Re: Phenmetrazine synth from propiophenone

[Rhodium]

Summary is fine for references from common journals - but I would appreciate an experimental part if the journal is obscure in any way, such as being more than 100 years old, or if it is russian/asian - because it is often impossible to find those even in large libraries.

[Mountain_Girl]

I can't help with the synth, except to say that the references the Merck mentions are (Phenmetrazine):

Patent US3018222

,
Clark, J. Org. Chem. 27, 3251 (1962) and,
Klosa, J. Prakt. Chem. 21, 12 (1963).

I know almost nothing about this compound but have recently been wondering if its psychedelic analogues have ever been tested, eg. 2,5 dimethoxy phenmetrazine or something ?

[GlaseIs]

For those that don't know, Phendimetrazine is the weight loss drug Bontril (ick who made that name?), and its only scedule 3. With the extra N-methyl, one would think that Phenmetrazine is to Phendimetrazine as Amphetamine is to Methamphetamine? Anyhow, these stimulate the release of Norepinephine like U4Euh does (notice the structural similarities there also)
On the 6th day God created man. On the 7th day, man returned the favor.

[ztion]

Actually I think that phendimetrazine is weaker than phenmetrazine. I have not researched this seriously yet but i will soon. (There's an article in Läkartidningen which deals with phendimetrazine, 1974 jun sometime).
But think about this: Preludin (phenmetrazine) was discontinued because of the massive abuse. Now they instead make Prelu-2 (phenDImetrazine), why would they do that if phendimetrazine would be even better to abuse?
Also I saw on the web some list of amounts of different medications you could take into some country. You could take in x mg of phenmetrazine, but the amount for dimetrazine was actually x * 3 mg or something. This indicates to me that it is much weaker.
This is somewhat annoying, since phendimetrazine is much easier to make. If the amine is tertiary you don't have to reduce the propiphenone to an alcohol to cyclize it. You can just reflux it in formic acid. Presto! (GB862198 but it is only in GB791416 they mention that it only works for a tertiary amine). I wonder though if a hydroxy group "counts" to make a tertiary amine.. then we could use n-hydroxyetanolamine and just cyclize with formic as above... If we interpolate all other amines the n-hydroxy version should be just as active.

[ztion]

Ok, now I've read that article in Läkartidningen.

They say that the recomended dose (by the medical company?), 35mg 2-3 times a day, doesn't differ between phenmetrazine and dimetrazine. Also the acute tox. is the same, the central stimulating effect is also the same, registered as the effect on spontanous movement in rats. Later they find that fenmetrazine increases the blood pressure but phendimetrazine doesn't. At first they speculate that this may be because the n-methyl group, but a bit later they mentition that it may be because the phenmetrazine was d,l while the dimetrazine was d-.(!) It seems obvious to me that THAT was the reason it didn't have any blood presure increasing effects, and maybe also why they seem to think it is equipotent.
They also say that phenmetrazine is a metabolite of dimetrazine, with dimetrazine being dominanit in urin samples up to 5 hours after an injection, while phenmetrazine is in majority afterwards. Also there is some n-hydroxy metabolite.

Look up these references to find out for yourself:

Toxicol Appl Pharmacol 2: 589-601 1960: Pharm. and tox. studies of phendimetrazine.
Läkartidningen 1974 Jun 5; 71(23) 2385-2387

[Rhodium]

Optisch Aktives 2-Phenyl-3,4-Dimethyl-morpholin
Walter Otto

Angew. Chem. 68(5), 181-182 (1956)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/phendimetrazine.isomers.pdf)

[Rhodium]

The Phenmetrazine synthesis references from

Post 287622

(Mountain_Girl: "Phenmetrazine synth from propiophenone'", Stimulants)

Cis- and trans-3-Methyl-2-phenylmorpholine
Frank H. Clarke

J. Org. Chem. 27, 3251-3253 (1962)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/phenmetrazine.clarke.pdf)
____ ___ __ _

_{Über Synthese spasmolytisch wirksamer Körper. XIX.}
Synthese von Estern der Benzil- und Mandelsäure mit 2-Phenyl-3-methyl-4-(?-oxyäthyl)-morpholin
Joseph Klosa

Journal für Praktische Chemie 12-17 (1963)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/phenmetrazine-klosa.pdf)