Chromic (Hive Addict)
11-13-01 20:24
No 236297
      anethole -> epoxide  Bookmark   

Since I have some anethole lying around, I've got some questions:

anethole + NaOCl + H2O -> anethole chlorohydrin + NaOH

1) Does this reaction work? Or is the only way to make the dibromohydrin?
2) What sort of reaction conditions? Does this reaction require a PTC? What temperature?
3) Will the anethole chlorohydrin sponanteously rearrange to form anethole epoxide, ie:

anethole chlorohydrin + NaOH(aq) -> anethole epoxide + NaCl(aq)

or if I'll need to extract with DCM, and react with KOH in IPA so I get:

anethole chlorohydrin + KOH -> anethole epoxide + KCl(s)


C) I'd be better off just pouring the anethole down the drain.
 
 
 
 
    Rhodium
(Chief Bee)
11-13-01 20:33
No 236303
      Re: anethole -> epoxide  Bookmark   

Yes, the reaction should work. "Dibromohydrin" does not exist, you must be talking about the bromohydrin (prep of bromohydrin: ../rhodium/chemistry /asarone.wacker.txt)

I believe the chlorohydrin does not spontaneously rearranges to the epoxide, you probably need concentrated base and heat (read more in the above ref).

Here is more info: http://www.chem.ucalgary.ca/courses/351/Carey/Ch16/ch16-6-ans.html
 
 
 
 
    Chromic
(Hive Addict)
11-13-01 23:55
No 236380
      Re: anethole -> epoxide  Bookmark   

Sorry, I meant "Or is the only way to make the dibromo and then convert to the bromohydrin" and not "dibromohydrin". (I lost a good part of a sentence there.... maybe I experienced a good-sized temporal drift?) smile

50mmol scale alkene, slowly dripping in 34.4g of 10.8% bleach with an additional 110ml water (fast stirring). I'll let you bees know if the alkene changes it's form.
 
 
 
 
    Chromic
(Hive Addict)
11-14-01 00:10
No 236393
      Re: anethole -> epoxide  Bookmark   

This seems to be a fast reaction. The smell of bleach is gone, and there's a whitish slushy liquid (perhaps, even a solid?) at the bottom. I'll let it stir overnight and work it up tomorrow afternoon.
 
 
 
 
    Chromic
(Hive Addict)
11-14-01 19:40
No 236703
      Re: anethole -> epoxide  Bookmark   

This reactions looks too good to be true. I got a quantative yield of epoxide (after KOH/IPA treatment)... there must be a good deal of unreacted alkene... I've got my hopes down.
 
 
 
 
    Chromic
(Hive Addict)
11-14-01 23:16
No 236761
      Re: anethole -> epoxide  Bookmark   

Ok, been reading more about this, came up with a revised procedure:

Using commercially available 10.8% NaOCl (w/w), we will need 4.8g pure NaOCl (65.0mmol, 1.3 mol equiv) in water (containing 0.2M NaOH) to oxidize 50mmol of a substituted alpha-methyl-styrene to its respective epoxide. So the procedure is very simple:

Add 7.4g anethole (50mmol) in 6.0mL DCM to a flask, under vigrous stirring drip in 44.8g bleach containing 0.4g NaOH.

The problem is, I don't have any Jacobsen catalyst but is this only necessary to ensure enantioselective epoxidation? The thing is, I know that this procedure WILL epoxide alpha-methylstyrenes in near quantitative yield (and -not- form the intermediate chlorohydrin), and it's just driving me crazy. This could be a massive leap forward for the hive. crazycrazycrazycrazycrazy
 
 
 
 
    Rhodium
(Chief Bee)
11-15-01 00:04
No 236785
      Re: anethole -> epoxide  Bookmark   

The jacobsen catalyst is only necessary if you want to make a chiral epoxide. We have no use of that for our purposes.
 
 
 
 
    Chromic
(Hive Addict)
11-15-01 02:49
No 236848
      Re: anethole -> epoxide  Bookmark   

So what simple catalysts would work (ie catalysts that are not enantioselective)? I have a feeling that the above procedure just leaves the bleach happily spinning away with the anethole.

Or would it make most sense to try and add the bleach and alkene together, then slowly drip in dilute hydrochloric acid so that the more reactive hypochlorous acid is produced (which should breakdown to free chlorine) and maybe that would form the chloronium ion which would breakdown in the presence of water to form the chlorohydrin?

PolytheneSam seems to have indicated that chlorine (atleast in the presense of a tertianary alkanol) and water will react with olefins.

Suggestions are more than welcome.
 
 
 
 
    Chromic
(Hive Addict)
11-15-01 11:29
No 236957
      Re: anethole -> epoxide  Bookmark   

Ok, I've read a bit more on halohydrins. My organic chemistry book states that usually halohydrins are formed using NXS--but that X2 will also work (even tho it's more dangerous and difficult to handle). It explicitly states that halohydrin formation doesn't take place by direct reaction of an alkene with HOCl (I wish I had read my organic chem book before experimenting), rather the addition is done indirectly by the reaction of the alkene with Cl2 in the presence of water (I think this explains why the smell of bleach was gone once the alkene was added, and why I never saw a big temperature jump--because the rate of reaction was so unbearably slow). This boils down to the realization that some sort of catalyst must be used for even non-enatioselective epoxide formation, as the intermediate chlorohydrin will not form (although, if it did, it would apparently rearrange in the basic conditions).

So that's somewhat good news, and somewhat bad news. It makes the epoxide formation a bit more tricky, but not necessarily impossible. HCl onto bleach would generate in situ chlorine gas, and making that solution basic with NaOH would rearrange to the epoxide. It's still might be able to be turned into a one pot synth, can't get much better than that.

But... this is the part I don't like. It says that in practice most alkenes are insoluble in water and the reaction is often carried out in aqueous DMSO. Does this mean that the reaction has to be carried out in aqueous DMSO (or as in PS post with electrolytic generation of chlorine, a tertiary alkanol)?

-- note --

It seems that it does not have to be carried out in aqueous DMSO/t-butyl alcohol, I ran across a patent (seaching for epoxide/alkene/hypochlorous) that does not use any organic solvent. But I do have a few questions, in all the patents talking about forming halohydrins from alkenes, it seems that they stress low-chloride concentrations to avoid chlorination of alkyl groups. Will this be a significant problem with my suggested method? Would it then make more sense to generate the chlorine externally? (or maybe switch the approach entirely, say to using bromine in aqueous DCM?)

Btw, does anyone know if I can use DCM when generating chlorine gas in the above way? Is the kinetics of chlorine reacting with DCM slow enough that it won't be chlorinated?
 
 
 
 
    Vibrating_Lights
(Hive Bee)
11-16-01 03:16
No 237212
      Re: anethole -> epoxide  Bookmark   

I believe the dcm will work.  It is not possible to add more clorine to the Dcm is it.  It has already been clorinated.  If you are really concerned about the dcm then do the reaction in a dark room.  The production of DCM is a reaction catalyzed by UV light. I do not know about the further clorination of DCM.  Let us knowsmile
VL_
 
 
 
 
    Chromic
(Hive Addict)
11-16-01 03:23
No 237213
      Re: anethole -> epoxide  Bookmark   

10.3g asarone (50mmol) (just to do something a bit different) in 6ml DCM and 44.8g 10.8% bleach(aq) (65mmol). Added stir bar and brought it up to a good speed. Slowly dripped in 15g 31% HCl(aq) (100mmol) in 80ml water.

It was an exothermic reaction (yay! there actually was a reaction!) which took a while to complete.

Worked up by extracting with 25,20mL DCM. DCM distilled. 10ml MeOH added, 2.5g KOH in 20ml MeOH added, refluxed and distilled off most of MeOH. Flooded with water. Extracted 25,20mL DCM. Washed extracts with 150,120mL water. Distilled off DCM. Tested with bisulfite....

NEGATIVE...

The only thing I learned during using this method is how to apply Excel to draft up a good set of reaction data and keep it nicely organized.
 
 
 
 
    Acme
(Hive Bee)
11-16-01 03:31
No 237217
      Re: anethole -> epoxide  Bookmark   

Maybee some kind of Phase Transfer Catalyst is called for.

Add some fabric softener to your bleachingwink 

Is there any way for you to monitor this reaction by using Thin Layer Chromatography?

Is the   
      2.5g KOH in 20ml MeOH added, refluxed

to rearrange the epoxide to the ketone?
 
 
 
 
    Vibrating_Lights
(Hive Bee)
11-16-01 03:58
No 237223
      Re: anethole -> epoxide  Bookmark   

I think you need to use more Dcm .  Also mabye the Cl needs to be produced seperatly.  Mabyee put dcm % bleech together then add the Hcl with stirring.  then seperate the Dcm Layer which now contains Cl2 and add the asarone to the Dcm to carry out the reaction.  Mabyee the other compounds present are intefering with the Rxn.  I think i have read somewhere that the Dichloro compound is a solid.  also think about extending the time of reflux with base. Also are you forgetting that the product of this rxn is the epoxide which then must be refluxed with a lewis acid to convert the epoxide to the ketone.  I did not see any where where you converted the epoxide to the ketone which could explain the negitave Bi-Sulfate test. The H2So4 rearrangement might not be suitable for the asarone epoxide.  I have read somewhere recently that the epoxide con be rearrangeds by simply heating the epoxide to 250' or something.  this might be suitable.  Try the Rxn with Iso and an final H2So4 reflux.  Iso is cheaper than the asarone.  I would find someone to try it but they are temporarly out of buisness.
VL_
VL_
 
 
 
 
    Chromic
(Hive Addict)
11-16-01 10:50
No 237307
      Re: anethole -> epoxide  Bookmark   

Sorry, I forgot to mention that I heated the epoxide to 300C before testing with bisfulite. I'll run the sample with NMR to see what actually happened. I got a viscous syrup, smelling unlike asarone. Btw, I did confirm that the mixture of NaOCl with no acid left the starting alkene intact. (ie Post 236380 (Chromic: "Re: anethole -> epoxide", Novel Discourse) did not work)

If I was to try this reaction again (assuming that acidic NaOCl doesn't work), I would use sodium bromide to generate bromine in aqueous DCM then react with the alkene to try and get the bromohydrin. I would not try to dissolve chlorine into DCM. That sounds like a very bad idea.
 
 
 
 
    terbium
(Old P2P Cook)
11-16-01 18:35
No 237375
      Re: anethole -> epoxide  Bookmark   

Or, perhaps HOCl in DMSO. The DMSO should provide a common solvent for both the olefin and the HOCl. Of course DMSO is going to be a more difficult work up than DCM.
 
 
 
 
    Chromic
(Hive Addict)
11-16-01 18:58
No 237383
      Re: anethole -> epoxide  Bookmark   

Getting a solution of HOCl in DMSO would not be easy--especially if low concentrations of halides are required to prevent side-reactions. Also, DMSO is not as easy to find as DCM and sodium bromide.

Btw, yes, the KOH in MeOH is done to do an internal Williamson ether synthesis. Converts halohydrins to epoxides.
 
 
 
 
    PrimoPyro
(Hive Addict)
11-16-01 19:07
No 237391
      Re: anethole -> epoxide  Bookmark   

You yahoos should really learn to use A F.S.E. because SWIPP bought a gallon of DMSO as his first acquisition piece, right off the net, for dirt ass fucking cheap, too. Point....clickity click, input cc#, enter, there, you just bought a gallon of DMSO from a hair gel supplier. (i agree: wtf???) Comes in your choice of gel or liqui. Guess which SWIPP bought....

P.S. dont give me crap about using a CC, its fucking solvent, used for.....errrr, something to do with waxing off leg hair, sound suspicious? Hell fucking no.

                                               PrimoPyro

Vivent Longtemps la Ruche! STRIKE For President!
 
 
 
 
    Acme
(Hive Bee)
11-17-01 02:42
No 237531
      Re: anethole -> epoxide  Bookmark   

I will refer you to post 29097


Bromohydrins from Olefins & NBS in water   
   
JACS 1955 2549

THe general proc illustrated by rxn of styrene (26g 0.25 mole) NBS (47g 95% pure 0.25 mole) and water 100mL.  Stir RT until NBS dissapears ~35 min Dissapearance of NBS a good crititereon for progress of rxn. The styrene bromohydrin layer was separated and the aq layer extracted with ether and after removal of ether 1/2 hr with NaOH (15g) in water 75mL at 60C.  Extraction with ether and distillation gave 85% of styrene oxide. bp 65C (5mm)

It was found that the bromohydrin could often be converted to the oxide by adding sufficient aq NaOH without separating the bromohydrin from the NBS-olefin mixture.

Table 1             yield (the oxides were obtained by taking the crude material directly to the oxides)

Allylbenzene  time 48H  56%

0.125 mole olefin in 100 mL Et2O stirred with 0.125 mole NBS in 100 mL water

a 50% yield of the oxide was obtained when the ether was removed and a 4 hr reaction time used.

bp 72-75C  (3mm)

 
 
 
 
 
    Rhodium
(Chief Bee)
11-17-01 03:05
No 237544
      Re: anethole -> epoxide  Bookmark   

And the synthesis of NBS can be found on my page (succinimide + Br2).
 
 
 
 
    Chromic
(Hive Addict)
11-17-01 10:59
No 237699
      Re: anethole -> epoxide  Bookmark   

Cool news. If it works with NBS/water, it should work with bromine/water as well.
 
 
 
 
    Rhodium
(Chief Bee)
11-17-01 14:08
No 237728
      Re: anethole -> epoxide  Bookmark   

Yes, but keep the bromine concentration low by dripping it in slowly into a stirred solution of the alkene/water (with a PTC perhaps?), or the dibromide may form instead. The reasoning behind using NBS is that the bromine concentration is always low when using that reaction.