Sciencemadness Discussion Board - Propiophenone rearrangement

Propiophenone rearrangement

Organikum - 11-12-2004 at 14:30

CA 12702b (1954) says that propiophenone can be rearranged to phenyl-2-propanone with catalytic amounts of H2SO4/HgSO4 in 75% MeOH in decent yields. (18g P2P from 26g propiophenone, 5-6h at 60°C, sounds doable)

Original reference is:
J. Pharm. Soc. Japan 73,1224-6 (1953)

Somebody able to retrieve this? Maybe we get it translated, or it has some nice drawings/tables at least.

HEY! moo ! If you are around, pls drop me a line, somebody wants to contact you.

regards
/ORG

S.C. Wack - 12-12-2004 at 20:39

I was surprised when I saw that. I've looked up every "2-propanone, -phenyl" up to the 60's, and didn't recognize it. So I went back and looked for it in the proper (1947-56) index. Not there, under any of the many P2P subheadings. I looked at the above citation, it's in vol 48(4). It is at the very end of an abstract of an article where Ichiro Hirao of the Ono Pharmaceutical Co. did a bunch of things to (3,4-methylenedioxy)propiophenone. But only the unsubstituted product is mentioned in the abstract in relation to the following experiment. This is what the abstract says:

"A mixt. of 50 ml. 75% MeOH and 0.6 g. H2SO4 at 60C treated with 0.6 g. HgSO4 and 26 g. PhCOEt in 20 ml. MeOH, heated 5-6 hrs at 60C, the product neutralized with Na2CO3, the MeOH removed, and the residue extd. with Et2O and distd. gives 18 g. BzCOMe, b13 151-2C; disemicarbazone, m 226-30C"

3 problems, besides this not being in the index under P2P. CA shorthand for P2P is usually PhCH2Ac, the temperatures are too high for P2P (bp760: 214-216, bp14: 100-101, semicarbazone mp 198), and obviously if it forms a disemicarbazone, it has two carbonyl groups. Someone screwed up, somewhere.

Organikum - 13-12-2004 at 01:43

Its probably not true.

Labrat posted in a very old thread at the-hive ("drone´s amphetamine contest"

that the rearrangement produces phenyl-1,2-propandione, which can be catalytically hydrogenated with PtO2 to the diol which is rearranged to P2P by refluxing it with 20% H2SO4.

He also speaks of thread at the-hive covering this, but this thread was not found in my archive, but I will look again now, this time for P1P to P2P instead of propiophenone to phenylacetone.

If somebody knows another nice P1P to P2P pathway - post it please!

/ORG

[Edited on 13-12-2004 by Organikum]

phenyl-1,2-propandion to diol

Organikum - 13-12-2004 at 03:58

The rearrangement of propiophenone with H2SO4/HgSO4 to phenyl-1,2-propandion wouldnt be so bad a way regarding the ease with which prpiophenone can be made from OTC compounds (benzoate/propionate dry distillation).

The missing link is the reduction of the dione to the diol, the following H2SO4 catalyzed hydrolysis to P2P is wellknown and should be no real problem.

So the prize question is:
how to do this reduction of phenyl-1,2-propandion to phenyl-1,2-propandiol without the need of catalytic hydrogenation, pressure and/or noble metal catalysts? Might zinc or aluminium suffice? Urushibara nickel? Electrolytic maybe? Praying?

PS: Thanks S.C. Wack for looking this up, I have to admit that I have no real clue what CA means with BzCOMe.
PhCOEt is propiophenone? This CA nomenclature is way over my head.

Labrat´s postings have been usually quite accurat and I have little doubt that phenyl-1,2-propandion is the product, I think this correspondends also with the disemicarbazone named, doesnt it?

The way to chemical enlightment is boobytrapped with nomenclatura......
/ORG

[Edited on 13-12-2004 by Organikum]

trilobite - 13-12-2004 at 10:35

Bz stands for benzoyl aka PhCO, which makes BzCOMe phenyl-1,2-propanedione. PhCOEt is propiophenone, it could as well be written out as BzEt but it isn't - don't know why.

The confusion probably originates from someone thinking that Bz is for benzyl, as it has been used elsewhere, but not in CA where Bn is benzyl. If it was so, BzCOMe would mean P2P. This is also the way I remember earlier discussions on this very same subject.

About the reduction of the dione. I think a Meerwein-Ponndorf-Verley reduction would do the trick, distilling acetone off the mixture of the substrate, IPA and aluminum isopropoxide, that is. With Urushibara catalysts there is the risk of reducing the benzylic carbonyl to a methylene (in this case producing P2Pol), but it depends on the conditions. Electrolytic reduction or an aluminum amalgam would most likely work, although it is possible to electrolytically reduce the benzylic carbonyl to a methylene. Again, it depends on the conditions. In any case too acidic conditions are to be avoided, as the diol can undergo a pinacol rearrangement to P2P which then is vulnerable to reduction to P2Pol.

It would surely be nice if someone got hold of that reference, as the reaction is so strange. Triple bonds can be hydrated in those conditions and that mercury salts can be used to activate double bonds as well, but I'm not sure about hydration. 1-Phenyl-2-propyn-1-one would surely be converted to 1-phenyl-1,2-propandione, the reaction is a typical preparation of methyl ketones from acetylenes, the same way one makes acetaldehyde from acetylene. With propiophenone I would understand the hydration of the double bond of the enol tautomer leading to 1-phenyl-1,2-propandiol, which could undergo a pinacol rearrangement to P2P.

The problem with the abstract is that the claimed dione product is much more unsaturated/oxidised than the diol or propiophenone... how can the reaction work without an oxidant? On the other hand rearrangement of propiophenone through the diol to P2P would make more sense.

More confusion is added by the fact that the boiling points listed in Beilstein for 1-phenyl-1,2-propandione are 222,8-223,6'C, 103-105'C/13mmHg, 102-103'C/12,5mmHg, 101-102'C/12mmHg, 98,8-99,2'C/10mmHg. In Chemische Berichte 89, 1016-19 (1956) the melting point of the disemicarbazone is stated as 228'C. How can they have the wrong boiling point and the correct melting point of the disemicarbazone?

Here is the full abstract. Note that the researchers do not prepare 1-phenyl-2-propyn-1-one at all, obviously PhCOEt really IS propiophenone, prepared in several steps from benzaldehyde.

Acetylenic alcohol and its derivatives. IV. Synthesis of propiophenone and 3,4-methylenedioxypropiophenone. Hirao, Ichiro. Ono Pharmaceutical Co., Yakugaku Zasshi (1953), 73 1224-6.

Abstract

BzH (4 kg.) in 7 l. 90% MeOH in an autoclave with C2Cu2 is adjusted to pH 7.8 with NaOH, charged to 10-15 atm. with C2H2, heated 4-5 hrs. at 120°, and the product extd. with Et2O and distd. to give PhCH(OH)C.tplbond.CH (I), b14 114-16°; benzoate, m. 81-3°; phenylcarbamate, m. 73-5°. Catalytic reduction of 60 g. I in 150 ml. MeOH with 5 g. Raney Ni and 60 atm. H 30 min. at 40° gives 58 g. PhCH(OH)Et (II), b15 108-10°; similarly is prepd. 3,4-CH2O2C6H3CH(OH)Et (III), b12 143-4°. II (39 g.) added dropwise to 45 g. K2Cr2O7, 60 g. H2SO4, and 400 ml. water, the mixt. stirred 1 hr. at 25-30°, and the product extd. with Et2O and distd. gives 36 g. PhCOEt, b7 85-6°; semicarbazone, m. 176-7°; similarly is prepd. 3,4-CH2O2C6H3COEt, b4 124-7°, m. 38-9°. A mixt. of 50 ml. 75% MeOH and 0.6 g. H2SO4 at 60° treated with 0.6 g. HgSO4 and 26 g. PhCOEt in 20 ml. MeOH, heated 5-6 hrs. at 60°, the product neutralized with Na2CO3, the MeOH removed, and the residue extd. with Et2O and distd. gives 18 g. BzCOMe, b13 151-2°; disemicarbazone, m. 226-30°.

Here is a P2P synth by the same researcher which uses the alkyne hydration reaction on 1-phenyl-2-propyn-1-ol.

Phenylethynylcarbinol and its derivatives. II. Synthesis of phenylacetone. Hirao, Ichiro. Osaka Univ., Nippon Kagaku Kaishi (1921-47) (1953), Ind. Chem. Sect. 56 265-6.

Abstract

Com. PhCH(OH)C.tplbond.CH was hydrated with H2SO4 to PhCH(OH)COCH3, which was hydrogenated with Raney-Ni catalyst by H of 50 atms. in an autoclave at room temp. The white crystals obtained correspond to 1,2-dihydroxy-1-phenylpropane (I) of m.p. 91-92°; yield, 95%. PhCH2Ac was prepd. by treating of I with H2SO4, oxalic acid, H3PO4, etc. at the b.p. of the soln.; yield, approx. 73%.

[Edited on 13-12-2004 by trilobite]

S.C. Wack - 14-12-2004 at 21:03

Well just in case the Japanese method doesn't work out and you happen to have propiophenone, there are other ways.

http://www.orgsyn.org/orgsyn/prep.asp?prep=CV2p0363
followed by
http://www.orgsyn.org/orgsyn/prep.asp?prep=CV3p0020

And this:
"A mixture of ethylphenyl ketone (134 g.), finely powdered anhydrous CaCl2 (35 g.) and alcoholic HCl (1 cc.), contained in a flask provided with an efficient mechanical stirrer, an inlet tube for the entry of N2O4 and an exit tube to accomodate the evolved gases, is treated with a stream of N2O4, the temperature being maintained at 60C. It is advisable to stir vigorously and introduce about 60 g. of the gas from a weighed tube in the course of 3 to 4 hours. Although there is considerable unchanged ketone in the reaction mixture at this stage, it is advisable to interrupt the reaction, since a point is reached where the rate of decomposition of diketone is nearly equal to the rate of its formation.

The reaction mixture is cooled somewhat and taken up in ether. The ethereal solution is washed with water, then exhaustively with aqueous NaHCO3 and finally with water. The ether is then distilled from the solution and the residue distilled under reduced pressure. Distillation is continued until the residue begins to decompose. The distillate is treated with an equal volume of alcohol and vigorously shaken with 60 cc. of a saturated aqueous solution of NaHSO3. In the course of a few minutes, a colorless crystalline solid separates and the mixture gradually becomes pasty, the yellow color fading almost completely. The mixture is then cooled, filtered with suction and the solid washed with alcohol and finally with a little ether.

The bisulfite compound is conveniently decomposed by treatment with a warm solution of Na2CO3. After cooling the diketone is extracted with ether, the solvent distilled and the diketone distilled in a rapid current of steam. The diketone is recovered from the steam distillate by extraction with ether and after drying and removal of solvent is distilled under reduced pressure. The yield of pure product boiling at 126-128C at 20mm is 26-28g.

The filtrate from the bisulfite compound may be worked up for the recovery of unchanged ethylphenyl ketone by addition of water and extraction with ether. The amount recovered varies from 60 to 70 g."

I think that the 5 in 151-2C in the abstract was supposed to be a 0. It was also odd that they call it BzCOMe, everywhere else it is BzAc. And it was indexed under the dione and its disemicarbazone.

I was curious, so I looked up reduction of benzoyl a-diketones to glycols. All I found was benzil. So anyone who tries using something other than PtO2 and gets the glycol should try to get their work published! Maybe someone could try all of the ketone reductions known. And when looking for this specific glycol from that diketone, only PtO2 was mentioned.

But if anyone is going to use PtO2 to make the glycol to make P2P, maybe they'd like this instead:

http://web.archive.org/web/20040204014359/www.rhodium.ws/che...

Um, no, I'm not trying to turn this into a drug board. Really. Rhodium didn't put up part 3 of that series (JACS 51, 2269-72 (1929)), which I typed up above. I would bet that it was posted in the Hive at some time.

For this, at least, there is an alternative on record - GB336412 uses the Hg/Al.

Organikum - 15-12-2004 at 04:51

There is no rule here against discussing synths which may or may not end up in regulated compounds as long this is done in terms of chemistry and not of cooking.
I see no problem in this thread.

Thanks for all the information, I was about to ask if the Meerwein-Ponndorf-Verley will work for the dion to diol as aluminium isopropoxide is easy from IPA/HgCl2/Al.

/ORG

ADDON:
Preparation of aluminium isopropoxide:
Patent US2965663

Without HgCl2 this takes about years, with HgCl2 its fast and easy. An excess Al is needed, the IPA has to be anhydrous.

Any suggestions for getting IPA anhydrous without Na-metal?

[Edited on 15-12-2004 by Organikum]

IPA

Mephisto - 15-12-2004 at 05:54

Römpp names calcium oxide, magnesium powder and 3 Å molecular sieves being suitable for IPA.

Organikum - 19-12-2004 at 06:23

- I propose propiophenone rearranges - if at all - to mainly P2P.
- I propose the rearrangement takes place
- I admit these proposals may be be influenced by wishthinking.

P2P is IMHO most favored energetically, there was a post of drone at the-hive regarding P1Pol and P2Pol which makes me think so.
As asked before, where should the new =O come from?

The HgSO4/H2SO4 in MeOH might be a nice mild method for rearrangement of hydratropic aldehyde too.

/ORG

alchemie - 19-12-2004 at 07:54

anhydrous IPA without Na:

1-IPA with less than 0,1% H2O can be obtained by the following method: Add CaO to the alcohol, distill and collect the fraction 82-82.4 ºC. Add anhydrous CuSO4 and let stand for two days. Distill, bp 82,4ºC. JACS 43, 1005 (1921).

2-Add 10% (weight) NaOH pellets to 90% IPA, stirr and discard the basic layer. IPA obtained by this method should not become turbid when mixing with 8 times it´s volume of CS2, xilene or pet. ether. JACS 54,1445 (1932).

If the IPA contains too much water (<90% IPA) it can be dried by adding NaCl. The Upper layer contains 87% IPA and 2 to 3% NaCl. By distilling the upper layer you can obtaing the azeotropic mixture with water (91% IPA(volume), 87.4%(weight) bp 80.3ºC)

Organikum - 20-12-2004 at 07:45

The attached article deals with ketone rarrangements and makes me think I might be right in believing that the propiophenone to P2P will work.

I would appreciate though if members with more background in org. chem. theory might have a look into this and comment - the article deals with proposed reaction mechanics and this make me always so - eh - unertain.

Thanks to lugh for retrieving the article on my request, lugh the most helpful hive-mod ever.

Attachment: fry.djvu (158kB)
This file has been downloaded 1337 times

Making phenylacetones

Kinetic - 31-12-2004 at 17:57

Hi Orgy

'Tis my first post here, but anyway...

How about :

1. Bromination of (substituted) propiophenone using molecular bromine, or perhaps bromide and oxidant (~ quantitative yield)
2. Reduction of the ketone to give the bromohydrin with NaBH4 (~ quantitative yield)
3. Addition of KOH, as per Uemura (http://web.archive.org/web/20040213205710/www.rhodium.ws/che...) to give the epoxide (85% yield)
4. Rearrangement with sulfuric acid to give your precious phenylacetone (approx. 70% yield)

Four steps, I know. But all are simple and high-yielding.

To the best of my knowledge, all steps have been performed by yours truly. Hopefully more info will come when the 'appropriate' site is restored.

Kinetic

yogi - 31-12-2004 at 19:52

Not that I really know anything about p2p's but here is something I came up with -

http://journalsip.astm.org/JOURNALS/FORENSIC/PAGES/475.htm
Stock #: JFS8410
Volume: 29
Issue: 4
Year: 1984
Pages: 1187-1208
Author(s): Dal Cason TA, Angelos SA, Raney JK
Title: A Clandestine Approach to the Synthesis of Phenyl-2-Propanone from Phenylpropenes
Keywords: amphetamine, clandestine drug laboratories, controlled substances, forensic science, phenyl-2-propanone, toxicology

Abstract: A number of published syntheses for the manufacture of controlled substances appear to be impractical for the average clandestine laboratory. A closer inspection of these syntheses may reveal modifications which greatly simplify their application. An excellent example of this is the preparation of phenyl-2-propanone (P-2-P) from allylbenzene. In the prototype published method, oxygen is introduced into the reaction vessel by using a tank of compressed oxygen with a balloon for a gas reservoir. In our modification, oxidation is accomplished with a 30% hydrogen peroxide solution. P-2-P has been prepared by both methods and a comparison made of the reaction mixtures at various times during their synthesis. Additionally, propenylbenzene, a by-product of these reactions, can be converted to P-2-P by modification of a second synthesis. Gas chromatography and nuclear magnetic resonance spectral data are presented for each method.

Organikum - 1-1-2005 at 16:20

Thanks Kinetic!

The propiophenone to P2P would actually only be interesting when a very simple way like the proposed rearrangement directly to P2P or with the Meerwein-Ponndorf for example, maybe even with PtO.

But good to see you, wasnt it you who told me about acetophenone - chlorination and rearrangement to PAA? Instead of styrene?
Do you remember? I didnt save it, it was just minutes before the-hive went down....

NaBH4 is out of reach for me. This is not urgent anyways, its more some explorations for the future, me plays more with yeast these days, thats so nontoxic...

Nevertheless I will give this a try after my baggy propionate arrives - christmas and newyear spoiled the transport timing.

Oh! What I thought about was...

How can one separate propiophenone and phenylacetone? Isomeres, almost identical bp........?

/ORG

S.C. Wack - 1-1-2005 at 17:29

AFAIK, only some methyl or cyclic ketones form bisulfite addition products.

trilobite - 1-1-2005 at 19:35

It looks like the mechanism can be explained with the one in that article very well, but it tells us nothing about the part mercuric sulfate plays. At first I managed to miss the scheme for the "alpha-unsubstituted" ketones, as referred to in the paper, completely. The only thing I wished for was a nice mechanism where the oxygen migrated through a transition state consisting of a three-membred ring, and the authors think so too!

Maybe a transition state of that type is formed where the positive charge is stabilized by the mercury atom somehow, from the enol maybe, and the sulfuric acid could be added in order to solubilize the mercuric sulfate and speed up keto-enol -tautomerism. But it's only a wild theory, not much without experimental proof.

The reason why the mechanism can't proceed by the way of "alpha-substituted" ketones' mechanism is, that in order to get there the reaction should proceed via formation of a very unstable secondary carbocation from the very stable protonated ketone, migration of the phenyl group to this secondary carbon with formation of protonated hydratropic aldehyde. This sounds quite incredible, as hydratropic aldehyde and cold sulfuric acid produce a mixture of P2P and the aldehyde, a reaction which can be explained with this mechanism. The mixture might represent the equilibrium mixture of the two, or it could be that the reaction is stopped early before reaching an equilibrium because of side reactions eating the yields... But no propiophenone is told to be produced. One could expect it if these two reactions proceeded by the same mechanism. It would be expected even if there is an equilibrium between P2P and propiophenone under very acidic conditions, though... go figure.

Anyway, reaction mechanisms are only explanations for thermodynamical facts. Thermodynamically the reaction sounded impossible because it requires breaking the conjugation of the carbonyl group and the benzene ring. NIST chemistry webbook lists the following standard enthalpies of formation for P2P as -151.9 ± 1.7, -152.3 and -162.5 ± 1.3 kJ/mol, and propiophenone as -167.2 ± 1.3 kJ/mol, the effect of the conjugation is obvious, but it's not as bad as I thought it would be. The conjugation also means that the bond between the carbonyl carbon and benzene ring in propiophenone doesn't rotate in the same sense as the bond between carbonyl carbon and a saturated carbon in P2P, loss of freedom. This is why entropic effects could favour P2P so that above a certain temperature the equilibrium would be on the side of P2P. So I think it really could work! That's actually quite amazing.

Maybe this reaction could work even better with propiophenones substituted with electron donating substituents on the ring.

I don't know about the bisulfite addition products. If there is little propiophenone present it might be possible to freeze it out (Mp's: P2P -15 - -16'C, P1P +21'C ). Maybe there's some info about their ketals and their boiling points somewhere...

[Edited on 2-1-2005 by trilobite]

Organikum - 2-1-2005 at 05:19

Quote:

hydratropic aldehyde and cold sulfuric acid produce a mixture of P2P and the aldehyde

I believe you are wrong here. The products of the reaction are P2P and some decomposition compounds where the chain is shortened. I remember this as there was the discussion about how to separate the aldehyde and the P2P after the reaction (what would be hard as Rhodium told) but it showed up that there is no aldehyde present anymore when its done. (I can look this up in the original german article when needed).

HgSO4 seems to work as "enhancer" in these kind of rearrangements and seems to make them possible using much less H2SO4 and a co-solvent like MeOH.
Why? Oh my god, who will ever know?

Actually I think that propiophenone WILL rearrange to P2P under certain conditions, and that similar to the hydratropic aldehyde rearrangement no propiophenone will be left over:
Rearrangement or destruction!
(could be the slogan of the coming Iran-invasion by Bush and his wild generals)

trilobite. although I understood your post better than the article I have to ask: You say you believe there is a good chance it will work when the reaction conditions are right?

"Rearrangement or destruction" maybe possibly read as "Rearrangement BY destruction" too. This would hint that the starting molecule is actually broken apart by the H2SO4/HgSO4 and some of the pieces reunite to P2P whereas others just stay broken down.
Sounds more plausible to me actually, I will share the Nobel-prize with you al,l no question!

Whatta think?
/ORG

[Edited on 2-1-2005 by Organikum]

trilobite - 2-1-2005 at 08:24

I haven't been to my trusty old library for a while, so I haven't checked out the old Berichte paper on the phenylpropanal rearrengement yet, the same goes for some of the refs in the paper you posted.

Actually some reactions like the Fries rearrangement (1,4-diacetoxybenzene --AlCl3--> 2,5-dihydroxyacetophenone for example) can proceed both by inter- and intramolecular pathways. The acyl group dissociates as an acylium ion complexed and stabilized by the Lewis acid, which then alkylates the aromatic ring in a Friedel-Crafts way... so obviously the ring can belong to a different phenol than the one the ion dissociated from. In this case it sounds unlikely, the conditions are mild and metal ions can interact with organic molecules in confusing ways, who knows?

This far I haven't seen a certain reason why a reaction like this won't work but I like to remain sceptical until I'm sure. The abstract makes me nervous because of the disemicarbazone, for one. I'd have much more hope for the HgSO4-catalyzed reaction than a plain acid-catalyzed one (which is a sure way to produce crap, it is only a matter of time), but thermodynamics is the biggest question... It is justifiable that entropic effects would favour P2P with increasing temperature but the NIST website contains no data about entropies for these compounds.

Extrapolating from pairs of other compounds gave no certain answer, and thermodynamics isn't the field I'm too comfortable with to begin with. It would be very interesting to find out what the outcome is, I suppose there is one? All this speculation without a clear no or yes! I'll see if there is anything more worth knowing to be found, holiday activities interrupted my digging.

Doing it with yeast

Kinetic - 2-1-2005 at 08:25

Just for clarification, transforming propiophenone to phenyl-1,2-propanedione is an oxidation, not a rearrangement. This can be done by several methods. Other than your route, there is the horribly toxic selenium dioxide oxidation (Riley Oxidation), although I have a review article where this has been accomplished with the more benign activated MnO2 (Synthesis, 1976, 133-167; it is mentioned on page 141).

There is also the reaction of propiophenone with a nitrite to give the oximinopropiophenone which can be hydrolysed to the 1,2-dione with e.g. aqueous sulfuric acid. But if the desired end product is what I suspect, then you'd probably be better off reducing this to phenylpropanolamine then removing the benzylic hydroxyl group.

Knowing how much you love yeast, I may have an especially nice answer to your 'prize question'. According to Beilstein, yeast can reduce phenyl-1,2-propanedione to the diol in 89% yield. I will retrieve the article - Chem. Pharm. Bull., 37(4), 1085-1086 (1989) - next time I go to the library and hopefully get it to you.

I don't think it was me who mentioned the oxidation of alpha-chloroacetophenone to phenylacetic acid. I missed the Hive's last two days. But if you have acetophenone, the best (and smelliest) method must surely be the Willgerodt-Kindler reaction. Here we go: Acetophenones to phenylacetic acids.

There are no hits in Beilstein for the overall rearrangement of any propiophenone derivative to the corresponding phenylacetone derivative.
It is true that phenylacetone is more thermodynamically favourable to propiophenone. I believe at least part of this is the greater strength of the bonds to an sp2 atom: in phenylacetone, all atoms in the side-chain are bonded to an sp2 hybridised atom, whereas in propiophenone this is not so. This doesn't mean that there is automatically a way to isomerise the former however - though admittedly I am yet to read the JACS paper you/lugh provided.

I highly recommend you get some sodium borohydride if ever get the chance. It is an excellent reagent.

I suspect Rhodium suggested a mild oxidation to remove any aldehyde present in you P2P after the hydratropic aldehyde rearrangement, to give the acid which could be removed as its salt. And, as S.C Wack said, propiophenone should not form a bisulfite addition product, unlike P2P, hence you may be able to separate the two this way.

trilobite - 2-1-2005 at 08:41

Kinetic: It is an oxidation, this was recognized already, but when you look at the proportions of the reagents in the abstract you will soon start to think: where's the oxidant? Or is the abstract really that crippled?

One might think that concentrating on some Japanese oddball reaction is complete waste of time... but it is kinda intriguing.

Oh, and good to see you here!

trilobite - 3-1-2005 at 11:12

Stupid me. Of course I calculated the reaction enthalpy the wrong way around. You're right Kinetic, P2P is more stable. The reaction is surely worth trying out at least. By the way, when I checked Beilstein under propiophenone in hopes of finding out what they have to say about this ref and the reaction, I couldn't find anything at all.

[Edited on 3-1-2005 by trilobite]

the article

Organikum - 4-1-2005 at 08:03

The japanese article is attached, thanks to lugh!

I have not even looked at it myself.

Attachment: hirao.djvu (86kB)
This file has been downloaded 1193 times

Bye bye wishful thinking

trilobite - 4-1-2005 at 08:34

The abstract is in error, it should read PhCOCCH not PhCOEt. The reaction is a standard alkyne hydration, the product being 1-phenyl-1,2-propanedione. No wonder it sounded too good to be true.

[Edited on 4-1-2005 by trilobite]

Organikum - 4-1-2005 at 09:46

Shit.

Nevertheless, I will work on my analytic capabilities and try a propiophenone rearrangement with H2SO4/HgSO4, not to do it would be somehow - unsporty?

Acetophenone and propiophenone from benzoate + carboxylic acid are on my to do list anyways, just to get a better grip on these dry reactive distillations which I regard as VERY interesting.
Rigid "product orientation" is quite boring in the long run, methods are more fun.
Uhh! A rhyme!

(Provided I get the method working of course)

Not today and not tomorrow, but this year for sure.
/ORG

Organikum - 16-1-2005 at 03:56

The reference kinetic spoke about, dion to diol by bakers yeast.

Retrieved by lugh.

Attachment: diol_yeast_takeshita.djvu (42kB)
This file has been downloaded 1479 times

Journal requested

UpNatom - 5-3-2005 at 14:01

Anyone have: A Modified Clemmensen Reduction Procedure for Conversion of Aryl Ketones into Aryl Alkenes
G. A. Hiegel and Carney, John R.Synthetic Communications, 26(14), 2625-2531 (1996) ?

A rather elegant method (if not quite so elegant as a straight up rearrangement) describes the reduction of propiophenone to propenylbenzene using Zn amalgam in EtOH and formic acid mixture, which can then of course be oxidised to p2p. Yields are high for both steps.

Article

Kinetic - 5-3-2005 at 15:14

This is a neat article, although I am a little put off by the use of mercury. I remember this was originally posted at the Hive by Regis, and it was archived by Rhodium. The best version of Rhodium's archive is surely that provided by mophead; thanks to him for providing the following: A Modified Clemmensen Reduction Procedure for the Conversion of Aryl Ketones into Aryl Alkenes.

I said earlier in the thread that I was working on a route to transform propiophenones to phenylacetones. I now know that the route is indeed successful and practical, at least when 1-(5-indanyl)-1-propanone is the starting material. The epoxide is made in about 80% yield from the propiophenone (bromine, then NaBH4 followed by KOH), and this is rearranged to the phenylacetone with 10mol% LiI in ethyl acetate in 63% yield. The low yield for the rearrangement was due to problems (severe bumping) with the distillation, leading to the loss of a significant amount of product. An NMR of the product obtained after redistillation was entirely consistent with the predicted spectrum for 1-(5-indanyl)-2-propanone.

P1P to P2P

FriendlyFinger - 21-3-2005 at 17:45

I've tried this route;

P1P -- P1POH -- B-Methylsytrene, in high yield. Then Standard and modified performic to P2P in low yield with many problems.

After the initial performic, (modified) the H2SO4 rearrangement yielded zip. The stuff I recove.red (lots of loss) was rearranged sucessfully with Tosic acid. The yield was about 88%.

Has anybody sucessfully turned B-Methylstyrene in to P2P via Performic. Id like to meet you!

Kind regards FF

Sandmeyer - 8-8-2005 at 06:35

Someone in this thread suggested use of aluminium isopropoxide in reduction of alpha-bromo ketone IIRC. Following old Meerwein-Ponndorf-Verley reference gives mixture of products in low yield, so trying alternative reducing agent for this purpose is better, but that's another saga. Aromatic a-halo ketones could give slightly better yields.

The Reduction of -Bromocyclohexanone with Aluminum Isopropoxide
S. Winstein;
J. Am. Chem. Soc.; 1939; 61(6); 1610-1610

78.8 g. (0.428 mole) of bromocyclohexanone, b. p. 69-71 O (1.5 mm.;, prepared by the method of Kötz (Ann., 868, 196 (1907)) dissolved in 200 ml. of anhydrous isopropanol (Shell) was added to aluminum isopropoxide solution prepared from 7.5 g. of aluminum and 75 ml. of anhydrous isopropanol, according to the directions of Young, Hartung and Crossley (JACS 58, 100 (1936)). The mixture was refluxed for three and one-half hours. Then it was concentrated to a thick residue by distillation first of acetone, then of solvent through a 20- cm. column of glass helices for two hours at atmospheric pressure and finally with the aid of an aspirator. One hundred ml. of water and 130 ml. of 6 N sulfuric acid were added to the residue and all lumps were broken up. A little ether was added and the oil phase was separated, washed with bicarbonate solution and dried over sodium sulfate. Distillation and then refractionation at reduced pressure through a 40-cm. Weston column yielded 22.6 g. (30%) of 2-bromocyclohexanol, b. p. (10 mm.) 85.5-86.5 C, and 14.3 g. (33%) of cyclohexanol, b. p. (10 mm.) 61.0-61.2 C.

-----

No doubt there are some oldschool chemistry fanatics at sciencemadness possibly interested in aluminium isopropoxide. I have bunch of unsorted references (not retrived papers) of its applications, in case someone is interested I can post. An interesting, and likely less known aspect of this wonderful reaction is that it is an equilibrium process - meaning that the reverse reaction (oxidation) can also be exploited. Pioneering chemist in this area was Oppenauer, he did a lot of work on steroids. He has oxidized steroids containing secondary alcohol groups in high yield (without harsh conditions) using acetone in benzene as the oxidation agent. Catalysts used were aluminum ter-butoxide as well as ordinary aluminium isopropoxide. When benzophenone, cyclohexanone, and quinones are used as oxizing agents the Oppenauer oxidations are extended to conversion of primary alcohols into their corresponding aldehydes. Advantage here over alternative methods for oxidation of primary alcohols to aldehydes is that overoxidation to carboxylic acid is fully avoided. It is shame that Meerwein-Ponndorf-Verley and especially Oppenauer has recived so little attention in litterature.

If someone can get these papers it would be cool:

Dehydration of secondary alcohols to ketones.I. Preparation of sterol ketones and sex hormones. Red. Trav. Chim. Pays-Bas, 56, 137, 1937. (Oppenauer)

This is supposed to be a review of the literature on Oppenauer oxidations up to date of publication:

Lehman, H., Houben-Weyl, 4th ed., Vol. 4/1 b; Muller, E., Ed.; Thieme: Stuttgart,
1975, p. 901.

Thanks!

Meerwein-Ponndorf-Verley

Kinetic - 8-8-2005 at 10:57

I agree, the trouble with the Meerwein-Ponndorf-Verley reduction for the reduction of alpha-haloketones is that there is a tendancy to reduce the halogen atom, leaving either the ketone or simply the alcohol, instead of the desired halohydrin. I would go so far as to say that this reduction system is unsuitable for this type of substrate, due to the side reactions and low yields. That said, there is an interesting article on the reduction of alpha-bromopropiophenone and the use of the resulting bromohydrin (obtained in low yield) in the preparation of ephedrine. The reduction step is below, taken from J. Am. Chem. Soc., 62, 1424-1428 (1938):

Reduction of alpha-Bromopropiophenone. -126 grams of the bromoketone, b. p. 127-129.5' (10 mm.), was added to a solution of 33.0 g of aluminum as isopropylate in 1200 cc. of isopropyl alcohol, and the solution boiled under a reflux distilling column for nine hours. The acetone was removed by fractional distillation. The combined distillate on treatment with alcoholic silver nitrate gave a precipitate of silver bromide equivalent to approximately 8% of the total bromine, indicating the presence of isopropyl bromide. Propylene was also present as evidenced by rapid reduction by aqueous permanganate. Most of the isopropyl alcohol was removed in vacuo, and the residual paste mass poured onto ice and dilute sulfuric acid, extracted with ether, washed with dilute acid, water, potassium carbonate, sodium hydroxide, water, dried over anhydrous potassium carbonate and distilled: first fraction up to 75' (0.1 mm.), second fraction, 44 g., b. p. 75-95' (0.1 mm.). The black tarry residue weighed 42.7 g. Redistillation of the second fraction yielded the bromohydrin, a somewhat viscous yellow-brown oil, b. p. 73-75' (0.1 mm.), n25D 1.5611.

If phenylacetones are the desired product and you really have an urge to use this reduction, it would be far better to reduce the propiophenone itself, then dehydrate it and oxidise to the phenyl-2-propanone. The reduction works beautifully on propiophenones; I posted a synthesis from an article towards the bottom of this thread: P2P via Tosic acid. Results.

I should have access to the Recl. Trav. Chim. Pays-Bas paper requested by Sandmeyer. Unfortunately I won't be able to get it any time soon, but I will add it to my ever-increasing list of 'Wanted References'.

epck - 8-8-2005 at 15:46

Here's that Oppenauer paper request by Sandmeyer. Somebody else will have to translate it and I couldn't find a electronic copy so the file is a scan.

[Edited on 8-8-2005 by epck]

aliced25 - 20-2-2012 at 01:55

Quote: Originally posted by Organikum

Original reference is:
J. Pharm. Soc. Japan 73,1224-6 (1953)
...

regards
/ORG

The reference trail proceeds through the J.Pharm.Soc.(Japan) to give

Ichiro Hirao, "Acetylenic Alcohol and its Derivatives. IV Synthesis of Propiophenone and 3, 4-Methylenedioxypropiophenone"
Yakugaku Zasshi, Vol.73(11) 1953 pp.1224-6 (Abstract)

There has to be a better route from propiophenone to the dione though, surely? Despite that, if the experimental details become available (from the Japanese language article) showing how to condense acetylene with benzaldehyde/piperonal to give the P-1-P-ol/P-1-P in good yield, I'm sure many will be interested - I do recall another article - maybe the same journal (for sure the same Country & period) which details a very similar reaction schema (with acetylides as an intermediate IIRC). There is also this one by the same author (same journal), very similar reagents:

Ichiro Harao, "Studies on Phenylethynyl Carbinol and Its Derivatives. I Synthesis of 3, 4-Methylenedioxyephedrine" Yakugaku Zasshi, Vol.72(8) 1952 pp.1006-9 (Abstract)

[Edited on 20-2-2012 by aliced25]