forsh
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Easy OTC oxidative cleavage of alkenes - Real or more BS?
Hi,
While doing a lit search on oxidative cleavage I stumbled on this new paper in tetrahedron Parida et al. (2014)
It sounds a bit too easy and too good to be true, does anyone have any thoughts?
3. Mechanism of oxidation
We believe that the initial double bond oxidation is a common step in the oxidation of all substrates for which the results are collected in Table 1,
Table 2 and Table 3. Oxone has been reported to convert olefins to epoxides,14 which under the employed conditions of the reaction open up to give
diols; it should be noted that the solution of oxone in acetonitrile–water (1:1, v/v) is strongly acidic, and we have found that the pH of the
solutions of oxone in acetonitrile–water (1:1, v/v) mixture employed for oxidations described herein is typically ∼3–4. Thus, the initially
formed epoxides should be expected to open up in acetonitrile–water to give the corresponding diols. We have indeed isolated the diol intermediates
in some cases, e.g., styrene (entry 1, Table 1), p-methylstyrene (entry 6, Table 1), and 1-phenylcyclohexene (entry 15, Table 1), when the reactions
were run for a short period. Indeed, the fact that the reaction of styrene with oxone in CH3CN–H2O (1:1, v/v) leads to dihydroxy products has
previously been shown by Vinod et al. 7 Further, the formation of diol intermediates is clearly revealed in the 1H NMR monitoring of the reactions for
some cases, e.g., p-nitrocinnamic acid, stilbene, and 4,4′-dibromostilbene, cf. Supplementary data. The oxidative cleavage of diols presumably
occurs via formation of the cyclic hypervalent sulfur intermediate with oxone and subsequent decomposition to the latter to aldehyde/s ( Scheme 1).
The fact that only dihydroxylated products are observed at 60 °C and that the reflux condition leads to cleavage products suggests that the initial
epoxidation followed by opening is much faster than equilibrium formation of the six-membered cyclic hypervalent sulfur intermediate that collapses to
the carbonyl compounds, cf. Scheme 1. When the product is aldehyde, it subsequently undergoes rapid oxidation with oxone; the latter, i.e., oxidation
of the aldehyde to the corresponding acid, is a well-known reaction. 15 Clearly, a cascade of oxidations that include dihydroxylation, cleavage to the
aldehydes followed by further oxidation of the latter to the corresponding acids occur in tandem.
5.2. General procedure for the oxidative cleavage of olefins
To a solution of the olefin (0.5–1.2 mmol) in 16 mL of acetonitrile–water (1:1) mixture at reflux was introduced oxone incrementally over the
entire duration of the reaction. Progress of the reaction in each case was monitored by TLC analysis. After completion of the reaction as judged by
TLC analysis, the reaction mixture was cooled to rt, and the organic matter was extracted with ethyl acetate. The combined organic extract was dried
over anhyd Na2SO4 and concentrated in vacuo. The residue was subjected to a short-pad silica gel column chromatography to isolate pure product/s. All
the products were characterized by their 1H NMR spectral data.
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forgottenpassword
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Try it and see. Why do you think it's bullshit? They did the reaction, isolated the products and did an NMR on them. What part of that is bullshit?
Their NMR interpretation?
[Edited on 25-3-2014 by forgottenpassword]
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Dr.Bob
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It looks perfectly reasonable. Oxone is a useful oxidant. This reaction gives "retro-wittig" type products. Might be useful along with olefin
metathesis to provide a few interesting compounds.
The main issue is that you will get two different compound out (in non-symettric cases) which will be hard to separate in many of those cases. So it
might be best used on symmetric alkenes that are easy to get hold of, which is a small number. The sad part is that most of their products are easier
to get a hold of than the starting materials.
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forsh
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Yeah. I'm getting everything together and i'm going to do the reaction tomorrow with styrene - just wanted to see if anyone else has any insight.
I've tried a lot of methods I read in papers published to low impact journals from work done in Indian universities, and i've never had a single one
work. It just seems too good to be true, I suspect they are lying, but its worth a shot anyway. The mechanism sounds reasonable but I thought it
always required a metal catalyst or dioxirane.
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forsh
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Quote: Originally posted by Dr.Bob  | It looks perfectly reasonable. Oxone is a useful oxidant. This reaction gives "retro-wittig" type products. Might be useful along with olefin
metathesis to provide a few interesting compounds.
The main issue is that you will get two different compound out (in non-symettric cases) which will be hard to separate in many of those cases. So it
might be best used on symmetric alkenes that are easy to get hold of, which is a small number. The sad part is that most of their products are easier
to get a hold of than the starting materials. |
I'm not very familiar with retro-wittig type reactions, i'm looking and its an interesting read! Thanks for drawing it to my attention.
I had a mind blank and didn't understand what you meant by symetrical alkenes, then I realised of course that if you cleave an alkene you're going to
have the other half you cleaved off! Yes, if they aren't quite different in properties then they could be very hard to separate.
I'm going to do the reaction on styrene and allyl phenol - both of which will yield formic acid as the other half, which isn't a problem.
I will report back before the weekend.
[Edited on 25-3-2014 by forsh]
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forgottenpassword
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Why?!
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FireLion3
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| Quote: Originally posted by forsh | | Yeah. I'm getting everything together and i'm going to do the reaction tomorrow with styrene - just wanted to see if anyone else has any insight.
I've tried a lot of methods I read in papers published to low impact journals from work done in Indian universities, and i've never had a single one
work. It just seems too good to be true, I suspect they are lying, but its worth a shot anyway. The mechanism sounds reasonable but I thought it
always required a metal catalyst or dioxirane. |
This is part of the reason why I never seek to try a reaction after reading it in just one paper. If you doubt the method do what I do and do some
investigative googling into the mechanism and try to find other examples of that mechanism or that particular use of the substrates. One paper may be
able to lie but having numerous papers lie about the same mechanism is unlikely.
Oxone is indeed a very useful oxidant. In fact, I believe I have looked into this particular use of Oxone before and if I recall correctly the
mechanism is very well known. Oxone is considered a useful source of Ozone in various reactions. The mechanism of ozonolysis is well known and
studied.
Check this out
| Quote: |
Ozonolysis is a way of cleaving carbon-carbon double bonds into two fragments useing oxone (O3) as a reagent. The fragments formed are either
aldehydes or ketones, depending on the nature of the R groups attached to the double bond.
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Believe it or not there are indeed an incredible amount of amazing reactions you can do with the correct over the counter compounds. The amount of
those useful reactions increases if you include various (non-otc) catalysts, that can be reused indefinitely.
[Edited on 26-3-2014 by FireLion3]
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forsh
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I've completed the reaction and i've just got the GCMS back. I did the reaction exactly as described in the paper, for 28 hours scaled up to use 1g
(~ 1ml) allyl phenol (Mr = 134 g/mol).
The GCMS gives me a major molecular ion peak at Mr 150, which corresponds to the methyl ketone, but the next major fragments along at 131, 119, 91
doesn't correspond with the loss of Me and CO that I would expect with this product. Also, i'm not sure I would even get a molecular ion peak with
the methyl ketone, and certainly not the major one I have. Alternatively, I could have the diol and i'm just not seeing a molecular ion because i'm
getting the McLafferty rearrangement (168 - 18 = 150), but again the rest of the fragmentation doesn't agree with this.
I ran regular TLC plates with both 50:50 hex:EtOAc, and 75:25 EtOAc:MeOH + a drop of acetic acid (for those polar carboxylic acids) then I tried
staining with bromocresole green for carboxylic acids. This gave a yellow dot at the starting line, but nothing else. This was at T=0 and T=28hours
so I don't think it is the carboxylic acid, but rather is oxone (stain is for low pH, not an actual specific organic group). The TLC plates didn't
show much else, nothing on there absorbed UV (unusual for a benzene ring I know), though I did get some absorbance and fluorescence in the blue light
range, this showed dark spot slow disappearing and then a fluorescent streak slowly getting stronger, though it didn't take long for it to appear
(t=30mins).
I will post a full write up soon when I scan in the TLC plate pics and the GCMS.
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forgottenpassword
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I do not have access to the paper, but from what you have quoted they did not use any phenols for their tests. It seems likely that a phenol would be
oxidized. What methyl ketone were you expecting from "allylphenol"?
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forsh
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Thats the reaction I think I have here.
True, they don't use any phenols, but they do use a few other substituted benzene derivatives and the oxidation still occurs.
Also, as far as oxidising the phenol ... I didn't think of that. Its entirely possible from the mechanism, but I can only find one phenol oxidation
product that fits the molecular ion from the mass spec, and thats the aldehyde derivative.
I don't think its the aldehyde because that is readily oxidised to the carboxylic acid with oxone.
:EDIT: A brief literature review tells me that you need a catalyst or basic conditions with the oxone in order to obtain the quinone.
[Edited on 31-3-2014 by forsh]
[Edited on 31-3-2014 by forsh]
[Edited on 31-3-2014 by forsh]
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Nicodem
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You sure picked up one of the least appropriate substrates to check an oxidative alkene cleavage method. I would certainly expect it to fail on
ortho-allylphenol. (By the way: Please learn to upload images on the forum. I hate to see images connected to links that are going to be dead
soon.)
| Quote: | | True, they don't use any phenols, but they do use a few other substituted benzene derivatives and the oxidation still occurs.
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The point is not in the oxidation of the vinyl group, but the unwanted reactions due to the phenolic group. Phenols are susceptible to oxidations by
Oxone. Furthermore, Oxone is an acid and 2-allylphenol is susceptible to acid catalyzed transformations.
Besides, it is quite pointless to use GC-MS data in order to propose products for which you have no viable and reasonable formation mechanism unless
there are no easier alternatives (remember the Occam's razor rule). Like proposing ortho-hydroxyphenylacetone as the product. Do you have a
reasonable proposal on how it is supposed to form? Why not 2,3-dihydro-1-benzofuran-2-ylmethanol instead? Same molecular weight and gives a stabilized
m/z = 131 [M-OH]+ fragment. And you can at least propose a mechanism for the transformation.
Can't you isolate the crude and run an NMR? Or at least an IR to check for the carbonyl?
| Quote: | | :EDIT: A brief literature review tells me that you need a catalyst or basic conditions with the oxone in order to obtain the quinone.
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You would be surprised of how much things change upon increasing the reaction temperature.
Check the reaction on styrene or cinnamic acid first. Both are in the article and both give benzoic acid. I assume you can easily get at least one of
these two substrates and you should be able to get benzoic acid as a TLC reference. As much as I believe many if not most Indian articles are more or
less BS, I would be cautious calling such an article that supposedly offers Supporting material with spectras and everything. Oftentimes Indian and
Iranian papers offer obvious evidence, or at least some indication of a BS story, but from what I can see, this article appears quite honest at first
glance (though, I have yet to read it all). You have no evidence for malicious claims and I expect you to have the decency to test on one of the
published substrates and possibly apologize to the authors, if the results are in accordance to what they claim.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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forsh
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I completely agree with everything you've said Nicodem.
I've ordered in some cinnamic acid and i'm just waiting for that to arrive before I repeat the experiment to the exact specifications of the paper. I
just had some allyl phenol lying around and I thought i'd try out the experiment with that (i'm interested in making benzofurans and hydroxyphenyl
acetic acid derivatives, and the idea of making these from o-allyl phenol is exciting) but I was being too hasty.
I would never infer that work was certainly fraudulent from the off, without trying it myself exactly as the authors did and trying it a couple times.
In fact, I never even considered that papers could 'lie' until you suggested so to me a few months ago when I followed a method from a paper coming from the same country. My point in bring up the validity of
the paper was purely to discuss if this was a 'too good to be true' incredibly simple and OTC method of achieving something quite fiddly - much in the
same way as that zinc catalysed Claisen was, which was also backed up by accompanying NMR.
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Nicodem
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| Quote: Originally posted by forsh | | I would never infer that work was certainly fraudulent from the off, without trying it myself exactly as the authors did and trying it a couple times.
In fact, I never even considered that papers could 'lie' until you suggested so to me a few months ago when I followed a method from a paper coming from the same country. My point in bring up the validity of
the paper was purely to discuss if this was a 'too good to be true' incredibly simple and OTC method of achieving something quite fiddly - much in the
same way as that zinc catalysed Claisen was, which was also backed up by accompanying NMR. |
I don't think you ever gave the reference for that zinc catalyzed Claisen rearrangement, so I never read the paper. But when compared to the claims
from the cleavage with Oxone article, the difference should be obvious. Articles with supporting material, mechanistically reasonable claims, proper
references, no examples in conflict to the general chemoselectivity rules, normal yields, properly reported analyses, no crappy introductions,
critical scientific discourse, etc., usually are no BS. For this reason, the BS papers are generally easy to spot. Usually the only ones that are
unable to spot them are the incompetent referees (usually the same type of type of people as the authors of such papers).
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Dr.Bob
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The article claims to make an acid from an allyl group, not the ketone, which is only made where there is a disubstituted alkene. So I don't even
understand the scheme shown by forsh. I would expect 2-hydroxyphenylacetic acid and formic acid to be made from that oxidative cleavage. And the
acid could certainly decarboxylate in GC, although I would expect to see a strong M-H+ peak for the acid in negative mode. Positive mode might not
show the acid well.
Another point that has been seen a few times in "metal free" reactions, if that trace amounts of many metals are present in most inorganic chemicals,
reagents, and dirty glassware. Thus the "Palladium free" Suzuki of years past that turned out to be working due to traces of Pd in the Na2CO3 used.
It woulds not surprise me at all if this reaction was not partly catalyzed by traces of heavy metals in the oxone, glassware, solvents, etc used in
some labs. But that simply mean that you could run this reaction with a very small amount of OsO4 (or many other metals), if you allow it to simple
go long enough and heat it up enough. There are several metals know to catalyze that reaction, so it might even be a combination of several
impurities all contributing to the reaction going forward.
[Edited on 2-4-2014 by Dr.Bob]
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