uemura (Hive Bee)
04-22-01 08:14
No 185841
      Epoxide Rearrangement Results  Bookmark   

On Rhodium's page there is around a procedure from Osmium 1] how to convert isosafrol to its methylketone. Here are two results for anethole and asarone using Osmiums approach (slightly modified) hoping to increase the intellectual honey of the hive bees.

The procedure is a two step reaction, first preparing the epoxide, which is then re-arranged to the ketone via a Lewis acid in EtOAc.

Step 1: Epoxide
10ml of the propenylbenzene (anethole/asarone) are added to 150ml of a 1:1 mix of MeOH and MeCN. 1.1 mol (based on the olefin of course) 30% H2O2 saturated with Na2CO3 is added at room temp over 20 minutes under stirring. After addition is completed, the mix is stirred at rt for 24hours 2]. The MeOH/MeCN solvent is removed by vac dest (approx 100Torr) using a waterbath with 40-45DegC 3]. The remaining residue is taken up with ether, washed with water and dried with MgSO4. Evap of the ether (waterbath with 40-45DegC) gave a clear light yellow oil. (for anethole and asarone).

Step 2: Rearrangement
The oil is added to 150ml EtOAc and 1.9g LiBr is added. The Ethylacetate is refluxed for 24hours 4]. Then the EtOAc is washed with water, dried with MgSO4 and evaporated.

Anethole: a slighly red viscous oil remained. Bisulfit test positive, so all of the residue is treated with a concentrated bisulfite solution, the whole stuff gave a heavy cristall mass 5], which was vac filtered washed with cold water, EtOH and dried. Yield about 80% bisulfite compound.

Asarone: a deeper brown oil remained. Bisulfite test negative! The residue was therefore vacuum destilled and at 160-165DegC under 6Torr 4-5ml of a green viscous oil destilled over. In the flask a deep red oil remained. The green destillate did give a negative bisulfite test as well (green color disappeared!). The green oil can be washed away from the glasware with hot water.

Big question: what have happened here?

1] http://rhodium.lycaeum.org/chemistry/safrolepoxide.html
2] After an hours or so, the yellow color of the asarone has disappeared. Solvent mix is water clear at this time.
3] The mix of MeOH and MeCN is recovered and can be re-used next time. This is an advantage with respect to Osmiums procedure.
4] The use of MeCN instead of EtOAc as mentoined in an US patent gave only 50% yield in case of the anethole.
5] Use a bottle with a wide stopper, otherwise you can't remove the compound!

Carpe Diem
(Chief Bee)
04-22-01 15:46
No 185901
      Re: Epoxide Rearrangement Results  Bookmark   

This sounds VERY interesting. Could you perhaps verify the reaction by aminating the ketones?

(Hive Bee)
04-23-01 12:59
No 186125
      Re: Epoxide Rearrangement Results  Bookmark   

Yes, interesting because it worked fine with anethole but failed(?) with asarone. Uemura is pretty sure that he got the methylketone of anethole. But what is the green oil? Is it the diol? And why does the green color disappear when it is shaked with bisulfite solution?
Have any bees an idea what green oil boils at 160DegC under 6 Torr.
What other (simple) tests could be done?

Carpe Diem
(Stoni's sexual toy)
04-23-01 13:19
No 186130
      Re: Epoxide Rearrangement Results  Bookmark   

Haloform reaction? Other derivatization maybe?
Or you could try to purify it by recrystallization from a NP solvent like hexane. TMP2P is a solid when pure (MP around 40C). And compare it to authentic TMP2P, e.g. made by reduction of TMPNP. Mixed melting points, TLC etc should give you a pretty good idea if it is the same stuff. But all that is lots of difficult and time consuming work, so I suggest you rather concentrate on the asarone first and investigate that stuff. Maybe do another bigger batch so you have enough material to work with and you can verify it really works.
Once it works for anethole and maybe some other propenylbenzenes (you don't have access to isosafrole?) the reaction can still be fine-tuned for asarone.