Sciencemadness Discussion Board

Piperic acid oxidation to Piperonal

600538411 - 9-9-2005 at 19:11

Does anyone have a tried and tested method for the oxidation of piperic acid to pieronal?

The most commonly known route of KMnO4 in THF or PTC/Alcohol has pretty bad yields, is there a better yielding route that anyone has used before? A workup would be better even again...

Any help would be greatly appreciated...

solo - 9-9-2005 at 20:36

Someone had the same question some time ago at the Hive ....here are some of the comments then, which I hope will help you make some choices........solo
Quote:


Everyman
(Member)
09-13-98 15:48
No 172238
Oxidation of Piperic Acid (Pepper to Piperonal)

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?





Everyman
(Member)
09-17-98 19:36
No 165765
Oxidation of Piperic Acid (Pepper to Piperonal)






spiceboy
(Member)
09-18-98 09:58
No 165766
Oxidation of Piperic Acid (Pepper to Piperonal)

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



Cherrie Baby
(Member)
09-19-98 04:30
No 165767
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
09-19-98 22:45
No 165768
Oxidation of Piperic Acid (Pepper to Piperonal)

how about high intensity UV, from a germicidal lamp.
dpHarma





Everyman
(Member)
09-20-98 15:49
No 165769
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
09-21-98 12:39
No 165770
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
09-21-98 18:44
No 165771
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
09-21-98 18:52
No 165772
Oxidation of Piperic Acid (Pepper to Piperonal)

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
( )
09-21-98 22:20
No 165773
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
10-01-98 01:16
No 165774
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
10-01-98 19:26
No 165775
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
10-01-98 19:35
No 165776
Oxidation of Piperic Acid (Pepper to Piperonal)

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



Cherrie Baby
(Member)
10-03-98 02:45
No 165777
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
10-14-98 05:20
No 165778
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
10-19-98 07:41
No 165779
Oxidation of Piperic Acid (Pepper to Piperonal)

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!"
8) 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
(Member)
10-19-98 07:48
No 165780
Oxidation of Piperic Acid (Pepper to Piperonal)

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
(Member)
10-24-98 01:29
No 165781
Oxidation of Piperic Acid (Pepper to Piperonal)

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



Rhodium
(Chief Bee)
04-24-04 19:24
No 502699
Alkenes to Aldehydes Using KMnO4
(Rated as: good read)

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.rhodium.ws/chemistry/alkene2aldehyde.kmno4-thf.h...)
The Hive - Clandestine Chemists Without Borders



starlight
(Hive Bee)
08-31-04 13:19
No 528471
inaccuracy/omission

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).,

CherrieBaby - 3-10-2005 at 08:11

I've edited my original reply a few times because I discovered that the topic has already been discussed, both at the hive and at synthetikal:

https://www.synthetikal.com/synthforum/viewtopic.php?t=414

I posted some details from a hive post below.

I think alkaline copper sulphate is a cheaper option.

CuSO4 + 2NaOH -> CuO + H2O + Na2SO4

2CuO -> Cu2O + (O)

Unfortunately the precise reaction is unpublished.

Which one of these is it?:

(1) MDP-CH=CH-CH=CH-COOH + 2(O) -> MDP-CHO + HOC-CH=CH-COOH

(2) MDP-CH=CH-CH=CH-COOH + 3(O) -> MDP-CHO + HOOC-CH=CH-COOH

(3) MDP-CH=CH-CH=CH-COOH + 7(O) -> MDP-CHO + 2 HOOC-COOH

My vote goes for (2) and here's why. We know that the alkene ajacent to the aromatic is oxidised (see below). But we also know that Fehlings oxidises aliphatic aldehydes. Nothing suggests that Fehlings will oxidise butenedioic acid (aka Maleic acid) because Fehlings does not (normally) oxidise alkenes. We can also be fairly sure that piperonylic acid won't be produced if the oxidiser is not in excess because aromatic aldehydes are oxidised very slowly by Fehlings (compared to aliphatics).

So my recommendation is 1 part piperic acid, 12 parts sodium hydroxide and 6 parts copper sulphate to go with rxn. (2) above. That's all theoretical. How about someone with decent analytical gear give this a test and report back to us please?

Fehlings Solution is alkaline Copper Sulphate + tartrate. In Fehlings, tartrate works to complex the CuO thereby making it available in aqueouse media and possibly acting as a phase-transfer catalyst. There is no write up for this precise reaction in the literature [rxn. (2) above]. I think it has only been done with Syringaldehyde and substances mentioned in US2516412.

This is the only report I can find on the rxn and I can't even remember which forum I copied it from. I don't necessarily agree what the proportions given below are correct. My estimated ratios for Piperic acid:CuSO4.5H2O:NaOH are 1:6:12.
Code:
Substance - MWt. - ratio - weight1 - weight2 Piperic acid - 218.21 - 1 - 218.21 - 5 CuSO4.5H2O - 249.68 - 6 - 1498.08 - 34.33 NaOH - 40 - 12 - 480 - 11.00
weight1: based on 1 mole piperic acid
weight2: based on 5g piperic acid.

So rather than use MistaMiyagi's numbers I would go for 5g Piperic acid, 34.33g CuSO4.5H2O and 11g NaOH. Of course if MistaMiyagi's numbers give better yields than mine then I'm wrong and he's right. Whatever MistaMiyagi's yield of 4.5g of piperonal from 5g of piperic acid is impossible.
Quote:
MistaMiyagi (Dream Team)
Posted: Fri Feb 25, 2005 4:25 am
Subject: Piperonal from Piperic Acid, CuSO4*5H20, NaOH

This is a condensed version of a Hive post. Unfortunately, I never saved a copy of the thread before the Hive went down.
If there are any enterprising individuals out there, the thread was accessed by this url:
https://www.the-hive.ws/forum/showflat.pl?Cat=&Number=32...

Materials
5g piperic acid
16.9g NaOH
25.6g CuSO4 * 5H2O
150mL DCM
205mL H2O
suff. HCl(aq) to acidify

Procedure

1. Combine piperic acid, NaOH, CuSO4 * 5H2O, and H2O.
2. Reflux for 8 hours.
3. Collect liquid via suction filtration, discarding solids.
4. Acidify with HCl(aq).
5. Extract product with 3x50mL DCM.
6. Distill extract to recover DCM, if desired.

Yield: 4.5g piperonal

From the Hive.
Quote:
Antoncho
Date: 04-06-02 21:26
Post No 293365
Subject: Double bond ox. cleavage (to aldehyde) with CuO
(Rated as: excellent)

This is from the same source that the preparation of 3,5-diMeO-4-OH-propenylbenzene, which i recently posted into Methods discourse - see Antoncho: "2,6-diMeO-4-allylphenol" (Methods Discourse).

Edit: the original info comes from Patent US2516412

I'm not sure if this hasn't been discussed bee4 - i just couldn't construct an accurate query on TFSE. But i think it hasn't since - why then no one ever thought of possibility of applying this to piperic acid?

EXAMPLE VII: Syringaldehyde from the isolated intermediate

Syringaldehyde may also be prepared by oxidizing the isolated 3,5-dimethoxy-4-hydroxypropenylbenzene of Example V with nitrobenzene in alkali or other low potential oxidizing agents.
Thus 195 parts 3,5-dimethoxy-4-hydroxypropenylbenzene are added to a cupric oxide mixture freshly prepared from 1000 parts hydrated copper sulfate, 660 parts sodium hydroxide, and 8000 parts of water and the resulting mixture is heated to boiling under reflux for eight hours. The separated red cuprous oxide is filtered and washed with water. The alkaline filtrate and washings are acidified and extracted with ether.
Bisulfite purification of the ether extract should yield approximately 155 parts or 90% syringaldehyde.
Other alkaline copper oxidizing agents such as Fehling's Solution, Benedict’s Solution, may be used with the same results. An alkaline copper oxidizing agent is particularly advantageous for replacing the propenyl group with the aldehyde group because the strength of its action in changing from a cupric to a cuprous compound is definitely adequate to oxidize to the aldehyde, and at the same time insufficient to continue the oxidation to the acid further or to destruction. However, in large scale operation, it will be obvious that oxidizing agents having no such automatic action may be employed for reasons of economy, and the extent of the reaction controlled by controlling the amount of the reagent.

So... What do you think?

One thing that confuses me is - AFAIK, Fehling's liquid is a Cu++/NH3 complex - which will certainly decompose at 100 C, with all ammonia going out of solution. What could they mean?

Antoncho


[Edited on 3-10-2005 by CherrieBaby]

CherrieBaby - 7-10-2005 at 12:19

1) Apart from using CuO (US Patent 2516412) there are at least another 3 simple possible ways to convert piperic acid to piperonal.

2) British Patent: 774,608 mentions the following oxidation using manganese dioxide.
Code:
O Ar-C=C< --> Ar-C=O + O=C< | |
3) The article from Rhodium "aldehyde.txt", in the archive below, describes an oxidative cleavage using NaHCO3/KMnO4

4) The article I uploaded, Arctander (below) describes large scale oxidative cleavage of piperic acid to piperonal using dichromate.

I have uploaded 5 articles which may be of interest to people:

http://rapidshare.de/files/5891157/Piperonal.zip.html

1) US Patent 2,516,412, "Method of Synthesizing Syringaldehyde"
2) British Patent 774608, 1957, "A Process for the Preparation of Aromatic Carbonyl Compounds from Aryl Ethylenes"
3) Oxidation of a Propenylbenzene (Asarone) to benzaldehyde (2,4,5-Trimethoxybenzaldehyde) using NaHCO3/KMnO4
4) Arctander, from "Perfume and Flavour Chemicals, 1969, Heliotropin, pp183-4
5) Cervený, Kozel & Marhoul, "Synthesis of Heliotropin", Perfumer & Flavorist 14, pp13-18, 1989

gorilla - 7-10-2005 at 12:48

Hi CherryBaby,

The thing about CuII oxidations is that they are selective and don't go further than piperonal. The other oxidising agents can go too far unless the reaction is tightly controlled.

Anyway, I don't like this board. I don't like the atmosphere. Bad manners, snotty fools - rationally ignorant, I believe is the correct term. I have started to run I2P and hang out there. There are only a couple of boards there so far - but the opportunity remains. The IRC is friendly.

possibilities

Epopteia - 8-10-2005 at 08:37

The CuO procedure does not work as published on substrates having no phenolic group in my experience. Maybe it is because you need the Phenolate anion in solution which is oxidised by the CuO.

The Manganese dioxide procedure may work on Piperic acid (I don't know) but the published procedure does not work on highly activated aromatics such as isodillapiole. You get a lot of brown tar with the reaction conditions specified in the patent. Perhaps a lower temperature may help in this case.

The dichromate is the way to go in my opinion, but then its toxic and an environmental toxin, so careful handling and responsible disposal are a must.

CherrieBaby - 8-10-2005 at 10:09

Quote:
Originally posted by Epopteia
The CuO procedure does not work as published on substrates having no phenolic group in my experience. Maybe it is because you need the Phenolate anion in solution which is oxidised by the CuO.
Maybe the phenolate complexes with CuO in a similar way to how tartrate does - enabling CuO to be transported into solution? Perhaps Fehlings might work better than CuO alone.

[Edited on 8-10-2005 by CherrieBaby]

CherrieBaby - 22-10-2005 at 00:33

Perhaps this may work to oxidise piperic acid to piperonal?

From, "The manufacture of chemicals by electrolysis", A. J. Hale, 1919, page 68.
http://www.sciencemadness.org/library/books/the_manufacture_...
Quote:
Vanillin can be formed by electrolytic oxidation of the sodium salt of iso-eugenol. According to the process of F. van Heyden Nchfg. a 15% alkaline solution of sodium iso-eugenol forms the anolyte, and the catholyte comparment is filled with caustic soda solution (10 to 20%). The temperature is kept at 60C, and the lead peroxide anode evidently acts as a catalyst, since with platinum the discharged oxygen is evolved without the oxidation:

CH3O(HO):C6H3.CH:CH.CH3 + 3(O) ==> CH3O(HO):C6H3.CHO + CH3.COOH

Refs:
DRP 92007 (1895)
Electrochem. Review, 1900, 1, 31.


[Edited on 22-10-2005 by CherrieBaby]

Birdy - 13-9-2006 at 09:10

Hello,

could anybody repost the article by Arctander (see below) or the whole Piperonal.zip synopsis, as rapidshare is no longer hosting the file. :-(
Quote:
Originally posted by CherrieBaby
1) Apart from using CuO (US Patent 2516412) there are at least another 3 simple possible ways to convert piperic acid to piperonal.

2) British Patent: 774,608 mentions the following oxidation using manganese dioxide.
Code:
O Ar-C=C< --> Ar-C=O + O=C< | |
3) The article from Rhodium "aldehyde.txt", in the archive below, describes an oxidative cleavage using NaHCO3/KMnO4

4) The article I uploaded, Arctander (below) describes large scale oxidative cleavage of piperic acid to piperonal using dichromate.

I have uploaded 5 articles which may be of interest to people:

http://rapidshare.de/files/5891157/Piperonal.zip.html

1) US Patent 2,516,412, "Method of Synthesizing Syringaldehyde"
2) British Patent 774608, 1957, "A Process for the Preparation of Aromatic Carbonyl Compounds from Aryl Ethylenes"
3) Oxidation of a Propenylbenzene (Asarone) to benzaldehyde (2,4,5-Trimethoxybenzaldehyde) using NaHCO3/KMnO4
4) Arctander, from "Perfume and Flavour Chemicals, 1969, Heliotropin, pp183-4
5) Cervený, Kozel & Marhoul, "Synthesis of Heliotropin", Perfumer & Flavorist 14, pp13-18, 1989

2bob - 14-9-2006 at 15:01

Can anybody here suggest a microwave assisted variant of oxidising rxn? I just did a google search on 'microwave + oxidation', but I can find nothing more than the abstracts?

Gorrilla: I concur wholeheartedly with your appraisal of this forum.

ex-hive'r

2bob - 14-9-2006 at 15:36

Anyway, after bitching (re.this board & lack of ref's), I found this...

http://www.pubmedcentral.gov/pagerender.fcgi?artid=1276483&a...

as these guys used H2O2 to oxidise the somewhat similar acid (piperonal + pyruvic acid) why couldn't it work for piperic acid (to piperonal)? Don't get me wrong, I am an ameteur (although I do try to learn;)).

PS. If I am wrong (and I am prone to being so), please provide constructive criticism not flames:(

not_important - 14-9-2006 at 19:10

Quote:
Originally posted by 2bob
...
http://www.pubmedcentral.gov/pagerender.fcgi?artid=1276483&a...

as these guys used H2O2 to oxidise the somewhat similar acid (piperonal + pyruvic acid) why couldn't it work for piperic acid (to piperonal)? Don't get me wrong, I am an ameteur (although I do try to learn;)).

PS. If I am wrong (and I am prone to being so), please provide constructive criticism not flames:(


The H2O2 oxidation there is of an alpha-keto acid, chopping off the CO2 and oxidising the C=O to CO2H. Without the oxidation you'd get an aldehyde.

But that's an alpha-keto acid, and piperic acid is an alpha, beta unsaturated acid - not the same thing. Look closely at the structures in that article you found, and at the of piperic acid.

There are H2O2 oxidations that will give the aromatic aldehyde, one using a vanadium peroxo complex was posted on this site but while many substrates had benzaldehyde yields in the 90-98 percent range, the target here gave only about 50% yields.

2bob - 14-9-2006 at 23:56

still, that is somewhat better than the yeilds to date with KMnO4 (by about 10-20x). In fact a 50% yeild would possibly make this attainable/feasible.:o

What about piperic acid and pyruvate?

Here is the Orgsyn file which demonstrates the difficulty in using KMnO4:

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0538

The only clue I've yet found is that the solution must be neutral:

http://www.henriettesherbal.com/eclectic/kings/piper-nigr_pi...

(this file also suggests that white pepper may contain even more piperine than the black?)

b

not_important - 15-9-2006 at 02:34

Quote:
Originally posted by 2bob
...

What about piperic acid and pyruvate?



Ummm, you've lost me - what about them?
Quote:

Here is the Orgsyn file which demonstrates the difficulty in using KMnO4:

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0538

The only clue I've yet found is that the solution must be neutral:

http://www.henriettesherbal.com/eclectic/kings/piper-nigr_pi...

(this file also suggests that white pepper may contain even more piperine than the black?)



Stopping the oxidation at the aldehyde is tricky, but that was the proccess for some time.

There's enough variation whith pepper from different locals that going for the more expensive white pepper isn't likely to be worthwhile. Another thing that should be noted is that there are several of acids (as amides) in pepper, these are piperic acid except for the cis/trans orientation of the double bonds. Doing much purification of the piperic acid will remove these, which is a waste when making the aldehyde since the double bonds are chopped in the process.

2bob - 18-9-2006 at 00:38

does piperonal form an addition product with sodium bisulfite (like benzaldehyde does)? If so, why not utilise a 10x excess of piperic acid, which is then neutralised with sodium bisulfite, to which 1 equiv of the oxidising agent is dripped in (along with a metallic tin catalyst to increase the oxidation rate)?

If this worked, what I envisage would be the almost immediate oxidation of the piperic acid to piperonal (which would then form the addition product with the bisulfite and precipitate out). The excess of piperic acid would of course be unaffected, and the next batch would simply replace 1 equiv of both piperic acid and sodium bisulfite, and the dripwise addition of the oxidant solution. Looking at the references for the procedure, one of the important requirements is that the solution be neutral when the oxidising reagent is added.

2bob - 18-9-2006 at 19:29

(Sorry, this bee has trouble with the 'edit' system: I cannot post after editing).

The reason I suggest using NaHSO3 is because of its dual capacity to bind to the aldehyde (piperonal) and to neutralise excess KMnO4, etc:

http://en.wikipedia.org/wiki/Sodium_bisulfite

Ephoton - 28-12-2006 at 00:11

dichromate and sulfuric acid mix with acid in mix then steam distill aldehyde out of mix has always given great results.

xwonchem - 8-1-2007 at 04:15

Hi
Why dont you use solid catalyst? Cu-KMnO4, Ni-KMnO4, Ni-Co-KMnO4...and reaction done by helping of sonic or microwave.

Maja - 9-1-2007 at 11:16

Look, I have an idea about protocatuchualdehyde syntheses starting from vanillin, converting it to 3,4-dihydroxibenzoic acid.
Here is the preparation published in orgsyn :
http://orgsyn.org/orgsyn/prep.asp?prep=cv3p0745
Easy to get materials. Then doing decarboxylation style like in plain Benzoic acid with NaOH/Ca(OH)2, but instead using hydroxides to use Mg/Ca(I was told by one chemist that those metals salts would work, but he wasn't sure about that) formate at high temperatures, aldehyde distills out at 180*C, so applying vacuum to lower boiling point and prevent oxidation of that again to benzoic acid. Nicodem ? Other experienced and smart chemists, please comment if that thing work or not, if not why not and maybe some references on that subject ? Thank you very much.

COOH + HCOOH -> COH + CO2 + H2O

P.S. I don't want to post new topic on that.

[Edited on 9-1-2007 by Maja]

Nicodem - 9-1-2007 at 11:41

Well, from 3,4-dihydroxybenzoic acid (protocatechuic acid) you would first have to prepare 3,4-methlyenedioxybenzoic acid since protocatechuic acid can not be used in the ketonization methods with formic acid salts (its hydroxy groups are acidic and the product would get "caught" in the required base and thus pirolyze before distilling; not to even mention the oxidation sensitivity of catechols at the oxygen from air).
For doing this you might need to temporarily protect the –COOH group. Esterification with methanol should be OK. Some methylenation methods might even work without protection so it would certainly be worth trying without protection first.
As for the ketonization step (or should I say "aldehydation"?) I already posted some patents in the "toluene --> benzaldehyde" thread in reply to Drunkguy's question. Any method that works on benzoic acid should work, more or less efficiently, also on 3,4-methylenedioxybenzoic acid. But since we all know why all this interest in piperonal wouldn't it be wiser to ketonize with propanoic acid, thus obtaining 3,4-methylenedioxypropiophenone?

Maja - 9-1-2007 at 12:04

I'm sorry for my lack of knowledge in organic chemistry, but maybe you can link me to methods protecting -COOH group and "some methylation methods". Thats just esterification with methanol in presence of conc sulfuric acid ? Or formaldehyde and H2SO4 ? Maybe you can tell me about that more ?
Quote:
wouldn't it be wiser to ketonize with propanoic acid, thus obtaining 3,4-methylenedioxypropiophenone?


What do you mean ? Using 3,4-methylendioxypropanoic acid instead benzoic and converting it to propiophenone ? Patents or some more info. PLEASE. THANK YOU VERY MUCH FOR SPOON FEEDING ME :)

Nicodem - 9-1-2007 at 12:34

Quote:
Originally posted by Maja
I'm sorry for my lack of knowledge in organic chemistry, but maybe you can link me to methods protecting -COOH group and "some methylation methods".

I would certainly try the methylenation on the unprotected acid before trying to use any protection. It should/might work with some methods. As for the various reagents and methods for the methylenation of various catecholes all you need to do is search the Rhodium archive. There are more or less all of the best references already compiled.
Quote:
What do you mean ? Using 3,4-methylendioxypropanoic acid instead benzoic and converting it to propiophenone ? Patents or some more info.

No. I was insinuating that most people interested in piperonal are actually interested in 3,4-methylenedioxyamhetamines anyway. So why piperonal from 3,4-methylenedioxybenzoic acid when you can make 3,4-methylenedioxypropiophenone by the ketonization of 3,4-methylenedioxybenzoic acid with propanoic acid? This way you need no nitroethane, 2-bromopropanoic esters or whatever you would otherwise require if starting from piperonal. Instead you start by the usual propiophenone routes. In addition, the ketonizations with propanoic acid are way more likely to work than with formic acid. Not to mention that one can then use 3,4-methylenedioxypropiophenone also for "methylone" which is at least legal in many countries (unlike the other target compounds). No other special reason.

Maja - 9-1-2007 at 13:09

Quote:
I would certainly try the methylenation on the unprotected acid before trying to use any protection. It should/might work with some methods. As for the various reagents and methods for the methylenation of various catecholes all you need to do is search the Rhodium archive. There are more or less all of the best references already compiled.
TOTTALY FORGOT ABOUT RHODIUM ARCHIVES, THANKS.

OK, one more time sorry .... Can you give me some syntheses for example using ketonization ? I was unable to find them in www.orgsyn.org maybe thats due that my English isn't native language so I don't know maybe reaction name :/
Quote:
No. I was insinuating that most people interested in piperonal are actually interested in 3,4-methylenedioxyamhetamines anyway. So why piperonal from 3,4-methylenedioxybenzoic acid when you can make 3,4-methylenedioxypropiophenone by the ketonization of 3,4-methylenedioxybenzoic acid with propanoic acid? This way you need no nitroethane, 2-bromopropanoic esters or whatever you would otherwise require if starting from piperonal. Instead you start by the usual propiophenone routes. In addition, the ketonizations with propanoic acid are way more likely to work than with formic acid. Not to mention that one can then use 3,4-methylenedioxypropiophenone also for "methylone" which is at least legal in many countries (unlike the other target compounds). No other special reason.]



[Edited on 9-1-2007 by Maja]

MargaretThatcher - 9-1-2007 at 16:31

Some things are best not said.

jim20/20 - 12-1-2007 at 14:03

Quote:
Originally posted by MargaretThatcher
Some things are best not said.


some things are best not sold

but one hand washes the other

womble - 25-1-2007 at 04:58

I was looking at the procedure listed in teh patents listed by Nicodem in the toluene to benzaldehyde through the overoxidisation of toluene to benzoic acid then the formylation of the carboxylic acid over a solid catalyst. I began to wonder. Could a solid catalyst be made utilising MnO2 or Cr2O3 using the same (or a similar) procedure?

If so, could the toluene/piperic acid be refluxed with an aqueous phase containing sodium bisulfite, with the reflux condenser taking the reformed liquid through a chamber containing the oxidant? This would take the liquid into contact with the solid oxidant, for a limited period, after which it would go back into the vessel containing the aqueous phase. The formed ?-aldehyde would form the addition product while any oxidant entering into the lower pot would be neutralised by the bisulfite and prevented from further oxidising anything. The fact that the oxidisation would be completely controllable and the oxidised product would be prevented, by virtue of it being a non-volatile addition product & precipitate, from further oxidisation should ensure that the overoxidisation could be avoided.

I realise that this has not been suggested previously, and I do not presume to suggest that this is correct, however, I cannot see any reason why it wouldn't work? Can somebody with actual knowledge please advise on the feasibility of this proposed route?

womble - 29-1-2007 at 17:58

is the structure of piperic acid as it appears to be, namely a MD-phenylacetic acid? (I AM guessing, I have been unable to find a structure diagram for it). If so, why would you want to take it back to MD-Benzaldehyde? If however it is more similar to a phenacetaldehyde, that is different. However, the patents for MD-mandelic acid to piperonal state that it can be done with either heat or with sulphuric acid or by the use of 1:2/3 (MD-Mandelic Acid:Nitric Acid) with a 1.5-2 x excess of hydrochloric acid.

stoichiometric_steve - 31-1-2007 at 12:13

Quote:
Originally posted by womble
If so, could the toluene/piperic acid be refluxed with an aqueous phase containing sodium bisulfite, with the reflux condenser taking the reformed liquid through a chamber containing the oxidant? This would take the liquid into contact with the solid oxidant, for a limited period, after which it would go back into the vessel containing the aqueous phase. The formed ?-aldehyde would form the addition product while any oxidant entering into the lower pot would be neutralised by the bisulfite and prevented from further oxidising anything. The fact that the oxidisation would be completely controllable and the oxidised product would be prevented, by virtue of it being a non-volatile addition product & precipitate, from further oxidisation should ensure that the overoxidisation could be avoided.


piperic acid would possibly react with sodium bisulfite to form a salt, making it non-volatile. if you are refluxing toluene with piperic acid, everything that will boil off and condense is - toluene.

i think you would just get a complete mess.

in Houben-Weyl's homework part, it says that Br2 + piperic acid -> tetrabromopiperic acid which yields piperonal on addition to dilute NaOH.

you could do that by purchasing a bromide salt, oxidising it with H2O2, and running the reaction in a 2phasic system. preferrably some ester like EtOAc.

womble - 31-1-2007 at 23:15

Piperic (piperinic) acid is oxidised to piperonal etc. ok, fine.

The following patent deals with the oxidisation of a methylene-dioxy-phenyl-carboxylic (or di-carboxylic) acid (3,4 methylene-dioxy-mandelic acid) to piperonal. It uses Nitric Acid to achieve this:

http://www.patentstorm.us/patents/6686482-claims.html

I am aware that it is a completely different molecule, however, why won’t it work for piperic acid?

Specifically, why can nitric acid oxidise a phenyl-glyoxylic acid and not a phenyl-carboxylic (or di-carboxylic) acid?

stoichiometric_steve - 2-2-2007 at 01:32

Quote:
Originally posted by womble
I am aware that it is a completely different molecule, however, why won’t it work for piperic acid?


you said it - because it is a completely different molecule.

not_important - 2-2-2007 at 03:01

Quote:
Originally posted by stoichiometric_steve
Quote:
Originally posted by womble
I am aware that it is a completely different molecule, however, why won’t it work for piperic acid?


you said it - because it is a completely different molecule.


To be more specific, it is an alpha-hydroxy-carboxylic acid. Oxidise it to the alpha-keto acid, which decarboxylates to give the aldehyde. Classic org chem stuff.

Seperation of Piperine from resin

jefferson987 - 17-5-2010 at 12:58

I've extracted piperine from 100g of balck pepper using methanol. The extraction worked, but along with piperine can the gooy and sticky resin from the pepper. When I tried to recrystalize in acetone it didn't work very well because the resin. How can I separate the piperine from the resin?

Nicodem - 17-5-2010 at 14:28

Quote: Originally posted by jefferson987  
I've extracted piperine from 100g of balck pepper using methanol. The extraction worked, but along with piperine can the gooy and sticky resin from the pepper. When I tried to recrystalize in acetone it didn't work very well because the resin. How can I separate the piperine from the resin?

The "extraction worked", but you got no piperine? If you were unable to extract piperine, then the extraction of piperine did not work. Utmost the extraction of a mixture possibly containing piperine worked.
Anyway, I find it surprising that so many beginners try to reinvent the wheel. Someone please explain what is the reason for not following a verified and published protocol? And why then asking how to separate piperine from the resin when there was no serious attempt to do so already in the first place. Am I missing something obvious?

Hexagon - 17-5-2010 at 15:09

jefferson987, did you tried an hexane:acetone (2:3) mixture for the recrystalization? I just extracted 50 gs of B.P. with 200 ml of EtOH and stirring without heating for 2 hours, filtered, washed the erlenmeyer with 50 mls more of EtOH and filtered them too. After this I obtained a little more than 225 mls of the extract, from this the alcohol was evaporated and to the resulting resinous goo I added 15mls of hot acetone and heated while swirling until it all was dissolved, then I added 10 mls of petroleum ether (lighter fluid) heated a little more, put a lid on the beaker and left it on the fridge.

Nicodem, dunno where is this revival on pepper coming from, I tried a pair of verified and published protocols, and every time what I got was resinous goo or nada, may be I'm a fool, but I tried my own protocol (you can see I didn't got smoke coming out of my head while thinking too much) and at least I obtained the crude solid, not bad! :D

jefferson987 - 17-5-2010 at 20:43

Wow Nicodem harsh... I was following the directions listed here: http://www.erowid.org/archive/rhodium/chemistry/3base/pipero...

Apparently there are many different solvents that can be used for the job but the resin makes things tricky. I WAS able to extract piperine from BP because I can see the yellow crystals among the resin.

Nicodem - 17-5-2010 at 23:28

Quote: Originally posted by jefferson987  
Wow Nicodem harsh... I was following the directions listed here: http://www.erowid.org/archive/rhodium/chemistry/3base/pipero...

Apparently there are many different solvents that can be used for the job but the resin makes things tricky. I WAS able to extract piperine from BP because I can see the yellow crystals among the resin.

Was I was harsh? Maybe not enough, given that you reply by supporting my arguments. You should also learn to differentiate your beliefs from real world - you know not if the yellow crystals were piperine! Until you have them isolated and characterized, they are just what they are, some "yellow crystals among the resin".
Have you bothered comparing the isolation protocol you linked to some published one or at least those used in educational lab practice? If it works for thousand of students each year, then how come it is not good enough for you? Why would you prefer some two line description of an unconfirmed extraction over a detailed and confirmed one? What I'm trying to tell you is to think by using your own mind rather that not think at all. Is the following supposed to be rational in your opinion?
Quote:
Piperine is extracted from B. Pepper with an organic solvent. Duh. Anhydrous alcohols are fine, ether is much cleaner. Solvent is evap'd to leave yellow crystals.

Where is the defating step? I see no petroleum ether mentioned there? So how is the resinous plant material and other fats removed? Where is the recrystallization step? At least Hexagon joined the defating and recrystallization step together and it seemed to work (though he does not mention what the mp of the product was). In that example above there is none of this!

Rich_Insane - 18-5-2010 at 08:56

Pepper is a plant. It is lipid rich like any living organism. It will also contain proteins and such. Your sticky resin is likely a mixture of lipids, complex sugars, and random proteins. The least you could do is add the MeOH to the pepper, wash the goo with some hexane or NP solvent, wash with cold water (piperine has low solubility in cold water, so just wash it off very quickly), and add some hot acetone. Recrystallize the result to yield fairly impure piperine.

There's a paper here that gives an extraction: A rapid method for isolation of piperine from the fruits of Piper nigrum Linn (Niranjan Kanaki, Mansi Dave, Harish Padh and Mandapati Rajani)

I couldn't obtain access to the full article, but basically it seems that they extract the black pepper powder with glacial acetic acid, then recrystallize with chloroform to yield piperine.

Here's a procedure from a chemistry course: Isolation of Piperine from Black Ground Pepper

First, CHCl2 was added to the mix. If I am not mistaken CHCl2 can be bought fairly cheaply. I think that it's been banned as a paint thinner though (I'm in USA). This mixture was set to reflux. The remaining waste pepper was washed with more CHCl2 and the mixture was filtered.

Then, to isolate the piperine, the CHCl2 was put in a rotovap (I'm sure that some other way could be used to separate the CHCl2), a brown oil was isolated. To this, in a very cold bath, add some cold ether. One could either extract ether from OTC sources, make it, or substitute with naphtha. It has to be very cold. The piperine will crystallize out.

Filter this, obtain the yellow crystals, and recrystallize with a 3:2 mixture of acetone and hexane. Filter out the crystals and obtain a melting point.

This procedure is very simple and could easily be simplified to OTC sources. Before asking a question, please do proper research.

Melgar - 19-5-2010 at 08:09

So piperine is soluble in alcohol, acetone, and dichloromethane, and insoluble in water? What about nonpolar solvents like xylene or hexane?

Rich - do you mean CH2Cl2? It's the main ingredient in lots of paint strippers in the US. The easiest way to find it is by looking for the ones that don't have flammability warnings on them, since CH2Cl2 is one of only a small number of nonflammable solvents. It will need to be distilled though, since paint strippers almost alyways have lots of thickeners and surfactants. It's usually listed as "methylene chloride" on the back of the container.

Chloroform can be used instead of CH2Cl2 in most cases, which can be made by carefully mixing acetone and bleach and siphoning out the resulting bottom layer.

[Edited on 5/19/10 by Melgar]

Rich_Insane - 19-5-2010 at 14:55

Yes, CHCl2 as in dichloromethane... Interesting. It is a useful solvent. Unfortunately I do not have a distillation apparatus. I either need to find a cheap one or build a makeshift one. The acetone and bleach method has horrible yield. I did the reaction twice with stoichiometric amounts of bleach and acetone in a 8-16 C ice bath, and only got around 40 or 50% yield. I'd just buy that dichloromethane. Look in the smaller hardware stores. They tend to have purer dichloromethane than big chains.

eesakiwi - 18-8-2010 at 23:10

Extract the pepper with alcohol & filter.
Boil off most of the alcohol untill it gets a little thicker.
Add water slowly & it will change colour a bit & the tar will drop out first.

As soon as you start to see the 'glints' in the liquid (coloured sparkles, different colours in each sparkle, millions of them)
Pour it all off the tar thats bottomed out of the liquid, into another similar tall jar & keep adding water untill it starts to turn green/creamish (typical oil/water/detergent mix colour).

About now the piperine will drop out (its the glints anyway) to the bottom.

Recrystalise from 3xAcetone/2xPet ether mix or just acetone & add Pet ether to drive the crystals out of the Acetone.

Big thing is to have a low amount of alcohol as you loose the ability to drive the stuff out of it with water if theres too much alcohol in there in the first place.
ie the liquids will still hold onto the piperine if theres too much alcohol.

Gualterio_Malatesta - 24-8-2010 at 09:01

Why would you need piperine?

Are you aware that no one succeded yet working the oxidation step later in the process?

So you can't really obtain any piperonal. Too bad.

Hexagon - 24-8-2010 at 09:16

Quote: Originally posted by Gualterio_Malatesta  
Why would you need piperine?

Are you aware that no one succeded yet working the oxidation step later in the process?

So you can't really obtain any piperonal. Too bad.


While piperine is an interesting compound on it self, people have reported obtaining low yields of piperonal (20% or so) from piperic acid, and that same compound straight from piperine via manganese compounds (III & IV)

Gualterio_Malatesta - 24-8-2010 at 09:37

That sounds quite interesting if it's actually true. Can you give me any links (PM)?

Polverone - 24-8-2010 at 11:34

Quote: Originally posted by Gualterio_Malatesta  
Why would you need piperine?

Are you aware that no one succeded yet working the oxidation step later in the process?

So you can't really obtain any piperonal. Too bad.


"No one" succeeded? KMnO4 oxidation of piperic acid is repeatedly described in late 19th century books on chemistry, pharmacy, and perfumery as a preparation of heliotropin (piperonal) before less expensive safrole-based methods were discovered.

I will admit that the standards of documentation in that time period are lacking, so you cannot go straight from the old books to a practical and optimized preparation as you would with e.g. a procedure from Organic Syntheses. But it is ridiculous to dismiss old results just because nobody in the small circle of hobby chemists posting on the internet in English has claimed to reproduce the work. We might as well say that no one has produced sodium via carbothermic processes, despite a wealth of 19th century writings to the contrary, since I have never seen it electronically documented by modern hobbyists.

Gualterio_Malatesta - 24-8-2010 at 20:25

Well, yes, what I meant was that no clandestine chemist going this route ever yielded piperonal. I wasn't talking about 19th cent.

It's a small circle of hobby (kitchen) chemists sure, but those chemists did much more complicated reactions, and it strikes me as odd that this fairly simple one doesn't yield what it should.

Nicodem - 25-8-2010 at 00:24

Quote: Originally posted by Gualterio_Malatesta  
It's a small circle of hobby (kitchen) chemists sure, but those chemists did much more complicated reactions, and it strikes me as odd that this fairly simple one doesn't yield what it should.

You are not thinking rationally. For obvious reasons only very few "kitchen chemists" are interested in piperine due to MD(M)A. If they consider extraction of pepper and piperine as a good starting point for such targets, it is only because they don't have enough knowledge to think of anything else and skills to do anything else. And if they don't have enough knowledge and skills then it is absurd to expect them being able to oxidise piperine to piperonal by any of the published methods. Just check the questions in this and other piperine extraction threads! Most of those posters don't know anything about how these extractions work and most never even bothered checking the literature or any of the schoolbook practicum instructions to see how it is properly done. Those who have the skills for performing the oxidation of piperine to piperonal would certainly not bother if their motivation is due to MD(M)A. Actually, the only chance for a "kitchen chemists" to do this oxidation is for someone with the required skills to do this out of pure enthusiasm rather than being motivated by any potential (mis)use of piperonal.

Gualterio_Malatesta - 25-8-2010 at 02:11

Well, I wasn't talking bout local (i.e. sciencemadness.org) chemists, I was talking the-hive/hyperlab. Trust me those guys failed oxidation, not due to the lack of skills. There's smth fishy with that oxidation write-up.

And by the way, this is the most easy and promising route for many ppl due to the fact that sassafras oil is pretty much unobtainable in many parts of the world, and other routes use non-OTC and dangerous chemicals.

Hence this method is more promising and is favourable to kitchen chemists not because they lack knowledge.
This method was tried by several skillfull chemists and failed! I must admit my info is couple of years old, maybe there were some improvements to this oxidation step which actually yielded the desired product - Hexagon's post above (he didn't reply me though).

Hexagon - 25-8-2010 at 10:56

Yep I've been out without regular access to internet connection this days, there you have your u2u, don't expect cookbook instructions ;)

Gualterio_Malatesta - 25-8-2010 at 20:12

Thanks!

cheeseandbaloney - 25-8-2010 at 20:39

I would think the reason the oxidation of piperic acid usually fails because the strong oxidizers could be tearing up the methylenedioxy bridge. Anything strong enough to rip apart a C=C bond seems like it would do somptin fierce to a R-O-CH2-O-R bond. It would be a surprise to me if the yields on a reaction like this were consistently high...

Hexagon - 26-8-2010 at 00:22

Quote: Originally posted by cheeseandbaloney  
I would think the reason the oxidation of piperic acid usually fails because the strong oxidizers could be tearing up the methylenedioxy bridge. Anything strong enough to rip apart a C=C bond seems like it would do somptin fierce to a R-O-CH2-O-R bond. It would be a surprise to me if the yields on a reaction like this were consistently high...


Nope, the oxidation usually fails because the aldehyde is oxidized all the way to the acid.

Bander - 26-8-2010 at 11:58

I made a thread on this a long time ago where I received very useful help from many here, but most notably Tacho's advice. Since then I have done the below to isolate piperine.
Quote:
113g Black Pepper (4oz)
~600ml Isopropyl Alcohol, anhydrous!
~120ml Acetone, anhydrous!

Reflux 113g black pepper in 600ml anhydrous IPA in a 1 L round bottom flask for 2-3 hours. Filter the ~80C olive translucent IPA through coffee filters into temporary jars. Remove the partially extracted ground pepper to save for further extractions and wash the remainder of solids out of the flask with water. *DRY* the water out of the flask completely with acetone wash and hot water bath. Pour the Piperine/IPA back into the ground bottom flask. Add broken glass chips or boiling stones. Distill off and recover the IPA until the viscous remainder starts to stick to and gum up the glassware above the bubble line. This usually happens with around ~30ml (+-10) left. Pour the remainder off and let it sit for a day undisturbed and covered.

A cake/mash of orange crystals under a brown oil appears. Crush the fanned out crystal cake under ~20ml acetone (dry! no water). Pour the acetone wash off the powder into a collection jar through a coffee filter for later. It will still contain substantial disolved piperine. Notice the lighter yellow color each time as you repeat this wash and crush three times. The remaining bright yellow <1mm needle crystal powdered piperine at the bottom of the jar should be set out to dry on filters. 2-4g usually results.

The waste should be evaporated over 2-3 days to retrieve another crystal cake and the above repeated.


[Edited on 27-8-2010 by Bander]

cheeseandbaloney - 26-8-2010 at 12:09

Quote: Originally posted by Hexagon  
Quote: Originally posted by cheeseandbaloney  
I would think the reason the oxidation of piperic acid usually fails because the strong oxidizers could be tearing up the methylenedioxy bridge. Anything strong enough to rip apart a C=C bond seems like it would do somptin fierce to a R-O-CH2-O-R bond. It would be a surprise to me if the yields on a reaction like this were consistently high...


Nope, the oxidation usually fails because the aldehyde is oxidized all the way to the acid.


aha! I was under the impression that the reaction failed completely and brought a mess of unwanted products. Piperonylic acid still seems useful. I wouldn't consider that a failed reaction! (unless one specifically wanted piperonal obviously).

Nicodem - 27-8-2010 at 01:00

Quote: Originally posted by Gualterio_Malatesta  
Hence this method is more promising and is favourable to kitchen chemists not because they lack knowledge.
This method was tried by several skillfull chemists and failed! I must admit my info is couple of years old, maybe there were some improvements to this oxidation step which actually yielded the desired product - Hexagon's post above (he didn't reply me though).

I'll skip the part about this being a promising method to kitchen chemists and lack of knowledge, because it sounds oxymoronic, but I'm seriously interested in those reports you mentioned of "tried by several skillfull chemists and failed". I don't remember any such report from the Hive and I do more or less regularly follow the developments at the Hyperlab, but I don't remember ever reading about what you talk. If skilled chemists tried and failed, this can mean the oxidations described in the literature are fraudulent, that even ozonolysis on piperine does not work, or that it is not possible to isolate piperonal from the mixture (or a combination of more of such factors). Please provide a few citations from these skilled chemists, so that we can see where the problem resides.

Gualterio_Malatesta - 27-8-2010 at 01:47

2 Nicodem

I will try to find links to those attempts.

Anyways, was there any success that you are aware of involving this method?

Polverone - 27-8-2010 at 08:16

Here is the original Annalen paper describing the cleavage of piperine. I don't recall seeing this paper posted before in conjunction with piperine -> piperonal discussions. I know little to no German so it will require much tedious machine translation and dictionary time before I can grasp much of it. It may be useful to anyone in this thread who understands German, though.

Attachment: annalen_1869_25-58.pdf (735kB)
This file has been downloaded 2657 times

Bander - 27-8-2010 at 09:15

Would it be possible to remove piperonal from solution as it is formed by using a bilsulfite adduct to precipitate it before it is oxidated to the acid? I have used this method after the entire oxidation, but ended up with only ~0.1g of very pale yellow precipitate.

S.C. Wack - 27-8-2010 at 13:40

How is it that everyone assumes that piperine isolation and piperic acid oxidation to piperonal have never come up here before?

It's almost as mysterious to me as is staff wasting valuable time in response to obviously clueless or trolling new nyms who refuse to search google or anything, and refuse to post in relevant threads.

The article has been posted here: http://www.sciencemadness.org/talk/viewthread.php?tid=1369#p...
And partially here: http://www.sciencemadness.org/talk/viewthread.php?tid=3007&a...
Naturally google books has it by now.
It was translated: http://www.sciencemadness.org/talk/viewthread.php?tid=3007&a...

The problem with the .txt procedure is that it was...fucked up...and any of these alleged failures by these top notch chemists is caused by their faith in internet teks, not chemistry. No doubt the original directions would be an improvement.

Forming a solid bisulfite adduct is unnecessary and surely lowers yields. I have heard rumors that one trick to the KMnO4 procedure is in the workup.

However any tricks, and possibilities known in the art (KMnO4-related or otherwise), seem ill placed in any thread titled "Seperation of Piperine from resin", much less in response to the posts in this thread.

[Edited on 27-8-2010 by S.C. Wack]

Hexagon - 27-8-2010 at 13:41

AFAIK the adduct you are trying to make is fucked up at anything but neutral conditions, so in the clasic synth. being basic the anvioronment, it's a safe assumption that trying to isolate the aldehyde as it's corresponding bisulfite adduct is not possible. Dunno what you ended with, but I can assure that piperonal is bisulfite aduccut is a powder (when dry) white as snow.

If you have enough piperate you can try the CuSO4 and tartrate/citrate in alkaline media oxidation, dont use an excess of sodium hydroxide since it'll turn the aldehyde in to the alcohol and the acid due to cannizaro, just use enough hydroxide to precipitate de Cu(OH)2 and neutralize the tartaric/citric acid, then add an excess of sodium (bi)carbonate or what ever, it'll foam a little bit at the beggining, after refluxing for 5 hours, I think that the piperonal should be steam distilled and from the resulting aqueous mess, add (meta)bisulfite to isolate the adduct. I tried all that with unproperly hydrolized piperate (turned to be fatty acid salts with a little bit sodium piperate) and obtained a vanillaish smell :)

Will not try it again with piperate because the hydrolisis of the amide plainly sucks. I'd rather extract pure piperine and then chuck that on a manganese-ammonium alum cell.

Another idea would be to drip very slowly a permanganate solution to boiling aqueous piperate and carbonate, from witch the piperonal is steam distilled as it forms, hopefully.

euxy - 9-5-2011 at 11:41

The rapodshare link by CherrieBaby is dead, has anyone the articles?

Antoncho - 10-5-2011 at 10:11

1. Extraction of 462 g ground black pepper with boiling acetone (1.5 l + 1 l, circa 1 hr, more isn't needed) gave 39.8 g resin.

2. Boiled for 1 hr with 483 mls 95% EtOH and 117 g urea (as in US Patent 6054585) and cooled overnight in the fridge, decanted from xtals of urea/fatty acids adduct, evaporated most EtOH and added a little water. Crude semi-solid piperine precipitate weighs 31.1 g.

3. Dissolved in 50 mls EtOAc, added 50 mls pet ether, chilled overnight in the freezer. Yield - 11,3 g of nice xtalline piperine .

4. Refluxed for 19 hrs (TLC shows completion at this time) with an equal weight of 85% KOH in 5x volume of 95% EtOH. Cooled, filtered, washed with IPA on the filter. Yield - 101% K piperate.

5. Recrystallized from 5x EtOH + 1x water. After cooling in the freezer 75% yield counting on piperine was obtained. Had an impression that mother liquor still held some piperate.

6. 2 g K-piperate dissolved in 50 mls water, added 50 mls DCM. Placed in ice bath, dripped in saturated aq. solution of 6.2 g KMnO4 with stirring, temp. kept at 5-10 C. Killed remaining oxidant with ascorbic acid. Separated organic layer, extracted with DCM, washed w/5% NaOH, then brine, stripped off solvent. Yield - 500 mg (42,5% on piperate) piperonal, which was solid at RT but melted in hands (lit. mp. 36 C)

The identity of the product was further confirmed by Henry reaction, which proceeded with good yield. Reduction of the intermediate also gave the product with all of the properties that were to bee expected ;)

[Edited on 10-5-2011 by Antoncho]

Antoncho - 12-5-2011 at 02:29

Just to not bee confusing - a pound of black pepper gives about 3,5 g of piperonal via the route described in the previous post.

The quantity that the author had actually gotten was about 1.5 g, but only beecause a lot of experimentaion has been made along the way (e.g., oxidation of piperine with CuSO4 was tried and found to bee not working at all).

Thus, a kilo of black pepper could give one about 7 g of piperonal, perhaps even more.

Hexagon - 13-5-2011 at 00:28

What can I say? BTW great work antoncho!

Just one thing, did you tried the cuso4 variation with a citrate or tartrate added? looks it needs a cu(ii) complexing agent added.

Palladium - 26-8-2011 at 06:58

Would a loaded salt of Mn+3 reduced to Mn+2 towards piperic acid which gets oxidized with cleavage to piperonal? Is this selective oxidation strong enough to cleave the double bonds of piperic acid?

Strong oxidizer is mentioned in this oxidative cleavage which KMnO4 is, but I'm sure that this also leads to oxidation all the way to the acid.

Mush - 5-2-2012 at 08:44

Quote: Originally posted by euxy  
The rapodshare link by CherrieBaby is dead, has anyone the articles?
Code:
http://www.4shared.com/zip/xDvE_KC_/200613113482_Piperolal-oxidati.html

thebishop - 12-3-2013 at 14:45

The following are mixed together under agitation at ambient temperature:

294.23 g (1.5 mole) of 3,4-methylenedioxy mandelic acid;

562 g of water;

258.75 g of 37% hydrochloric acid being 2.625 moles;

2.1 g of 69% nitric acid being 23 mmoles.

The suspension obtained is heated under agitation at 43°±2° C., then 103.5 mg (1.5 mmole) of sodium nitrite dissolved in 4 g of water is introduced rapidly at this temperature, then 107.5 g of 69% nitric acid, being 1.177 mole, is introduced slowly, over about three hours, in such a way so that the temperature of the reaction medium is maintained at between 40° and 50° C. without using external heating or cooling. At the end of the introduction, the reaction medium is left for one our under agitation at 43°±2° C., then it is cooled down to ambient temperature and finally extraction takes place three times with 600 g of trichloro-1,1,1-ethane. The re-united organic phases are then washed successively, once with water, three times with a saturated aqueous solution of sodium hydrogen carbonate and finally once with water before being concentrated under reduced pressure.

Thus 220 g (1.46 mole) of crude piperonal is isolated which is purified by distillation under reduced pressure.

Thus 178 g (1.186 mole) of pure piperonal is isolated distilling at 106° C. under a vacuum of 2.4 mbars and having a melting point of 37°+1° C. The yield is established at 79% of the theoretically calculated value relative to the 3,4-methylenedioxy mandelic acid used.

http://www.freepatentsonline.com/5095128.html

I expect i'll use DCM rather than trichloro-1,1,1-ethane.

maximumpat - 31-3-2013 at 20:08

...thank you. long time lurker here, I shall try and make my first post of consequence a proof of concept on this.

chemplayer... - 4-7-2016 at 03:16

We've tried in the past to perform the permanganate oxidation of piperinic (piperic) acid, and it's possible to do a DCM extract of the reaction mixture and get a tiny tiny amount of something rather nice smelling, but until now nothing isolated. So we tried something different and random:


Preparations:

Solution P (Piperinate):
100ml of water
3.7g of piperinic acid, derived originally from black pepper (17 mmol)
0.68g of sodium hydroxide (17 mmol)

Solution O (Oxidisers):
500ml of water at ~20C
3.9g potassium periodate (17 mmol, 1 x mole equiv)
5.4g potassium permanganate (34 mmol, 2 x mole equiv)

Solution Q (Quench):
75ml of water
5.3g sodium bisulfite (51 mmol)
2.1g sodium hydroxide (51 mmol)


Procedure:

1. Solutions P, O and Q prepared using magnetic stirring in various beakers (P in the large 800ml beaker).
2. 3 ice cubes (~50g) were added to solution P with vigorous stirring.
3. Solution O was agitated with a glass rod (to ensure no residual insoluble periodate had settled).
4. Solution O was added to rapidly stirred solution P over about 15 seconds.
5. Stirring continued and reaction allowed to proceed for 2 minutes.
6. Solution Q added over about 15 seconds, and then the mixture allowed to settle.
7. Mixture filtered (heavy brown-black precipitate), and the precipitate washed with 30ml water.
8. Precipitate washed with 2 x 30ml of dichloromethane.
9. Filtrate (2 layers) placed into separating funnel, shaken, and the bottom DCM layer separated.
10. Aqueous layer extracted with a further 15ml of DCM, and DCM layers combined.
11. DCM dried using anhydrous MgSO4, then decanted and evaporated down (outside, warm day).
12. An oil remained which solidified at room temp into a crystalline pale yellow solid.
13. 0.5g obtained whose melting point range was found to be 34-37C.


Ponderings:

- This was a total guess and we figured we'd see what would happen if periodate and permanganate were combined. We're still not totally sure if the periodate is really playing a responsible role here, but this is the best yield by far we've ever got, an isolated product, and what seems to be a relatively high purity.
- Crude yield is 20% (3.3 mmol) of piperonal from starting piperinic acid.
- Aroma is an incredible vanilla + cherries + toasty buttery ('jelly belly toasted marshmallow flavour') scents. Even slightly 'soapy' and balsamic.


Complete video of the process is here: https://www.youtube.com/watch?v=6r9elLR2WjI

clearly_not_atara - 4-7-2016 at 11:34

If you have any more piperic acid, there's an interesting variation where FeSO4 is used to halt the oxidation at the aldehyde stage:
Quote:
The oxidation of ethyl alcohol by the action of potassium per-
manganate was first reported by Morawski and Sting1 (72) who
found that the alcohol was oxidized to acetic acid. The acid in
turn combined with excess of the permanganate to produce po-
tassium acetate and a brown unidentified precipitate was formed.
Doroshevskii and Bardt (31), working under these conditions,
found that with the inclusion of ferrous salts as catalysts in the
oxidation of ethyl alcohol by potassium permanganate, the results
varied with the catalyst selected. If ferrous sulfate was em-
ployed the oxidation stopped with the formation of acetaldehyde,
but if ferrous oxalate was used as the catalyst, the product was a
mixture of aldehyde and acetic acid.
(^the above procedure is for ethanol, but we were speculating it could extend to alkenes)

There is also a procedure which uses triethylbenzylammonium permanganate as a homogenous oxidant in DCM solution, quenched with aqueous AcOH to yield aldehydes selectively (Et3BnNCl + KMnO4 (DCM) >> Et3BnNMnO4 sol'n):
Quote:
The procedure is as follows: To a stirred solution of endo-dicyclopentadiene (2.27mmol) in dichloromethane (20ml) was added drop- wise the oxidant solution freshly prepared with KMnO4(3.41mmol),7 triethylbenzylammonium chloride (3.41mmol) and dichloromethane (40ml) at such a rate that the temperature was maintained at 0-3°C under cooling with an ice-bath (40-50min). After addition was complete, stirring was continued until permanganate ion was completely consumed (30-40min). The homogeneous dark brown solution was then treated with aqueous solutions of variant pH.
When the reaction mixture was treated with 3% NaOH solution (30ml) under nitrogen atmosphere at room temperature for 18 hours, a crystalline product (2), mp 47-52° (lit. 48-51°), was obtained in 83% yield from the organic layer upon usual work-up. The product was identified as the exo,cis-diol (2) by its ir and nmr data, which was previously obtained in 28% yield by the oxidation of endo-dicyclopentadiene in EtoH with aqueous potassium permanganate.8 No other products were detected on tlc and glc.
On the other hand, when the reaction mixture was treated with an acetate solution (30ml) at pH 3, the dialdehyde (3), mp 42-44° (lit. 36-42°), was obtained in 81% yield as the single product(tlc,glc). The compound (3) is known as a key intermediate for prostaglandin synthesis
and has been synthesized indirectly through periodate oxidation of the diol (2).


The last procedure which I think is really cool is to use horseradish peroxidase, which cleaves anethole (and piperic acid is pretty similar!):
Quote:
Mutti et al. have recently shown that some peroxidases (i.e., horseradish peroxidase, lignin peroxidase, and Coprinus cinereus peroxidase) catalyse the cleavage of a C=C double bond adjacent to an aromatic moiety for selected substrates at the expense of molecular oxygen and at an acidic pH (Scheme 5) [32]. Among the three active peroxidases, HRP turned out to be the most active when an equal concentration of enzyme was employed. A thorough study of the reaction showed that the highest activity was obtained at ambient temperature, at pH 2, and at 2 bars of pure dioxygen pressure. Addition of DMSO as cosolvent up to 15% v v?1 increased the conversion, probably due to the improved solubility of the substrates in the aqueous reaction medium, while a further addition of DMSO led to a progressive decline of the enzymatic activity. Using trans-anethole as substrate (9) (6 g L?1 ) and HRP at low catalyst loading (3 mg, equal to 0.2–0.3 mol%), quantitative conversion was achieved within 24h. The main product was para-anisaldehyde (11) (i.e., 92% chemoselectivity), whereas the side product accounted completely for the vicinal diol (12). The substrate spectrum was quite narrow, since only other two substrates, that is, isoeugenol (10) and indene (13), could be cleaved by HRP with 12% and 72% conversion, respectively.


I'm not entirely sure how to extract horseradish peroxidase from horseradish, but it offers a manganese-free -- hence nontoxic - cleavage of this substrate.

[Edited on 4-7-2016 by clearly_not_atara]

chempropharm - 9-7-2016 at 20:03

Nice work.. just a question..

If oxidation of piperine will do the job.. why going to piperic acid intermediate step?

Mush - 3-8-2019 at 13:30

Quote: Originally posted by chempropharm  
Nice work.. just a question..

If oxidation of piperine will do the job.. why going to piperic acid intermediate step?


Yes, it will do the job .

Forensic Sci Int. 2012 Nov 30;223(1-3):306-13. doi: 10.1016/j.forsciint.2012.10.006

2.4. Piperonal from pepper
2.4.1. Oxidative cleavage of piperine by ozonolysis
A stream of ozone gas. generated by a HAILEA HLO 100 Ozone Steriliser
(— 100 mg of ozone per hour), was passed through a solution of piperine (1.00 g. 331 mmol) in a 5% solution of water in acetone. After 8 h. the ozone generator was switched off and the solution extracted with two 10 mL portions of diethyl ether. The combined ether extracts were dried over anhydrous sodium sulphate and the solvent evaporated in vacuo yielding bright yellow oil. Yield: 508 mg (97%). 'H NMR: see Fig. SI3. GC-MS: see Fig. 2.

2.42. Oxidative cleavege of piperine with aqueous KMn04 in THF
An aqueous solution of KMn04 (2.00 g. 12.6 mmol in 40 ml. of water) was added dropwise over a period of 4 h to a solution of piperine (1.00 g. 3.51 mmol in 40 mL of THF] at 60 C. After the solution had been added, the mixture was stirred for 4 h before the MnO2 precipitate that had formed was filtered off leaving a pale yellow solution. The sample was extracted with diethyl ether and the combined extracts were dried over anhydrous sodium sulphate. The ether was evaporated in vacuo to
yield a dark yellow orange oil that solidified on cooling. Yield: 340 mg (65%). 'H NMR: see Fig. SI4. GC-MS: see Fig. 2.

I believe the authors used this paper as reference:
1, https://erowid.org/archive/rhodium/chemistry/alkene2aldehyde...
2,
Code:
https://pubs.acs.org/doi/abs/10.1021/jo800323x



It worked as it was predicted by Hive members.

Note:
Ozonolysis yields a mixtures of piperonal (1, GC) and 3,4 methylenedioxycinnamaldehyde (6).
Aqueous KMn04 in THF results less byproducts.



[Edited on 3-8-2019 by Mush]

Mush - 5-7-2020 at 12:02

Odorographia a natural history of raw materials and drugs used in the
perfume industry intended to serve growers manufacturers and consumers.

John Charles Sawer, 1892, London

Artificial Heliotrope

Piperonal, C8H6O3, , commercially known as " Heliotropine,"
has a very agreeable odour very much like that of heliotrope. The
starting-point in its manufacture is Piperine, C17H19O3. Ground
pepper, preferably the white Singapore pepper, as it contains the
largest amount of alkaloid (9.15 per cent.), is mixed, with twice
its weight of slaked lime and a sufficient quantity of water; the
solution is then evaporated to dryness on a water-bath and the
powder exhausted with commercial ether, from which the piperine
can be obtained nearly pure on evaporation, in large crystals of a
faint straw-yellow colour. To obtain it perfectly pure, it must be
dissolved in alcohol and re-crystallized. Another process of
preparing piperine is to exhaust the pepper with alcohol of sp. gr.
0*833 and distil the tincture to the consistence of an extract.
This extract is to be mixed with potash-lye, which dissolves the
resin and leaves a green powder; by washing this in water, dis-
solving in alcohol, crystallizing and re-crystallizing, it is obtained
colourless *. *Poutet, Journ. de Chim.Med. i.p. 531.

Piperine is converted into potassium piperate by boiling it for
24- hours with its own weight of caustic potash and from 5 to 6
parts of alcohol in a large retort, using an inverted Liebig's
condenser. On cooling, the potassium piperate crystallizes out in
shining yellow laminae. It is washed with cold alcohol and
re-crystallized from hot water. If coloured, it is bleached by animal
charcoal. As thus obtained, it is in nearly colourless crystals,
which become yellow under the influence of light.
One part of potassium piperate is dissolved in from 40 to 50 parts
of hot water, and a solution of 2 parts of potassium permanganate is
gradually poured into the hot liquid with constant stirring. Each
drop of the latter is almost instantly dissolved, and the solution
acquires a very pleasant odour. A pasty mass of brown manganic
hydrate separates, which is placed on a filter and washed with hot
water until the washings cease to smell of heliotropine. These
washings are added together and the whole distilled over an open
fire. The first portions of the distillate contain the largest
proportion of piperonal, the greater part of which crystallizes out
on cooling. The remainder may be obtained by agitation with
ether *. * Chemiker Zeitung, Feb. 1884, and Ann. Ch. Pharm, clii. p. 35.

Piperonal crystallizes from water in colourless, transparent,
highly lustrous prisms, an inch long. It is sparingly soluble in
cold water, easily in cold alcohol, and in all proportions in boiling
alcohol or ether. It melts exactly at 37° and boils without
decomposition at 263°, forming a vapour which has a sp. gr. of 5.18+.
Tiemann and Haarmann state" that the odour of piperonal is
possessed by 'vanillon' a kind of vanilla, which forms thick, fleshy
capsules and is obtained from the West Indies. This sort of vanilla
is employed in perfumery for the preparation of essence of
heliotrope; it contains no piperoral, but vanillin and an oil which
is not yet identified. The perfumers, in preparing essence of
heliotrope, add a little of this oil to the extract of vanillon. If a
little be added to a solution of pure vanilllin, both substances can
be recognized by their smell for some time, but after standing for
months the mixture acquires the smell of heliotrope."
The perfume of " Heliotropine " is completely destroyed by the
action of direct sunlight; it is also injured by heat; it should
therefore be stored in a cool place in the dark, such as a cool cellar,
and be kept in yellow glass bottles, the yellow glass intercepting
the chemical rays.

Attachment: heliotropine, piperonal John Charles Sawer, 1892, London, pages 187-189.rar (637kB)
This file has been downloaded 410 times

Mush - 5-7-2020 at 12:41

A practical treatise on the manufacture of perfumery

Carl Deite, William T. Brannt, 1892, Philadelphia

Heliotropin or piperonal is of great importance in
the manufacture of perfumes. It forms small, colorless
prismatic crystals, which have an agreeable odor of
heliotrope. Upon the tongue heliotropin produces the same
sensation as oil of peppermint under the same conditions,
the sensation being, however, more lasting. It melts at
about 104 F., and volatilizes at a higher temperature
without leaving a residue. It is soluble in alcohol and
ether, and insoluble in cold water ; in hot water it melts
to an oily liquid which floats upon the water.

Exposed to the action of heat and air, heliotropin
acquires an uncomely appearance, balls together and, under
very unfavorable circumstances, turns brown. It is
then entirely decomposed and useless, and, hence, should
be kept in summer in as cool a place as possible. A
temperature of 95 F. has already an injurious effect
upon the perfume, and it is best not to buy it at all in
the hot summer months. To preserve the perfume in
its entire freshness, it is advisable for consumers in hot
climates to at once dissolve the heliotropin in alcohol
and to keep the solution in a cool place.

Pepper serves as the initial point for heliotropin or
piperonal, the white variety being the best for the purpose.
To obtain piperine, contained in varying quanties
(7 to 9 per cent.) in pepper, the latter is repeatedly
extracted with boiling alcohol. The extract is then
evaporated to one-third its volume, or the greater portion
of the alcohol is distilled off, and the resinous mass,
obtained after the addition of water, is repeatedly washed
in water with the addition of a small quantity, of potash
or soda lye, dissolved in alcohol and purified by repeated
recrystallization. To convert the white-yellow piperine
thus obtained into potassium piperate it is, together with
equal parts of potassium hydroxide and 5 to 6 parts of
alcohol, kept gently boiling for 24 hours in a well-closed
flask provided with an ascending Liebig cooler. A
capacious flask should be used, as the mass pounds quite
vigorously. After cooling, the precipitate, which is
obtained in yellowish, lustrous lamina, is separated through
a filter from the dark-brown mother-lye, washed with
cold alcohol and several times recrystallized from hot
water. A further discoloration may be effected by the
addition of animal charcoal.

The potassium piperate thus obtained forms nearly
colorless prisms in verucose groups, which, however,
turn yellow when exposed to light. By boiling the
alcoholic mother-lye with 1/3 of the previously used potash-
lye, further small quantities of potassium piperate may
be obtained.

To obtain piperonal from the potassium piperate,
dissolve 1 part of the latter in 40 to 50 parts of hot water,
and then slowly introduce, with constant stirring, a
solution of 2 parts potassium permanganate in 50 parts of
water. This precaution is absolutely necessary, as
otherwise the piperonal formed would be partially further
oxidized and lost. The paste-like mass formed is passed,
while still hot, through a straining cloth, and the residue
repeatedly washed with boiling water until it shows
nothing more of the characteristic odor of heliotrope.
The wash-waters are combined with the first filtrate,
and subjected to distillation over a free fire.

The first distillates are richest in piperonal, it
generally separating already in the cooler. The fractionally
caught distillate is allowed to stand one or two days in
as cool a place as possible, whereby the greater portion
of the piperonal separates in a crystalline form or in fine
lamina. To obtain the piperonal still remaining
dissolved in the water, the mother-lye, after the separation
of the crystals through a filter, may be repeatedly
agitated with ether, whereby the piperonal dissolves in the
ether. The latter is carefully distilled off at as low a
temperature as possible (104 to 122 F.) in the water-bath
or allowed naturally to evaporate.

A practical treatise on the manufacture of perfumery 1892 Piperonal See page 193.djvu

Attachment: A practical treatise on the manufacture of perfumery 1892 Piperonal See page 193.part1.rar (3MB)
This file has been downloaded 544 times
Attachment: A practical treatise on the manufacture of perfumery 1892 Piperonal See page 193.part2.rar (3MB)
This file has been downloaded 412 times
Attachment: A practical treatise on the manufacture of perfumery 1892 Piperonal See page 193.part3.rar (3MB)
This file has been downloaded 423 times
Attachment: A practical treatise on the manufacture of perfumery 1892 Piperonal See page 193.part4.rar (2.1MB)
This file has been downloaded 428 times


Attachment: heliotropine, piperonal A practical treatise on the manufacture of perfumery 1892 pages 193-195 .rar (1.5MB)
This file has been downloaded 528 times

[Edited on 5-7-2020 by Mush]

Mush - 4-3-2023 at 15:31

:D Fab lab videos, aint the best lab practice everywhere but all in all super cool .
SBO Lab A Piperonal Synthesis Phase 1 Part 1 Extraction of Piperine from White Pepper
https://www.youtube.com/watch?v=mgGpQZIxZ6E&list=PLlPqsv...

SBO Lab A Piperonal Synthesis Phase 1 Part 2 Piperine Recrystallization
https://www.youtube.com/watch?v=w_I8k71UyyY&list=PLlPqsv...

SBO Lab A Piperonal Synthesis Phase 2 Part 1 Piperine Hydrolysis
https://www.youtube.com/watch?v=E3Tgs8c-eCs&list=PLlPqsv...

SBO Lab A Piperonal Synthesis Phase 2 Part 2 Vacuum Distillation of Piperine Hydrolyzate
https://www.youtube.com/watch?v=7lhZDfgLsE8&list=PLlPqsv...

SBO Lab A Piperonal Synthesis Phase 2 Part 3A Acidification of Potassium Piperinate to Piperinic Acid
https://www.youtube.com/watch?v=KIOe9r4GGxU&list=PLlPqsv...

SBO Lab A Piperonal Synthesis Phase 2 Part 3B Acidification of Piperidine - Piperidinium Hydrochloride
https://www.youtube.com/watch?v=bctxAvckn-Y&list=PLlPqsv...

SBO Lab A Piperonal Synthesis Phase 2 Part 3C Vacuum Distillation Piperidinium Hydrochloride Solution
https://www.youtube.com/watch?v=OMC8Jv3ltgU&list=PLlPqsv...

SBO Lab A Piperonal Synthesis Stage 3 Oxidation of Piperine to Piperonal
https://www.youtube.com/watch?v=9hNvW6nY3pU&list=PLlPqsv...

From 1,85 g piperic acid the yield was 0,26 g crude (13,8%) piperonal.

clearly_not_atara - 4-3-2023 at 16:25

The video is some 28 minutes long, so hopefully you can forgive the stupid question: it says oxidation of piperine to piperonal, does it not? Not piperic acid? But then why the hydrolysis?

DraconicAcid - 4-3-2023 at 16:26

I see that they have similar results from trying to recrystallize piperine. Goopy oil. Again.

Mateo_swe - 6-3-2023 at 02:44

You can oxidize piperine to piperonal using an ozone generator supplied with oxygen from a oxygen concentrator.
In another stinging insect forum one can read all about it.
It will make peroxides (explosion hazard) so caution must be taken until the bisulfite adduct has been separated, then its peroxide free.
Use peroxide test strips.
Both piperine and styrene is working well.

But it would probably be easier (and also less dangerous) starting from vanillin, de-metylate with AlI3/DMSO to protocatechuic aldehyde then methylenate to piperonal.

DraconicAcid - 6-3-2023 at 23:20

Quote: Originally posted by Mateo_swe  

But it would probably be easier (and also less dangerous) starting from vanillin, de-metylate with AlI3/DMSO to protocatechuic aldehyde then methylenate to piperonal.


One thing that occurred to me is that one could react said aldehyde with dibromoethane and get a six-membered ring. The resulting benzodioxancarbaldehyde doesn't seem to be very common in organic chemistry, which is kinda surprising to me- I thought six-membered rings were the most stable ones.

https://www.sigmaaldrich.com/CA/en/product/aldrich/264598

Anyone know anything about this compound, or why it's not so common?

clearly_not_atara - 7-3-2023 at 09:29

The amphetamines with that ring (affectionately "EDMA") do not produce the desired effect.

Quote:
You can oxidize piperine to piperonal using an ozone generator supplied with oxygen from a oxygen concentrator.

As I was mentioning on the last page, it would seem desirable to use ozonolysis on potassium piperate, in water (the sodium salt is poorly soluble), rather than on piperine, in a flammable organic solvent, since water is much less likely to explode. It is still important to consider that ozone is an extremely dangerous gas.

[Edited on 7-3-2023 by clearly_not_atara]

DraconicAcid - 7-3-2023 at 11:54

Quote: Originally posted by clearly_not_atara  
The amphetamines with that ring (affectionately "EDMA") do not produce the desired effect.


While that is a fair point, it's also worth noting that amphetamines are not the only reason to do organic chemistry. The 6-membered version doesn't seem to appear in natural products, and doesn't even have a cool trivial name.

For the record, I want to find things that smell cool, or can be used as unknowns in my organic lab. (Admin won't let me buy piperonal.)

clearly_not_atara - 7-3-2023 at 21:03

I suppose it's also notable that the unsubstituted dioxane is a carcinogen, and the dibenzo-fused version is none other than the infamous dibenzodioxin, so the remaining benzo[b]dioxane is not from a very reputable family of rings.

EDIT: Ring fusion notation was misinterpreted as bold

[Edited on 8-3-2023 by clearly_not_atara]

DraconicAcid - 7-3-2023 at 21:25

Also a fair point, but the infamously toxic dioxins are all chlorinated. Most of the references I've found to the aldehyde are about it being tested as an anti-inflammatory.

I'm just surprised that it never shows up anywhere.

[Edited on 8-3-2023 by DraconicAcid]

andyloris - 8-3-2023 at 05:36

Some derivatives of benzodioxane are used as pharmaceuticals such as piperoxan which was also the first antihistamine to be discovered.

Jenks - 8-3-2023 at 17:03

Quote: Originally posted by andyloris  
Some derivatives of benzodioxane are used as pharmaceuticals such as piperoxan which was also the first antihistamine to be discovered.

Interesting, but Wikipedia says about it:

"Piperoxan and analogues themselves were not clinically useful due to the production of toxic effects in humans and were followed by phenbenzamine (Antergan) in the early 1940s, which was the first antihistamine to be marketed for medical use."