Author Topic: KMnO4/CuSO4 system for ketone synthesis  (Read 2657 times)

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Ziqquratu

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KMnO4/CuSO4 system for ketone synthesis
« on: March 14, 2003, 08:33:00 AM »
I was in the library the other day, killing some time between classes, when I came across an article relating to the use of a Permanganate/Copper Sulfate pentahydrate system for the formation of ketones and azobenzenes.  It also dealt with the use of this reagent in the synthesis of ketones from alcohols.  This led me to two ideas for novel syntheses.

First, the oxidation of a primary amine to a ketone could be used to convert MDA to MDP-2-P, probably (according to the article) in high yeild.  If there is a simple, high yeilding synthesis of MDA from safrole (I dont know, I havent looked it up), this could be used to get ketone.  The yeild from safrole to MDP-2-P would only have to be 50% or so to be comparable to the peracid routes.  Also, it would be a useful synthesis when using piperonal and nitroethane to make MDA - a complete and reasonably easy synthesis for those who prefer MDMA without buying any sassy!
Second, there have been many reports of failed attempts at making MDP-2-P via MDP-2-Pol from safrole and sulfuric acid.  It has been suggested that perhaps this is because of the choice of oxidant and not because of migration of the OH group to the 1-carbon.  Perhaps this system could work - the paper reports 100% yeild of dacan-2-one from 2-decanol, and 90% yeilds of 1-phenylbut-1-en-3-one from 1-phenylbut-1-en-3-ol, indicating by the fact that it leaves the double bond alone that it is a mild reagent.
The preparation of this reagent is simple - potassium permanganate and copper sulfate pentahydrate (usually in slightly less than a 2:1 ratio) are ground together in a mortar until homogeneous.  Then the oxidant and the amine are mixed in DCM under reflux for 24 to 48 hours, typically in high (even quantatative) yeild.  Presumably oxidising the alcohols used the same procedure.

Reference:  Noureldin, Nazih A.; Bellegarde, Jody W.:
A Novel Method. The Synthesis of Ketones and Azobenzenes Using Supported Permanganate, Synthesis 1999, No. 6, pp. 939-942.

Rhodium

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Isosafrole + DMSO + Heat = MDP2P
« Reply #1 on: March 15, 2003, 12:16:00 AM »
I am not aware of any method for making MDA from safrole which is easier or higher-yielding than making MDP2P from safrole.

According to Chemical Abstracts 97, 23367 (1982), heating isosafrole in DMSO to 100-120°C for an unspecified amount of time results in autooxidation of the isosafrole, forming MDP2P as the major product, but the precise yield is also unspecified in the abstract.

The details for this incredibly easy MDP2P synthesis has been published in Yukagaku 31(4), 222-225 (1982) (ISSN: 0513-398X), which unfortunately is a Japanese journal.

hypo

  • Guest
isosafrole + DMSO --> MDP2P ???
« Reply #2 on: March 15, 2003, 05:16:00 PM »
stupid question: where does the =O come from!?

Rhodium

  • Guest
oxygen origin
« Reply #3 on: March 15, 2003, 05:36:00 PM »
As the reaction is labelled as an "auto-oxidation" I suppose that it comes from the air, or else they would label the DMSO as the oxidant (and dimethylsulfide would form). Another similar reaction I have seen mentioned bubbled dry air through the reaction mixture.



The full Abstract of the originally dicussed article:

Autoxidation of benzene and phenolic compounds containing isopropyl, isopropenyl, vinyl or allyl group in polar aprotic solvents.
Iwamuro, Hajime; Kanehiro, Masahiko; Matsubara, Yoshiharu.    Fac. Sci. Technol.,  Kinki Univ.,  Higashiosaka,  Japan.
Yukagaku 31(4), 222-5 (1982)  CODEN: YKGKAM  ISSN: 0513-398X.  Journal  written in Japanese. CAN 97:23367 AN 1982:423367

Abstract

Autoxidn. of cumene, m- and p-diisopropylbenzene, p-cymene, and 1-isopropenyl-4-methylbenzene in Me2SO at 100-20° gave AcPh, 3- and 4-Me2CHC6H4COMe, and 4-MeC6H4COMe in 100% selectivity, whereas similar oxidn. in DMF and 1,3-dimethyl-2-imidazolidinone (I) gave Me2C(OH)Ph, 3- and 4-Me2CHC6H4C(OH)Me2, 2-p-tolyl-2-propanol.  Autoxidn. of styrene, isosafrole, anethole, and isoeugenol in Me2SO at 100-20° gave PhCHO, piperonylacetone, and (p-methoxyphenyl)acetone as major products, whereas in I, DMF, or AcNMe2 they gave PhCHO, 1-phenyl-1,2-epoxyethane, piperonal, p-anisaldehyde p-MeOC6H4CH2COMe, 1-p-anisyl-1,2-epoxypropane, and vanillin.

SPISSHAK

  • Guest
yes that's correct
« Reply #4 on: March 15, 2003, 06:03:00 PM »
Rhodium is right the oxidant is air, I think the DMSO has properties like a high dielectric constant that make isosafrole more suseptible to oxidation.

Sunlight

  • Guest
Oxydation of tryptamine
« Reply #5 on: March 16, 2003, 02:53:00 AM »
Please post details of the procedure of oxydation of amines to ketones, it could be used to oxidize tryptamine into indol 3 acetaldehyde, then easily converted to DMT or other with NaBH4 reductive amination .

Ziqquratu

  • Guest
Oxidation of Amines to Carbonyl Compounds
« Reply #6 on: March 16, 2003, 04:29:00 AM »
The oxidant was prepared by grinding equal amounts, by weight, of KMnO4 and CuSO4.5H2O in a mortar until homogeneous.

Oxidation of Amines; General Procedure
The amine (2.0mmol) in CH2Cl2 (20mL) was placed in a 50mL round bottomed flask.  The oxidant (2.0g) was added and the heterogeneous mixture stirred at ambient temperature or under reflux for 48 h.  The progress of the reaction was followed by tlc or glc until no starting material could be detected.  After cooling to ambient temperature, the product was then filtered through Celite and the residue washed thoroughly with CH2Cl2 (3 x 10mL) and Et2O (3 x 10mL).  The product was isolated by flash evaporation and identified from spectroscopic analysis.

Ref: A Novel Method. The Synthesis of Ketones and Azobenzenes Using Supported Permanganate, Synthesis 1999, No. 6, pp. 939-942.

Rhodium

  • Guest
Isosafrole to MDP2P by auto-oxidation!
« Reply #7 on: August 05, 2003, 04:21:00 AM »
Autoxidation of benzene and phenolic compounds containing isopropyl, isopropenyl, vinyl or allyl group in polar aprotic solvents.
Iwamuro, Hajime; Kanehiro, Masahiko; Matsubara, Yoshiharu. 

Yukagaku 31(4), 222-5 (1982)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/isosafrole.dmso.oxidation.pdf) (Retrieved by PolytheneSam)



Here is Ref #1 from the article:

Autoxidation and Condensation Reactions of Carbanions in Dimethyl Sulfoxide Solution
Glen A. Russell, Edward G. Janzen, Hans-Dieter Becker, Frank J. Smentowski

J. Am. Chem. Soc. 84, 2652-2653 (1962)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/dmso.autooxidation.pdf)

nitrous351

  • Guest
Rhodium...
« Reply #8 on: September 10, 2003, 06:32:00 PM »
I'd bee more than happy to try the iso-safrole->mdp2p reaction and post results....however, I'm not so sure I can get any DMSO. Do you think that DMF would work (or another solvent with a high dielectric constant)?
I am looking for someone at my university to translate the Japanese journal article, but in the meantime, if you would care to think up a general procedure to get me started, that would bee great.
I don't have access to analytical equipment, but I could post yields based on how much (if any) mdp2p I was able to recover by distillation. Thanks

EDIT: After looking at the Japanese article's tables (which are in English...yay!) it appears that isosafrole refluxed with DMSO for 26 hours at 120C will yield 60% mdp2p... refluxing isosafrole with DMI for 8 hours at 120C results in 56% mdp2p... but this doesn't help with the procedure, so can anybee suggest a procedure/ratios to get me started? thanks


Rhodium

  • Guest
Article: KMnO4 supported on CuSO4
« Reply #9 on: September 17, 2003, 02:12:00 AM »
Here is the full article mentioned in the first post in this thread:

A Novel Method. The Synthesis of Ketones and Azobenzenes Using Supported Permanganate
Noureldin, Nazih A.; Bellegarde, Jody W.

Synthesis 1999, No. 6, 939–942 (1999)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/kmno4.on.cuso4-oxidation.system.pdf)

Abstract

The heterogeneous use of potassium permanganate, supported on copper(II) sulfate pentahydrate, provides a simple and effective means for oxidizing amines. Primary aliphatic amines, such as sec-butylamine, are oxidized to the corresponding carbonyl compounds in good to excellent yields. Primary aromatic amines, such as 4-chloroaniline, are converted quantitatively into the corresponding azo compounds. Carbon–carbon bond cleavage, which usually occurs when alkylbenzene side chains are oxidized by permanganate under homogeneous conditions, does not occur. Under appropriate reaction conditions carbon–hydrogen bond cleavage at the benzylic position, known to occur under heterogeneous permanganate conditions, is also eliminated. For example, a quantitative yield of bis(2,4,6-trimethylphenyl)diazene is obtained from the oxidation of 2,4,6-trimethylaniline using small amounts of permanganate and copper(II) sulfate pentahydrate.

GC_MS

  • Guest
Olefin auto-oxidation
« Reply #10 on: September 21, 2003, 08:27:00 PM »
When thinking about the auto-oxidation of olefins as isosafrole, anethole and/or isoeugenol, you have to imagine some sort of intermediary complex between a molecule of O2 and the olefin double bond. There will be an oxidative cleavage of your olefin, which in case of isosafrole will yield piperonal (anethole -> anisaldehyde, isoeugenol -> vanillin) and acetaldehyde.

In the past, I have tried some Na2Cr2O7 and KMnO4 mediated oxidations of isosafrole, isoeugenole, anethole and asaron. In case of isoeugenol and anethole, I have had performed a GC/MS analysis as well, and I found that in both cases, their corresponding benzaldehydes were present as the major substances. However, other concomitant substances were the original starting product and also their corresponding P2Ps! At the time, I was rather surprised as I didn't expect the latter to show up. However, I have no idea for how much their P2P analogues contributed to the composition of the final product: 5%? 10%? Anyway, not sufficient to isolate them for further synthetical needs. So, to summarize, auto-oxidation of anethole and isoeugenol does result in 4-methoxy-P2P and 4-hydroxy-3-methoxy-P2P, albeit in small amounts.

And all the sudden, there is a group of crazy Japanese writing a possibly interesting article in a language the majority of the Bees unfortunately doesn't understand. It seems that bubbling oxygen in a solution of olefin in DMSO results in the P2P analogue as the major product and the benzaldehyde as the minor one. This, however, does not fully agree with the theoretical principle of the olefin auto-oxidation. So, might there be something else going on?

No... and yes. At least, that is my theory. My theory goes as follows:

You dissolve for instance a certain amount of isosafrole in DMSO and introduce a stream of oxygen into the mixture. The oxygen will form an intermediary complex with isosafrole, which will decompose into piperonal and acetaldehyde. These two aldehydes, however, are subject to auto-oxidation as well! In

Post 415088

(GC_MS: "The synthesis of peracids", Chemistry Discourse)
, I describe how perbenzoic acid can be formed by introducing oxygen in a solution of benzaldehyde in acetone. Acetaldehyde will result in peracetic acid while piperonal will yield 3,4-methylenedioxy perbenzoic acid. The actions of peracids on alkenes as isosafrole is (or should be) well known. No? Well, you might want to read

some pages on Rh's site...

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/peracid.html)
And this is where the fun starts  ;D . The epoxide (formed by the reaction between isosafrole and peracid) can rearrange to a zwitterion (positive charge on C1 and negative charge on O of the side chain), which on itself is a substrate in a Pfitzner-Moffatt oxidation reaction.



And voila, there you have your MD-P2P. I must add that the zwitterion I just talked about can also rearrange to MD-P2P spontaneously.

So, how did I pull this theory out of my ass all the sudden? The abstract mentions the presence of epoxidated alkanes, benzaldehydes etc if they used DMI, DMAc or DMF as solvent. Only when they used DMSO, there was a major presence of the P2P analogue. To me, it seems that DMI, DMAc and DMF allow the auto-oxidation to happen "the normal way". DMSO "rearranges" the equilibria of the side-reactions and oxidizes an intermediary zwitterion, yielding the beloved MD-P2P.


Rhodium

  • Guest
Oxidation of Isosafrole to Piperonal by Oxygen
« Reply #11 on: November 28, 2003, 05:23:00 PM »
Oxidation of Isosafrole to Piperonal by Oxygen Gas
N.M. Baranova & A.D. Yakusheva

J. Appl. Chem. USSR (Engl.Transl.), 47, 2840-2841 (1974)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/isosafrole2piperonal.oxygen.pdf)
Zh. Prikl. Khim. 47(12), 2751-55 (1974)