para-methoxy-prodine, worth dreaming about?

[pickle11]

if alpha-ethylstyrene were replaced with anethole and propionc acid replaced with glacial acetic acid in the Prodine synth

https://www.thevespiary.org/rhodium/Rhodium/pdf/prodine.pdf

  I think the product be something
like 1,3-dimethyl-4-(4-methoxy-phenyl)-4-acetoxypiperidine.  Anyone think it would be active?
In "Future Synthetic Drugs of Abuse" it is stated that a "limited scope of (prodine) derivatives"
have "appreciable analgesic activity." and cites (Berger et al. 1947; Ziering and Lee 1947;
Beckett et al. 1957; Loew and Jester 1975).  I dont have access to those articles, but i wonder what they mean by "appreciable".  If it takes 500mg to get a buzz and there are no neurotoxic impurities, it would be worth imagining such an easy synth.

[Rhodium]

Anethole is a betaalkyl-styrene, while the prodine synth calls for an alpha-alkylstyrene.  Is there anything in particular making you believe they could be interchanged, or is that an oversight on your part?

[pickle11]

I read this from the Complete book of ecstacy:

From alpha-methyl styrene
Alpha-methyl styrene (1-phenyl-1-propene; Benzene, 1-propenyl) and Bromine in 15% sulfuric acid. (51.5% yield). Alpha methyl styrene can be prepared by isomerizing allyl benzene with any of the methods used for isosafrole from safrole. Inoi, Japan 69 09,892 (1969); Chemical Abstracts vol 71, 61016x (1969). Use of the peracid oxidations for isosafrole can also be applied for alpha methyl styrene to yield phenylacetone. 

I just assumed alpha methyl styrenes were propenylbenzenes.  are there any OTC or naturally occuring alpha alkyl styrenes.  what about bromobenzene and and alkyl halides.  Any suggestions?

[Rhodium]

On what page did you find that information? It is definitely wrong, and should read "beta-methylstyrene" instead.

I don't know any OTC sources for alpha-alkylstyrenes. The needed alpha-ethylstyrene can be made by a wittig reaction of propiophenone.

[pickle11]

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tcboe/chapter5.html

the last paragraph on the page

[pickle11]

http://amorgos.pharm.auth.gr/alexidis/

confabstracts/abstract1.html

.N. Alexidis, E. Rekka, V.J. Demopoulos and P.N. Kourounakis.
Synthesis and protective effect of two new thiol containing compounds against mercuric acetate intoxication.
XIIIth International Symposium on Medicinal Chemistry, Paris 1994, abstract book, P142.
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Abstract

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Mercury has been identified as a highly toxic metal to man. It is well known that inorganic mercury, accumulated predominantly in the kidney, causes oxidative damage to renal tissue mainly in the proximal tubule cells. Furthermore, many data have shown that mercury can promote lipid peroxidation as well as loss of cell viability in isolated hepatocytes. In the present communication the synthesis of two novel thiol containing piperidine derivatives (I and II) and a preliminary study on their action against mercuric acetate intoxication are reported. For the synthesis of the two compounds different routes were followed. For compound I 4-piperidone monohydrate hydrochloride and propyl bromoacetate were reacted to produce n-propyl 4-oxo-piperidine-1-acetate, from which compound I was obtained after reaction with cysteaminum chloride. Compound II was obtained by reaction of cysteaminum chloride and 1-(2-phenylethyl)-4-piperidone, which was synthesized from phenethylamine and methyl acrylate, followed by a Dieckmann condensation and decarboxylation. The structures of the synthesized compounds were supported by spectral data and elemental analyses. The in vivo experiments were carried out in female Fischer 344 rats divided in eight groups, each containing 5-10 animals. Group 1 was given mercuric acetate, 6.2Ìmol/Kg, intraperitoneally once daily for six days. Groups 2, 3 and 4 were given mercuric acetate as in group 1 and compound I (15Ìmol/Kg), compound II (15Ìmol/Kg) and penicillamine (100Ìmol/Kg), subcutaneously, twice a day, for six days, respectively. Groups 5, 6 and 7 were given compound I, compound II and penicillamine as described above. Group 8 was given water intraperitoneally and used as control. The seventh day all animals were anesthesized with ether, blood was collected from the aorta, and liver and kidneys were removed. For the estimation of the cytoprotective activity of these compounds, serum alkaline phosphatase (ALP) and serum alanine aminotransferase (SGPT) were determined, liver and kidneys weight was recorded. From our results it can be concluded that both compounds I and II offer significant protection against mercuric acetate intoxication which is comparable to that offered by penicillamine, at doses much lower than penicillamine. Furthermore, the examined compounds were found to be less toxic than penicillamine as estimated by the parameters determined. The mechanism of this protection is also discussed.

[Rhodium]

Thanks, I have corrected the TCBOE document now.

Yes, the above procedure is a classic route to N-phenethyl-4-piperidone in the synthesis of fentanyl.

[pickle11]

did some research at the library and found out:
reacting ketene gas (from acetone) with formaldehyde in the presence of aluminum (or ferric) chloride yields beta-propiolactone.  This is reacted with methanol in the presence of a strong base to yield methyl hydracrylate, which is converted to methyl acrylate by the use of a catalyst. +  Phenethylamine via reduction of the nitrostyrene formed from benzaldehyde and nitromethane. Add some aniline, sodium borohydride, propionyl chloride (from propyl alcohol); and fentanyl doesn't look impossible. Probably pretty dangerous though.