pHarmacist (Newbee)
09-29-02 15:48
No 362090
      Novel route -> P2P  Bookmark   

Didn't want to post this on the "stimulants" becouse this ketone isn't only used in the amphetamine synth..
I never heard of using oxiranes (with Gringard reagent) for the preparation of P2P. I don't know if the route is novel, I searched and hive, no results, but I could be wrong. I hate the fact that I can't post the complete mechanism (I wrote it on paper). But I can describe in words and the little applet drawing below. Actually a Gringard reagent can be prepared from bromobenzene and Mg-tunings. This is then reacted with the oxirane (look below), the intermediate is protonated to give phenyl-2-propanol (don't want to show up in the applet :( the alcohol is oxidized with PCC or KMnO4 to give the desired ketone.

This is actually a Gringard at it's best, mechanisticly speaking we got a nucleophile attack from the Gringard  reagent on the primary (1*) carbon of the oxirane, this additionaly gives us the secondary (2*) alcohol, the alcohol is then oxidized to the ketone. enjoy:

Molecule: reaction ("Br[Mg]c1ccccc1.CC1CO1>CC(O)Cc1ccccc1>CC(=O)Cc1ccccc1")

Many thanks to Organikum for helping me out with the Java-applet...

Greetings: Siegfried, Organikum

(Chief Bee)
09-29-02 17:12
No 362113
      Oxiranes to P2P  Bookmark   

I have had the outline posted on my page for quite some time - ../rhodium/chemistry /p2pol.html - but I haven't gotten around making a real writeup on it.
09-29-02 17:51
No 362132
      Ah ok.. I searched oxirane on your page with no ...  Bookmark   

Ah ok.. I searched for "oxirane" on your page with no results... what now? By the way, this method is amazing, elegant, clean, why lack of popularity, anyone?

(Chief Bee)
09-29-02 18:11
No 362142
      Steep learning curve  Bookmark   

Most people at this board couldn't get a grignard reaction going if their life depended on it. They would need to learn to pay attention to using pure reactants, anhydrous solvents and a controlled laboratory environment.
(Hive Bee)
09-29-02 18:30
No 362150
      So what about in TSII, when the guy said he ...  Bookmark   

So what about in TSII, when the guy said he didn't use a N2, and he said all he did to dry his ether was run it through Na2SO4, and he did fine. 

That always made me wonder whether or not he was telling the truth.

Who is that masked man?
(Chief Bee)
09-29-02 18:34
No 362151
      It is not hard to get a grignard going if you ...  Bookmark   

It is not hard to get a grignard going if you know what you are doing. I have never used inert gas, and how much you need to dry the ether depends on how reactive your substrate is.
(PVC-Analog Taste-Tester)
09-29-02 18:37
No 362154
      "They would need to learn to pay attention to ...  Bookmark   

"They would need to learn to pay attention to using pure reactants, anhydrous solvents"

  I learned the hard way; Listen to what Rhodium says, and don't cut any corners.tongue

Love my country, fear my government.
09-29-02 19:00
No 362159
      dry Et2O  Bookmark   

just put some elemental Na in your ether and put it all in freezer it will keep it dry... As far as N2 atmosphere goes, it's not a must, just take a bent glas-pipe, throw in piece of cotton now some CuSO4 (anhydros) then some more cotton over it (like a sandwich) and connect it to the reflux condenser. it will keep the Gringard alive

09-29-02 19:38
No 362176
      Actually one can instead of "original" Gringard ...  Bookmark   

Actually one can instead of "original" Gringard use Li-benzene, Li-benzene could be prepared from bromobenzene and Li, product is more reactive than Gringard reagent, mechanism is the same...

(Hive Bee)
09-29-02 19:44
No 362177
      Rhodium wrote: Re: Most people at this board ...  Bookmark   

Rhodium wrote:

Most people at this board couldn't get a grignard reaction going if their life depended on it

This is the same as with the BIRCH I assume?

Its on the bromobenzene I think. Schedule 1 precursor like P2P. A real and easy OTC way to bromobenzene might make also this popular when pills and anhydrous ammonium are out of reach.

Looking at the ghetto-stylish but in reality highly sophisticated "pill-cures", I cannot say there is something impossible for lovers of strong stimulanzia. wink


~ Love is the law, love under will. ~
(Chief Bee)
09-29-02 19:45
No 362179
      Mg and Li are definitely not interchangeable!  Bookmark   

Mg and Li are definitely not interchangeable!
(Hive Bee)
09-29-02 20:09
No 362188
      Rhodium you are absolutely right !  Bookmark   

Mg and Li are definitely not interchangeable!

no doubt, thats right.
I wanted to express the opinion that some years ago no chemist would have believed if told that farmerboys perform a Birch-like reaction. Many wont believe it nowadays either.

I dont hope the reaction gets popular as it is risky for health and a catastrophe for the enviroment if done in the bushes by many.

no offense intended

~ Love is the law, love under will. ~
09-30-02 01:55
No 362283
      Of course it can be used  Bookmark   


Of course, you can't make a Gringard with Li, but this is compleatly possible:

Ar-Br + 2Li ---Et2O--> Ar-Li + LiBr

Ar-Li can then preform a nucleophillic attac on the primary carbon of the oxirane just like the Gringard did... That was my point...

(Chief Bee)
09-30-02 14:58
No 362447
      alkyllithiums, grignards & birch  Bookmark   

pHarmacist: What I meant was that alkyllithiums are less chemically selective, and that you cannot automatically use a R-Li when a synthesis calls for R-MgX (there are more added dangers too, but that wasn't my objective).

Organikum: As long as you aren't breathing/touching the ammonia, the birch reaction is extremely simple. You just have a container of ammonia, add an alkali metal "plop, plop, fizz", then add your aromatic "plop, plop, fizz", let the solvent evaporate and you have your product. No big deal. But a grignard reaction is comaratively involved.
(Old P2P Cook)
09-30-02 20:50
No 362604
      Ghetto Grignard cooks.  Bookmark   

But a grignard reaction is comaratively involved.
But a lot of near illiterate ghetto cooks in the US were using Grignard reagent in the 70's and 80's for the synthesiis of PCP. It really used to amaze me that these people could learn to perform a synthesis that involved cyanide and a Grignard reagent.

Baseline Does Not Exist.
(Chief Bee)
09-30-02 21:50
No 362625
      Maybe morons were smarter 25 years ago? ;-)  Bookmark   

Maybe morons were smarter 25 years ago? wink
(Title on BackOrder)
09-30-02 22:04
No 362631
      BASF - we don't make morons, we make them dumber  Bookmark   

ahhh, the wonders of science.  Try to make a reaction idiot-proof, and we will breed a better idiot. 

All paths are the same: they lead nowhere
09-30-02 22:10
No 362633
      terbium: good point... true...  Bookmark   

terbium: good point... true...

[pH]armacist - Elite Killing Technique
(Chief Bee)
09-30-02 22:36
No 362637
      By the way, would styrene oxide (non-suspicious ...  Bookmark   

By the way, would styrene oxide (non-suspicious bulk plastics monomer) and OTC MeMgI also make P2Pol,  or would it be the wrong isomer?
(Hive Bee)
09-30-02 22:57
No 362642
      Rhodium, unfortunately, that would give ...  Bookmark   

Rhodium, unfortunately, that would give phenyl-ethyl-ketone, as the nucleophillic attack takes place on the primary carbon...

[pH]armacist - Elite Killing Technique
(Hive Bee)
09-30-02 23:06
No 362643
      But there might be a way to use this ketone ...  Bookmark   

But there might be a way to use this ketone anyways, introducing a pi-bond (condensation) would yield phenyl-2-propen, that can be reacted with p-bensoquinone (Wacker Oxidation) to yield p2p, now off to school.. bbl

[pH]armacist - Elite Killing Technique
(Hive Bee)
03-07-03 13:38
No 414664
      Rhodium: possible  Bookmark   

By the way, would styrene oxide (non-suspicious bulk plastics monomer) and OTC MeMgI also make P2Pol,  or would it be the wrong isomer?

I have two ref on that reaction I will try to get soon.... This reaction is possible!cool

(And that is not this one: Post 396757 (Fomalhaut: ", , ...", Russian HyperLab))
(Hive Bee)
03-11-03 14:33
No 415832
      First ref
(Rated as: excellent)

The Reaction of Styrene Oxide with Methylmagnesium Iodide Calvin Golumbic and D.L. Cottle JACS, 61, 996 (1939)


Fourneau and Tiffeneau [6] found that methyl- and ethylmagnesium bromides reacted with styrene oxide as if it were phenylacetaldehyde...


Some rambling about the iodohydrin of styrene, made from styrene oxide and HI, I skipped the experimental on it too


The Preparation of Styrene Oxide:

When prepared from styrene and benzoyl hydrogen peroxide, prepared according to the method of Brooks and Brooks [20], the oxide always contained aldehyde but treatment of 2-iodo-1-phenyl-1-ethanol with potassium hydroxide gave an oxide which gave no test for aldehyde with Tollens' reagent, formed no precipitate with sodium bisulfite and only slowly gave a coloration with Schiff's reagent.

Powdered iodine (1.2 moles) was added, during four to five hours, to a mechanically shaken mixture of 0.6 mole of yellow mercuric oxide and 1200 cc. of a water-saturated ether solution of 1.2 moles of styrene. The mixture was filtered, the filtrate washed with dilute sodium bisulfite and potassium iodide solutions and dried. Finely powdered potassium hydroxide (3 moles) was added, during one to two hours, to the ice-cooled and mechanically stirred ether solution; finally the ice-bath was removed and stirring was continued for one and one-half days. The ether solution was decanted, the residue washed with ether, the solvent distilled from the combined, dried solutions and the residue distilled. The yield of oxide was 51%, bp 87-88C (23 mm).

The reaction of Styrene Oxide, Styrene Iodohydrins and 3-Bromo-2-butanol with Methylmagnesium Iodide.
Solutions of one mole of methylmagnesium iodide in 350 cc. of ether, analyzed by Gilman's titration method [25], were used in each of the experiments reported in Table I with the exception of expt. 8. The molar ratio of Grignard reagent to the oxide was 1:1 and to the halohydrin, 2:1. The moles of compound treated with methylmagnesium iodide varied from 0.18 to 0.37, with the exception of expt. 6, in which 0.05 mole of iodohydrin was used. In expts. 1-7, the oxide or halohydrin, without solvent, but diluted with ether in expts. 9 and 10, was added to the well-stirred and ice-cooled Grignard reagent.


Soon after reaching RT, the reaction mixture boiled spontaneously in every experiment, except 6, 7 and 10. No external source of heat was used in expts 3, 4 and 6. In expts 1,2,5,7,9 and 10, most of the ether was distilled on a water bath; the mixtures reacted violently in expts 7 and 10.

The reaction mixtures, with the exception of expts. 6, 9 and 10, were hydrolized, extracted with ether and the ether extracts steam distilled from 30% potassium hydroxide solutions. This separated the alcohol from the resin that was formed in all experiments, with the exception of 6, and converted the halogen in the unchanged halohydrin to halide ion, which was determined and is reported as percentage of unchanged iodohydrin. The resin in expt 8, extracted from the alkaline mixture with chloroform, weighed 13.8g.

The alcohol from all experiments, with the exception of 6,9 and 10, was extracted from the steam distillate with ether, the ether extract dried over potassium carbonate, distilled and the alcohol fractionated through a 3- or 6-bulb Snyder column under reduced pressure. The products from expts 9 and 10 were not steam distilled.

The products were identified by their phenylurethan and by mixed melting point with a sample prepared in 56% yield from phenylacetaldehyde and methylmagnesiumiodide.

Table I:
Expt.          compound w/MeMgI      Et2O dist on bath?       Products     yield, %

1      styrene oxide             Yes               P2Pol     53
2      PhCHICH2OH                Yes               Phenylethanol + a s-alcohol     13
3      styrene oxide             No                P2Pol     51
4      PhCHICH2OH                No                P2Pol     9.8
5      CH3CHBrCHOHCH3            Yes               Hexene    13
6      PhCHOHCH2I                No                recovery of the iodohydrin    ...
7      PhCHOHCH2I                Yes               Phenylethanol + a s-alcohol     15
8      styrene oxide + MgI2       ...              P2Pol     15
9      PhCHICH2OH                Yes               P2Pol     56
10     PhCHOHCH2I                Yes               P2Pol     42


[6] Fourneau and Tiffeneau, Compt. rendu 146, 698 (1908)
[20] Brooks and brooks, JACS, 55, 4309 (1933)
[25] Gillman, Wilkinson, Fishel and Meyers, JACS, 45, 156 (1923)
03-11-03 16:15
(Rated as: insignificant)
03-11-03 16:21
(Rated as: insignificant)