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        Epoxidation of propenylbenzenes using dimethyldioxirane or oxone
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Acme:

For totally kickass epoxidation, SWIM has a sweet spot for dimethyldioxirane as
a solution in acetone. 

ref Chem Ber 2377, 124 1991
Using Oxone, (Ald 22,803-6 1Kg/$24) and NaHCO3, in acetone

So simple and safe a chimp could do it.

Need dry ice, mechanical stirrer and dist apparatus, but in 45 min you might
have 750 mL of 0.1 M Dimethyldioxirane. If yall use 1.1 eq/alkene then would be
enough (at that scale) for 11 g alkene. I agree, it isn't ideal for idustrial
scale syn. Very clean though and simply strip off solvent (recycle?) to yield an
epoxide, so with rearrangement to ketone it could be interesting for the skilled
and well equipped.

Forgive me in advance, please tho, if this idea totally stinks. I realize it
aint catalytic; fuck it, blow it off and ignore it if you want, and I'll just
contentedly fuck off into the woodwork.

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K.C. Nicolaou:

These questions are in reference to a possible propenylbenzene -> epoxide ->
ketone synthesis using dimethyldioxirane as the epoxidizing agent under slightly
basic conditions(pH 7.5-8.0). >95% yields of the epoxidation product have been
reported for a wide variety of alkenes(including styrene, stilbene, an
1-phenylpropene) using this reagent. Also, since the epoxide *should* not
hydrolyze to the diol under these conditions, it may be possible to perform the
epoxide -> ketone rearrangement using a mild lewis acid catalyst instead of the
usual refluxing with H2SO4. If properly developed, this method could be an easy,
fairly OTC, high yielding procedure for conversion of propenylbenzenes
(isosafrole, asarone, etc) to 1-phenyl-2-propanones.

1. Osmium mentioned a method of rearranging the epoxide formed from epoxidation
of propenylbenzenes to give the 2-propanones using a Li salt as a lewis-acid
catalyst. Can anyone direct me to any literature references for this procedure
and/or suggest a set of reaction conditions(solvent/temperature/catalyst
amount/rxn time/etc)? The most convenient solvents in this particular case would
be CHCl3, acetone, or toluene. Any alternatives as far as different lewis
acids(AlCl3, ZnCl2, FeCl3, etc) might also be useful.

2. One of the journal refs I have for this rxn gives a procedure for a biphasic
reaction(H2O and CHCl3) which uses (nBu)4NHSO4 as a PTC to shuttle
peroxymonosulfate ions(HSO5-) into the organic phase where they react with
acetone to generate dimethyldioxirane in situ. However, they use what seems to
me like a riduculously large amount of PTC(.12 molar equivalents) in their
procedure. Does anyone know a general rule for choosing a more modest amount of
PTC for a scaled-up run based on either molar equivalents or solvent volumes?
All of the reactants and products *should* be relatively stable under the rxn
conditions, so rxn time is not a critical issue.

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Osmium:

1) http://rhodium.lycaeum.org/chemistry/guest.phenylacetone.txt

Deals with the electrolytic oxidation of propenylbenzenes (--->epoxides).
These are rearranged in high yield by refluxing with LiI or LiBr in EtOAc.

2) When reaction time is not critical, use less PTC. I guess it will work with
only half the PTC or even less.

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Acme:

A proposal was made like 3 monthes ago, about dimethyldioxirane. However, the
simple prep listed was to get a 0.1 M solution in acetone.

http://hive.lycaeum.org/ubb_board/Forum5/HTML/000581.html

This solution would react (when used in molar excess say greater then 1.1 at the
very least) to epoxidize cleanly the olefin. Strip it off and you got it,
basically.

However, the solvent: olefin ratio is rather high. (I figured 11 g to 750 mL of
the solution). But it looks like LiI/EtOAc would give good conversion to the
carbonyl compound of interest.

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K.C. Nicolaou:

Dammit, I thought that was an original idea . I had the same problem as Acme
with the procedure where the acetone/dimethyldioxirane solution is isolated and
then used, although one of the refs I have indicates that concentrations of up
to .185M could be obtained.

One of the refs I had (J. Org. Chem. 1985, 50, 2847) gives a procedure for doing
a dimethyldioxirane oxidation (It's not an epoxidation, but that shouldn't 
really make a difference) in a CHCl3/water system. Basically, the compoung to 
be oxidized was dissolved in CHCl3 and then acetone, an aqueous solution of
bicarb(to control pH), and the PTC were added. Then an aqueous solution of
Oxone(2 KHSO5/1 KHSO4/1 K2SO4) was added. Transport of peroxymonosulfate ions
into the aqueous layer by the PTC allows for in-situ generation of
dimethyldioxirane, which should rather quickly epoxidize the alkene. Also, since
the pH of the aqueous solution is held between 7.5 and 8.5 during the entire
rxn, and the epoxide is in the organic layer, I would assume that the epoxide
would not hydrolyze(never worked with epoxides much, so if I'm wrong, tell me).

My assumption would be that this rxn could be run with 100g alkene dissolved in
500-1000mL of CHCl3, making it a hell of a lot more efficient than the acetone
procedure. As for the aqueous phase, I was kind of hoping that instead of using
Oxone, which has a lot of extra bisulfate and sulfate salts lying around that
you need to dissolve, I could prepare a solution of monoperoxysulfuric acid from
sulfuric acid and H2O2, and slowly add that to the two phase system. I would
have to up the amount of bicarb by 4/3, but I still should be able to get away
with a much smaller volume of water that way.

As for the rearrangement using a Li salt, the link Osmium posted looks nice, but
I wonder about the emphasis abou using "alkyl acetates" as solvents(ethyl
acetate isn't really that easy for me to get, although I have come to love it's
smell when using it as an extraction solvent). I'll probably try to do the
rearrangement in CHCl3 or CHCl3/acetone before I start fucking around with
trying to get EtOAc.

The chemical formula of dimethyldioxirane is C3H6O2. The structure can be 
visualized by considering the addition of an oxygen atom across the C-O double 
bond in acetone in the same manner as an epoxide. You can also find the structure 
on page 700 of March's Advanced Organic Chemistry (4th ed.) if you have that. 
The description of this reagent given by a professor of mine who is a very 
accomplished synthetic chemist reads as follows: 

Dimethyldioxirane

Review: Chem. Rev. 89, 1187, (1989)
Prepared from acetone and NaHCO3 by addition of oxone, and used in solution in 
acetone. Solution of the reagent is yellowish. Reactions are fast and take place 
at -40-(+)25C. Epoxidation proceeds under mild neutral conditions. Reagent of 
choice for the synthesis of sensitive epoxides of enol esters, enol lactones, 
and enol ethers.

A lot of emphasis on enols, but when he presented this in class, it seemed that 
he was saying that it was an all-purpose alternative for epoxidizing acid 
sensitive compounds that wouldn't survive epoxidation with peroxy acids. 

As far as I know, persulfate is not a good epoxidizing agent by itself. However, 
under slightly basic conditions(pH 7.5-8.0), persulfate reacts with acetone to 
form dimethyldioxirane(three membered cyclic peroxide with both oxygens bonded 
to what used to be the carbonyl carbon of acetone), which is a very good 
epoxidizing reagent. I am looking into that as an epoxidation system for asarone 
and there is a thread under my name in the chemistry discourse about it. 
Persulfate is VERY easy to get. You can either make persulfuric acid from 
sulfuric acid and H2O2, or you can buy Oxone, which is a Dupont trade name for 
a mixture of 2KHSO5/KHSO4/K2SO4, at any home depot or pool supply place as a 
non-chlorine pool shock. The main difficulty with most dimethyldioxirane 
methods is that you can only use fairly dilute solutions(~.15M) of the reagent, 
so I am looking into some alternative procedures using a two-phase CHCl3/water 
system that generates the dimethyldioxirane in-situ. That procedure requires a 
PTC though, and you're still talking about having a total volume of ~2L to 
oxidize 100g asarone.

Actually, I have quite a few refs for the epoxidation rxn/generation of 
dimethyldioxirane part of this. And armed with the LiI rearrangement ref Osmium 
was so kind to give the link for, I plan to check out that end next time I'm at 
the library. I actually have most of the information I need, but I'm trying to 
tie up a few loose ends. What I am really looking for here is the following.

1. A general rule for amounts of PTC to use per solvent amount and/or per mole 
of reactant. Something akin to the rule of thumb you use for determining the 
amount of adsorbent/gram of material when running columns(ie, 50:1 for good 
separation, 300:1 for tight separation).

2. Whether solvent effects are very important for the rearrangement step. I 
would like to be able to use a solvent other than EtOAc, as this would be the 
hardest material for me to get that I might concievably need for this rxn.

3. The location of the equilibrium for the H2SO4 + H2O2 <--> H2SO5 + H2O rxn. I 
would assume that the peracid is kinetically favored because H2O2 is a much 
better nucleophile than H2O, but I'm not really sure about how to best generate 
the persulfate ion needed for this rxn. Using H2SO4 and H2O2 to generate 
peroxymonosulfuric acid would be much nicer than using Oxone if that rxn is 
anywhere near quantitative. I'll look at the performic procedures, as I'm sure 
the issues involved are similar.

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Psychokitty:


SWIM has used powdered OTC potassium peroxymonosulfate (oxone) purchased at any 
pool supply in any amount desired in a modification of the performic reaction on 
our favorite 2-alkene. SWIMM got back 30% ketone -- but only because SWIM 
allowed the reaction mix to heat up CONSIDERABLY beyond the safety margin.  

SWIM has total faith in this reaction but just couldn't afford to experiment on 
any more precious 2-alkene, so SWIM switched to the modified performic, a method 
with which SWIM has more experience.

The reference that details the macroscale reaction SWIM just described can be 
found in somewhere in JOC 1993, SWIM thinks.  Just look up "epoxidation" or 
"epoxide" as keywords in the index.  You'll find the article.  The yield for B-
methyl-styrene (propenylbenzene) was above 90%.

Perform the reaction at 40 deg C for 5 hrs but DON'T let the temp climb above 50 
deg C as this caused EXCESSIVE decomposition in SWIM's first trial.  And even 
then, SWIM still got (after dehydration of the diol) 30% of the ketone. Room 
temp gave low yields even after 12 hrs.  Also, be sure to filter the aqueous 
potassium peroxymonosulfate solution BEFORE you add the 2-alkene, as the 
cloudiness that exists is caused by a "clarifier" that if not removed will cause 
a BITCH of an emulsion later on.

This method is VERY VERY OTC.  All you need is 1-alkene reacted with KOH in EtOH 
to effect double bond migration to the 2-alkene.  This can then be oxidized into 
the 1,2-diol by stirring at 40 deg C for 5 hrs in a water solution of potassium 
peroxymonosulfate.  The diol is then dehydrated by
15% H2SO4 to the ketone.

Potassium peroxymonosulfate (oxone; pool bleach) is the way to go. In a JOC 
article that I don't have on hand, potassium peroxymonosulfate is used to either 
epoxidize or hydroxylate (depending on the pH) B-methylstyrene, better known as 
propenylbenzene. The reaction was performed in a biphasic mixture: water 
containing the oxidation salt was one phase, while the other was the alkene. No 
solvent was used. In my opinion, to get the reaction to work for ring 
substituted propenylbenzenes, heat may have to be applied. The method however, 
is definitely OTC all the way.

No acetone was used. Just water (quite a bit actually), the oxidizing salt, and 
the alkene ONLY. The article can be found in JOC 56, p.7022, 1991. It indicates 
that co-solvents and even PTC catalysts do not affect the reaction 
advantageously. Just stirring and in some cases, heat, were required. Looks 
promising to me. I did mention in the original thread, however, that some soot 
might need to be removed from the water solution before the reaction is 
commenced. It seems harmless, but makes the solution cloudy. Letting the 
solution sit for about 12 hours, maybe less, allows the soot to settle. 
Decantation might work for it's removal. Or filtration. Questions?

J. Org. Chem 1991, 56, 7022-7026 "Oxidations of Alkenes with Aq. Potassium 
Peroxymonosulfate and no Organic Solvents."

"Aqueous KHSO5 oxidizes many alkenes to diols in acid mixtures and to epoxides 
in neutral mixtures with no organic solvents."

The mechanism is similar to the epoxidation of alkenes by organic peroxy acids. 
The researchers feel that this is more cost efective and more practical for 
industrial processes than your standard peroxy acid epoxidations.

"Epoxidation of cyclooctene: In a vigorously stirred two-phase mixture 
(1800rpm), 1.7 molar equiv. of aqueous KHSO5 epoxidizes cyclooctene to >80% 
epoxide with no significant by-products in 5hrs. at room temp (23C). The oxide 
crystallizes and is isolated easily by filtering the reaction mixture."

Example:

3g cyclooctene 185ml of .26M KHSO5 (17.2g Oxone) Stir 1800rpm for 5hrs. Oxide 
produced: 2.85g

All the standard alkenes tested with similar results: (40-90%)

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