I have a few hundred grams of phenylpropanolamine and would like to make ephedrine out of it - can anyone suggest a method for the reductive methylation?
n-methylation procedures are a pain in the ass, the only method that would yield something usable works as follows: form the benzaldehyde imine of PPA, treat with dimethylsulfate (have fun with that crazy toxic fuming shit...it does also methylate your DNA very well), hydrolize the imine and extract.
or you could reductively alkylate it with formaldehyde, but that method yields mostly di-N-methylated product, which is crap. i could figure out better uses for PPA
In going from NH2------>NHCH3 you are methylating an amine hence the methods proposed by *Rhodium do just that and doesn't methylate the asymetric carbon on the opposite side where the remaining H sits on the c2 carbon. To avoid dimethlated products.....
Quote:
To avoid this happening, we must usually resort to indirect methods of introducing the methyl group. One way is to react the amphetamine with formaldehyde (either as an aqueous solution, or as paraformaldehyde) to get the amphetamine formaldehyde imine, which can then be reduced to the N-methylamphetamine using a several different reducing agents, for example Al/Hg or Pt/H2.
Once you reflux your PPA in formaldehyde you can reduce as suggested in above quoted article or also use NaBH4- AlCl3 to reduce it to the secondary amine or catalytic hydrogenation with Pd 10% in methanol.
there's oodles of ways to methylaminate, formaldehyde and cyanoborohydride, methyl halides and dehalogenating reducing agents, formic acid/ammonia formate/formamide type leukart type reactions. The difficulty with the reactions is in restricting the methylation to monomethylation. the most accessible looking reaction i've seen so far is sodium borohydride and MoO3 or NiCL2 as catalysts. UTFSE (it's been discussed here recently) to find a PDF describing this reaction scheme.
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