Asarone epoxidation by Oxone

[Chromic]

100mmol of asarone reacted in the usual oxone manner, gave some 70mmol of sweet smelling, very crude viscous brownish-orange epoxide that was turned into ugly brown tar by H2SO4 hydrolysis that yielded nothing when trying to form the bisulfite adduct.

Moral: buffered oxone might work (although it undergoes numerous side-reactions) as it does have that usual epoxide smell (sort of like barq's creamsoda or rootbeer?), but boiling asarone epoxide in H2SO4 is a sure way to get a nasty tar.

I've got doubts about using LiI, LiBr or MgBr2 to rearrange the epoxide (which obviously contains much gunk), but who knows.

[Rhodium]

Try thermal rearrangement by distilling the crude asarone epoxide with low or no vacuum.

[Chromic]

At 60mmHg, should I expect the ketone coming over at ~230C?

Can you give any links to thermal rearrangement working with isosafrole epoxide or anethole epoxide?

[uemura]

100mmol of asarone reacted in the usual oxone manner, gave some 70mmol of sweet smelling, very crude viscous brownish-orange epoxide that was turned into ugly brown tar by H2SO4 hydrolysis that yielded nothing when trying to form the bisulfite adduct.

Chromic, the reason why Uemura takes for asarone different routes than for the other propenylbenzenes is easy: asarone (and most of its derivates) are very very acid sensitive.  You just got a victim of this fact. And you made the right to proposal to follow: rearrangement by EtOAC/LiBr! Uemura would first destille the crude epoxide in the highest possible vacuum you can achive, not going over 170DegC. Make sure you get rid of any acid trace in the crude product. (170DegC temp should be on the save side before the thermal rearragment may start)
OR
Slowly heat the crude product and hope that about 200DegC the thermal rearragement takes place. Uemura would do this first with a small amount of the crude product in a test tube, slowly heated in an oil bath.
Let us know on the outcome!

Carpe Diem

[Chromic]

Some of the epoxide residue was saved, and some of the epoxide that that was attempted to be formed with NaOCl-water/KOH-IPA was saved. I'll pass along the results of what's in the reaction products.

[boppesz]

Could somebee explain to me why asarone and anethole are that much acid-sensitive? I can't hardly believe that the differences in acidsensitivity between asarone and safrole are that much. When asaron/anethole-epoxides can't be rearranged with H2SO4 coz they decompose, safrole has to do this but maybe in lower extents. So if I understood everything right: safroleepoxide can be rearranged by H2SO4 to ketone, but anethole/asaroneepoxide has to be rearranged with a lithiumsalt in EtOAc? How about the epoxides from myristicin, (dill)apiole and elemicin?

[Rhodium]

Yes, your observations for asarone is correct, but not for anethole. The latter is not acid-sensitive. It seema like the problem with asarone lies in the 2,5-oriented methoxy groups of the propenylbenzene, making di/polymerization reactions possible (my theory as indicated by other texts, this is not an absolute proof).

[Chromic]

My guess is that the side chain becomes increasingly activated by addition of more ether subsitution groups. 4-meo- is more stable than 3,4-mdo- which is more stable than 2,4,5-tmo-.

Rearranging anethole epoxide in h2so4 works beautifully. I'll let you guys know if rearrangement by heat works well for this group as well.

[uemura]

Chromic,
you are doing good work    Keep us informed on the asarone topic. Uemura will try this weekend another batch of the H2O2/MeCN epoxidation of anethol but he will isolate the epoxide prior to go ahead. Results will be posted. Check out Uemuras Houben-Weyl investigation in the novel discourse Ccarpe Diem

[boppesz]

Okay. According to rhodium the 2,5 position is MAYBE responsible for the instability. According to Chromic is has to do with the numbers of methoxy's. Both sound reasonable to me. If chromic is right, then the relative low conversion of safroleepoxide to ketone is due to the methylenedioxy. So when safroleeopxide is coverted to the ketone, there will allways form some dimer/polymer/tar?

Chromic: do you think a methylenedioxy is more or less activating than 2 methoxy's? I think less. Anaway, if chromic is right, EtOAc/LiBr is allways preferred above H2SO4, maybe except for anethole. Am I right? If it has only to do with the 2,5 position of the methoxy's, than myristicin and elemicin are not acidsensitive, whilst apiole and dillapiole are. So the performicacid procedure won't work also for asarone, apiole and dillapiole? I hope only Rhodium is right, orherwise only safrole and anethole can be used in the performic acid procedure and then I have to look for some other procedure for the oxidation of all the other precursors and that would be a pity cpz I don't have the reagents for that.... we struggle on.

[uemura]

It's in Uemura's opinion more the positions than the number of methoxy groups. The 2,4,5 trimethoxy derivates from asarone are much more a 'problem' than the 3,4,5 trimethoxy derivates. All mescaline published synthesis never reported acid sensitive problems with compounds, but with tma-2 they do.

[boppesz]

So there should be one problem left: the oxidation of (dill)apiole with performic acid. Has anybee ever did the performic acid procedure on (dill)apiole? Maybe you think: try it out yourself but I only have a 60 ml (dill)apiole and I don't want to waste it.

[Rhodium]

The modified performic works all right on dillapiole, but for some reason, some DMP2Pol is formed in the H2SO4 rearrangement. This is probably not an ansolute truth, it seems like Sonson who performed the experiment did not allow the epoxidation to go on long enough, so some isodillapiole was still present in the post-reaction mixture, and this was hydrated to the alcohol by the sulfuric acid.

See

Post 208300 (missing)

(Sonson: "2,3-DM-4,5-MD-P-2-P", Methods Discourse).

[boppesz]

Wow what a coincedence Rhod, I just read in our bible that it is possible to oxidize apiole with the performicacid procedure. Than is your theory about the 2,5 position not wholy true. But what do ya mean with "some"?  It's a bit strrange that he collected 155 g dillapiole from 200 grams of oil as dillseed oil only contents 10 %

[Rhodium]

The dillseed oil he used was not the whole natural one, but from a company selling a fraction of the whole oil enriched in the dillapiole fraction, much like camphor oil is sold in different fractions with safrole amounts varying between 0-90%.

[boppesz]

Should I somehow can get the name of this suplier. Maybe you can mail it to me? Or isn't that allowed? Or am I even not allowed to ask this here? Sorry then.

[Rhodium]

Correct, asking for suppliers is not appreciated here, and sharing of suppliers expressively prohibited.

Besides, the supplier in question does not supply that particular oil any longer.

[catastrophe]

Will oxone work for all propenyl benzenes? It seems the only trouble Chromic is having is rearrangement of the epoxide, but he did indeed create the arasone epoxide using oxone. Other propenyl benzenes shouldn't have this problem when it comes to H2SO4 rearrangement to ketone, correct??

[Rhodium]

Catastrophe: Yes, it should work on all propenylbenzenes (and probably even allylbenzenes). The non-asarone propenylbenzene epoxides should be all right to rearrange with H2SO4, and all allylbenzene and propenylbenzene epoxides should be rearrangeable to P2P's with LiI.

[Chromic]

It should work, but weird things happened with asarone when trying to form the epoxide. I got a very odd viscous tar. The alkene group had completely reacted. I wonder if one should decrease the molar excess of Oxone (which is 2mol KHSO4 to 1mol alkene in the writeup, maybe something like 1.3mol KHSO4) when running it on asarone.

And uh, I post some info in Uemura's thread in Novel Discourse that would be best put here (sorry about that, I'm sure this is old info to bees who read -every- thread):

When the oxone reaction on asarone was attempted, the H2SO4 rearrangement seemed to chew the molecule apart, when NMR was run on the epoxide, it showed some interesting, but confusing info. It indicated that the methoxy groups were not cleaved by the oxone (good news, apparently oxone can do this in certain conditions), and the benzene group was not affected either. It also showed that the E-olefinic group was gone, and it looked as if there was some E/Z action going on (chiral centers in the epoxide), but the multiplicity did not work out correctly (the hydrogen containing one of the epoxide links, alpha to the methyl does not have the correct mulitiplicity). Something odd is going on. I'm going to tell my friend to run an anethole/oxone reaction (which I know works) to figure out if the same sort of spectra is generated. If not, then more tweaking of the oxone reaction will be needed for asarone.