The Hive > Serious Chemistry
Hydrogenolysis of Phenylalaninol.....
java:
Noted in the post listed under Chapter 3 "Ligans for Asymmetric Catalysed Cross Coupling Reactions"
Post 525324 (java: "ENANTIOSELECTIVE CROSS COUPLING REACTIONS", Chemistry Discourse)
......alpha-Methyl-amino acids are now accessible in enantiomerically enriched form via an enzymatic process, developed at DSMResearch Geleen.*8
--- End quote ---
Ref.
8. a) Kamphuis, J.; Boesten, W.H.J.; Broxterman, Q.B.; Hermes, H.F.M.; van Balken, J.A.M.; Meijer, E.M.;
Schoemaker, H.E. New Developments in the Chemo-Enzymatic Production of Amino Acids in Advances in
Biochemical Engineering/Biotechnology, Fiechter, A. Ed., Springer Verlag, Berlin Heidelberg, 1990, and references
cited therein. b) Kaptein, B.; Boesten, W.H.J.; Broxterman, Q.B.; Peters, P.J.H.; Schoemaker, H.E.; Kamphuis, J.
Tetrahedron: Asymmetry 1993, 4, 1113.
Note: this Tetrahedron article would be interesting to read.......java
java:
Phenylalanine is either refluxed with formic acid under a dean-stark trap or mildly reacted with acetyl-chloride or acetic-anhydride to form the formyl or acetyl amide, respectively. Then phenylalanine or any of the amides mentioned above are reduced with sodium borohydride and iodine in THF to form the aminoalcohol or its N-alkylated version. Yes, you read right! In an analogue to the reduction of phenylalanine using sodium borohydride/sulfuric acid formerly posted -- I think -- at the beginning of this thread, amides of phenylalanine are successfully reduced into their respective N-alkylated aminoalcohols in about 85-95%, if I remember correctly.
--- End quote ---
........as read in Post 108597 (missing) (dormouse: "drone's amphetamine synthesis contest -drone 342", Novel Discourse) the comment by Psychokitty
Hence a summery of where we are. Now we are able to either reduce Phenylalanine with the NaBH4+I , and get Phenylalaninol or we can first methylate the amine by the above method and react it with NaBh4 + I in THF and get N-Methyl-Phenyalaninol. Employing the method and reference provided by Psychokitty NaBH4Al(II) will reduce this amino acid to it's respective hydrocarbon. the alternative is the method that was proved by .....
Labrat
Member posted 12-24-98 09:38 AM
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.......This aminoalcohol is reduced by HI/red P at reflux to amphetamine. The validity of this method has recently been proven by Assholium (thanks!). Lr/
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found in the same post Post 108597 (missing) (dormouse: "drone's amphetamine synthesis contest -drone 342", Novel Discourse)
So now we have a method to either amphetamine or methamphetamine depending which route you take. However the essential catalyst and solvents remains being NaBH4, I2, THF, acetic anhydride.
I will find the thread were Assholium talks about this method of reducing with the well known RP/I but with some modifications from what I herd, 11/2 the amount of I as normally used in the reduction of ephedrine /Pseudoephedine.........java
References offered by Psychokitty in the comments quoted, the synthesis article is posted on this thread the others would be nice to secure to include with this thread....
JOC 1993,58,3568-3571 "A Convenient Reduction of Amino Acids and Their Derivitives".
And for the subsequent reduction of the primary alcohol I offer some super-duper stratagies and their references:
JOC 1992, 57, 2143-2147 "Reductive Deoxygenation of Ketones and Secondary Alcohols by Organoaluminum Lewis Acids".
SYNTHETIC COMMUNICATIONS, 26(24),4647-4654(1996) "Deoxygenation of Acylferrocenes with Sodium Borohydride and Zinc Chloride".
And the very fucking best of the lot:
Synthesis 1987, pp.736-738 "Hydrogenolysis of Diaryl and Aryl Alkyl Ketones and Carbinols by Sodium Borohydride and Anhydrous Aluminum (III)Chloride"
java:
I have a question which I need some help answering , in the hydrogenolysis of OH to CH3 of Phenylalaninol as mentioned in my last post where Assholium proved that RP/I would reduce the alcohol to the respective hydrocarbon, keeping in mind that Phenylalaninol is slightly soluble in water.
Now water is needed for the chemistry of RP and I to work into making HI and catalyse it to reduce the OH to CH3. As noted and mentioned by Rhodium Post 521414 (missing) (Rhodium: "Note the formation of HCl salts in the reaction", Serious Chemistry) on this thread the solubility of phenylalaninol and most amino alcohols are soluble in chloroform and DMF. But does that mean that the reaction solvent will be chloroform? Doubtful, hence it would be nice to find out the solvent Assholium used in his method which he showed this reduction of the alcohol to hydrocarbon.
So if there is anyone out there that has the answer, since I wrote to Assholium and no response, It would be nice to add to this project.......java
java:
I found this info as to using RP/I .....
Yes, it is possible to reduce most alcohols to the corresponding hydrocarbons with Hydriodic acid (for example made in situ by RP/I2). But as Phenylalaninol is a standard aliphatic alcohol rather than a benzylic alcohol (as in the case of (pseudo)ephedrine) the reduction is harder to perform, and you may need a larger excess of Hydriodic acid or a longer reflux time to pull it off. If you are going to try to reduce Phenylalaninol, I suggest that you start out with at least a 24h reflux and 1.5 times as much HI (or RP/I2) as you usually use to reduce (pseudo)ephedrine.
--- End quote ---
........as posted in Post 459611 (missing) (Rhodium: "Reduction of Phenylalanine to Phenylalaninol", Stimulants)
Note: I sometimes feel like I'm talking to myself.....
Edit: here are some articles that deal with RP/I ....
I would like to read this two
Reagents for Organic Synthesis, Vol. 1,
Wiley, 1967, p. 449.
L. Fieser and M. Fieser
Survey of Organic Synthesis, Wiley andSons, 1970, p. 7 and p. 332.
C. Buehler and D. Pearson
this last one is available ....
Methamphetamine Synthesis Via HI/Red Phosphorous Reduction of Ephedrine
Harry F. Skinner
Forensic Science International, 48 128-134 (1990)
aound here....Post 58319 (missing) (SuperAssman: "Interesting info from legit sci-dude", Stimulants)
Organikum:
There are more methods available some of which have not been talked about by now:
I except those which for sure only work on alpha-alcohols like the Li/ammonia (Birch)and those already mentioned.
Here we go:
1. Fe(CO)5
2. Diiododimethylsilane
3. Zinc iodide/sodium cyanoborohydride
4. Triphenylsilane in trifluoroacetic acid/methylene chloride
5. Sodium borohydride/trifluoroacetic acid
1. Alper, H.; Salisova, M. J. Org. Chem. 1980, 21, 801.
(this one would 9interest me in special as I have never heard of Fe(CO)5 as reducing reagent before - very curious I am!
2. Ando W.; Ikeno M. Tetrahedron Lett. 1979, 1979.
3. Lau C. K.; Dufresne C.; Belanger C. P.; Pietre S.; Scheigetz J. J. Org. Chem. 1986, 51, 3038.
4. Olah G. H.; Tremper H. S. J. Am. Chem. Soc. 1968, 90, 2578.
5. Gribble G. W.; Leese W. M.; Evans B. E. Synthesis 1977, 763.
And onto the RP/I a remark: Acetic or phosphoric acid are the solvents of choice here. The low solubility of the substrate is not really important - the reaction is heterogenous anyways and the solid substrate being where the HI is formed - at the bottom where the RP is - might even be favorable.
btw. I am rather sure that a suitable noble metal catalyst reduces ANY alcohol when trifluoroacetic acid is used as solvent and perchloric acid as moderator.
Also there was a post times ago by "chicken" AFAIK, where it was told that triethylsilane/aluminiumchloride in trifluoroacetic acid reduces aminoalcohols in yields up to 100%. No reference was given, the post has vanished like so many useful posts did.
Looking at the reagents used in the above references it seems very probable that this works. Silanes have become a mass-product in the last years, not too expensive and not watched by now. They are produced in tons over tons by Wacker-Chemie Burghausen in Germany. (thats no source, you cant buy it from them directly, but your industrial chem-supplier can do so)
ORG
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