posted 09-22-1999 12:07 PM         

from 9/16/98 >>--------------------------------------------------------------------------
Modified performic acid oxidation of Isosafrole
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Beagle:

Here is a small modification to the performic proceedure that I overheard
at a bar. I don't know if it will increase yields at all, but mearly submit
it for your approval. The chemist that worked it out seemed very
knowledgable, so it might be worth a shot.

Combine 41.5 g. iso, 3.8 g Na2CO3, 130 ml CH2Cl2 in 500 ml RB flask w/ a
reflux condenser. Pour 37 g 30% H2O2 in flask, heat to 40 deg. and stir 5
min. Pour 63.8 g 88% formic SLOWLY through condenser. Let cool then reflux
6 hrs. Cool, rotovap off CH2Cl2. Take 68 ml H2SO4, dilute to 450 ml., add
to reaction mixture and heat at 70 deg 2 hrs. Cool, pour into H2O, extract
w/ ether, wash ether w/ sat'd NaHCO3, dry w/ MgSO4, filter, rotovap to
crude brown residue, 65% pure by GC.

Not sure what that Na2CO3 is doing in there. Stabilizes performate?

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Beagle:

Sigh. No one is even going to critisize my post. I guess that I will have
to do it myself:

Why you miserable worm! You worthless cretin! How dare you post this
garbage. Everyone knows that there are better methods of making ketone now.
So what good is this? 65% yield? That sux! And that bit about heating the
reaction? Everyone knows that the reaction must be kept at lower temps to
work well. Fuck Off and Die!

To which I reply:

Jeeze, you don't have to be nasty about it. So there are better methods
talked about here for making ketone. People are still obviously dreaming
with this method so I wanted to post some independant knowledge. Not
everyone has Palladuim salts lying around you know. Yeah 65% yield doesn't
sound so good to me either, and I question heating the reaction too. Seems
like that leads to byproducts. The real point that I wanted to make was the
use of Na2CO3 to buffer the reaction. I just felt like maybe use of
carbonate in Shulgin's modification may be advantageous. Maybe wouldn't
help, but I don't think that it would hurt either.

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Ritter:

Finally someone else came across this synth. This was first published in
1975 and is detailed in CA of that year. Will try to dig up a copy of that
CA article later on to get the complete citing. The CA abstract reads as
follows: 130g of 35%H2O2 in 250g 86% formic acid is added dropwise to a
rapidly stirred mixture of 162 g isosafrole, 500ml dichloroethane and 15g
sodium carbonate. Reaction is exothermic (much more so than performic rctn
TS#1) and addition of performic acid should be done at a rate which does
not allow temp to go above 40'C. The journal article says to stir for only
5 hours but experience has proven that it is best to stir for a full 24
hrs. After 24 hrs has passed mix will look like orange juice. Kill the
stirring and allow the layers to separate. Rotovap off the dichloroethane
from the organic layer and add the resulting orange syrup to 1.8Kg of 15%
H2SO4. Heat at 70-80'C for 2 hours, extract ketone and vacuum distill to
collect about 120g 3,4 MDP2P. Beagle boy substituted CH2Cl2 for the
ClCH2CH2Cl which is fine but a reflux condenser will be needed to condense
the boiling solvent. This is by far the best performic method and the CA
article claims yields of 73%. Experience proves that this yield is easily
reproducible. This method is also very nice because it uses much less
formic acid than TS#1. Most of the time all isosaf is converted to ketone
however occasionally there will be a small fore-run of isosaf during
distillation. Considering that no formic acid is vacuum distilled and
yields are higher in this procedure, I reccomend that this procedure take
over the position as the TS#1 ketone synthesis. Literature states that the
purpose of the carbonate is to form a buffering solution however I wonder
how effective the rctn. would be w/ out the carbonate. One last thing to
stress--This rctn can be very exothermic and quickly get out of control if
temp isn't carefully monitored.

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Gyrogearloose:

On the above method, I followed a inch worm to a toadstool, after inhaling
some on the toadstool smells I dreamed the following :

This reaction seems for all purposes crap. Followed it to the letter
including the dicloroehthane still got only about 30%. Might try it without
the neutralizer. post again later.I would love to find out I did something
wrong. I like the idea of no formic to deal with, I also tried to extracty
it anyway just to see if there was any present, nix. none...

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You did indeed do something wrong. It works at least as well as I said
(65%) and apparently up to 73%, as Ritter said.

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Gyrogearloose:

I used a overhead stirrer at 3000 rpm for the 24 hours, I put the mix
togeather just like the post says. I let it sit for 6 hours after to
enshure seperation, the thing looked like two layers, the formic art bottom
dark red, the dicloroethene orange, I seperated the two in funnel, I then
rotovaped the orange syrup, took results to 1.8kg of 15 % H2SO4 at 80 C for
two hours, I did smell the ketone smell, candy sweet vinella,. But after
distallation got small yeild. Used 2 stage vac, pump, fancy high temp
still.

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1. Sodium Carbonate + formic acid -> sodium formate + carbon dioxide + water.
You end up with more dilute acid.

The carbon dioxide will bubble out of solution.

At first it doesn't appear to make sense - to add Sodium Carbonate. But...

2. Sodium Percarbonate (which is found in washing powders) has been used as
an epoxidating agent. I think Sodium Percarbonate is made from Sodium
Carbonate + Hydrogen Peroxide (so on second thoughts - it might make some
sense).

The only thing you can do is try it to see whether there's an improved yield!

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Yes, that bit about sodium formate always bothered me too, but the
carbonate is added to the peroxide B4 addition of formic. Never heard of
sodium percarbonate, but I've seen H2O2 sold as a complex w/ Na2CO3. It
apparently has some advantages, maybe just stability.

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Well thankyou for that tidnit on adding it to H2O2 first, I will try that
RXN again and get back to you on that. I mixed the carbonate with the
diclroethane and issosafrole, then dripped the formic and h202 into it.
That was what prob. went wrong......DUH

But really see what I mean when I say please God ask people to not assume
anything when posting a RXN, God maybe the pygmys don't know how to add
things to stew. I for one would live to know every step on a post so I
don't waste precious items, I think this is a statement for everyone.

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Atomicdog:

In the Modified performic, is one supposed to add the H2O2 first, then the
formic? Or should the H2O2 and formic be dripped in together as in CA?

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Entropy:

The formic acid and H2O2 are mixed together first. This forms the "performic
acid". This is then dripped into the isosafrole/DCE/Na2CO3 mixture. Follow
the CA article to the letter and you will have no problem.

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Atomicdog:

Oh yeah, DCE. DCM is an exeptable substitute right?

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Entropy:

SWIM normally uses DCE, however, DCM is an acceptable substitute, but you better
have a good condensor if you use the DCM. During the addidion of the performic,
this reaction is VERY exothermic....much more so than with the acetone. If you
use DCM instead of DCE, the reaction MUST be carried out in a 3 neck flask or
equivalent: One neck fitted with a reflux condensor, one neck for the addition
funnel, and the third neck for the thermometer. The reaction must be kept below
50 degrees, but the DCM is gonna start boiling at 37 degrees, therefore the
necessity of the condensor. The other thing to remember with this is that even
after the addition is complete, the temperature must still be monitored until
it is stable. The first time SWIM tried this, he walked away once the addition
was complete with temp at 35 degrees and came back 30 min later with the temp
at 75 degrees, so you have to keep a good eye on it for the first hour or so.

Also, evidently the sodium carbonate is very important for buffering this
reaction. SWIM has had very good success with this method, usually with results
in the 65-75% range consistently! Even the time when the temp went to 75, SWIM
got a 55% yield, which ain't too bad. That is the beauty of this method..even
with really bad technique, you get SOME yield. If you follow the CA as written
there is no reason you cannot achieve 65-75% yields.

As far as the time on the reaction, SWIM lets it run for 6-8 hours.

Another point, during the addition of the 15% h2SO4, only run the reflux for
2 hours as stated in the CA. DO NOT run for 4 hours as suggested by some
others...this could definitely lower the yield.

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Gyrogearloose:

Well I will tell you why the yields were low. according to Ritter the
sodium bicarbonate had to be added to the H2O2 first and then preceed to
add the other things, it was true.

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It seems to me the 'way' to do the rxn is to combine the iso and bicarb and DCM, stir for 3 hrs. add the H2O2 heat to 40^C w. stirring, remove from heat, then drip the formic in at such a rate as to keep the rxn between 36 and 40^C.