Graf-Ritter rxn: allylbenzenes to amph's directly

[Antoncho]

Good morning oh my dear friends!

Ever heard of Graf-Ritter reaction? There are many variants to it (AFAIUTFSE'd, the classic one uses HCN), but the one you're about to read is thus far the best. It was submitted to

HyperLab forum

(http://www.voy.com/12987/) by our dear friend and comrade Zhenya aka ChemTrip.

It uses MeCN in H2SO4 to make amphetamines directly from allylbenzenes, although the yields are low (circa 30-35%)



Well this process's applicability is certainly narrowed by the need for strongly acidic conditions, esp. during hydrolysis - however, in PiHKAL/DON Shulgin mentions that DON's N-formyl derivative was easily hydrolized w/3 N HCl. I don't know if the same will bee true for acetamides, but evidently methoxies may survive where amides don't. I also wonder if there are any other ways to cleave that amide bond...

Whatever - hope you liked it.

Antoncho

[lugh]

Despite the fact that safrole is specifically mentioned in US 2,573,673; no bee has reported any success, though not for lack of effort. Polymerization seems to bee the problem  

[Osmium]

Os. knows someone who tried that reaction on a 1 mole scale using safrole many many years ago.
The temp rose slowly to 40°C, and then in about 2 seconds to 80°C. Almost all the flask contents came out of the reflux condenser, spraying the table, ice bath, walls and ceiling with dark black ugly sulfuric acid containing reaction mix and solvent vapors.
The leftovers were worked up anyway, yielding a few hundred milligrams of brown sticky gooey crystals. The desperate researcher swallowed them anyway. There was some eye dilation and a certain lightheadedness but none of the honey magic.
What was that shit he isolated there? An isoquinoline derivative?

[lugh]

Probably, use of cyanogen chloride and methanesulfonic acid may bee more fruitful  

[Antoncho]

A side note/question: i know that p-bromo-A is a neurotoxin, but is it active? I heard from a Russian bee a report that p-chloro is, but he didn't give any details.

Because SWI-mentioned-above-Zhenya made it w/this method (w/50% overall yield!) and says it didn't do anything. So is p-Br-A really inactive or what else could have happened?

Antoncho

[Rhodium]

Para-haloamphetamines should have a subjective pharmacology between amphetamine and MDA in doses of ~100-150mg, but I don't reccommend human experimentation.

Edit: Also see

Post 280053

(Rhodium: "Why the Ritter Reaction Fails for Safrole", Chemistry Discourse)

[halfapint]

Ritter in the patent prefers sulfuric/sulphonic acids, but does mention use of phosphoric acid, SnCl2, and BF3. None of which will do asarone any good.    HCN, short or long chain nitriles will work; cyanogen, even cyanamide. Nitriles formed by rearrangement of Hofmann isonitriles, (from an amine with chloroform and lye,

Post 261573

(halfapint: "Re: HCN, NaOH and BzCN", Methods Discourse)) save the HCN/NaCN handling problems.
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1000000 heads high