Hydrogenolysis of Phenylalaninol.....

[nightshade]

[Rhodium]

Überführung optisch aktiver ?-Aminocarbonsäuren in optisch aktive Amine mit gleichem Kohlenstoffskelett
P. Karrer & K. Erhardt

Helv. Chim. Acta 34, 2202-2210 (1951)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/pha2amph.ehrhardt.pdf)

Summary:
This is one of the first published methods for the conversion of L-Phenylalanine to d-Amphetamine. First phenylalanine is condensed with methanol to form phenylalanine methyl ester, which is reduced with LiAlH₄ to L-Phenylalaninol. This aminoalcohol is reacted with tosyl chloride in pyridine to give L-Phenylalaninol O,N-ditosylate. The O-tosylester was reduced to the hydrocarbon with LiAlH₄ to yield D-Amphetamine N-tosylamide, which finally was cleaved to give D-Amphetamine.

The same scheme was applied to L-Tyrosine, transforming it into 4-Hydroxy-Amphetamine.

[java]

This aminoalcohol is reacted with tosyl chloride in pyridine to give L-Phenylalaninol O,N-ditosylate. The O-tosylester was reduced to the hydrocarbon with LiAlH4 to yield D-Amphetamine N-tosylamide, which finally was cleaved to give D-Amphetamine.

Rhodium....I'm wondering , since I can't read german, if the author also gives an option to reduced the O-tosylester through catalytic hydrogenation since the tosyl are easy leaving groups or would you know if that is also an option , say using Pd in (don't know ) solvent.......java

[Rhodium]

They do not offer any such procedure in that publication, but I'm sure that it would work, somehow. Someone just needs to perform a literature search for it.

[java]

In searching for a confirmation in March's text,  on the reduction of Phenylalaninol  to Amphetamine  by using the RP\I method....I was able to find this study, once quoted as a needed reference

Post 172334 (missing)

(Rhodium: "HI/P reduction REFERENCES?", Stimulants) and never made available,  in which an arene aliphatic alcohol is reduced to the hydrocarbon with this system.....java


Synthesis of Desoxybenzoins . Deoxygenation with the Red Phosphorous /Iodine system

Tse-Lok Ho, C.M. Wong

Synthesis 161, 1975

[java]

Mining the web and following up leads in related articles , I came upon a couple of studies dealing with the reduction of arene aliphatic alcohols, checked the archives and found no listings on the HIve and so I present them here now for discussion.......java

Chlorotrimethylsilane/SodiumIodide/Zinc as a Simple and Convenient Reducing System:One pot Deoxygenation of Alcohols and ethers

Tsuoshi Morita, Yoshiki Okamoto, Hiroshi sakurai
Synthesis 32, 1981

Note: with this method both primary and secondary alcohols are reduced to hydrocarbons

Synthetic Method and Reactions;47. AlCl/Pd-Catalyzed Reduction of Aryl Substituded Alcohols and Olefins by Hydrogen Transfer from Cyclohexene

George A. Olah ; G.K. Surya Prakash

Synthesis 397, 1978

Note: with this method it seems only benzylic alcohols are reduced, might be a good way to reduce Pseudo-ephedrine......


Edited.....by java

[nightshade]

Fermenting phenylalanine in a bio brew like that producing L-Pac will will produce phenylalaniol, which can be extracted with a non polar solvent then reduced by electrochemical reaction to amphetamine is this correct?

[java]

nightshade....  do you have some references for that?..........I myself not familiar with the way you've outlioned the procedure.....java

[indole_amine]

[nightshade]

Post 9775,Post 10417

[java]

I just put brackets around the post number you volunteered as reference and this is what came up, hence it's easier to just click and go to it than having to go to the search engine looking for them. This will help your posting next time you want to reference a post number............java

Post 9775

(in_outsider: "Tryptophol from Tryptophan via yeast", Tryptamine Chemistry)

Post 10417

(psyloxy: "Re: Tryptophol from Tryptophan via yeast", Tryptamine Chemistry)

P.S. Thank you for the reference as I will read it and comment if I have any questions or suggestions

[java]

Thanks to gsus he has provided the referenced article

Post 533954

(gsus: "Fieser and Fieser for java", Novel Discourse)....that was posted by Labrat...on the reduction of Phenylalaninol with the RP/I method ......java

Labrat
Member   posted 08-31-98 09:57 AM          
--------------------------------------------------------------------------------
Labrat has already proposed a method to reduce that -OH to an alkane by a known method: HI/red P reduction. This reagent is
used in the literature to reduce carbonyl, nitrite, halide and ALCOHOL groups.
For those who like literature:

"Reagents for Organic Synthesis" vol 1: p.449 ('67)
"Survey of Organic Synthesis" vol 7 .332 ('70)

Thanks Stony for the refs!~ Lr/

......... as read in

Post 108462 (missing)

(dormouse: "Action of (CH3)2SO4 on phenylalanine  -Labrat", Novel Discourse)
                         

Post 101706 (missing)

(Labrat: "Re: DLPA reduction with H2SO4", Chemistry Discourse)

Reagents for Organic Synthesis, Vol. 1, Wiley, 1967, p. 449.
L. Fieser and M. Fieser

Note.....edited by java

[java]

Preparation of alpha ,alpha -Dimethyl- and N,alpha ,alpha -Trimethyl-beta -cyclohexylethylamine
Bernard L. Zenitz, Elizabeth B. Macks, Maurice L. Moore

J. Am. Chem. Soc. 70, 955-957 (1948)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/hi-rp.aminoalcohol2amine.pdf)

Excerp......
A reduction of alpha-methyl-norephedrine to alpha-methyl-amphetamine (Phentermine) with HI/P (80-88% yield). They use 20g RP to 0.4 moles of the aminoalcohol (66g, it has the same molar weight as ephedrine) together with 170 mL 57% HI. The mixture is reacted for 25h at reflux and 12h at room temp before workup (filtration, thiosulfate addition, acid/base extraction, distillation, gassing w/ HCl).

pdf is located at ......

Post 511694

(Rhodium: "HI/RP reduction of aminoalcohols", Stimulants)