Author Topic: Ritter Reaction: No Go For MD-Amphetamines? Why?  (Read 913 times)

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PrimoPyro

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Ritter Reaction: No Go For MD-Amphetamines? Why?
« on: March 10, 2002, 05:49:00 AM »
Why not? I don't understand why the Ritter Reaction "does not work" for methylenedioxy-amphetamines?

Does it fail for all substituted benzenes? How come? I does not understands...

                                                   PrimoPyro

Vivent Longtemps La Ruche!

Rhodium

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Why the Ritter Reaction Fails for Safrole
« Reply #1 on: March 10, 2002, 12:14:00 PM »
The Ritter Reaction involves the use of 50/50 acetonitrile:sulfuric acid as reaction medium, which turns added allylbenzene into 3-phenylpropyl hydrogen sulfate, which via a carbocationic intermediate adds across an acetnitrile molecule, and under the extremely acidic conditions the alkyl chain add to nitrogen and the sulfate to the carbon, forming an oximidic acid sulfate, which upon dilution of the reaction mixture with water forms the corresponding oximidic acid, which quickly tautomerizes to N-acetyl-amphetamine.




The conditions used - hot 50/50 acetonitrile:sulfuric acid - does not allow the reaction on any substrate with acid-sensitive functionalities like a methylenedioxy ring. A low yield may perhaps be obtained with methoxybenzenes, but the ritter reaction fails with safrole1, and the major isolable product after the reaction is 3,4-dihydro-1,3-dimethyl-6,7-methylenedioxyisoquinoline2.



[1]

J. Am. Chem. Soc. 74, 763 (1952)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/ritter.reaction.safrole.pdf)
[2]

Journal of Clandestine Laboratory Investigating Chemists Association

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/clic.html)

Offline nomud2.0

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Re: Why the Ritter Reaction Fails for Safrole
« Reply #2 on: July 20, 2017, 08:59:50 PM »
 title="View this image">[/url]

>[1] <html><body><p>J. Am. Chem. Soc. 74, 763 (1952)</p></body></html> (https://www.thevespiary.org/rhodium/Rhodium/pdf/ritter.reaction.safrole.pdf)
>[2] <html><body><p>Journal of Clandestine Laboratory Investigating Chemists Association</p></body></html> (https://www.thevespiary.org/rhodium/Rhodium/chemistry/clic.html)
[/quote]     

The above result of the Ritter rxn w/ safrole MDisoquinoline(image) If HCN is used instead of CH3CN the methyl group beta to the aromatic ring wouldn't be there, and if the  imine was reduced.It might,just might cleave off the aromatic ring under "reverse Mannich disconnection reduction" conditions eg; Heat formic acid/formamide similar to the cleavage of tetrahydro-B-carbolines.Kind of a reverse Pictet-Spengler Rxn. = P/S
for MDMA ;D

The odd thing is in general when a benzyl group is used as amino protection.As in benzphetamine,hydrogenation cleaves it off as toluene giving methedrine.

As a starting material 3,4-MD-benzylamine with HOCH2CHXCH3--then Ac amino protection -> 3,4-MD-ArCH2N(Ac)CH(CH2OH)CH3, then Friedel-Crafts subs the hydroxyl w/ -H20; for the  MD-tetrahydroisoquinoline.That might cleave also under reverse Mannich rxn for MDMA.

Where the first example given by Pictet-Spengler which used a unsubstitued ring  PEA.
For the tetrahydroisoquinoline from PEA and formaldehyde.

Later investigators couldn't reproduce P/S results with PEA.Actually, the P/S rxn is a Mannich rxn.. P/S reported this one year before Mannich reported the Mannich rxn.Thus, in reality P/S invented the Mannich rxn.P/S's  first reported rxn wasn't repeatable by later researchers.

I have a lot to say about this scheme,and will go into it later when time permits.
It's one of my pet peeves.
« Last Edit: July 30, 2017, 07:55:04 PM by nomud2.0 »
All that and a bag of chips too ;)