Oxidation of Piperic Acid (Pepper to Piperonal)

[Everyman]

[spiceboy]

Try sodium dichromate in acid solution. It seems to be gentler than KMnO4.

[Cherrie Baby]

Uranium - for those special disco-biscuits that glow on the dance floor?

I think ozonolysis is a possibility. Patents exist for the manufacture of piperonal from safrole. Strike forgets that dichromate is 1) not OTC and 2) produces toxic chromate waste products. But... ozonolysis is difficult to control.

[dpHarma]

how about high intensity UV, from a germicidal lamp.

dpHarma

[Everyman]

Cherrie - Any chance of a brief description of the ozonolysis process or a ref on one of those patents?

When you say difficult to controll is that as in by-products, or explosions?

[Piglet]

using O3: H.E.Carter 'Journal of Biological Chemistry' vol.36 p4273-8 (1966) - 96%
(also CAS vol.50 16890g).

using K2Cr2O7 (like SP said): 'J.Chem.Ind.Tokyo' 23 p56-79 (1920).

Good luck finding that second reference!

[spiceboy]

you can too get dichromate OTC.....
Go to a Ceramic Supply in your area...I found the shit way, WAY cheaper than any chem or photo supply....

[Piglet]

Dichromates are controlled as poisons in the UK. Destroys rivers and what not. Still, I for one am not messing with 03. There is a design for an O3 generator in Vogals.
KMnO4 will most likely give you acid. I think...

[Sailor Moon]

It is time to call Drone 342 and inquire as to the possibilities of using a milder oxidant such as hypochlorite. I have heard her espouse this idea several times....

[Cherrie Baby]

Jerry March - (pages 1181-82) on oxidative cleavage of double bonds:

With ordinary solutions of permanganate or dichromate the yields are generally low and the reaction is seldom a useful synthetic method; but high yields can be obtained by oxidising with KMnO₄ dissolved in benzene containing the crown ether dicyclohexano-18-crown [J. Am. Chem. Soc. 94, 4024 (1972); J. Org. Chem. 43, 1532 (1978)

With certain reagents the oxidation can be stopped at the aldehyde stage, and in these cases the products are the same as the ozonolysis procedure. Among these reagents are:

chromyl trichloroacetate: Liebigs Ann. Chem. 659, 20 (1962)
t-butyl iodoxybenzene: Tetr. Lett. 26, 4955 (1985)
KMnO₄ in THF-H₂O: J. Org. Chem. 51, 3213 (1986)
NaIO₄-OsO₄: J. Org. Chem. 21, 478 (1956)

That KMnO₄ in THF looks very enticing - I'll mail the procedure ASAP.

[spiceboy]

What about attempting to slow the rate of KMnO4 oxidation ala the 'cold cat' method?

The supposed knock on that was that the permanganate would overoxidize the p'fed...blahblahblah

but it doesn't if treated correctly.
diluting the FUCK out of it and chilling it seems to really take a lot of oomph out of the Rx.....?

[Piglet]

KMnO4 is weaker in alkali media. Maybe in ammonia solution?

[Cherrie Baby]

The following abstract appears to contain a mistake - it talks about making MDP-acetyl carbinol by fermenting vanillin with yeast. I thought I'd flashed back to acidtopia when I first saw it - funky yeast - yeh!! They probably meant via fermentation of piperonal. US pat. 3338796 will, hopefully, have more info. on MDP-acetyl carbinol.

MDP-acetyl carbinol is easily reduced to b-Me-MDP-glycol, from which MDP2P can be obtained by our dear friend the Pinacol rearrangement. The total process is untried so yields are as yet unknown. But everything is very OTC.

Piperonal can, itself, be obtained by oxidation of piperic acid (from pepper) with KMnO₄ in THF or with PTC. [see the references above, in my previous post]. The amount of KMnO₄ used must be strickly limited so as not to over-oxidise to the MD-benzoic acid.

I hope to get this patent next Monday.

Chemical Abstracts   Vol. 67, 1967, page 8432, 89797u
Converting veratraldehyde to L(-)3,4-dimethoxyphenylacetyl carbinol. John W. Rothrock (to Merck & Co. Inc.). U.S. 3,338,796 (Cl. 195-28), Aug. 29, 1967, Appl. Aug. 19, 1964, and Oct. 13, 1966; 2 pp.

L(-)3,4-Dimethoxyphenylacetyl carbinol (3,4-(MeO)₂C₆H₃CH(OH)Ac) is produced by contacting veratraldehyde with a growing acyloin-producing culture of Aerobacter aerogenes ATCC 211; the product is isolated by extn. and crystn. Thus, medium contg. com. yeast ext. 20, dextrose 20, MgSO₄ 7 H₂O 0.5, KH₂PO₄ 0.2, and Na₂HPO₄ 0.2 g./1., with pH adjusted to 7, is inoculated with a strain of Saccharomyces cerevisiae; the medium is aerated and agitated at 28° for 48 hrs. The agitation and aeration are stopped. Vanillin is added to give a concn. of 4 g./1. The agitation and aeration are resumed and continued for 7 hrs. to produce L-3,4-(methylenedioxy)phenylacetyl carbinol. The fermentation broth is sterilized and filtered to remove the cells. The filtrate is satd. with NaCl and extd. 4 times with ¹/₃ vol. of EtOAc. A crude product is obtained after evapg. the EtOAc. A by-product of the fermentation process is removed by crystn. from an EtOAc-petroleum ether soln. of the crude product. The mother liquor contains the desired product, the solvents are removed by evapn. and the residual oil is subjected to partition column chromatog. using diatomaceous earth and a solvent mixt. of C₆H₆-EtOAc-MeOH-H₂O (9:1:5:5). The fractions eluted are vanillyl alc., vanillin, and a mixt. of vanillic acid and L-3-methoxy-4-hydroxyphenylacetyl carbinol. The last fraction is fractionally crystd. from a mixt. of EtOAc-petroleum ether to remove vanillic acid. The mother liquor contg. the product is further purified by extn. by aq. Na₂SO₃ to ext. acetyl carbinol as a bisulfite. The bisulfite addn. product is decompd. by addn. of an excess of an aq. soln. of Na₂CO₃. The product is extd. with EtOAc. The ext. is evapd. to a small vol. to cryst. L-3-methoxy-4-hydroxyphenylacetyl carbinol; m.p. 69-73°, [a]_D²³ = 211° (c 1.02%, acetone). L-3,4(Methylenedioxy)phenylacetyl carbinol, m.p. 44-6°, [a]_D²⁵ = 228° (c 1.2% EtOAc), and L-3,4-dimethoxyphenylacetyl carbinol were also produced by the method.   S. P. Marino

[Cherrie Baby]

Last post was a little off topic but the same error occured in the patent - as well. So that's a grand total of 1 author, 2 patent examiners and 1 Chem. Abstracts transcriber who failed to notice the obvious error - 1 mentioned previously!!

Everyman Are you serious about the pepper? - I don't have time to do this until about 12 days from now but I've figured everything out in theory and have all the refs.

Isolation of Piperine from Black Pepper - J. Chem. Ed. 70(7), 598-9 (1993)

Hydrolysis to Piperic acid (might not be needed (at Rhodium's)

Oxidative cleaveage to Piperonal with cetyltrimethylammonium permanganage - see Synthesis 1984, p 431-3. They also give details for making CtMe₃N MnO₄ from CtMe₃NBr - but I can't see why CtMe₃NCl shouldn't work just as well (CtMe₃NCl is ubiquitous in loads of OTC skin & Hair products) - I intend to try this first with fabric conditioner - it's cheaper but is less hydrophilic (so might not work!).

Also J. Chem Research - Synopses 1986, p 458-9 for "Cetyltrimethylammonium Permanganate: a Useful Reagent for the Selective Oxidative Cleaveage of Aryl-substituted Olefins"

R₄N⁺ MnO₄^- is one reagent to use - expected yield of piperonal ~ 74% with this:

The benzylic alkene of piperic acid should cleave to aldehydes (either side) and other, purely aliphatic alkene group will give a diol.

Alternatives are to use (2) aq. KMnO₄ with substrate in THF - it might work - see J. Org. Chem. 51, p 3213 (1986). Or (3) PTCs, which include: Crown ethers (too expensive), TDA-1 - see Synthetic Commumications 17 p 647-55 (1987), Dimethyl polyethylene glycol - see J. Org. Chem. 43, p 1532, (1978).

General Procedure for the Oxidative Cleavage with CTAP

To a stirred solution of the alkene substrate (1 mmol) in DCM (7 mL) was added a solution of CTAP (1 mmol) in DCM (6 mL) at 25°C. After 2-6 h, diethyl ether  (50 mL) was added and the reaction mixture was filtered through a pad of Celite and anhydrous MgSO₄. The filtrate was concentrated in vacuo and the crude product was purified by chromatography on silica gel to afford the pure carbonyl product. [From: J. Chem. Res. (S), 1986, 459]

Note (mine): CTAP: cetyltrimethylammonium permanganage.

Why do they add diethyl ether and not more DCM? Surely better to stick with just one solvent so that it can be recycled?

Cetyltrimethylammonium Permanganate, CTAP

To a stirred solution of potassium permanganate (3.168 g, 20 mmol) in water (100 mL) at 20°C is added, dropwise over 20 min, a solution of CTAB - Cetyltrimethylammonium Bromide (8.02 g, 22 mmol) in water (100 mL). A fine violet precipitate forms immediately. Stirring is continued for 30 min, the precipitated product is isolated by suction, washed thoroughly with water, and dried in a dessicator over phosphorus pentoxide in vacuo for 3 h at room temperature to give the salt as a fluffy violet solid; yield: 6.5 g (80%). The reagent is stored in a brown bottle in the refrigerator. [From Synthesis 1984, p 431]

Notes: a suitable alternative to CTAB is CTAC aka Cetrimide or Cetrimonium Chloride - found in hair conditioners. [A small cosmetics company would have no difficulty getting hold of mucho supplies of this in mega quantities]

An alternative dessicant to the P₂O₅ is KOH or NaOH? Why not? Dessication is essential and these quaternary ammonium compound are very hygroscopic.

[The Cook]

The other day, I was eating breakfast when I tried to dump some black pepper on my eggs.
It seems that someone had unscrewed the lid!
As pepper poured over my food, I became so irate that I passed out and dreamed I was watching a show called Ghetto Precursors-It was a generalization of several runs.
Here's what was on it.
Someone put 1 cup of blk pepper in a snapple bottle then added a goodly amt of IPA (drygas)
They capped it and shook like hell and the IPA turned yellow/brn. Then they filtered out the pepper from the yellow IPA, and heated the filtered IPA to dryness.
They were left with roughly 15-20g of yellowish powder. When they washed it with acetone, it looked much cleaner.
The yellow powder was dumped into the now clean snapple bottle, and IPA was once again added. Sodium Bicarbonate was also added, about 2 Tbsp(but more was added if it was consumed). This mixture was boiled to dryness in the microwave, stopping periodically to stir/let the soln calm down.
Before it boiled dry, it formed two layers, the bottom one was light yellow, the top was brown/dark yellow. 
Again, IPA was added and the crystalline mush was filtered to give about 10-15g of lt. greyish crystals.  The people on the show could not get this shit to melt! Even when it  was heated extremely hot, it only turned white.. I guess they burned off some imputities, though...  Oh, well.
They then added the white crystals to some hot dH2O, but solubility was bad, even with stirring.  Then some .5 molar soln of KMnO4 was added, with stirring.  What it looked like they were doind was: They heated the mixture, added some KMnO4 soln, and stirred until the purple turned brown.  I could see that the crystalline mass at the bottom of the jar was being digested, as the entire soln turned chalky tan.  As soon as the KMnO4 soln was not immediately used (i.e. it stayed purple for a few sec.) IPA was added to quench the soln (although the show said IPA sometimes fucked up cat synths).  Now the soln was allowed to cool, and some ether/hexane was added to try to extract whatever made the mixture turn yellow again.  The show said be careful with ether, especially doing dumb shit like adding it to hot water. (overboil)
The ligroin (ether/hexane) was sep'd in a ghetto sep funnel (ziplock bag-cut off corner).
This ether extraction was repeated several times, at different temperatures.  All ether solns were mixed, and evaporated at steam bath temp (>100)to give funky looking yellow oil.
SO WHAT???, I asked! then the people on the show threw the plate of yellow oil in the fridge and it froze quickly into a very pale yellow-almost white (when broken up)
crystalline mass.
Wow, I thought, those bastards made a pepper extract that's liquid at room temp, but a solid when cooled. It's kinda waxy looking, and rather unspectacular.  Then the show ended, and the announcer said next week, at the same bat time, same bat channel, they would couple this nasty shit with nitroethane... i wonder why they'd want to..
Anyway, that's the bizarre ass dream I had, Sorry if it's rambling or hard to follow, my memory is kinda foggy from the pepper overdose.  Anyway, here are some things I remember them saying as they worked.

1)As they filtered the pepper from the IPA..
    "Damn this shit smells peppery"
2)One got the yellow pepper extract on his face...
  "Ouch, this burns like pepper on my face"
3)After the acetone wash of above extract.
  "Boy, that's bright yellow"
4)When they boiled the yellow extract with bicarb...
  "Look! 2 layers! How'd that happen"
5)After above reflux
  "What happened to my yellow powder? All I have now are whitish crystals!"
6)While adding the permanganate...
  "Hey, that funky pepper smell is changing into a more pleasant odor!"
7)After yellow oil extraction...
  "This doesn't smell like pepper very much at all!"
While playing with room temp melting point.
  "This stuff should be kept in the freezer!"

  Once again, I apologize for any and all typos, and sorry I didn't have their measurements, the program said it would make the whole game too easy..  Post any related dream stories. This seems to be QUITE ineffiecient, but if blk pepper is $5.00 a pound, it ain't that bad. Plus, it's OTC.

*I miss ZWITTERION's kitchen chemistry tales.

[The Cook]

Yeah, I know the plot was from Natural Products-A Lab Guide. Just thought y'all might be interested in just how easy & dirt fucking cheap this rxn might be.  If anyone dreams in a manner similar to this one, pls post.. I wondered if there was a better solvent for the oxidation product, but I woke up before I could ask the announcer.
P.S. Total dream time was roughly 2hrs continous (Yeah I nap hard)

[The Cook]

Hey, if you're effieciency freaks, this sucks for you. My dream ended with >1g
And my roommate washed the plate it was on.

[Everyman]

Cherrie Baby recently mentioned Piperine - Piperic Acid - Piperonal as a good route.

This guy here :

http://www.lycaeum.org/~rhodium/chemistry/piperine.txt

seems to have had trouble with the oxidation of Piperic Acid via KMnO4, reporting *piperonyl, piperonylic acid and/or piperonyl acetone in varying quantities.*

Would some sort of catylised Oxidation work better? Someone recently said something about KMnO4 being non-selective. Perhaps there is a better route?

If this could be made to work in reasonable yeilds youd be looking at Piperonal OTC for $100/Kilo.

Perhaps its not that tempting now, but in a few years it may be.

So has anyone got any ideas?

[Rhodium]

Article mentioned in

Post 165774

(Cherrie Baby: "Oxidation of Piperic Acid (Pepper to Piperonal)", Chemistry Discourse)

Cleavage of Alkenes to Aldehydes Using Potassium Permanganate
P. Viski, Z. Szeverenyi, and L. I. Simandi

J. Org. Chem. 51, 3213-3214 (1986)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/alkene2aldehyde.kmno4-thf.html)

[starlight]

The procedure described in the paper on Rhodium's page calls for dissolving 10g of potassium permanganate in 100ml of water.

The solubility of potassium permanaganate in water at 20C is 6.3g/100ml.

Either the volume of water is wrong or the permanganate solution needs to be prepared and kept at a higher temperature during the addition.

Do you think it is safe to add permanganate solution to THF and concentrate it afterwards? (thinking of peroxides here).,