I was reading M. V. Smith's book and stumbled upon this:
Amphetamines from Bromobenzenes JACS 63,602(1941)
0.2 M p-methoxy (or other group)-Br-benzene (see this paper for preparation) and 4.6 g Mg. Rapidly add 18.5 g chloroacetone in 50 ml ether. Evaporate the ether by heating in oil bath and then at about 135ø for one hour. Cool and add ice and dilute HCl; extract the oil with ether and dry, evaporate in vacuum to get about 11 g product (can distill 106/18). 0.057 M of the ketone product in 16 g formamide in 100 ml round bottom flask, with an air condenser. Heat twelve hours at boiling and then reflux with 35 ml 30% NaOH eleven hours and separate the amine layer and dry, evaporate in vacuum to get the amphetamine.
Now, this was somewhat discussed a long time ago - see
Post 108627 (missing)
(dormouse: "P2P -niteflier", Novel Discourse) But nothing particularly conclusive was voiced.
What is completely confusing about this synth is - is this a Grignar or it's just as simple as that - mixing chloroacetone, Ph-Br and some magnesium?
Sounds way too easy to bee true.
Maybee, someone can say smth informative about this? Any input will bee very appreciated.
Another similar possibility is to react a subst. benzene w/haloacetone in friedel-Crafts-like fashion.
However, i've never seen a proc. like that for a substituted ring (i thought i have but it turned out to bee a mistake so i edited it out). Has anyone?
Disclaimer: i have read absolutely everything concerning haloacetones that is on this site, so don't bother telling me it's too dangerous to work with.
Well, that's true, but someone i know did that quite easily with a help of an ordinary gas mask. OTOH, such rxns, should someone make them applicaple to subst'ted rings, would bee a revolutionary breakthrough, IMHO.
I also have an
excellent bromoacetone preparation procedure (which actually inspired my looking into these routes), submitted onto HyperLab by
Zealot, which i will post soon. Zealot says it can bee made w/out a gas mask, but not washed or transferred.
Antoncho