Antoncho
(Official Hive Translator)
06-06-02 10:40
No 318289
      N-monomethylation of ampetamines
(Rated as: excellent)
 Bookmark   

This is from Patent GB481397. It has a direct relation to ../rhodium/chemistry /amphetamine.methylation.html , but there's quite a bit of further useful info here - like the yields and more detailed descritions of the procedures.










100 g of p-hydroxy-amphetamine, 250 cm3 of alcohol and the calculated qtty of formaldehyde soln were mixed together and stirred for 6 hrs in the warm with 70 g of aluminium turnings. After filtering and evaporating the soln in vacuo, the residue was dissolved in alcohol and the calculated (Does that mean 'quantitative yield??) qtty of dilute H2SO4 is added, whereupon the sulfate of p-hydroxy-metamphetamine precipitated; mp freebase 163 C.






22,6 g of p-hydroxy-amphetamine were mixed with 17,4 g of benzaldehyde and warmed on a waterbath with frequent shaking. After removing the water which resulted from the rxn, the syrup-like product was heated (here we have soventless conditions - on Rh's page the rxn is done in benzene/Dean-Stark trap,  - note, the addition of DMS is exotermic) w/70 cm3 dimethylsulfate (BTW, earlier in the patent they say MeI can also bee used as well) and when the rxn was completed, the mixture was heated w/70 mls dilute HCl until the benzaldehyde separated out. The cooled soln was shaken w/ether and the base pptated w/ammonia.

Yield 23 g (90% of theory).





More later - stay tunedwink,


Antoncho
 
 
 
 
    Antoncho
(Official Hive Translator)
06-07-02 09:06
No 318587
      N-monomethylation with diazomethane  Bookmark   

As submitted by Zealot to HyperLab:




"...the procedure is so simple (as all diazomethane procedures are) that i at 1st didn't even want to waste the bees' time posting it, but since you asked....
The amine is dissolved in hexane or ether, to it there's added 1-2% by weight of the amine CuSO4 (unhydrous) and an equimolar qtty of diazomethan in hexane is dripped into the mixtr. That's it.

The only difficulty would bee during separation of amines (an insignificant qtty of dimethyl derivative is formed). To do that one'd have to add to the HCl salts' soln a saturated soln of NaNO2. The monomethylamine's nitrosoderivative is xtracted w/ether and then hydrolized (i don't know exactly how - never bothered w/that). Dimethylamino salt doesn't react w/NaNO2 and stays in the aqueous phase. The non-methylated amine is converted to alcohol during the hydrolysis stage (BTW, i've heard that it's rather harmful to the body if not got rid of). So , IMHO, i just ain't worth bothering - esp. considering the fact that the qtty of impurities is negligible. The yield is usually around 95%, and the most part of the other 5% (~4%) is polymethylene, which is completely removed during A/B extraction."





See Post 288566 (Antoncho: "Diazomethane. Methylations with diazomethane.", Novel Discourse) for the preparation of diazomethane. BTW, Garin of HyperLab has made a great compilation on diazomethane from various literature sources - it contains several synthetic pathways to it as well as a ton of useful info on handling this compound safely - if anybee has a practical interest in any of the DM procedures, i'll gladly translate the meaningful parts.
Just let me repeat once again that every author i read says that DM is not so horrible in dealing with at all - if you follow the safety precautions and isn't dangerous at all in dilute solutions. Poisonous anyways, yessmile.

Regards to EveryBee,

Antoncho