Sciencemadness Discussion Board

oxidizing limonene to carvone/carveol

gardenvariety - 2-4-2011 at 08:49

Wikipedia makes a comment that limonene "oxidizes easily in moist air to produce carveol and carvone", but does not have a source for that. Does anyone have any thoughts on oxidizing/hydroxylating terpenes, cyclic or otherwise, that could be perhaps edge this idea closer to a mechanism?

[Edited on 2-4-2011 by gardenvariety]

[Edited on 2-4-2011 by gardenvariety]

Random - 2-4-2011 at 10:47

The most widely practiced conversion of limonene is to carvone. The three step reaction begins with the regioselective addition of nitrosyl chloride across the trisubstituted double bond. This species is then converted to the oxime with base, and the hydroxylamine is removed to give the ketone-containing carvone.

Reactions with carvone: MPV reduction using propan-2-ol and aluminium isopropoxide effects reduction of the carbonyl group only to provide carveol (5); a combination of sodium borohydride and CeCl3 (Luche reduction) is also effective.

from wikipedia

blogfast25 - 2-4-2011 at 10:50

Not sure about carveol and carvone but similar (also a terpenoid) to these is alfa-terpineol, which can also be synthesized from limonene by reaction with trifluoroacetic acid (followed by de-esterification) (see link).

Any particular reason for the interest in carvone?

gardenvariety - 2-4-2011 at 17:32

Yes, I saw the nitrosyl reaction. I'm more specifically interested in mechanisms that could oxidize from air, or otherwise mild conditions. The win here would be a reaction that can oxidize the limonene in oils like caraway or spearmint (half limonene, half carvone) into carvone without those reaction conditions destroying the carvone as well. It would be, I expect, easier to purify a 90% fraction than a 50% fraction.

Random - 3-4-2011 at 01:14

Cold you just put limonene into aqua regia and then add a base to convert it to the oxime? I think carvone wouldn't get destroyed as it wasn't yet formed.

spong - 3-4-2011 at 02:11

I've been wanting to make carvone from limonene for a while but can't find the nitrite to make the nitrosochloride. I don't think an air oxidation would be feasible though. You could however separate the carvone from the mix of chemicals in spearmint oil with the H2S addition product (something I'm now going to do instead).

blogfast25 - 3-4-2011 at 07:40

Much of organic chemistry is a bit of a distant haze to me, I'm afraid. So bear with me and can someone explain why when oxidising limonene (to carveol or carvone) the attack seems to be on the cyclohexene ring and not on the double bond of the dangling 1-methylethenyl group? When using trifluoro or trichloroacetic acid, it’s that latter double bond that’s attacked…

Random - 3-4-2011 at 12:20

Quote: Originally posted by spong  
I've been wanting to make carvone from limonene for a while but can't find the nitrite to make the nitrosochloride. I don't think an air oxidation would be feasible though. You could however separate the carvone from the mix of chemicals in spearmint oil with the H2S addition product (something I'm now going to do instead).


You need nitrosyl chloride, the product of aqua regia, not nitrosochloride.

starman - 3-4-2011 at 17:15

Dye sensitised photo oxidation of limonene with O2 leads to limonene hydroperoxides.Reduction of these (Sodium sulfite) leads to a mixture of menthadienols.Limonene peroxides can form explosive mixtures,so caution is required.I doubt you will find a useful route to carvone or carveol.Wiki can be kind of incomplete and misleading.

[Edited on 4-4-2011 by starman]

spong - 3-4-2011 at 19:56

Quote: Originally posted by Random  
Quote: Originally posted by spong  
I've been wanting to make carvone from limonene for a while but can't find the nitrite to make the nitrosochloride. I don't think an air oxidation would be feasible though. You could however separate the carvone from the mix of chemicals in spearmint oil with the H2S addition product (something I'm now going to do instead).


You need nitrosyl chloride, the product of aqua regia, not nitrosochloride.


I meant the limonene nitrosochloride, using EtONO, I don't think making the nitrosyl chloride from aqua regia would work, wouldn't the chlorine also produced interfere? I've attached the article I was wanting to follow (don't have pyridine though :()

Attachment: ed057p741.pdf (1.6MB)
This file has been downloaded 1338 times

[Edited on 4-4-2011 by spong]

roamingnome - 4-4-2011 at 18:29

nitrosyl chloride can be made by passing NO2 over KCl or NaCl


Formation of nitrosyl chloride from salt particles in air
Environ. Sci. Technol., 1974, 8 (8), pp 756–758
DOI: 10.1021/es60093a015
Publication Date: August 1974

4 M H+, NO2 reacts with Cl- to produce nitrosyl chloride (ClNO).
Removal of Chloride from Acidic Solutions Using NO2
Ind. Eng. Chem. Res., 2007, 46 (8), pp 2372–2376
DOI: 10.1021/ie061167p

cheeseandbaloney - 4-4-2011 at 20:45

Quote: Originally posted by blogfast25  
Much of organic chemistry is a bit of a distant haze to me, I'm afraid. So bear with me and can someone explain why when oxidising limonene (to carveol or carvone) the attack seems to be on the cyclohexene ring and not on the double bond of the dangling 1-methylethenyl group? When using trifluoro or trichloroacetic acid, it’s that latter double bond that’s attacked…


Hmmm, I was thinking the same thing. Puzzling. Also, why is tri(halogen)acetic acid always quoted when doing this acid-catalyzed hydration? I see the more common sulfuric acid's lower pKa working just as well...

blogfast25 - 5-4-2011 at 07:11

cheeseandbaloney:

The choice of trihaloacetic acids is usually explained by their protonating capability (pKa, essentially). I've also seen recipes calling for glacial acetic acid...

And in a current experiment I'm trying (following a recipe) to hydrate alfa pinene (source = turpentine) to terpin hydrate using dilute H2SO4 as catalyst...

Nicodem - 5-4-2011 at 11:06

Quote: Originally posted by blogfast25  
Much of organic chemistry is a bit of a distant haze to me, I'm afraid. So bear with me and can someone explain why when oxidising limonene (to carveol or carvone) the attack seems to be on the cyclohexene ring and not on the double bond of the dangling 1-methylethenyl group?

The addition of NOCl is an electrophilic addition on the double bond. The mechanism of this reaction determines the observed chemoselectivity. Electrophiles react faster with stronger nucleophiles and in this specific case, the endocyclic double bond is slightly more Pi-nucleophilic (having one more electron donating alkyl group). But the thermodynamic stability of the carbocation formed during the addition of the electrophile also plays a very important role (influences the activation energy of the reaction). In this case, the endocyclic tertiary carbocation is more stabilized due to geometrical restrains that allow for a better stabilization via hyperconjugation. Thus the addition of the nitrosyl chloride on the endocyclic double bond has a lower activation energy than the same reaction on the isopropylidene group.

This would be a formal (simplified) explanation based on basic theory, but is not necessarily exact, neither necessarily true.
Quote:
When using trifluoro or trichloroacetic acid, it’s that latter double bond that’s attacked…

Can you give us the reference where the electrophilic addition of CF3COOH or CCl3COOH on limonene occurs on the isopropylidene group while leaving the endocyclic double bond intact? I would expect the opposite, that the addition on the isopropylidene group occurs more slowly to give the diester as the end product.

[Edited on 5/4/2011 by Nicodem]

blogfast25 - 5-4-2011 at 13:34

Nicodem:

Sure. This one (courtesy Eclectic) is limonene + trichloroacetic acid ==> alfa-terpineol trichloroacetate:

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S...

Followed by de-esterification.

cheeseandbaloney - 5-4-2011 at 19:26

Quote: Originally posted by blogfast25  
cheeseandbaloney:

The choice of trihaloacetic acids is usually explained by their protonating capability (pKa, essentially). I've also seen recipes calling for glacial acetic acid...

And in a current experiment I'm trying (following a recipe) to hydrate alfa pinene (source = turpentine) to terpin hydrate using dilute H2SO4 as catalyst...



I was curious if there were other factors involved, i.e. solubility and volatility. Like I said, I assume Sulfuric acid's lower pKa should work just as well, and is more accessible to the home chemist.

I might hafta try that myself one day though. I happened to pick up a fractionating column not too long ago and happen to have some turpentine sitting around. I'd be curious to hear your results.

edit:
Quote: Originally posted by Nicodem  

The addition of NOCl is an electrophilic addition on the double bond. The mechanism of this reaction determines the observed chemoselectivity. Electrophiles react faster with stronger nucleophiles and in this specific case, the endocyclic double bond is slightly more Pi-nucleophilic (having one more electron donating alkyl group). But the thermodynamic stability of the carbocation formed during the addition of the electrophile also plays a very important role (influences the activation energy of the reaction). In this case, the endocyclic tertiary carbocation is more stabilized due to geometrical restrains that allow for a better stabilization via hyperconjugation. Thus the addition of the nitrosyl chloride on the endocyclic double bond has a lower activation energy than the same reaction on the isopropylidene group.

This would be a formal (simplified) explanation based on basic theory, but is not necessarily exact, neither necessarily true.


Hey Nicodem! I'm wondering why in the oxidation of limonene to carvone the oxygen attaches to the alpha carbon of the alkene and not to one of the double bonds themselves. Any intermediates I am over looking? I guess I haven't researched reactions like these in a while so I'm a little sloppy. Thanks!

[Edited on 4/6/2011 by cheeseandbaloney]

[Edited on 4/6/2011 by cheeseandbaloney]

Nicodem - 6-4-2011 at 09:13

Quote: Originally posted by blogfast25  
This one (courtesy Eclectic) is limonene + trichloroacetic acid ==> alfa-terpineol trichloroacetate:

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S...

Followed by de-esterification.

That's would be quite an interesting problem for our "help with mechanisms" sticky thread if I only had the time to review the literature on the electrophilic additions on limonene. Why does the regioselectivity of the different types of electrophilic additions on limonene varies? In principle there should be little difference in the selectivity of nitrosonium attack or protonation. Both electrophiles are too small to blame the steric factors. Their hardness does indeed differ somewhat, but I find it hard that this makes for a huge difference in the observed selectivity. Furthermore, a cursory search indicates that other electrophilic additions on limonene (the Ritter reaction, hydrohalogenation, etc.) also have inconsistent regioselectivity. Personally, I find the chemistry of terpenes and their annoying tendency toward Wagner–Meerwein rearrangements too much for my tranquil chemical life.
Quote: Originally posted by cheeseandbaloney  
Hey Nicodem! I'm wondering why in the oxidation of limonene to carvone the oxygen attaches to the alpha carbon of the alkene and not to one of the double bonds themselves. Any intermediates I am over looking? I guess I haven't researched reactions like these in a while so I'm a little sloppy. Thanks!

Which reaction are talking about? Do you mean the above talked about chloronitrosation? The oxo group comes from the deoximation step and its position is where the less substituted side of the double bond was. The new double bond in carvone comes from dehydrochorination. I still remember this synthesis from my education as it was part of the lab practice (from oranges to carvone). If I remember correctly the reference was from the J. Ed. Chem. or something similar, but I'm sure you can find more references in Ullmann's, because that's where the Wikipedia entry directs.

DJF90 - 6-4-2011 at 12:11

Quote: Originally posted by Nicodem  

Personally, I find the chemistry of terpenes and their annoying tendency toward Wagner–Meerwein rearrangements too much for my tranquil chemical life.


Couldn't have put it better myself. Its annoying when substrates don't behave "as they should", i.e. in a simple and predictable manner.

[Edited on 6-4-2011 by DJF90]

cheeseandbaloney - 6-4-2011 at 17:18

Quote: Originally posted by Nicodem  

Which reaction are talking about? Do you mean the above talked about chloronitrosation? The oxo group comes from the deoximation step and its position is where the less substituted side of the double bond was. The new double bond in carvone comes from dehydrochorination. I still remember this synthesis from my education as it was part of the lab practice (from oranges to carvone). If I remember correctly the reference was from the J. Ed. Chem. or something similar, but I'm sure you can find more references in Ullmann's, because that's where the Wikipedia entry directs.


Yeah, simply my sloppiness of overlooking the chlorine attacking the tertiary carbocation followed by the dehydrochlorination forming another double bond! I was missing the fact that the double bond on carvone is a completely different alkene than the one on limonene. Never seen a chloronitrosation reaction surprisingly. Thanks for the info and clarification.

Eclectic - 7-4-2011 at 08:27

http://pubs.acs.org/doi/abs/10.1021/ed057p741

Actual PDF would be appreciated.

Nicodem - 7-4-2011 at 11:52

I can't make sense of the regioselectivity issue. There seems to be no logic about which electrophilic addition occurs on which double bond of limonene. The only thing that I figured out is that protonation occurs at the exocyclic double bond, while electrophiles other than proton can attack either one or the other. For example, bromomethoxylation occurs selectively at the endocylic double bond while the formylation with the Vilsmeyer reagent occurs at the isopropylidene. The epoxidation occurs again on the endocyclic double bond, and so on and on... see the review article on limonene chemistry (Natural products reports, 1989, 291-309).
Quote: Originally posted by Eclectic  
http://pubs.acs.org/doi/abs/10.1021/ed057p741

Actual PDF would be appreciated.

Yes, that's what we used. Funny how smells bring up so many memories of the old times. Find it attached...

[Edited on 7/4/2011 by Nicodem]

Attachment: Conversion of Limonene to Carvone.pdf (1.6MB)
This file has been downloaded 923 times

kmno4 - 7-4-2011 at 13:48

Similar, but a little simpler procedure (and DMF instead of Py):
Code:
http://www.umich.edu/~chemh215/CHEM216/HonorsCup/hcproposal/231__D.pdf

spong - 13-4-2011 at 00:45

Roamingnome, I never thought of passing NO2 over NaCl, thanks for that. Seeing as the nitrosochloride can be broken down with DMF, perhaps NMP (which I have) could be used here?
I'm going to try the following:
NO2 generator (air pumping into a flask of HNO3 and Cu) passing through a tube of NaCl to form NOCl [roamingnome's ref]. The NOCl can then be bubbled through limonene to form limonene nitrosochloride. The limonene nitrosochloride can then be reacted with EtOLi (t-BuONa was used in the ref I've attached, can't get sodium metal or t-BuOH) giving carvoxime which can then have the usual reaction with H2SO4 performed to give the carvone which will be distilled off.
Does this seem reasonable?
Edit, forgot to attach file.

[Edited on 13-4-2011 by spong]

Attachment: dl carvone.pdf (292kB)
This file has been downloaded 755 times