methedrine from amphetamine

brain · Linguist Extraordinaire

from rhodium:

brain · Linguist Extraordinaire

or maybe the next method will be better?

IndoleAmine · Dreamreader Deluxe

both formaldehyde and formic acid do the same in these rxns: they form the amphetamine n-formyl derivative (which is an amide) when heated with amphetamine freebase..
(the thing is called reductive methylation and is known as the "leuckart reaction")

So: first amine + formaldehyde, heat and dehydrate; then add the result to Al/Hg to reduce the n-methylamide to the n-methylamine. Sounds logical, no?

cheers

i_a

brain · Linguist Extraordinaire

yes, but how to dehydrate the mixture? i broke my dean-stark Sad

... mgso4-will be fine?? or mabey silicagel??

IndoleAmine · Dreamreader Deluxe

I would choose silica gel. MgSO4 is more likely to react with any of the reagents when being heated, but silica is fairly damn inert to anything, excluding very strong acids like conc.H2SO4 of course, but still better than MgSO4 for most purposes, and silica works better, less water/liter solvent remains!!)

Heat to reflux with enough silica gel to take up all water (check drying agent selection guide found in the rhodium archive!), should work to form the imine.

Maybe you can also use ethylformate for forming the amide, anyone experience with it?

(and you can also use simple dist. setup instead of dean-stark: just use separatory funnel as receiving flask, and from time to time drain the water off and return the remainder to the distillation flask, this removes the water too....
(then for the last small amnt. remaining use silica, thats what I would do)

i_a

IndoleAmine · Dreamreader Deluxe

And this route to n-methylated phenylisopropylamines generally sucks, so to speak. You have to make p2np, then reduce to amph, then methylate...

Better make some methylamine from your formalin solution, reduce the p2np to p2p with iron/HCl, then condense/dehydrate p2p with methylamine (silica gel!) to give the n-methylated shiff base(imine), then reduce that with Al/Hg.

Thats how it is done. In theory of course...

i_a

java · Consumer

Interesting reading on the subject.......java

Note:
( previously posted.)

https://www.synthetikal.com/synthforum/viewtopic.php?t=272
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The Action of Formaldehyde on Amines and Amino Acids
H. T. Clarke, H. B. Gillespie & S. Z. Weisshaus
JACS 55, 4571-4587, Nov. 1933

PDF

Excerp
The convenient method due to Sommelet and Ferrand [1] for the preparation of trimethylamine from ammonium formate, formaldehyde and formic acid, though its usefulness has recently been demonstrated
[2]in the case of anabasine, appears not to have attained general recognition as a means for the methylation of amines.

This process furnishes excellent yields of tertiary bases from simple primary and secondary aliphatic amines, including piperidine. Its ready applicability is illustrated by the complete methylation of tetramethylenediamine, the hydrochloride of which is extensively decomposed by heating at 125° with aqueous formaldehyde,
[3] and yields the tetramethyl derivative only when heated to 200° with dry paraformaldehyde. [4]
The reaction appears to be specific for formaldehyde, in contrast to its homologs, which apparently require higher temperatures [5] for corresponding changes to take place. Thus, a mixture of acetaldehyde, formic acid and ammonium formate yielded no carbon dioxide on heating on the steam-bath, and from the resulting bases only 2-methyl-5-ethylpyridine could be isolated. The reaction also fails with compounds which strongly polar groups are attached to nitrogen, such as amides,urea, guanidine and hydroxylamine; these appear to yield hydroxymethyl derivatives only.