g H2O,  with 15mol GAA, he would end up with a 28.8% solution of peracetic acid.  Would the remaining 11mol GAA (650ml) be suitable to dissolve 200g isostuffrole, if no addition solvent with iso is used?  Would be 2mol less than the writeup above using same amount, though there would exsist 1.3mol more peracetic acid. 

Thanks if you can answer any of the above,

PB

Rhodium

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Re: Possible Peracetic Revision
« Reply #24 on: October 05, 2001, 01:42:00 AM »
I belive that would work. However, with less solvent volume, the temperature must be CLOSELY monitored, as there is not much excess solvent to absorb the generated heat. Preferably, you should cool the reaction with an ice-bath, and make sure the reaction temperature NEVER exceeds 40°C. Otherwise a runaway reaction may occur, or the high temp lowering yields. Don't forget to report back on this experiment.

foxy2

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Re: Possible Peracetic Revision
« Reply #25 on: October 05, 2001, 01:43:00 AM »
What DMDO cannot be formed in situ???

EPOXIDATION PROCESS WITH A PARTIALLY NEUTRALISED CARO'S ACID SOLUTION
This invention concerns a process for the epoxidation of alkenes.

Alkenes represent convenient starting materials in the synthesis of organic chemicals because they are often readily available in good purity and at relatively low cost. Much of their utility arises from the presence of a relatively reactive functional group - the carbon - carbon double bond - within the molecule. Additional or alternative functional groups can conveniently be added to the aikene by reaction at this site.

One common way of introducing functionality is to employ an epoxidation of the double bond(s). Many reagents and processes have been proposed for carrying out such epoxidations. In recent years, one particular class of reagent that has attracted much interest comprises dioxiranes on account of their relatively high reactivity. Dioxiranes can conveniently be formed by contacting a suitable oxidant with a ketone, and two distinct methods of employing them as reagents can be identified. The first is to preform a solution of dioxirane, usually as a solution in the corresponding ketone. This solution can then be stored until it is desired to employ it in a reaction. Such processes are less favoured because dioxiranes are generally not very stable, and readily decompose on storage, even at low temperatures.

Unless the dioxirane solution is used relatively quickly, the solutions can therefore suffer from significant loss in activity.

A more convenient method is to employ dioxiranes generated in situ in the reaction medium. This avoids the need for low temperature storage units for dioxirane solutions and allows the use of more stable oxidants which can be more readily stored.


foxy2

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Re: Possible Peracetic Revision
« Reply #26 on: October 05, 2001, 03:45:00 AM »
Dioxirane mediated steroidal alkene epoxidations and oxygen insertion into carbon-hydrogen bonds
Tetrahedron Letters
Volume 32, Issue 4
21 January 1991
Pages 533-536

Dioxirane generated in situ from reaction of ketone with KHS05 at O-5C in aqueous phosphate buffer/methylene chloride containing Bu4NHS04 - pH maintained at 7.5 by pH stat controlled addition of 5M KOH.




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Chromic

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Re: Possible Peracetic Revision
« Reply #27 on: October 05, 2001, 10:30:00 AM »
I stand corrected. All of the refs I've read up to this point have always isolated it. Good news.

PoohBear4Ever

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Re: Possible Peracetic Revision
« Reply #28 on: October 07, 2001, 02:43:00 PM »
Noticed that Shulgin uses 40% peracetic acid (in acetic acid) extensively in his synthesis (epoxidations?), and I wonder at the fesibility of creating this concentration without decomposition if GAA and H2O2 are allowed to mix in a fridge, at say 10C. This percent seems LG standard, no? 

PB

* BTW, is technical grade celite sufficent for filtering, or must it be analytical?

Rhodium

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Re: Possible Peracetic Revision
« Reply #29 on: October 07, 2001, 04:32:00 PM »
That 40% peracetic acid is made by adding strong (over 50%) H2O2 to acetic anhydride, which makes it not only strong, but also anhydrous. Some stabilizing agents are probably also added to the commercial product.

Shulgin uses it primarily in the bayer-villiger oxidation of aromatic aldehydes to phenols.

PoohBear4Ever

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Re: Possible Peracetic Revision
« Reply #30 on: October 08, 2001, 03:14:00 AM »
Could one dissolve isosafrole in peracetic acid prior to addition in flask, or would the two react in the addition funnel, and produce too much heat?  How viscous is isosafrole?

PB

Rhodium

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Re: Possible Peracetic Revision
« Reply #31 on: October 08, 2001, 03:52:00 AM »
No, they would react in the addition funnel. The viscosity is lower than olive oil.

PoohBear4Ever

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Re: Possible Peracetic Revision
« Reply #32 on: October 08, 2001, 04:35:00 AM »
Alrighty, well besides DCM and acetone, SWIP can't think of any other NP solvents suitable, and will proceed without.  Here's the experiment:

325g Isostuffrole (~2mol)
1150ml GAA (~19mol)
450ml H2O2 (30%) (~4mol)
9ml H2SO4 (~ 1% )

Should get a 20% peracetic acid solution, which is 2x mol necessity.  In the review, the concentration was 12%, so this is 8% stronger.

PB


Chromic

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Re: Possible Peracetic Revision
« Reply #33 on: October 08, 2001, 06:20:00 PM »
Rhodium, have you ever handled isosafrole? It's a heavy colorless white liquid that has a viscosity like water. It doesn't evaporate easily (unlike water) and hence, doesn't "cool down the hands". It has most of the properties of GBL in those respects, however it has a distinctive smell that is unlike safrole but quite similar.

PB, I would cut back on the H2O2 to what is recommended. I would try and scale back the amount of acetic acid that Semtex used because it's just more solvent that will have to be extracted and is present in a very, very healthy excess. I'd still go with:

325g iso (2mol) in 500ml dcm
340g 30% H2O2 (3mol)
360-720g HOAc (6-12mol)
5g H2SO4 (1wt% of the mass of H2O2+HOAc)

The DCM should have in theory kept the temperature around 30-40°C, however I found that mixture didn't boil until it got considerably hotter than 40°C.

PoohBear4Ever

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Re: Possible Peracetic Revision
« Reply #34 on: October 08, 2001, 08:01:00 PM »
Ok, thanks for the tips an suggestions.  Just last night, I came across the the thread in which your dreams were discussed (Chromic).  I noticed that only a few bees (3 maybee) used DCM in peracetic, goiterjoe being one. He didn't get his desired ketone; however, he also used sodium acetate to buffer, which could also have been a factor.  It seems that DCM has been used successfully in performics, so it shouldn't really be any different in the peracetic, right?

The only problem I saw in cutting back the HOAc would be going over the 30% concentration rule. Will try to get my original 20% solution still, and will likely scale back the H2O2 to your suggested ratio. When mixing the peracid, would it be best to slightly cool in fridge while mixing for 12hr to advoid decomposition, or have most used room temp when doing so?  Should one use stirring during this time frame, or just upon addition of chemicals?

Also, it seems in the above post I was figuring the catalyst without compensating for the water in the H2O2.

Thanks for the help,

PB

Rhodium

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Re: Possible Peracetic Revision
« Reply #35 on: October 08, 2001, 08:41:00 PM »
Chromic, that GBL similarity is a good example. It is also less viscous than olive oil, but more so than water.

PoohBear4Ever

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Re: Possible Peracetic Revision
« Reply #36 on: January 06, 2002, 04:16:00 AM »
Here's what SWIP is dreaming of dreaming in a few weeks:



A) Distill
·   Add .5g Hg  to each (8) tincture bottles for 3days min.
1)   Use grease on joints, insulate up to column with foil, room temp water through column, give air-leak when heating without vacuum.
2)   Add 250ml stuff with to 500ml RBF, 250ml RBF receiving.
3)   Slowly bring stuff to 130C to boil off water, with stirring, till no steam is left, then bring up to 234C (BP of stuffrole), and let cool to room temp.
4)   Begin vacuum slowly, with heavy/fast magnetic stirring, then slowly bring to ~121C (depends on vacuum; see bottom).
5)   Try to get 5-10 drops a minute, and do not go above 160C (try to keep 5 degree range for distillate), do not distill dry.
6)   Use safflower oil bath, in aluminium or copper bowl with stir bar in oil bath, along with one in flask, flask not touching bowl.
*About the first 7-10% of the distillate is crap, the next ~85% is stuffrole, and the deep red shit in the boiling flask is more crap.

B) Isomerize
       *Start peracid sometime 12hr prior to being done.

1)   Fit flask with reflux condenser with vacuum attached as per distillation.
2)   Add 3g KOH in small portions to 200g stuffrole, then bring to reflux under vacuum (130C) with damp-rid in condensor and receiving flask.
3)   Reflux for 10-12hr (boiling will be smoother when finished), and then turn off heat, let cool 2hr.
4)   Heat stuffrole to BP, then allow flask to cool, and change receiving flask and  wash with acetone.
5)   Begin vacuum slowly, and distill isostuffrole at ~ 136C (15C over stuffrole; ~ 240C bath temp).

C) Oxidation
1)   Add 650ml AA(90%), 140ml H202 (25%), and 8ml H2SO4(32%), to 3L RBF, stopper flask, and shake thoroughly.
2)   Once well mixed, let sit 11hr, then chill 1hr in fridge to 20C min.
3)   Add 140g isostuffrole with 220ml acetone, then chill in freezer (~5C).
4)   An ice/salt/water bath used to keep flask cool, ~ 5C.
5)   Slowly add isostuffrole/acetone solution to flask (~35min), with good stirring, keeping temp below 20C (temp stabilizes after ~1hr).
6)   Remove ice bath, let stir for 16hr (keep flask temp 20-30C).
7)   Add flask contents to 3.6L water, then separate glycol/epoxide, and extract this with 3x with 210ml DCM (may break down into three portions; if emulsion forms with DCM, use a little salt to break up).
8)   Wash with dH2O, strip off DCM and save for step 11, then add syrup to 2L flask with 200ml MeOH, and gently heat to ~ 80C. 
9)   Bring 1.1L H2SO4 (15%) to 80C, then quickly dump in this syrup, with hard stirring.
10)   Lightly reflux only for 2hr (75C-80C; steaming, but not boiling), then allow flask to cool, then flood with 500ml dH2O, and set in cold water bath for 20min.
11)    After at room temp, add to sep funnel and seperate off crude stuffrone (on bottom; D=1.2), and extract acid in funnel with 3x180ml DCM, and combined with other seperation. 
12)   Wash once with 500ml dH2O, then once very, very easily shaken with 500ml NaOH (5%) (use black light to determine layers; stuffrone green, on bottom).
13)    Strip off DCM, then distill stuffrone at 25C more than isostuffrole temp (135C-150Cmax).

D)  Animation
1)   Carefully add 60g aluminium and 1.5L MeOH to 3L RBF, and heat to ~ 55C (made before hand by adding 2x tincture bottles to 500ml dH2O + 500ml MeOH with 60g Al, allow 17-30min to react, until grey precipitate forms, likely to be 30 mins,  decant liquids, wash foil with dH2O, then with MeOH; do not expose to air after, store in 1.5L MeOH).
2)   Carefully pour 40ml MeNO2, then 80ml MeOH, then 50g stuffrone to addition funnel, and set into position.
3)   Place 500ml condenser with, optional steel wool, into position; run off heat; start drip rate at 3dp/sec carefully, letting stirrer stay on constantly, 2dp/sec set after.
4)   Try to come to the peak, back off a sec, and then finish addition before amalgamation is done (~ 30min)(try not to let rxn run-away;  there is little un-dissolved Al when done).
5)   After 2hr from initial addition, may need to add more MeOH, then let contents reflux for 3hr, then cool for 30min.
6)   Make NaOH (35%) (mix 530g NaOH per 1500ml water or ice), make sure cool, and slowly add to flask with use of addition funnel.
7)    Let stir for 1hr, then add 900ml xylene to 4L flask, or split into two batches, then decant xylene, and wash contents of flask once more with 200ml more xylene.  
8)    Chill xylene in freezer for 30 min, then decant, leaving garbage in flask.
9)    Wash out sep funnel, then add xylene solution, then wash 3x dH2O (1L) or until clear, then 2x with brine (1L), then once more with dH2O.
10)     Add 60g MgSO4 to xylene in container and shake, then let sit 30 mins.
11)    Filter out MgSO4, wash filter cake with fresh xylene

Crystallization
1) A/B extract (50ml dH2O + 5-6drops muratic (pH 6), dry until syrup, crash out with ice cold acetone, followed by 2x ice cold acetone washes.
2) (*Optional): Dissolve in minimal amount of hot, anhydrous IPA, let cool to room temp.
 3) Add 2x acetone, then seal and place in freezer for 12hr.
 4) Filter out crystals.



Any last words of advise? Should he buffer peracid with sodium bicarbonate, or could this induce any side-rxns?

PB


unnilhexium

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Re: Possible Peracetic Revision
« Reply #37 on: January 06, 2002, 08:11:00 AM »
Well, old unnilhexium, in a profound state of mind at the time of this writing, is going to take advantage of his mental clarity to post EVERYTHING HE KNOWS ABOUT PERACETIC!!!!  Not to mention how we can make it better.

>SWIM believes that the reason that a buffered peracetic doesn't (to the best of my knowledge) work, is that the buffer salt would neutralize the h2so4.  This might sound like a good thing, but wouldn't that stop the further formation of peracetic acid?  Swim believes so.  SWIM feels that the solution is to A)Use a lot of external cooling instead, or possibly, B)Start dripping in a buffer solution at oh... the 8 hour point(untested).

>Peracetic acid is MUCH more brutal to isosass than we give it credit for.  Where else do the yields go?  SWIM doesn't get an iso forerun.  It seems that destruction of iso is not solely related to ph.  Swim plans on testing the ph of a buffered performic, and trying to use an excess of acetic to bring it closer to the same ph at the finish of the addition, for research purposes, and then go from there.

>The obvious flaw of peracetic is, the slow formation.  SWIM is as we speak experimenting with more h2so4, to hopefully catalyze the peracetic more completely in the 12 hour standing time.  SWIM does not believe it will fuck up yields at all.

>From swims experience, it seems that while 2 hours of 75-80C is hot enough for performic h2so4 rearrangements, SWIM thinks it might be better for cleaving the acetyls with a longer/hotter reaction.  SWIM always ran his a little hot, but one time, exactly 2 hours, carefully monitored at 75-80C temps, yielded some obviously fucked up ketone, which was aminated for shits and giggles, and yielded NOTHING.

>DCM and Acetone.  As far as swim can tell, the reduced reaction/surface area of dcm, does wonders for performic, but probably makes it a little to hard for peracetic to function.  Acetone on the other hand, seems to lead to side reactions in performic, and is overkill on the peracetic as well.  Not to mention the risk of acetone peroxide WHICH SWIM STILL HAS NEVER SEEN!!!!  SWIM still feels acetone is the answer, but thinks that using a very small amount (barely enough to co-solvate the peracetic/iso solutions together) might bring us to a high yielding happy medium.

And please, everyone with knowledge, experience, or ideas, contribute what you know to this thread.  Formic is a hard to get for those lacking the courage to buy it, and I am positive that peracetic has not reached its potential yet.  I think the biggest flaw is that all posted synths try to substitute it for formic, rather than treat it by it's own properties.

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Rhodium

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Re: Possible Peracetic Revision
« Reply #38 on: January 06, 2002, 09:01:00 AM »
Unnil: You speak about very probable error sources. Especially that the formation of peracetic takes time. However, the acetone peroxide formation is very real, it is just a matter of chance if it crystallizes or not. Using MEK or THF instead of acetone should take care of that problem. Their peroxides are not so easily crystallizable (and hence not as shock sensitive).

unnilhexium

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Re: Possible Peracetic Revision
« Reply #39 on: January 06, 2002, 09:47:00 AM »
Rhodium:  I don't quite follow what you are saying about "peracetic taking time."  However, I think that MEK would actually work very well, and it is just as easy to get stateside(even though SWIM has thus far perceived a low risk factor from acetone).  I just wanted to ramble off some new ideas, based on the observations of the peracetic oxidations swim has done(quite a few).  Nothing in that post is referenced, or based on anything other than personal(fictitious) observations and experiences.

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