Barium
(Hive Bee)
10-06-02 17:09
No 365055
      N-alkylated amines by CTH
(Rated as: excellent)
 Bookmark   

After trying the method, found and tried, by Sunlight and Foxy 2, I decided to try another variant of the procedure. What I wanted was to imitate the conditions in a regular reductive alkylation by hydrogenation. This is how it went...

100 mmol 2-fluorophenylacetone, 1g 5%Pd/C and 120 mmol methylamine in 70ml MeOH[1] was combined in a 250ml round bottomed flask equipped with a reflux condenser and a magnetic stirbar. Glacial acetic acid was added dropwise until pH 6.5 was reached. The mixture was heated to 60 deg C and 400 mmol sodium hypophosphite was added in one portion along with 20ml water. Hydrogen evolution started immediately. The mixture was the allowed to stir for four hours at 60-65 deg C. When the reaction was over diluted HCl was added until pH 2 was reached, then 2 tablespoons celite was added and the catalyst removed by filtration. The solution was distilled under reduced pressure to remove the MeOH. The acidic aqueous solution was extracted twice with 50 ml toluene then basified with NaOH and extracted twice with 50ml toluene. The extracts were combined and dried with MgSO4 and the solvent removed by distillation. This left a amine smelling, slighly yellow oil. The oil was dissolved in 100ml EtOAc and dry HCl in IPA added dropwise until pH 5 was reached. The solution was heated to boiling and concentrated to 50ml. Slow cooling and occacional scratching of the walls induced crystallisation, 100 ml EtOAc was added and the solution was alloved to stand at room temp until crystallisation was complete.

Yield 18.94g 2-fluoro-N-methylamphetamine hydrochloride (93%)


The same procedure gave 2,5-dimethoxy-N-methylampetamine hydrochloride in 89% yield and 2,4-dimethoxy-N-ethylamphetamine in 90% yield. 


[1] The solution of methylamine in MeOH was made by dissolving 130 mmol KOH in 55ml MeOH and add a solution of 120 mmol methylamine hydrochloride in 15ml water.

Hypophosphites generates hydrogen in the precense of a catalyst according to: NaH2PO2 + H2O __> NaH2PO3 + H2

Catalytic hydrogenation freak
 
 
 
 
    Barium
(Hive Bee)
10-06-02 17:21
No 365057
      The acidic washes were combined and solvent ...  Bookmark   

The acidic washes were combined and solvent removed by distillation. This left 0.7g of 2-fluorophenylacetone. Good news in other words smile. No losses, or very little losses due to reduction of the ketone to the alcohol.

Catalytic hydrogenation freak
 
 
 
 
    Rhodium
(Chief Bee)
10-06-02 17:26
No 365058
      Five Stars!  Bookmark   

If this is reproducible for any phenylacetone, then this is truly revolutionary! Good work!

This system couldn't possibly be used for alkylation of tryptamines too, while we're at it? wink

<edit>With the risk of sounding stupid, I assume you mean that the 2-F-P2P was isolated from the 100ml of toluene used to extract the acidic solution right after the MeOH evaporation, right?</edit>
 
 
 
 
    Barium
(Hive Bee)
10-06-02 18:00
No 365066
      Im pretty sure this system would work for ...  Bookmark   

Im pretty sure this system would work for aldehydes as well as for ketones. As soon as an imine is formed, its reduced. Tryptamines should be of no problem to make either.

Yes, I recovered the ketone from the toluene extractions prior to the MeOH removal. I prefer not to comment on the stupidity...winkwinkwink

Catalytic hydrogenation freak
 
 
 
 
    Rhodium
(Chief Bee)
10-06-02 18:22
No 365069
      Contradiction in terms  Bookmark   

You cannot both answer yes to my question, as well as contradicting what I said wink
 
 
 
 
    lurk42long
(Stranger)
10-31-02 05:31
No 374807
      how sure is pretty sure?  Bookmark   


OK sorry, how bout this,

If i was to try this with an aldehyde can I assume that molar ratio's, ph, solvent volumes, what not, remain the same? Can I simply replace with the same molar concentration of an aldehyde? Sorry if this question is on the newbee side of things but my dreams of benzaldehyde and 3,4,5 trimethoxy benzaldehyde are few and far between. Dont want to waste it in the name of stupidity. Better sure than sorry.

BTW  Lilienthal gives the tryptamine angle the two thumbs down in the tryp forum.frown

thanks, Lurk
 
 
 
 
    SPISSHAK
(Hive Bee)
10-31-02 05:52
No 374815
      I don't understand where your'e coming from?  Bookmark   

If Your'e talking about applying this reaction to trimethoxybenzaldehyde to yeild mescaline it won't happen.
Maybe if you did this using the acetaldehyde version of your compound, but this specific catalytic transfer hydrogenation would not give mescaline on reaction with a benzaldehyde, maybe a benzylamine but not a phenylethylamine.