P2P [Phenylacetone] via aldol & Baeyer/Villiger

Cyrax · Sat Mar 19, 2005 6:00 pm

Persulfate oxidation of ketones (general procedure):

The oxidizing agent is prepared in a 500 ml flask equipped with a magnetic stirrer and cooled in as ice bath as follows: In the flask are placed 60 ml of concentrated H2SO4 and 20 ml of H2O, and the solution is cooled to 10 °C. K2S2O8 (42 g, 0,15 mole) is added slowly to the stirred solution while maintaining the temperature below 10 °C. The solution is diluted with an additional 65 ml of water maintaining the temperature below 15 °C. (EDIT: as you can see, the persulfuric acid is obtained in situ by hydrolysis of K2S2O8: K2S2O8 + H20 + H2SO4 --> H2SO5 + 2 KHSO4) The solution is now cooled to about 7 °C and 0,08 mole of ketone is added over 40 minutes. After the addition has been completed, the solution is allowed to com to room temperature and stirring has been continued for 20 hours. The solution is diluted carefully with 150 ml of water and axtracted twice with 75 ml portions of ether. The ether is washed with NaHCO3 solution, followed by water, and the ethereal solution is dried. Removal of the solvent, followed by fractional distillation (EDIT: in our case, followed by hydrolysis of the enol ester), affords the product ester.

ref.: Monson, Richard S.; Advanced organic synthesis: methods and techniques (1971), p 11

Mabey somebee should try out this reaction on 2-acetylpropenylbenzene Very Happy

Another possibility is to prepare Baeyer-Villigers 'dry reagent' by mixing 10 g potassium persulfate with 11 g concentrated H2SO4 in a mortar, adding 30 g of K2SO4 and grinding the mixture in a dry powder. This reagent is stable in absence of moisture. Oxidations have been carried out using suspensions of dry reagent or solutions of persulfuric acid in concentrated or dilute sulfuric acid, in glacial acetic acid, in petroleum ether, and in ethanol-sulfuric acid.

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Cyrax · Mon Mar 21, 2005 10:27 pm

Great work, that performic oxidation ! That reaction has also been done with peracetic acid on 2-acetylpropenylbenzene, in 1936 (Rec. Trav. Chim. vol 55 p 786) ... but not with performic acid, as far as I know.

There is some article in JACS or JOC (this bee forgot to write down the name of the journal when he copied the stuff) from 1946, p 907: "The convenient preparation of per-acids", where they reach a maximum performic concentration of 4,7 % after 2 hours:

Procedure (*): '9,2 g of formic acid (98 - 100 %) was added to a specially cleaned volumetric flask containing a catalytic amount of concentrated sulfuric acid (1 % concentration on total contents). The flask was immersed in a water-bath, agitated with an air stirrer, and maintained at about 20 °C: 33,7 g of 30 % hydrogen peroxide was then added to the flask contents. Maximum performic concentration is 4,7 %, reached within 2 hours.'

Remark: Performic acid is less stable than peracetic acid, gassing being noticeable after a few hours of standing, and the effective concentration showing a definite decline in 2 hours

The effect of ageing is nicely illustrated with a beautifull graph. The Frank P. Greenspan article rules Smile

I shall elaborate further from this literature, where an example of the peracetic oxidation of 2-acetylpropenylbenzene is given:

'En mélangeant 2-acetylpropenylbenzene, avec une molécule d'acide peracétique en solution d'acide acétique glacial, la solution contenant environ 20 % de l' oxidant, il faut refroidir pour maintenir la températue sous 30 °C. Après 8 heures tout l'oxydant est consommé.'

Further in the article, they prove that the substance made is the acetate of the enolized ketone Idea

.

Discussion: 20 % concentrations of peracids aren't made easily. I rather do not dabble with 90 % hydrogen peroxide solutions, but a 8,6 % hydrogen peroxide solution is easily made by following the earlier mentioned the procedure (*) with 10 grams of glacial acetic acid (instead of the formic acid, of course Smile

), 28,8 g of 30 % hydrogen peroxide and 0,4 g of sulfuric acid. Maximum peracetic acid concentration is 80 to 90 hours. Idea

Now, since according to the french article the reaction takes about 8 hours, one can simply age a 30 % H202 / glacial acetic acid / drop of H2S04 for 80 - 90 hours (in the 90 - 100 hours period, the high concentration remains stable) & in that period of time, one can carefully & portionwise add the 2-acetylpropenylbenzene to a cooled (!) peracetic solution. One can do the math for the right stoichiometry.

If somebee speaks better French than me, please translate (I give it a try upon request).

Cyrax · Mon Mar 21, 2005 11:45 pm

Here is another example of the H2SO5 Baeyer-Villiger oxidation:

'A mixture of chalcone (i.e. Ph-CH=CH-CO-Ph) (2,08 g, 10 mmol), potassium peroxydisulfate (5,4 g, 20 mmol), conc. sulfuric acid (5 ml), and glacial acetic acid (70 ml) were kept at room temperature (~17 °C) with intermittent shaking, for 170 hours. The mixture was neutralized with potassium hydroxide solution (10 g in 60 ml of water) with ice cooling so as not to allow the temperature to exceed 20 °C. The precipitated salts were removed by filtration and the filtrate was extracted with ether. The ethereal layer was dried (MgSO4), solvent distilled off, and the residue was chromatographed on a column of silica gel. Elution with petroleum ether afforded trans1-phenyl-2-benzoyloxy-ethylene (i.e. Ph-CH=CH-O-CO-Ph) as colorless needles. Yield: 450 mg, 20 %.'

ref.: Synthesis, communications, (september 1973) p 542

Cyrax · Tue Mar 22, 2005 7:34 am

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Cyrax · Sat Mar 26, 2005 1:40 am

I think it is a good idea to hydrolyze the product of the BV reaction anyway, by refluxing it for 10 hours in 15 % H2SO4. If the double bond of the 2-acetoxypropenylbenzene oxidized further to the epoxide, the hydrolized product of the epoxyester would be Ph-CH(OH)-CO-CH3 whereas the hydrolysis product of the normal BV product would be P2P, of course. If an epoxyketone was formed (not by the BV, but epoxidation) hydrolysis gives benzaldehyde.

I hope this makes analysis easier.

Which procedure did you experiment with, if I may ask?

Good luck,
Cyrax

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bio · Working Bee

Cyrax, you said;

........ reaction has also been done with peracetic acid on 2-acetylpropenylbenzene, in 1936 (Rec. Trav. Chim. vol 55 p 786) ...
If somebee speaks better French than me, please translate (I give it a try upon request).........................

I am hereby requesting your services as translator of subject article. Laughing

I spent a loooong time trying but finally gave up.
IndoleAmine tried as well. Those f......g french words they use have 10-20 meanings and in a chemistry context I didn't have a clue which was closest, so times and temps were about all I got out of it.

The pertinent part is quite short and there could be a real gem hiding somewhere in the Boeseken articles in general.

Interesting stuff on the intermediate ester/epoxide. Yes, Boeseken did get the mechanism wrong as the instrumentation/equipment in his day was nothing compared to today. I need to go back and read the two B/V review articles again and Cyrax if you haven't read the perborate/percarbonate review article please do and compare the peracid formation time with the JACS article.

twodogs · Sun Apr 03, 2005 8:02 am

Bio said ...

"SWIM always used dry HCl gas, but there was some mention from twodogs in some of his rantings that mention using H2SO4. He stated he got good yeilds by adding catalytic amount of H2SO4 to the mix and refluxing."

...rantings??? ..and I never said that!

bio · Working Bee

Hi twodogs nice to see you're around.

That statement from the WD thread was made by Madchemist.

It certainly was NOT made by me.

I have almost never used the term SWIM and recall being somewhat alarmed when I first read it. This is not the first time you have been misquoted either. Perhaps the price of fame, lol.

What I did say recently was

"Twodogs the person that introduced this method to the Hive some years ago said in the original thread that he tried aqueous sulfuric acid and also concentrated HCl acid but did not get the results he did with the HCl gas. There was no further elaboration on the difference in yields."

This was to correct another misstatement by others. Just want to set the record straight and no hard feelings.

bio

twodogs · Sun Apr 03, 2005 2:23 pm

Not a problem Bio. Have you made much progress with this procedure?
I remember commenting back at the Hive that I thought what was needed was a catalyst. In the review of the B-V reaction in "Organic Reactions" someone has got a 90% result using a catalyst. Have you looked at that review?

Cyrax · Sun Apr 03, 2005 7:33 pm

bio · Working Bee

Yes, twodogs, the oxidation yield is up to about 47g/100g and the workup of the aldol product is more or less eliminated with the recycle improvements.
IndoleAmine proved out the peracid method you suggested but not much has really been done with the catalyst development. A couple bees from the Hive that were working together w/ me were lost touch with so progress is slooow.
I am familiar with the article but need to review it again for that specific reaction which may be the tin on zeolite I think. This catalyst I have a patent on and making it is more work than the rest of the procedure put together. Other than the exotics like rutheniumwhateveritis no simple ones have been found or tried by me other than 98% H2SO4. Indicators point to MnSulfates as the one to try first. BTW recycling does work as you expected.

Cyrax; thanks for the translation. I was hoping for more at least a yield. If you need the other Boeseken articles I can send them. Perhaps you could read them over for clues as they all pertain to ketone oxidations. Even benzylideneacetone must have a use even if it is missing one carbon damnit.