Ketones from Propenylbenzenes via the di-bromides

[uemura]

Rhod,
You said

If you make the 2,3-epoxide, it can be rearranged to MDP2P using LiI, LiBr and MgBr2 (among other reagents), but if it is subjected to the regular isosafrole treatment, there is a big risk that undesired aldehydes are formed instead.

Do you mean by 'regular treatment' the rearrangement of the (2,3) epoxide using H2SO4? Or the whole peracid / rearrangement process applied to safrol?

[Osmium]

H2SO4.

[Vibrating_Lights]

So what we gonna do here is throw some iso into some DCM throw that in the bucket then throw some bleech in the bucket.  then take a big glass broomstick and start stirring.  whiles't yous's stirrin start droppin Hcl in.  when the cl that did not go into the dcm makes you feel like you gonna die you stop and.  then take your DCM layer and remove the DCM and then put the product in some acetone and a little water and some marble hest it a bit then extract with Dcm distill and reflux product with KOH to get the epoxide.  which an be rearranged with H2SO4.  That sounds more kick ass than a peracid.  how long yall reckon you would have to stirr the iso cl mix.

[Rhodium]

This sounds lethal.

[Chromic]

Rhod, it doesn't sound that bad. I think I'm going to try it (mind you, uhh... I think I'm going to try and use something more elegant than a bucket and a broomstick... lol), I'll let you know how it goes in

Post 236297

(Chromic: "anethole -> epoxide", Novel Discourse). I also wonder why no one has investigated this route... and I don't get why no one has investigated the route to the diol by slowly dripping in a concentrated solution of KMnO4.

[Rhodium]

Chromic: Your proposal sounds great, I was referring to VL's suggestion of mixing HCL and NaOCl in a bucket...

[Vibrating_Lights]

the remark about the bucket was going along with the mental picture that VL_ had of a one tooth hilbilly thinking he could make some drugs by simply reading this post and killing himself in the proscess.  This came right after a PM I recieved from someone who asked  "hey man i just want an ez recipee from sassafras to Mda in one pot with eazy to find chems and i already Utfse" .  you must notice the attempt at hilbilly dialect.
VL_

[Rhodium]

VL: Don't post aything like that int the future though, okay. We want no hillbilly syntheses around here.

[improv_chem]

Wow!  I just read this thread for the first time and It blew me away! 
So you are saying for sure that If you make the epoxide using say, Oxone/isosafrole,
you can re-arrange it to the ketone by simply distilling it!
That's one less step for SWIM's next dream.  Has anyone here actually done this?
Swim's a little paranoid because of chatter he's heard about epoxides exploading upon heating etc.
What you also seem to be discussing is the possibiltiy of skipping the making of isosafrole and just using your safrole in a Chromic's Oxone rxn or a peracid.
Two steps down would give a two step synth of MDMA from safrole with totally otc. stuff!
Keep it comming!!!!
-improv      
Let's play with nature a little, I'm sure we can make her a little higher....

[Chromic]

AFAIK, safrole will not work in a peracid reaction, I think VL got confused by what Rhod said. I will attempt the rearrangement of anethole epoxide (by forming it thru oxone) to anethole ketone by heat sometime in the near future and report back on it. If that succeeds, I may also try and form asarone epoxide again and instead of an 15% H2SO4 hydrolysis, I'll check out the rearrangement by heat for that compound. I wish I had dry bromine to attempt at forming the dibromide, although I'm sure my lungs are thankful that I don't.

[Vibrating_Lights]

I do not know for sure but i think the temp needed to rearrange the iso epoxide would also decompose it.  Not sure though.  if you try it watch for the temp to jump as the epoxide is converted.
Rohd Sorry about the hilbilly post  sometrimes i forget who all reads these.

[Chromic]

Btw, an oxone reaction on asarone was attempted. Although the H2SO4 rearrangement chewed 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, 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.

[uemura]

Good to know that such old stuff catches the interest of the hive bees .

Now, Uemura had a nice afternoon in his library and of course checked the Houben-Weyl reference which was provided by Otto. In the volume VII/2a Ketones, on page 934 he indeed found the section on thermal rearrangement. Unfortunately, the examples given there are not for asarone, but cite the experimental details of the Höring paper for isosafrole.

So, the precise mp of the asarone ketone is still a mystery and there is no literature reference so far what epoxide rearrangement method is applicable to arrive at it. Uemura, Chromic and hopefully other bees will continue to explore the possibilities to end up with the asarone ketone.

Nevertheless Uemura provides two tables from the Houben-Weyl section which talks about acid and thermal rearrangement of 2,3 glykols and epoxides. The Houben-Weyl is in German, but the tables shouldn't be a problem to be 'decoded'. There are also some non-german references Uemuras library doesn't have, perhaps some interested bee may consult the cited articles.



"Umlagerung" = Rearrangement
"Kochen" = "Cooking" aka Boiling
Carpe Diem

[cilliersb]

This just mean that you can follow the oxone route to Asarone Epoxide and do the rearrangement with ALCl3.

This = Ketone
Ketone + AL / Hg = Smangled beez!

HeHe

[Rhodium]

AlCl3 probably wouldn't be good, as it is such a strong lewis acid that it attacks the aromatic methoxy groups. You need to use a less active one, preferably LiI.

[cilliersb]

I can make My LiI from Li and I2 right, but how?

[Rhodium]

The direct reaction between the two elements are probably too violent and crude, so I would suggest that you slowly dissolve your lithium in methanol to form Lithium methoxide, and when it has all reacted and the solution cooled down, you add an equimolar amount of hydriodic acid solution (can be made from I2, see my page) dropwise to get a solution of lithium iodide.

Then the solvents are evaporated under vacuum in a flask situated in a boiling water bath to give crude lithium iodide. The lithium iodide is then recrystallized from boiling acetone (or from boiling water, using 0.5ml per gram LiI, followed by cooling in a freezer, preferably below -20°C to precipitate it all), filtered, and dried in a vacuum desiccator over phosphorous pentoxide for 1h at 60°C followed by 1h at 120°C (lithium iodide is extremely hygroscopic, so it must be rigorously dried to remove all the water).

Methanol is used to dissolve the lithium, because the reaction between lithium and water is too violent. The purification procedure is from a textbook, I don't know how much it can be simplified and still get a usable product. H2SO4 may substitute for the P2O5, and maybe the vacuum can be omitted, but I believe the dessiccator (or a ghetto version thereof) is a must. Could anyone comment on this idea?

[lugh]

Lithium iodide can be prepared in a quantitative yield by reacting iodine with lithium hydride in ether solution [JACS 77, 1507-8 (1955)]; lithium hydride may be formed by the action of molecular hydrogen on molten lithium [Ann Chim Phys 2, 273 (1874)], and may also be precipitated by the reaction between lithium methyl and triphenyl tin hydride in ethereal solution under nitrogen [JACS 75, 3592-3 (1953)]. Lithium iodide can also be prepared by more bee friendly but unreferenced methods ie neutralization of the hydroxide or carbonate with hydriodic acid, or by neutralization of lithium sulfate with barium iodide, followed by filtration of the barium sulfate.

[Rhodium]

Repost of an old Osmium post:


Asarone dibromide:

1) from asarone and Br2 in CS2
    Chem. Ber. 39, 1906, 2420
2) Br2 and CCl4
    Chem. Ber. 17, 1884, 1160
3) Br2 and pet ether
    Gazz. Chim. Ital 40 I, 1910, 114

Isosafrole dichloride:

1) CCl4 and Cl2
    Chem. Ber. 42, 1909, 263
2) Et2O and Cl2
    same ref.

Isosafrole dibromide:

1) Et2O and Br2
    Chem. Ber. 38, 1905, 2719
2) Br2 and pet ether
    Arch. Pharm. 248, 1910, 166
3) Br2 and CS2
    J. Chem. Soc. 105, 1914, 1971

[sunlight]

Lithium hydroxyde and lithium carbonate are not expensive.