Sciencemadness Discussion Board

Oxidation of styrene to phenylacetaldehyde

phendrol - 20-11-2012 at 02:32

I'm thinking about oxidizing styrene monomer to phenylacetaldehyde. I know styrene can be oxidized to the epoxide and then further to phenylacetaldehyde. Styrene oxide can be prepared from styrene via a chlorohydrin. Nicodem posted a nice, OTC recipe with TCCA:
http://www.sciencemadness.org/talk/viewthread.php?tid=15284#...
The method is simple and fast. The chlorohydrin can be surely prepared using sodium hypochlorite as well. But how can I rearrange the epoxide to the aldehyde? Is there any way to oxidize it further with TCCA or sodium hypochlorite? Can a one pot oxidation from styrene to the epoxide and then further to the aldehyde be done?

In this thread:
http://www.sciencemadness.org/talk/viewthread.php?tid=7641
Nicodem wrote that he was able to do a one pot oxidation of styrene all the way to phenylacetic acid, using H2O2, H2SO4 and formic acid in water. Now phenylacetic acid is not what I'm after, but if a reaction like that is possible, I'm sure it could be modified just a bit to stop at the aldehyde. I was trying to find some info on this and the closest thing I found is the oxidation of isosafrole with peracids.
https://www.erowid.org/archive/rhodium/chemistry/peracid.htm...
So if I'll use styrene instead of isosafrole what can I expect? Is it possible to get phenylacetaldehyde this way? Or maybe it would go even further with the oxidation and yield PAA?

Methyl.Magic - 20-11-2012 at 09:09

If you want to get the phenylacetaldehyde I dont know where is the problem of the peracid method. Styrene oxyde are not usually formed with peracid because they are very prone to be opened an acidic environement because of the stabilised benzylic carbocation. But to form the phenylacetaldeyde you MUST open the epoxide, so for me I don't see any problem here.

Another problem is the stability of the phenylacetaldehyde. it's not very stable. Moreover the commercial product is never sold as the pure form but always in solution. Maybe it's very prone to overoxydation to phenylacetic acid by oxygen the same way as benzaldehyde. If the case it's possible you cannot use strong oxydant such as peroxide especially with the presence of acid but check the stability of the compound first.

FSO3Me

phendrol - 21-11-2012 at 06:20

Well the peracid is advantaging because it can be a one pot synthesis and as soon as I'll get some formic acid I'll attempt it.

I want to follow one of the methods from rhodium archive (link in the first post) substituting styrene for isosafrole. It looks promising and the only thing I worry about is that phenylacetaldehyde may be further oxidized to phenylacetic acid.

SM2 - 21-11-2012 at 06:47

if you want phenylacetaldehyde in copious amounts, react D-LPhenylalanine to a well stirred solution of strong bleech, or HTH. The yellow oil with the sickly sweet smell is immediately apparent. Try to distill it out and separate ASAP, and make the bisulfite adduct, which IS stable.

Nicodem - 21-11-2012 at 07:52

But what exactly is wrong with the already published procedures for the styrene oxide to phenylacetaldehyde transformation?

I can understand the reluctance to consider some of the references for the rearrangement in the liquid phase which use non-trivial reagent or conditions, but what for example is wrong with the procedure described in DOI: 10.1080/00397919508011817? Or US4650908 and DE3708737? The setup is somewhat involved, but it is nothing that an average amateur could not do with some effort.

SM2 - 21-11-2012 at 17:29

Nicodem;

My intuition tells me such a reaction benefits greatly from experience working the procedure. I recently had a straight forward synthesis fail on me, and I did everything (or so I thought), strictly, according to the instructions. As to the beginning of your question "what is wrong...", I'd say the person in question would prefer an easier route, like, for instance, titration until a color change occurs. The Styrene oxide route>PhenylAcetaldehyde is far cheaper than starting from the pure amino acid as your feedstock.;)

kristofvagyok - 22-11-2012 at 14:11

I am reading an old (1995) Aldrichimica Acta and there is a reaction in it what fits to this topic.

It is about catalytic oxidative rearrangements made with Tl(III)-nitrate (TTL). There is 3 article mentioned here what are about to turn styrenes to phenylacetaldehyde-dimethyl acetals by some methanol and some TTL.

Check them out, they could be interesting:
J. Am. Chem. Soc. 1973, 95, 3635
Liebigs Ann. Chem. 1962, 656, 204
S. Can. J. Chem. 1973, 51, 2366

P.S.: TTL is quite toxic, but it is needed in catalytic amounts, could be reused, and it is a pretty awesome reagent.

tetrahedron - 22-11-2012 at 16:30

Quote: Originally posted by kristofvagyok  
pretty awesome reagent.

and especially OTC =)

check this out for more on that route:

McKillop, A., Hunt, J. D., Taylor, E. C., and Kienzle, F., "Thallium in Organic Synthesis: XX. Oxidative Rearrangement of Olefins with Thallium (III) Nitrate--A Simple One-Step Synthesis of Aldehydes and Ketones," Tetrahedron Letters, No. 60, 1970, pp. 5275-5280.

phendrol - 27-11-2012 at 10:31

The reaction is attractive because there is no problem with acquiring the reagents where I live. Furthermore the peracid oxidation looks like it can be run in a one pot reaction, which is very advantageous. Oxidation via the chlorohydrin uses OTC reagents and gives decent yields, but leads only to styrene oxide. I'm wondering if it's possible to oxidize it further with hypochlorouse acid? Maybe a ring opening with an acid and rearrangement?

Anyway I'm waiting for my order of chemicals and after I'll get them I'm planning to do as follows

I'll prepare some performic acid by mixing formic acid with hydrogen peroxide. Next I'll prepare a solution of styrene in DCM with a sodium carbonate/bicarbonate buffer. The performic acid will be then added dropwise to the solution with stirring left for 16 hours. Followed by extraction of the organic phase, and after some work up, dissolving it in methanol and lightly boiling with dilute sulfuric acid.

As an alternative I was thinking about preparing the epoxide via the chlorohydrin route, then forming styrene glycol as described here:

http://www.scribd.com/doc/55131328/furanoside-rhee

and boiling it in methanol with dilute h2so4 to form the aldehyde.

[Edited on 27-11-2012 by phendrol]

[Edited on 27-11-2012 by phendrol]

Nicodem - 28-11-2012 at 07:00

Quote: Originally posted by phendrol  
Followed by extraction of the organic phase, and after some work up, dissolving it in methanol and lightly boiling with dilute sulfuric acid.

It appears to me that you did not do the literature work properly. There is a reason why silica-gel is used as an acid in that Synth. Commun. article. Phenylacetaldehyde decomposes in such acidic environment as diluted sulfuric acid. Also, how is such an rearrangement supposed to be easier than the given literature example which claims nearly quantitative yields, easy to obtain solvent and catalyst, and a ridiculously simple isolation? You shouldn't be believing every nonsense that Fennel Ass Ih Tone manages to post - I bet he didn't even bothered reading the article before hitting the reply button!

phendrol - 30-11-2012 at 03:15

Nicodem you are right.

The extra work up is not a big problem. Most of my work will be consumed by building an aspirator vacuum satation. I'll need it in the first step (styrene --> chlorohydrin --> styrene oxide). Unless someone has an idea how to separate styrene oxide from unreacted styrene and side products without using any vacuum. Maybe forming an azeotrope?

[Edited on 1-12-2012 by phendrol]

phendrol - 13-12-2012 at 06:42

I've managed to prepare some styrene oxide and I'm getting ready to rearrange it in the gas phase. I need an advice thou. I'm not sure how the silica gel catalyst should be placed. Should it just be like a tube packed with silica dioxide powder or beads? Or should the catalyst be placed on something?

I just don't want the whole thing to explode because of high pressure.

US4650908

TheCatalyst - 12-1-2013 at 23:38

Phendrol,

Have you had any success ? By the way why don't you use the liquid phase isomerization of styrene oxide. Seems to me it would be much easier.

Lemini, C. , Ordo≁ez, M. , Pérez-Flores, J. and Cruz-Almanza, R.(1995) 'Synthesis of Aldehydes from
Oxiranes using Silica Gel as Reagent', Synthetic Communications, 25: 18, 2695 — 2702
To link to this Article: DOI: 10.1080/00397919508011817
URL: http://dx.doi.org/10.1080/00397919508011817

General Procedure for the conversion of oxiranes into aldehydes. In a threenecked
round bottom flask equipped with a magnetic stirrer a solution of 1 g of
oxirane in 20 ml of ethylacetate or acetone was placed and, 1 g of silica gel was
added. The reaction mixture was stirred vigorously at room temperature until the
oxirane disappeared (monitoring by TLC). Most of the reactitvis were finished
within 30 min. When the reaction was completed the silica gel was removed by
filtration, the filtrate dried on Na,SO, and the solvent evaporated under reduced
pressure.

phendrol - 30-1-2013 at 08:57

Well to be honest I couldn't do much because I haven't got a vacuum pump. An aspirator is no good because water pressure is to low at my place. Because of that I can't purify the epoxide via vacuum distillation. When I made a run with it, the silica gel was covering with tar pretty fast.

But this method sounds super easy. I definitely will try it and post results. Thanks!!!

Nicodem - 12-8-2013 at 08:33

An example of the acid catalyzed styrene oxide rearrangement to phenylacetaldehyde (applying H3PO4) and its concurrent acetalization with another styrene oxide equivalent is described at the Synthetic Pages:
Acid mediated cyclodimerization of styrene oxide to 2-benzyl-4-phenyl-1,3-dioxalane; ​​​​acetal formation (DOI: 10.1039/SP312)

Crowfjord - 1-2-2016 at 12:10

Tetrahedron Letters 55 (2014) 5047–5051 describes the reactions of several amino acids with sodium hypochlorite in phosphate buffer. The buffer, pH, dilute conditions, and slow addition are necessary to achieve good yields and avoid side reactions. From the supplementary materials:

Quote:

General Procedure for sodium hypochlorite oxidation. To a vigorously stirring solution of amino acid (1 mmol) in 250 mL of sodium phosphate buffer (10 mM, pH 7.0) was added a solution of NaOCl (1 equivalent as a 0.1 M aqueous solution) slowly over 10 minutes via syringe pump in a 37 °C warm room or water bath. The resulting solution was stirred vigorously at this temperature until the reaction was judged to be complete by HPLC (1-2 hours). In general, the reaction may be stopped after 2 hours if monitoring is inconvenient. The solution was then extracted into dichloromethane (4 x 40 mL), washed with brine (2 x 50 mL), dried over MgSO4, and the solvent removed under reduced pressure in an unheated water bath to afford the desired aldehyde.

Quote:
2-phenylacetaldehyde (2e). DL-Phenylalanine (0.165 g, 1 mmol) was dissolved in 250 mL of 10 mM pH 7 phosphate buffer and reacted by the above procedure for 2 hours to yield 72 mg of 2e (60 %) as a yellow oil. 1H-NMR, LRMS, and HPLC data matched an authentic commercial sample (Sigma-Aldrich).

clearly_not_atara - 1-2-2016 at 17:34

Step 1: styrene + HBr + H2O2 >> phenethyl bromide

Step 2: http://pubs.acs.org/doi/abs/10.1021/ja01524a080?journalCode=...

chemrox - 9-2-2016 at 13:18

would you please post the pdf? in refs? or here..

clearly_not_atara - 10-2-2016 at 13:08

Sure. The reaction is like this:

RHBr + AgOTs >> RHOTs + AgBr (s)
RHOTs + DMSO >> RO + HOTs + Me2S (g)

Silver tosylate is soluble in organic solvents but not water, so can be precipitated from a solution of AgNO3 and a tosylate. I do not know, but I strongly suspect, that other sulfonic acids work just as well (as long as they're inert).

Attachment: tosylatealdehyde.pdf (684kB)
This file has been downloaded 410 times


madcedar - 10-2-2016 at 18:50

Quote: Originally posted by clearly_not_atara  
Step 1: styrene + HBr + H2O2 >> phenethyl bromide

Step 2: http://pubs.acs.org/doi/abs/10.1021/ja01524a080?journalCode=...


Thank you for the reference. My problem is with your Step 1, I think it makes styrene dibromide and not phenethyl bromide.

DraconicAcid - 10-2-2016 at 18:55

Quote: Originally posted by madcedar  
My problem is with your Step 1, I think it makes styrene dibromide and not phenethyl bromide.


HBr will add across a double bond following Markovnikov's rule in the absence of peroxides, and add the other way in the presence of peroxides. The hydrogen peroxide isn't going to turn the HBr into bromine.

S.C. Wack - 10-2-2016 at 22:28

Does there exist actual preparations that used hydrogen peroxide in step 1, that got a phenylacetaldehyde in step 2?

clearly_not_atara - 11-2-2016 at 10:15

See http://en.wikipedia.org/wiki/Markovnikov's_rule#Anti-Markovnikov_reactions

The method with HBr/cat. H2O2 is a classic; you can find examples in most chemistry textbooks (you can usually find a cheap one at charity book-selling events and the like). Wiki does describe a synthesis of phenylacetaldehyde using a similar methodology with water and phenylacetylene. See also:

http://www.chemicalforums.com/index.php?topic=58919.0

madcedar - 11-2-2016 at 16:09

Thank you for the clarification DraconicAcid and clearly_not_atara, great stuff.

zed - 11-2-2016 at 16:50

And then, there are modifications of the Wacker.

Looks interesting, maybe Iĺl finish reading it tomorrow.

http://www.google.com/patents/US7582750

S.C. Wack - 11-2-2016 at 17:03

Quote: Originally posted by clearly_not_atara  
See http://en.wikipedia.org/wiki/Markovnikov's_rule#Anti-Markovnikov_reactions

The method with HBr/cat. H2O2 is a classic; you can find examples in most chemistry textbooks (you can usually find a cheap one at charity book-selling events and the like). Wiki does describe a synthesis of phenylacetaldehyde using a similar methodology with water and phenylacetylene. See also:

http://www.chemicalforums.com/index.php?topic=58919.0


In other words, no. OK.

PS: Has any chemistry book ever mentioned a HBr/H2O2 in any preparative context? BTW that's bromine and water, etc.

Really I want to know if these things are out there, but I'm also kind of hinting that if they're not...the directions that are out there to put the Br at that spot are specific and it looks like they have to be. But that's not all that important because no one will go to the aldehyde from there anyways.

[Edited on 12-2-2016 by S.C. Wack]

clearly_not_atara - 11-2-2016 at 20:45

Quote:
In other words, no. OK.


http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch06/ch6-4-...

Quote:
PS: Has any chemistry book ever mentioned a HBr/H2O2 in any preparative context? BTW that's bromine and water, etc.


http://pubs.acs.org/doi/abs/10.1021/ja00176a075
http://pubs.acs.org/doi/abs/10.1021/jo00110a040

I guess it turns out other catalysts are better. Either hv or RCOCBrR'R"/O2 (hv sounds much easier).

[Edited on 12-2-2016 by clearly_not_atara]

S.C. Wack - 12-2-2016 at 04:10

Peroxide and hydrogen peroxide continue to be different things, in your links there is no hydrogen peroxide. Also, organic peroxide gives mainly the wrong isomer under these nonspecific conditions (solvent should be mentioned).

clearly_not_atara - 12-2-2016 at 10:05

One is a subset of the other. Regardless, your complaint is offtopic. The anti-Markovnikov addition of HBr to styrene is simple to achieve; H2O2 might not be the best catalyst, but who is going to publish a synthesis of something so trivial, especially if the method is suboptimal? The other papers provide much better ideas.

zed - 12-2-2016 at 14:47


http://www.google.com/patents/US7582750

Oh, the above paper? About a page or two in, they cut to the chase.
The tables of results, and conditions, are present, but they have been compressed.

When styrene (20) was treated with 1.03 equiv Cl2pyNO and 1.0 mol % 1 in refluxing CH2Cl2 for 5 h, a mixture of styrene oxide and phenylacetaldehyde (27) was obtained in 90% and 10% yield, respectively (Collman et al. J. Am. Chem. Soc. (1986), Vol. 108, page 2588; Burrows et al. J. Am. Chem. Soc. (1988), Vol. 110, page 6124; Minisci et al. J. Am. Chem. Soc. (1995), Vol. 117, page 226; Gross et al. Angew. Chem. Int. Ed. (2000), Vol. 39, page 4045; Gray et al. Angew. Chem. Int. Ed. (2001), Vol. 40, page 2132). To our surprise, adding more catalyst 1 and allowing the reaction to proceed for a longer time resulted in complete conversion of styrene oxide to aldehyde 27. For example, reaction of styrene with 1.03 equiv Cl2pyNO in the presence of 2.0 mol % 1 in CHCl3 at 60° C. for 12 h afforded 27 in 99% yield; no benzaldehyde was observed (Gray et al. Inorg. Chim. Acta (1998), Vol. 270, page 433). Other styrene derivatives 21-25 could also be converted to the corresponding arylacetaldehydes 28-32 in excellent yields (FIG. 6). However, for the non-aromatic alkene 26, only the epoxide product was obtained.

[Edited on 12-2-2016 by zed]

[Edited on 12-2-2016 by zed]

S.C. Wack - 12-2-2016 at 17:26

Quote: Originally posted by clearly_not_atara  
One is a subset of the other. Regardless, your complaint is offtopic. The anti-Markovnikov addition of HBr to styrene is simple to achieve; H2O2 might not be the best catalyst, but who is going to publish a synthesis of something so trivial, especially if the method is suboptimal? The other papers provide much better ideas.


You're telling me how easy it is, but I bet you haven't even read the original literature that started these textbook sentences. H2O2/HBr preparations are in fact out there and numerous, as expected the reactions are those of bromine and are obviously not radical additions. Feel free to cite a preparation with radical hydrobromination on any double bond that uses just H2O2 and HBr.

There is no such thing as a catalytic amount of hydrogen peroxide in HBr, or vice versa. There is no propagation, there is a reaction until one is gone and that's it. Bromine, water, and styrene is a recipe for styrene bromohydrin.

(EDIT: vice-versa was a step too far!!! Obviously HBr with H2O2 oxidant and the molecule being operated on gives bromine then HBr then back to bromine.)

It's true, responding to your post, I have nothing on topic to say. The reactions of styrene chlorohydrin in the vapor phase however is on topic regardless of a certain lack of convenience:

Attachment: jacs 67_518_1945.pdf (384kB)
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[Edited on 13-2-2016 by S.C. Wack]

clearly_not_atara - 14-2-2016 at 11:06

1. You're wrong, I have read it.

2. No. I'm obviously referencing a reaction that's common knowledge, if I were specifying conditions I'd give them. I've no reason to encourage your flamebaity nitpicking.

S.C. Wack - 14-2-2016 at 11:42

Quote: Originally posted by clearly_not_atara  
1. You're wrong, I have read it.

2. No. I'm obviously referencing a reaction that's common knowledge, if I were specifying conditions I'd give them. I've no reason to encourage your flamebaity nitpicking.


There is absolutely no common knowledge about using hydrogen peroxide in place of organic peroxide in this reaction, because it isn't possible. Hydrogen peroxide is not going to be regenerated from water full stop. If saying that your impossible reaction is impossible is nitpicking, maybe you're at the wrong site. If you wish for me to stop telling you that you're wrong, all you have to do is either prove you're right or stop making these claims.

[Edited on 14-2-2016 by S.C. Wack]

Nicodem - 15-2-2016 at 08:34

Before this end up with unnecessary misunderstanding and accusations...

Neither hydrogen peroxide or any other peroxide can be used as a catalyst for the radical addition of HBr on alkenes. In fact, I know no catalysts for this reaction (though they might exist). Radical additions of HX (where X is Br, I, SR, PR2, etc.) require some kind of radical initiation which can be chemical (with radical initiators like AIBN, diacyl peroxides, oxygen, etc.), photochemical (UV) or radiochemical (gamma or other ionization type). The reaction is rapid (it's a radical chain reaction) and for this reason it does not even need catalysis.

Hydrogen peroxide is rapidly reduced by HBr to yield H2O and Br2 and cannot be used neither as a catalyst or radical initiator. In fact, for this reason hydrogen peroxide is commonly used as an in situ oxidant for HBr in electrophilic aromatic brominations.

Radical addition of HBr on styrene is not some trivial reaction. A lot of conditions need to be fulfilled to slow down the otherwise much faster competing reactions like the electrophilic addition and polymerization. Anhydrous conditions and a highly non-polar solvent are used to prevent the electrophilic addition of HBr (already gassing the reaction mixture with dried HBr is not trivial). Traces of water will catalyze the electrophilic addition yielding 1-bromo-1-phenylethane. Low styrene concentrations (e.g., by slow addition of styrene) and higher HBr concentrations can slow down the polymerization.

Preparative examples of phenetyl bromide preparations from styrene using the radical HBr addition do exist, but as far as I could find, they are all but one written in Chinese (though admittedly, I did not spend much time searching). Yields can be excellent, except that achieving them is not simple. Here are a few Chinese references from a 5 minutes SF search:

Huaxue Shiji, 2006, 28, 326-328 (in CCl4, UV initiation, 96% yield)
Huaxue Gongye Yu Gongcheng (Tianjin, China), 23(5), 385-388 (in heptane, AIBN initiation, 92% yield)
Shandong Huagong, 2004, 33, 8-34 (in petroleum ether, unspecified initiator, 91%)
CN101255095 (in heptane, (BzO)2 initiation)
CN1429799 (in 1-bromohexane, AIBN initiation)
JP09040591 (O2 initiation)

clearly_not_atara - 15-2-2016 at 10:56

I posted a ref in English four posts up:

http://pubs.acs.org/doi/abs/10.1021/jo00110a040

It discusses the reaction in some detail. In any case, is it *really* too much for me to expect people to be familiar with the radical addition of HBr to alkenes (other HX suck for this reaction so they don't matter) and either know how to do it or know where to look it up? Yes, I got the conditions wrong. Congratulations. But I subsequently got the conditions right and yet here we are arguing about a line in a post from a week ago that doesn't even have any words in it.

[Edited on 15-2-2016 by clearly_not_atara]

S.C. Wack - 15-2-2016 at 21:21

We're using the term catalyst loosely, obviously. The particular examples I've had in mind are JACS 61, 2693 (1939) and the patent it mentions, GB438820.

madcedar - 16-2-2016 at 16:11

Quote: Originally posted by phendrol  
Well to be honest I couldn't do much because I haven't got a vacuum pump. An aspirator is no good because water pressure is to low at my place. Because of that I can't purify the epoxide via vacuum distillation. When I made a run with it, the silica gel was covering with tar pretty fast.

But this method sounds super easy. I definitely will try it and post results. Thanks!!!


You may not have used enough solvent and I think everything has to be anhydrous to get from stryene oxide to phenylacetaldehyde via silica gel, otherwise you'll end up with the diol.

Any comments on this will be very welcome.

Chemi Pharma - 8-5-2016 at 08:21

Everybody here in this discussion post are talking about styrene as starting material to sintesize some phenylacetaldehyde. Anybody thought about the use of phenethyl alcohol as starting material?

Phenethyl alcohool is sold at cheap prices by perfumery flagrancies stores as a litre bottle.

Just oxidate the alcohol with CA(OCL)2 - HTH pool and alumina in a microwave for 2 minutes or reflux the mixture for 4 hours and you get pure phenylacetaldehyde in >95% yeld.

See the papers below about alcohol oxidation to aldehydes by HTH pool and alumina:





Attachment: alcohol oxidation by CaOCL to aldehydes.pdf (161kB)
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Attachment: Microwave Assisted Selective Oxidation of Benzylic Alcohols with Calcium Hypochlorite under Solvent-Free Conditions.pdf (62kB)
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byko3y - 9-5-2016 at 08:00

None of those articles mentiones 2-phenylethylalcohol. And that's for reason, because the procedure does not work for this substrate, yielding a complex mixture of products.

Chemi Pharma - 9-5-2016 at 13:40

Do you have references about that? about only working with benzilic alcohools and not with phenyl alkyl alcohols with alifatic chains?

I trace a parallel with the oxidation of alcohols to acids with nickel peroxide (hipoclorite + nickel salt) that i read from an japanese article, that i bring to you all, below, as an attachment.

If you oxidate the phenyl alkyl alcohol at cold temperatures like 0º C, this afford phenyl alkyl acid with no chain split. See somewhere in the paper that they got this result with phenyl propyl alcohol with 70,5% yield of phenyl propionioc acid and a small amount of benzoic acid:

"...In the cases of alcohols possessing an active
methylene group in the molecule, the methylene
group was in part simultaneously oxidized at room
temperature to give compounds with less carbon
atoms. When the reaction temperature was low-
ered in such cases, however, the oxidation of a
carbinol group proceeded so predominantly that
the corresponding acid was obtained in good yield.
Thus the oxidation of y-phenylpropyl alcohol at
0" afforded 70.5% yield of y-phenylpropionic acid
together with a small amount of benzoic acid,
whereas at 30" it gave 56.7% yield of y-phenyl-
propionic acid and 17.6% yield of benzoic acid..."

Hey! Isn't a good way to produce tons of ever watched Phenyl Acetic Acid?:cool:

Attachment: Oxidations with nickel peroxide (NICL2 + NAOCL).pdf (567kB)
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[Edited on 9-5-2016 by Chemi Pharma]

clearly_not_atara - 9-5-2016 at 15:24

Just use an Oppenauer oxidation with benzoquinone, much simpler. You can use aluminum t-butoxide or just react your 2-phenylethanol with Al amalgam to get things started, IIRC.

https://www.researchgate.net/publication/244761206_On_Quinon...

This is usually the easiest alcohol oxidation.

Chemi Pharma - 9-5-2016 at 16:19

Thanks Clearly for the reference.

Ok I understood about the oppenauer, but didn't understand what you means about "just react your 2-phenylethanol with Al amalgam to get things started".

The latter thing you said it's about a reduction reaction, given probably phenylethane.

Could you make the things clear(ly) to me?:D

byko3y - 10-5-2016 at 00:40

Chemi Pharma, I have no references at hand, that's just my speculations, which happen to be true.
2-phenethyl alcohol is extreemely labile to oxidation at benzylic position, even more than 3-phenylpropanol. Of course, nickel peroxide might give as high as 50% yield for phenylethanol oxidation to phenylacetic acid.

Chemi Pharma - 10-5-2016 at 04:03

Ok byko3y, what do you think about a moffatt oxydation of 2-phenylethyl alcohol with DMSO and P2O5 and Et3N? By analogy to the Swern procedure, it seems the different mechanism of this type of alcohol oxidation doesn't affect the benzilic carbon.

Do you think i can achieve phenylacetaldehyde this way?

Attachment: DMSO - Phosphorus pentoxide - triethylamine (PDT) oxydation to aldehydes and ketones.pdf (278kB)
This file has been downloaded 311 times

[Edited on 10-5-2016 by Chemi Pharma]

clearly_not_atara - 11-5-2016 at 12:12

The reaction of an alcohol with aluminum amalgam or activated aluminum produces an aluminum alkoxide and hydrogen:

6ROH + 2Al >> 3H2 + 2Al(OR)3

The alkoxide is oxidized to the aldehyde by benzoquinone.

Chemi Pharma - 11-5-2016 at 12:24

Thanks for the explanation Clearly. I've got it.

Do you have any papers about aluminium alkoxides oxidation with benzoquinone?

And what do you think about a moffat oxidation of 2-phenethyl alcohol?

Could afford phenylacetaldehyde in reasonable yields?

CuReUS - 12-5-2016 at 00:09

atara,that's a smart idea,using the alcohol you want to oxidise to make its own alkoxide.Then you wouldn't have to use Al-tert butoxide separately. But isn't there a chance of condensation of the aldehyde formed due to the primary alkoxide(from phenyl ethanol ? ).Isn't that why they use a sterically hindered and bulky alkoxide like t-butoxide ?

if oppenauer oxidation is done,instead of using benzoquinone,cinnamaldehyde could be used,which would get reduced to cinnamyl alcohol.

other amateur friendly ways to oxidise alcohols to aldehydes would be NBS,lead tetracetate/pyridine, SeO2,DMP,Oxone to name a few.

[Edited on 12-5-2016 by CuReUS]

clearly_not_atara - 12-5-2016 at 12:53


Big problem with DMSO oxidations is the Me2S byproduct. This flammable toxic gas is not easy to scrub from efflux gas because it's very nonpolar. The safer modification is the Corey-Kim version, using a haloimide and catalytic amounts of a thioether.

It's not clear what the best thioether is -- methionine hydantoin comes to mind, but has solubility issues. Dodecyl methyl sulfide is popular. There are few OTC options; dibenzyl sulfide isn't too hard I guess.

CuReUS - 13-5-2016 at 09:48

Quote: Originally posted by clearly_not_atara  

Big problem with DMSO oxidations is the Me2S byproduct. This flammable toxic gas ...

not to mention the stench :D
Quote: Originally posted by CuReUS  

if oppenauer oxidation is done,instead of using benzoquinone,cinnamaldehyde could be used,which would get reduced to cinnamyl alcohol.

cinnamyl alcohol could be converted to propenylbenzene with this reaction
https://en.wikipedia.org/wiki/Barton%E2%80%93McCombie_deoxyg...

or this-http://www.organic-chemistry.org/abstracts/lit3/641.shtm

also I was thinking,How about using alcohol dehydrogenase enzyme to oxidise phenylethanol to phenylacetaldehyde ?

karlos³ - 13-5-2016 at 13:53

Pyridinium chlorochromate is also a very amateur friendly oxidant, especially for the conversion of alcohols to aldehydes. I like it very much, as it is easy to prepare and a convenient reagent.

gravityzero - 2-11-2016 at 15:39

After reading the thread in full, it is still unclear if anyone is able to get to Styrene Oxide simply using a peracid, such as performic acid or peracetic acid.
It is assumed it would work, but OrgSyn uses perbenzoic acid which I had never heard of until today. Not really a miracle or anything.

If anyone can confirm a success using a more convenient peracid or oxone that would be helpful.

Then it is stated using silica gel to isomerize the oxirane to the aldehyde.
Sorry for any spoonfeeding. Just want to make sure I'm understanding all this.

NitreRat - 2-11-2016 at 18:35

Quote: Originally posted by gravityzero  
After reading the thread in full, it is still unclear if anyone is able to get to Styrene Oxide simply using a peracid, such as performic acid or peracetic acid.


I have performed a few epoxidations of alkenes with peracids (including in-situ peracetic acid), albeit in a formal lab setting. Peracids are strong oxidising agents so the actually reaction occurs quite readily, the real difficulty is trying to isolate the epoxide before any nasty nucleophiles can attack the poor epoxide and break open its ring with their electrons...

Because of the inherent acid present with peracid epoxidations, any water, amines or alcohols present in the reaction mixture can react with the epoxide after it's formed - creating alcohols and vicinal diols. These alcohols and diols/glycols can then be oxidized and cleaved by the peracid forming aldehydes, ketones, hydroxy-ketones, diketones and carboxylic acids.

If you're using anhydrous peracetic, performic or (m-chloro)perbenzoic acid the hydrolysis can be avoided. If you're doing a one-pot in-situ peracid epoxidation with H2O2(aq) + acid + alkene, you will inevitably end up with the hydrolysis and oxidation products. With styrene, I would expect phenylacetic acid, phenylglyoxylic acid and benzoic acid to be the main products of this reacation.

[Edited on 11/3/2016 by NitreRat]

purplephanta - 5-1-2017 at 05:00

Hello Phendrol, or anyone else for that matter,

Have you had success using the method referenced by Nicodem and TheCatalyst?

DO.108/00397919508011817 (http://dx.doi.org/10.1080/00397919508011817)

If so, what were the pitfalls;

Is the reaction not scalable?
Is very pure, anhydrous styrene oxide required?
Can the ethyl acetate be recycled or is it consumed?

Thanks

styrene oxide to phenylacetaldehyde via the pinacol rearrangement?

madcedar - 17-6-2017 at 23:14

In theory, mixing styrene oxide and a non-halo acid (H2SO4) should give styrene glycol. A halo acid such as HCl will give a halohydrin instead.

styrene glycol.png - 3kB

On further mixing and heating phenylactaldehyde should be the product (see this Youtube video on the Pinacol Rearrangement).

phenylacetaldehyde.png - 3kB

I'm assuming roughly following this procedure in the attached pdf (Organic Syntheses, Coll. Vol. 1, p.462 (1941); Vol. 5, p.91 (1925)) and substituting an equal molar amount of styrene oxide for pinacol will give the desired results.

I don't have any glassware to try this out myself but any comments on the theory are welcome.

Attachment: Pinacol Rearrangement cv1p0462.pdf (298kB)
This file has been downloaded 241 times

[Edited on 18-6-2017 by madcedar]

JJay - 18-6-2017 at 00:02

I ran across this paper a while back. I can't read most of it, but according to the authors, it's possible to do the rearrangement from styrene oxide to phenylacetaldehyde using a catalyst consisting of nitric acid on activated carbon in ethyl acetate at 75 C:

Preparation of Phenylacetaldehyde and 1, 3-Dioxolanes from Styrene Oxide with Mineral Acid-Treated Activated Carbon Catalyst

Chemi Pharma - 22-6-2017 at 09:08

Better produce phenylacetaldehyde from the isomerization of styrene oxide with silica gel in acetone, at room time for an hour, like said in the paper i bring below.

I think the better route to phenylacetaldehyde is dissolving styrofoam in acetone, mix with MgSO4 as a cataliser and distill at 250-300ªC the styrene monomer with the acetone all onto the same flask.

The styrene in acetone obtained react with TCCA to form the chloridrine and further with KOH to form the epoxide.

Finally, proceed with the epoxide isomerization with silica gel as I said above.

Here's the papers:

Attachment: styrene oxide to phenyl acetaldehyde with silica gel.pdf (981kB)
This file has been downloaded 380 times

Attachment: styrene from polystyrene.pdf (1MB)
This file has been downloaded 203 times

Attachment: styrene to styrene oxide with TCCA and KOH.pdf (234kB)
This file has been downloaded 307 times

JJay - 14-7-2018 at 20:57

I've read a number of interesting papers about isomerization of styrene oxide with exotic catalysts, and there is a U.S. patent regarding the use of silica gel in the vapor phase, but doing it with silica gel in half an hour at room temperature... is that really possible?

Apparently, it is pretty easy to isomerize styrene oxide to phenylacetaldehyde in a bomb reactor with heat:

US3860614A - Thermolysis of Styrene Oxide

Attachment: Thermal Rearrangement of 1,2-Epoxyethylbenzene.pdf (252kB)
This file has been downloaded 96 times

I'm not terribly familiar with sealed tube reaction protocols, but I think the thermolysis could be performed using the ol' toaster oven with a long extension cord trick and some sandbags. I'm not seeing why you couldn't use an unlined iron pipe sealed with plumber's tape to contain the reaction, although I would advise extreme caution of course.

If you wanted to get really fancy, you could use an autoclave or a Parr reactor.

notoxicshit - 15-7-2018 at 10:17

Works in acetone over silica gel in high yield. Forgot the name of the paper though it should be easy to find.
However they dont mention how dry the acetone has to be. That may be the reason I failed once but I got too confident and didnt check before the follow-up reaction.
But it seemed legit.
Report back please.

JJay - 15-7-2018 at 11:18

Chemi Pharma posted the paper directly above. Silica gel 60 is pretty expensive... I'd be more inclined to try heat/pressure... the temperatures required are nothing ridiculous, and no fancy apparatus is required.

Nicodem mentioned an expired Dow Chemical patent on a continuous vapor phase process for isomerizing styrene oxide to phenylacetaldehyde. It uses silica gel and water. The process looks a little involved, but it might be useful if you want to produce more than a liter or so of phenylacetaldehyde.