H3PO4 instead of sulphuric for hydrolysis

[wacko_reaco]

Has anyone tried using the gentler phoshporic for the conversion of the epoxide to the ketone, anyone have any ref's, seems like a sensible trial to undertake, any ideas.
Also I have just secured some BF3 in ether, just need to look up some ref's for conditions and will post results soon.
Any comments on the H3PO4 would be appreiacted.
wacka wacka wacka

[Flip]

I don't believe that such a mild acid would hydrolize the epoxide. No offense to you as a may be wrong, but I believe you are probably thinking of the use of p-tosic acid which Chromic has some dank info on and to which he dedicated a lot of time.  The p-tosic works better I think not because it is really less potent as an acid than sulfuric but because it is more soluble in organic solvents, forming more of a single phase.

For those of you who didn't know, Chromic is obviously a genius.  My hat is off to you.  Keep the wisdom coming.


Refer to :

Post 288713

(Chromic: "Getting higher yields with p-tosic acid", Methods Discourse)
and

Post 261000

(Chromic: "p-toluenesulfonic acid", Chemistry Discourse) (Chromic's observations)
for more information



Then again, given some really long reaction times, you might be right, but I haven't read anything on the topic.

Flip

[El_Zorro]

Maybe you should try it.  The phosphoric isn't as strong as sulfuric, but it also won't break safrole's ether bonds as much as sulfuric.  So IF it works, I'd bet it would work better than sulfuric.
It means 'The Fox' in Spanish

[Flip]

While there's no doubt that phosphoric would not rupture the MD ring, it also is most likely not strong enough to open the oxirane and form the double bond with oxygen that makes the ketone.  In comparison of the acidity of sulfuric which is the standard and phosphoric which is proposed here I would say almost conclusivley that it will not work and conclusively that it is not viable for this reaction.  You can try it but I think other lewis acids would make better substitutes in this case.

[Rhodium]

I do not believe that phosphoric acid would be too weak to use. Please try, and post your results.

[GC_MS]

Phosphoric acid can easily form phosphoric acid esters. Maybe this would be the case here?
-[ A Friend With W33D Is A Friend Indeed ]-

[Rhodium]

That is good for hydrolyzing the glycol - a phosphate is a much better leaving group than a hydroxyl.

[Ritter]

Chromic is the first to publicly post the fact that tosic acid is the best acid for the pinnacol reaction, however yours truely has worked on this reaction for months and this is well known by the Hive Elders.  Tosic acid is capabale of rearranging a mole of formyl glycol in under three minutes in perfect yield when the reaction is run at high temps.  The problem with this reaction is that once the ketone is formed, the tosic acid catalyst proceeds to convert the desired product into tar in a matter of a few minutes.  SWIM has finally solved this problem after much tinkering.  As soon as the exothermic rearrangement is complete, the acid is neutralized by addition of a high boiling tertiary amine (N-methyl morpholine or whatever) to stop the acid from chewing up our precious ketone.

The highest performic yields possible are obtained using this pinnnacol variation in combination with a wiped film evaporator for distilling the crude ketone.

I was planning on keeping this between friends but now that the cats out of the bag I guess everyone will want a writeup.  You'll all get one eventually.

[Flip]

You must have been holding on to that one for awhile now.  I think with this innovation that p-tosic, for those with the patience, will become a standard practice.  I don't really even feel worthy of posting under this.

My hat is off to you sir.  Thank you for sharing this knowledge with us all.  I do believe I am going to re-read Chromic's p-tosic synths tonight and I await your writeup as I am most certainly going to endeavour this now.

Flip

[El_Zorro]

oh shit, I think the Hive's on the verge of a breakthrough......

But how high are these yeilds?  Are they up to quantitative?
It means 'The Fox' in Spanish

[Chromic]

The yields are higher than the sulfuric acid rearrangement. Read the electro epoxidation of isosafrole in Novel Discourse by Scooby Doo (this was actually the first public posting of the rearrangement method). Trying to synthesize p-tosic acid is rather difficult. I wouldn't try it without a dean-stark trap.

With the buffered performic/peracetic in dcm, I'm sure one could get stellar yields from this method of rearrangement. Maybe I should order myself a dean-stark trap and have a go at it.

[wacko_reaco]

The point of it is that H3PO4 is milder, I am not thinking to use it at the normal 15% level as with the h2SO4 but maybe a higher level.
I am wanting do a course of trials but only have the time to do one system properly, so it is either the epoxide re-arrangement with BF3, the glycol to ketone with H3PO4 (it will kinda work). As an after thought does ALCl3.6H2O have any lewis acid activity, the anhydrous version would be too extreme, but it would be nice to re-arrange the epoxide with deodorant, keep your lab smelling nice and all. Anyways, blah blah, still speculating, i am not interested in doing anything until I have more info, have some ref's to look up, would try PTSA but don't have any and it is expensive and annoying to work with as are LiSalts, sorry make that 'fucking annoying'.
Anyhow I have a flask shaker/water bath setup so i can run several variants at once at temps to ~100C.  Give it a few weeks though.
Anyhow keep discussing it as our little research co-operative is informative and encouraging.
caio

wacka wacka wacka

[Barium]

The epoxides from a darzen reaction can even be hydrolyzed by KH₂PO₄

[Flip]

  If you are resolved on doing this, there is a lot more to it than you would imagine.  If you really want to try this, and do it right, you have to understand the basic properties of a phosphate solution.  The H3P04 will not hydrolize the epoxide by itself, perhaps it could work but definately would not do so consistently and I will explain to you why. 

Now, you say that you will attempt this by increasing the concentration to have the same percent of availiable H+ as the sulfuric.  But let me ask you a question.... what are you going to increase it to, to reach this equivalent pH?

  The fact is that with phosphoric acid, unlike most other acids, there is no precise way of calculating this.

Orthophosphoric acid, unlike the mono or dibasic strong acids recommended for the pinacol, is a weak tribasic, it has three replacable hydrogens and can form three different salts when ionized in water.

First, the alkaline phosphate, PO₄^3-
Second, the neutral hydrogenphosphate, HPO₄^2-
Third, the acidic dihydrogenphosphate, H₂PO₄^- (which is only a monovalent radical)

Now in addition to this the phosphate is a very strong proton acceptor, and it is hydrolized in the aqueous phase.

PO4 +  H2O  >  HPO4 + OH

The product is an additional hydroxide ion and another hydrogen phosphate.

Now the real bitch here is that both H2PO4 and HPO4 are amphoteric, meaning that they will react with an acid OR a base to form different salts.  These reactions are based on random mathematics which keep the two competing  for equilibrium.  At no point in time do you know the how many moles of each salt is present, and therefore it is impossible to mathematically predetermine the precise pH.  However, just for you, I pulled up a graph which 'approximates' the figures.  They based it on the the Henderson-Hasselbalch equation.

http://www.sfu.ca/chemcai/AQCHEM/ABG07.html

Oh, and it gets worse.  I read a report that tried to eliminate the acidic species by titration with NaOH.  Unfortunatly because of the unique desire of this solution to maintain an equilibrium around the neutralization points (on the titration curve) of each of the three protons, even LARGE variances in acid concentration will produce only very slight effects on the log concentration. 

Potentiometric Titration Analysis

http://www.wku.edu/~henrich/mixedacid.pdf

A phosphate solution is acutally an organic buffering agent operating on Le Chatelier's Principle.  It will try to hold the solution pH at pH 2.1±1, pH 6.7±1 and pH 12.7±1.  It tends to prefer the neutral condition, however.  The phosphate buffer is also important in the kidneys and urine for controlling acid base balance and regulating the concentration of Na+. In the kidneys sodium ions are retained and replaced by hydrogen ions. The pH of urine is normally 5.6 i.e. more acidic than blood plasma as a result of this process.

For those of you who are curious, the ionization constants and corresponding pK values are:

K1 = 7.5 x 10n3 pK1 = 2.13
K2 = 7.5 x 10n8 pK2 = 7.13
K3 = 4.8 x 10n13 pK3 = 12.32

So now with an understanding of the reaction I would suggest giving it a shot.

  Use the graph and find out how concentrated it the solution would have to be to reach a log concentration where the pH is around 2, which is a rough estimation of a 15% conc sulfuric solution.  Maybe it's more like 1.8.  You should double check.  But in any case keep in mind that this concentration will not make too much of a difference past a certain point.

Now check the pH, and if it isn't right don't bother trying to adjust your numbers (as I am not even sure it is volumetrically feasable to get it right), but instead titrate the solution with aq HCl until you reach the desired pH.  Once you start don't stop until you reach one of the three neutralization points, as the solution will be constantly retaliating and trying to form an equalibrium.

I couldn't tell you anything about reaction times but at similar pH i'd start with similar times and then go by observation.

Then again, I might be leaving something out, or not thinking about something, so chances are this might not work at all.  It is not really a good substitute in my opinion, and because of it's ionization properties it would be more trouble than it is worth.

Hell, i'll go ahead and make this little write-up complete for you.  Here's the density of the solution and the maximum concentration as well, take a look.

http://www.food.us.rhodia.com/brochures/acid/page12.asp

Here's your bp/mp information if you want to try to make a saturated solution.

http://www.food.us.rhodia.com/brochures/acid/page11.asp#table4

And here is a good supplier.  Hopefully no one in the stimulants forum sees this.

http://www.starchemicals.com/phosphorustechnical.htm

Oh yeah, and I almost forgot the MSDS, don't hurt yourself dude.

http://www.jtbaker.com/msds/p3973.htm

But, yeah, definately do give it a shot. Post your results to this thread.

Flip