foxy2
(Distinctive Doe)
09-23-01 16:53
No 216485
      Methampetamine from Amphetamine the easy way.
(Rated as: excellent)
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Here is a one step procedure that should definately work to go from Amphetamine to Methamphetamine.  Or MDA to MDMA, or phenylethylamines to n-methyl phenylethylamines if you want to try something new.  You get an approximate 9:1 ratio of secondary amine to tertiary amine, while not perfect it is pretty dam good for one step with no reduction necessary.

Cesium Hydroxide Promoted Chemoselective N-Alkylation for the Generally Efficient Synthesis of Secondary Amines

Org. Lett., 1 (12), 1893 -1896, 1999.

Abstract
Selective N-alkylation of primary amines was developed using cesium hydroxide to prepare various secondary amines efficiently. A cesium base not only promoted monoalkylations of primary amines but also suppressed overalkylations. Various amines and alkyl bromides were examined, and the preliminary results demonstrated this methodology was highly chemoselective, favoring mono-N-alkylation over dialkylation. In particular, use of amino acid derivatives afforded the desired secondary amines exclusively.

Representative Experimental Procedure:
To activated powdered 4 molecular sieves (500 mg) in anhydrous N,N-dimethylformamide (8.3 mL), was added cesium hydroxide monohydrate (280 mg, 1.7 mmol), and then the white suspension was vigorously stirred for 10 min. After phenethylamine (0.21 mL, 1.7 mmol) was added and followed by additional 30 min of stirring, 1-bromobutane (0.21 mL, 2.0 mmol) was added into the white suspension. The reaction was stirred for 20 h, filtered to remove the molecular sieves and undissolved inorganic salts, and rinsed several times with EtOAc. After the filtrate was concentrated to a nominal volume by blowing air, the residue was taken up in 1 N NaOH, and extracted with EtOAc (4 20 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Flash column chromatography (EtOAc-EtOH, 9:1 v/v) afforded the secondary amine, N-butyl phenethylamine (260 mg, 1.5 mmol; 89%) as a colorless oil as well as tertiary amine, N,N-dibutyl phenethylamine (40 mg, 0.17 mmol; 10%) as a pale yellow oil.

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    terbium
(Old P2P Cook)
09-23-01 20:15
No 216515
      Re: Methampetamine from Amphetamine the easy way.  Bookmark   

Due to steric hindrance the n-butyl-phenethylamine may be much more resistant to accepting another butyl than an n-methyl-phenethylamine would be to accepting another methyl. I believe that Shulgin comments on this re alkylating tryptamine.
 
 
 
 
    foxy2
(Distinctive Doe)
09-24-01 00:17
No 216575
      Re: Methampetamine from Amphetamine the easy way.
(Rated as: good read)
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You are right steric hinderance would be less with methyl however i don't think steric effects are dominating here.  There is something else that is key, the cesium makes the second alkylation which forms the tertiary amine less favorable than the first alkylation going to the secondary amine. 

The problem with DMT and any primary amine under typical conditions is that each subsequent alkylation makes the next alkylation more favorable, as related by Lili Post 126957 (Lilienthal: "Breath of Hoax? / PTC tryptamine alkylation on the test bench", Tryptamine Chemistry).  And DMT is a completely different case as we want to dimethylate it, NOT monomethylate it.  The butyls of DBT do build up steric hinderance when two of them have added to tryptamine, however I would bet that it is impossible to get a good yeild of N-butyltryptamine by conventional alkylation. I think you will get mainly N,N-dibutyltryptamine.

I predict that using a molar ratio closer to 1 of methylateing agent/amine will result in even better yeilds than reported.  They performed an identical reaction starting from a secondary amine (N-butylPEA) instead of a primary (PEA).  As you can see below, they could NOT even force the tertiary amine to form in higher than a 10% yeild when cesium was present. 

Here is what they say in the article.

Among the cesium bases examined, cesium hydroxide monohydrate, in general, gave the highest yields and selectivities although cesium carbonate also worked well, depending on substrates.6 To confirm the possible cesium effect, defined by the enhanced reactivities in the presence of cesium salts,7 comparative studies between cesium bases and other bases were performed, demonstrating that cesium hydroxide was superior to other alkali bases tried with the regard to the observed chemoselectivities. As depicted in Table 1, other alkali hydroxides produced moderate yields of the desired product along with a considerable amount of the tertiary amine 5, whereas cesium hydroxide allowed for a greater selectivity of 9/1 in preference for the monoalkylation product 4. It was apparent that an unprecedented "cesium effect" in N-alkylation was observed as seen in O-alkylation.7
Interestingly, the next comparative study implied that the cesium base not only promoted N-alkylation of primary amines, but also inhibited the formation of tertiary amines. As illustrated in Scheme 2, the intended alkylation of secondary amine (N-(n-butyl)phenethylamine) was very sluggish under our conditions, affording the tertiary amine (N,N-(di-n-butyl)phenethylamine in only 10% yield, whereas 72% of (N,N-(di-n-butyl)phenethylamine was obtained along with the recovery of 25% of (N-(n-butyl)phenethylamine) in absence of cesium hydroxide after the same duration. Under our cesium base promoted N-alkylation conditions, primary and secondary amines exhibited opposing reactivities, suggesting that the improvement of chemoselectivity would stem mainly from the retarded overalkylation or reversal of normally observed alkylation rates.8


I passed the article on to Rhodium so you may get to see all the details with diagrams.


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    bluemoon
(Stranger)
09-24-01 17:00
No 216822
      Re: Methampetamine from Amphetamine the easy way.  Bookmark   

Out of complete curiosity, what if swim has a dex 5mg, amp 5mg mix of salts.  There are actually four salts, and swim has heard one salt is innactive (this could be wrong).  Would this procedure change dex?  Would it change the other amp salt?  And lastly, cesium hydroxide swim hasn't heard of.  One already can hear screams of UTFSE.    wink
 
 
 
 
    terbium
(Old P2P Cook)
09-24-01 19:12
No 216887
      Re: Methampetamine from Amphetamine the easy way.  Bookmark   

And lastly, cesium hydroxide swim hasn't heard of.  One already can hear screams of UTFSE.
Or, one could try a table of the elements.  
 
 
 
 
    bluemoon
(Stranger)
09-25-01 05:48
No 217044
      Re: Methampetamine from Amphetamine the easy way.  Bookmark   

Let swim rephrase swim's original dumb question.  Cesium, and/or it's salt, might be found where?  Now swim needs to go to a forum called acquisition.  Actually, no, swim doesn't need to aquire anything.  Swim was merely speculating.  Therefore, swim will stick with everything except swim's last question in swim's former post.

Swim will be promptly beaten at the bus stop this morning.
 
 
 
 
    Rhodium
(Chief Bee)
09-25-01 06:32
No 217049
      Re: Methampetamine from Amphetamine the easy way.  Bookmark   

Cesium salts has no OTC uses whatsoever as far as I know, so regular chem suppliers are the only place to find it.
 
 
 
 
    Lilienthal
(Moderator)
09-25-01 10:46
No 217086
      Re: Methampetamine from Amphetamine the easy way.  Bookmark   

I think you can extract it without any problems from cesium clocks.