pHarmacist
(Hive Bee)
10-31-02 15:21
No 374967
      Methcathinone to Methamphetamine
(Rated as: good read)
    

Clemmensen Reduction:

In a 1-L flask fitted with a re-flux condenser, 5,3 mol of mossy zinc is treated with 800 mL of a 5% aq solution of mercuric chloride for 1 h. The solution is decanted; then 0.835 mol of methcathinone freebase is added followed by as much HCl diluted with the same V of water as needed to cover all the Zn. The mixture is re-fluxed for 8 h during which time additional dilute HCl is added in small portions. After cooling, the the upper layer is separated, washed free of acid, dried, and distilled to give methamphetamine free-base.

[NOTE]: Addition of HCl is critical and it should be added slowly in order not to destroy methcathinone.

EDIT: Forgot the yield: Mad Hatter (a no-bee friend) got 45 % of theory, but according to him there was a loss during the workup due to a accident (spillage).

Oh and he actually called me now and told me that he protected the amino group of ephedrone prior to the reduction. Basicly he claims that he re-fluxed methcathinone base along with the formic acid and acetic anhydride (details to come later). Removal of formyl group was accomplishied by heating of n-formyl meth in aqueous NaOH. I can post the details tommorow from his computer.

Ref: Reductions In Organic Chemistry (Milos Hudlicky)

Never underestimate the power of retrosynthesis.
 
 
 
 
    Jetson
(Title Addict/Eraser)
10-31-02 17:07
No 375006
      hmmm.....     

seems to swij to be alot of wasted time effort.  why would one take the time to make methcathinone just to then reduce it to methamphetamine?  unless there's some novel synth for cat that doesn't use ephedrine/psuedo as a precursor?  did jetson miss something somewhere?

the devil is so lonelymad
 
 
 
 
    Rhodium
(Chief Bee)
10-31-02 17:40
No 375024
      Who is Mad Hatter, and where did he publish his ...     

Who is Mad Hatter, and where did he publish his results?
 
 
 
 
    pHarmacist
(Hive Bee)
10-31-02 17:48
No 375030
      as i said a friend, he followed the procedure ...     

as i said a friend, he followed the procedure described in the Reductions In org chem. I now borrowed the book from him in order to post the procedure here. He didn't gave me any details on protection besides telling me that he protected the amino group prior to the reduction.

Never underestimate the power of retrosynthesis.
 
 
 
 
    Rhodium
(Chief Bee)
10-31-02 17:53
No 375034
      Oh, I replied before you had finished your ...     

Oh, I replied before you had finished your editing. Yes, with protection of the nitrogen I can readily accept those yields.
 
 
 
 
    JoeCool25
(Newbee)
10-31-02 19:08
No 375060
      Because...     

....seems to swij to be alot of wasted time effort.  why would one take the time to make methcathinone just to then reduce it to methamphetamine?...

Perhaps because swim have so much CAT laying around from his first lessons to fly ...??
 
 
 
 
    JoeCool25
(Newbee)
10-31-02 19:25
No 375066
      ..Yes, with protection of the nitrogen...     

...Yes, with protection of the nitrogen I can readily accept those yields...

Hi all,
can someone tell what must be done for the protection on the aminogroup (nitrogen) ?

Anybody there done this before ?

/J
 
 
 
 
    alphacentauri
(Newbee)
10-31-02 20:01
No 375085
      Why Clemmensen, if it worked     

Simply because RP or hypo are not always so easily available, while you can get Zn and HCl at the butcher's too. Dichromate is not controlled, but P is. About me, I work with cubic metres of melted Zn, and if Clemmensen worked properly WITHOUT RACEMIZING the product, I wouldn't think twice about doing it. Then a consideration: meth is a stable molecule, but cat is not. Could cat sustain boiling temperature for hours in the reflux? .
 
 
 
 
    Jetson
(Title Addict/Eraser)
10-31-02 23:55
No 375171
      ok...     

ok some one correct me here if i'm wrong(i'm sure someone will)  but zinc in itself(zinc dust/powder) has the ability to do a hydrogenation of ephedrine.  now the amount may be high and the pressure/time of hydrogenation may be increased(perhaps alot) but.......

the devil is so lonelymad
 
 
 
 
    Jetson
(Title Addict/Eraser)
11-01-02 22:02
No 375459
      oops...     

sorry jetson's bad,  seems he was thinking chloroephedrine...

the devil is so lonelymad
 
 
 
 
    alphacentauri
(Newbee)
11-01-02 22:31
No 375471
      Jetson, let me think......     

......a bit about what you wrote. About you Zn can hydrogenate ephedrine. Do you know how I check the amount of Zn in an iron wire? I put a little piece of the wire in a special buret closed on top, then i fill it with HCl, and the H2 developed pushes the liquid down, so I read the number. Development of H2 is nearly istantaneous, giving a lot of effervescence. If you use a thin sheet of Zn the formation of a big quantity of hydrogen is even faster. Now you mean that you can hydrogenate ephedrine so, like Ni, Pd or Pt hydrogenation of a double bond? This means that Zn metallic cristals have the same bravesian lattice of Ni. That's very interesting. Definitely deserves a detailed investigation. But a doubt now: HCl protonizes the alcoholic function, this becomes a good leaving group as H2O, thus forming a carbocation that loses a H+ generating an enamine which (I quote from Rhodium's "P2P from ephedrine derivatives")spontaneously rearranges to the isomeric imine - Schiff base -. It is a reversible equilibrium. Practically the pi orbital shifts at both sides of the N-group bearing carbon, tha same carbon that loses a H atom as H+, thus liberating a sigma doublet that turns to a pi double bond doublet. So we should obtain more than a product. Then if Zn has a catalysing surface, the pi orbital interacts with it, making possible a radicalic hydrogenation. But after a very short time the metallic surface will desappear leaving only Zn++. I don't know, but something doesn't convince me....
 
 
 
 
    josef_k
(Newbee)
11-07-02 04:50
No 377218
      The reason you want to reduce methcathinone to ...     

The reason you want to reduce methcathinone to methamphetamine, is that it is pretty easy to make. Just brominate propiophenone and then react it with methylamine. Pretty unwatched too i guess.

It's great that someone has finaly tried this reduction. I have wondered about it for some while now.

Btw, isn't the hydrolization of N-formyl,N-metyl-amphetamine more effective in dilute HCl than NaOH? At least according to festers book. But then again, his speciality is the leuckart reaching which proceedes through the n-formyl.
 
 
 
 
    Jetson
(Title Addict/Eraser)
11-07-02 15:45
No 377323
      ...     

ok firstly.  alpha- that indeed is something to think about.  jetson himself never has hands on experience just research.  it's been a while though.  jetson's currently "on it"  wink

now, joe- methylamine's unwatched eh? 

the devil is so lonelymad
 
 
 
 
    RepVip
(Hive Bee)
11-10-02 04:47
No 378269
      That was a great experiment, pharmacist.     

That was a great experiment, pharmacist.

Couldn't you also use a Wolff-Kishner reduction of the Cat to Meth?  It also is a deoxygenation reaction.  Except you need to use N2H4 in the first step and a strong base (OH-) and heat in the second step.

I must admit I don't know anything about protecting groups.  Would you need one with this reaction?

Thanks
 
 
 
 
    RepVip
(Hive Bee)
11-10-02 09:13
No 378321
      pseudo -> cat -> meth     

Some knowledgable bee please respond and tell me whether this would work or not.

1) Synthesize Cat from pseudo by oxidation using either KMnO4, chromate, or preferably (if you ask me) bleach (aqueous NaClO).

2) Now, reduce the Cat to Meth using hydrazine (N2H4) hydrate and a strong base, via Wolff-Kishner;
   Or do what was proposed here with Clemmensen reduction, depending on how hard it is to obtain/make zinc amalgam. 

Questions:

1) the bleach solution is already basic.  Perhaps after the oxidation is finished, you could simply add some hydrazine hydrate and reflux until finished?

2) Protection of the amino group?  I'm worried it will also oxidize into hydroxylamines frown.  Does the salt/freebase form make a difference, and can this group be protected?

3) I'm also worried that the hydrazine will react adversely with the amine group.  Can this be protected maybe with acetyl chloride, at the very start, and later hydrolysized with H3O+ back to the amine?
 
 
 
 
    RepVip
(Hive Bee)
11-10-02 12:20
No 378338
      god damn it     

I'm sorry.  Just found this excellent post
Post 363715 (pHarmacist: "Wolff-Kishner/Huang-Minlon reduction of Ephedrine", Stimulants)
and now I feel like an ass. 

I think this is the first time I actually found what I was looking for!  umm... I'll shut up now.
 
 
 
 
    pHarmacist
(Hive Bee)
11-10-02 20:09
No 378396
      RedVip: Unfortunatly, we are not sure if the ...     

RedVip:

Unfortunatly, we are not sure if the wolff-kishner will work as described in that post, but we can be pretty sure that it will work if the amino-group is protected prior to the reduction... just as in clemmensen...

1-2-3 ACiD
 
 
 
 
    RepVip
(Hive Bee)
11-10-02 20:24
No 378400
      pHarmacist     

I eagerly read all your posts.  I just love a bee who knows his shit!  Were you still planning on updating this thread with some more info of the reaction above?

You probably saw this other thread I started Post 378349 (RepVip: "Bromobenzene -> P2Pol -> Meth", Stimulants)
I would really like your comments.  Anything at all, just shoot! I'm all ears.
 
 
 
 
    WizardX
(Wizard Master)
11-11-02 00:34
No 378488
      N2H4 + 2I2 ==> 4HI + N2
(Rated as: excellent)
    

RepVip: Why? If you can get hydrazine (N2H4) hydrate then you can reduce ephedrine directly to meth.

N2H4 + 2I2 ==> 4HI + N2  Very rapid, close to explosive.
Very slow addition of hydrazine (N2H4) hydrate (dropwise) to I2 in H2O.

By adding small amounts of hydrazine (N2H4) hydrate in the 4HI + 1 ephedrine reaction mixture while refluxing, you will convert I2 => HI and iodoephedrine to meth.
 
 
 
 
    Rhodium
(Chief Bee)
11-11-02 00:58
No 378497
      Hydrazine/Iodine reduction of benzyl alcohols     

Wiz: Really? Cool! Do you have any references for the use of this combination for the reduction of any organics?
 
 
 
 
    RepVip
(Hive Bee)
11-11-02 01:02
No 378499
      Well... good question. I didn't know you could.     

Well... good question.  I didn't know you could.  I was originally just looking for alternative routes that didn't employ RP.  And making Cat from Pseudo is relatively easy. I'm going through a massive learning process - trying to absorb all this information at once.  I've come a long way (compared to just 2 months ago) and there still is a long way to go.  I think it's amazing you can go through so many different routes and still obtain the same thing.  I have to wonder why there is not more talk of other routes to meth.  The prospect of turning a gallon of toluene into a bucket (exagerated) of meth just grabs my full attention smile

It's not even about the meth anymore.  It's the chemistry that I'm attracted to.  Eventually I will "graduate" from this forum to the fun stuff!
 
 
 
 
    pHarmacist
(Hive Bee)
11-11-02 01:21
No 378509
      Master     

Wizard: do you have any details on this, i think this is (if it works as wiz claims) as revolutionary as hypo-method...

1-2-3 ACiD
 
 
 
 
    WizardX
(Wizard Master)
11-13-02 02:53
No 379112
      Rhodium, RepVip, pHarmacist: Yes, I'll find the ...     

Rhodium, RepVip, pHarmacist: Yes, I'll find the info in my spellbook and post it. This method of reduction is old school for me. Anyway, give me sometime as I'm flat-out.
 
 
 
 
    pHarmacist
(Hive Bee)
11-13-02 03:05
No 379121
      nice     

I've allready started collecting my urine in order to get urea and eventually N2H4, no seriously, i can't wait for your post....

1-2-3 ACiD
 
 
 
 
    WizardX
(Wizard Master)
11-15-02 01:21
No 379789
      Hydrazine Synth.
(Rated as: good read)
    

Look at this if you want to make your own Hydrazine.
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0309 Hydrazine (N2H4) Sulphate

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv5p0030 Reduction with Pd/C & N2H4

The Hydrazine, N2H4 is the hydrogen donor.
 
 
 
 
    java
(Hive Addict)
10-29-04 23:12
No 538609
      Hydrazine Hydrate
(Rated as: good read)
    

Hydrazine Hydrate(NH2NH2H2O)
Compiled by Asheesh Kumar Jain
Synlett 2004, 2445-2446




Introduction
The synthetic utilities of hydrazine hydrate have been extensively investigated in organic chemistry. Among reducing agents, hydrazine hydrate stands out for its application to a broad variety of reductive transformations.
It is easy to use and reduces many functional groups, such as carbonyl compounds, alkenes, alkynes
and nitro groups under mild reaction conditions. Hydrazine hydrate is commercially available. It is a liquid (mp 52 C, bp 120121 C, d = 1.027 g/mL), and issoluble in water, ethanol, methanol, propanol and isobutanol.

It is better to die on your feet than to live on your knees...Emiliano Zapata