Author Topic: Hydrogenolysis of Phenylalaninol.....  (Read 4693 times)

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java

  • Guest
Hydrogenolysis of Phenylalaninol.....
« on: July 31, 2004, 06:32:00 PM »
In mining through the large archives here at the hive I read 

Post 108597 (missing)

(dormouse: "drone's amphetamine synthesis contest  -drone 342", Novel Discourse)
from which psychokitty contributes to the amphetamine contest where she introduces her way to Methamphetamine starting with Phenylalanine .....anyway read it yourself but the point is a reference which she gives ,
Hydrogenolysis of Diaryl and Aryl Alkyl Ketones and Carbinols by sodium Borohydride and anhydrous Aluminum(III) chloride

AoiOno, Nobuko Suzuki, Junko Kamimura



for which deals with the reduction, to the respective Hydrocarbons, of Phenylalaninol alcohols  but it also works for the benzylic alcohols in ephedrine and Pseudoephedrine and phenylpropanolamine. One thing also she discusses the acylation of the amine prior to reduction to the alcohol in order to obtain at the end methamphetamine. Thank you psychokitty for your research........java


java

  • Guest
Syntheses of amino alcohols.....
« Reply #1 on: August 01, 2004, 01:18:00 PM »
Syntheses of Amino Alcohols and Chiral C2-Symmetric Bisoxazolines
Derived from O-Alkylated R-4-Hydroxyphenylglycine and S-Tyrosine


Vesna ^aplar,a,* Zlata Raza,b Darinka Kataleni},a and Mladen @ini}a

CROATICA CHEMICA ACTA CCACAA 76 (1) 23-36 (2003)
ISSN-0011-1643
CCA-2849



Abstract

Chiral C2-symmetric bisoxazolines 1b–f and 2b,c, derived from 4’-O-alkylated R-4-hydroxyphenylglycine or S-tyrosine, were prepared. As intermediates, a series of chiral amino alcohols
possessing substituted phenolic groups was prepared and fully characterized.

CONCLUSION
Chiral amino alcohols with free and substituted (alkyl,benzyl) phenolic groups have been prepared in high yields, using easily available reagents and mild conditions. They served as precursors for the preparation of either macrocyclic or acyclic chiral C2-symmetric bisoxazolines, designed
as ligands for metal-catalyzed enantioselective transformations.


josef_k

  • Guest
Re: for which deals with the reduction, to the
« Reply #2 on: August 02, 2004, 05:33:00 AM »

for which deals with the reduction, to the respective Hydrocarbons, of Phenylalaninol alcohols  but it also works for the benzylic alcohols in ephedrine and Pseudoephedrine and phenylpropanolamine. One thing also she discusses the acylation of the amine prior to reduction to the alcohol in order to obtain at the end methamphetamine. Thank you psychokitty  for your research........java




I wonder if it really works with ephedrine and related compounds. The article says they think the reduction works by first reducing the ketone to the benzylic alcohol, which is then dehydrated to the alkene, which is then further reduced to the alkane. But in the case of ephedrine the doublebond may migrate to make an imine, which could be hydrolized if you're unlucky. (See

https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenylacetone.html#ephedrine

)
But who knows if it will work until someone has tried it.  :)


java

  • Guest
Hydrogenolysis......
« Reply #3 on: August 02, 2004, 09:46:00 AM »

.....but in the case of ephedrine the doublebond may migrate to make an imine, which could be hydrolized if you're unlucky





josef_k At most the activity in the hydrogenolysis would be around the -OH making it an easier leaving group for the catalyst action of NaBH4 , however I don't see how it would revert to a double bond intermediate to reduce to its hydrocarbon.....unless you think there may be some activity with the methylamine group for which I doubt . The main activity with the Aluminum would be with the O.........java




armageddon

  • Guest
Pd/C and solvents
« Reply #4 on: August 05, 2004, 06:36:00 PM »
Java: Water is out of the question because of thionyl violent reaction to water , hence I need something that will put the alcohol in solution so it can react with the acid.

I thought of using chloroform, as I've used this in the reduction of ephedrine and pseudoephedrine to a chloroephedrine, but not sure that the alcohol will work in this solvent. I guess I will try a small sample for solubility.



For dehalogenations, DCM and chloroform are a good choice - but for hydrogenations, alcohols (maybe with additional acetic acid) are the solvents to be used with Pd/C...

http://www.strem.com/code/degussakit.html




Greetz A


java

  • Guest
Alpha-methyl-Aminoacids .....
« Reply #5 on: August 13, 2004, 05:20:00 PM »
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




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

  • Guest
Summary of Phenylalanine to Amphetamine
« Reply #6 on: August 18, 2004, 06:10:00 PM »

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.




........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          
--------------------------------------------------------------------------------
.......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/



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

  • Guest
Phenylalanine to amphetamine continuation.....
« Reply #7 on: August 19, 2004, 11:47:00 AM »
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

  • Guest
RP/I in the reduction of Phenylalaninol....
« Reply #8 on: August 19, 2004, 03:02:00 PM »
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.





........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

  • Guest
Deoxygenation of benzhydrols
« Reply #9 on: August 20, 2004, 06:43:00 AM »
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


java

  • Guest
Other methods.....
« Reply #10 on: August 20, 2004, 11:47:00 AM »
Organikum...check the reference Alper, H.; Salisova, M. J. Org. Chem. 1980, 21, 801.
it doesn't seem to be the right date or page , anyway check so I can find it.

Here is one that I found....

Reactions of Sodium Borohydride in Acidic Media; VII. Reduction of Diaryl Ketones in Trifluoroacetic Acid

GRIBBLE, Gordon W.; KELLY, William J.; EMERY, Sanford E.:
 

 



Will look for ...........

Carbonium ion-silane hydride transfer reactions. I. Scope and stereochemistry
Francis A. Carey and Henry S. Tremper
J. Am. Chem. Soc. 1968, 90, 2578.

Reductive deoxygenation of aryl aldehydes and ketones and benzylic, allylic, and tertiary alcohols by zinc iodide-sodium cyanoborohydride
C. K. Lau, Claude Dufresne, Patrice C. Belanger, Sylvie Pietre, and John Scheigetz
Org. Chem. 1986, 51, 3038.

Copper-complexes of pyridazine N-oxides; The synthesis and x-ray studies
 Akio Ohsawa, , Toshio Akimoto, Akio Tsuji and Hiroshi Igeta
Tetrahedron Letters Volume 19, Issue 23,  (1978)Pages 1979-1982


Organikum

  • Guest
Uhh ?
« Reply #11 on: August 20, 2004, 04:07:00 PM »
Alper, H.; Salisova, M. J. Org. Chem. 1980, 21, 801.

This is exactly how its referenced in the article from which I quoted this, with italics and bold......

Cant help it, sorry. Any chance to get hold of it by the authors or the reagent, Fe(CO)5 ?

Damn.


gsus

  • Guest
Alper and Salisova
« Reply #12 on: August 20, 2004, 06:57:00 PM »
right year/volume/page, wrong journal, i think. try Tet Lett.


java

  • Guest
The correct Reference on FE(CO)5
« Reply #13 on: August 20, 2004, 08:44:00 PM »
The iron carbonyl induced deoxygenation of alcohols

Howard Alper* and Marta Saliová

Tetrahedron Letters volume 21 773-890 1980

Abstract

Alcohols, able to form stable carbanions, are deoxygenated to hydrocarbons by treatment with potassium, iron pentacarbonyl, and then hydrochloric acid. Use of an alkyl halide in place of HCl results in reductive alkylation.


7is

  • Guest
Articles
« Reply #14 on: August 20, 2004, 08:50:00 PM »
A convenient reduction of amino acids and their derivatives
Marc J. McKennon, A. I. Meyers, Karlheinz Drauz, and Michael Schwarm
JOC 1993,58,3568-3571



Organometallic compounds of Group III. 49. Reductive deoxygenation of ketones and secondary alcohols by organoaluminum Lewis acids
John J. Eisch, Zhi Rong Liu, and Marek P. Boleslawski
JOC 1992, 57, 2143-2147



Carbonium ion-silane hydride transfer reactions. I. Scope and stereochemistry
Francis A. Carey and Henry S. Tremper
J. Am. Chem. Soc. 1968, 90, 2578.



Copper-complexes of pyridazine N-oxides; The synthesis and x-ray studies
Akio Ohsawa, , Toshio Akimoto, Akio Tsuji and Hiroshi Igeta
Tetrahedron Letters Volume 19, Issue 23, (1978)Pages 1979-1982



The iron carbonyl induced deoxygenation of alcohols
Howard Alper and Marta Salisova
Tetrahedron Letters 1980, 21, 801.


java

  • Guest
Phenylalaninol reduction .......
« Reply #15 on: August 21, 2004, 02:26:00 PM »
Organikum...maybe it's this article that you mentioned that dissapeared....

Selectivities in ionic reductions of alcohols and ketones with triethylsilane/trifluoroacetic acid
Herbert Mayr*a) and Barbara Doganb)

Tetrahedron Letters Volume 38, Issue 6  ,  10 February 1997,  Pages 1013-1016
DOI:

:10.1016/S0040-4039(96)02484-7

       

Abstract
The relative rates of reduction of alcohols and ketones by Et3SiH/CF3CO2H have been determined by competition experiments in order to derive scope and selectivities of these reactions.
-------------------------------------------------------------------------------------

As for the articles mentioned in the removal of OH groups I think the Fe(CO)5 has the most viability as the others seem to get busy real fast. Thanks to 7is there is a chance to read all of them and evaluate for one self.


Although the reduction of such secondary alcohols by this procedure proceeded smoothly and in satisfactory overall yields, the attempted reductions of primary alcohols and phenols, such as 1-nonanol and p-cresol, led to no conversion at all.




.....from"JOC 1992, 57, 2143-2147 "Reductive Deoxygenation of Ketones and Secondary Alcohols by Organoaluminum Lewis Acids"., hence althugh it may be good for Ephedrine ,a secondary alcohol, for our case it won't work.

My favorite so far is Hydrogenolysis of Diaryl and Aryl Alkyl Ketones and Carbinols by Sodium Borohydride and Anhydrous Aluminum(III) Chloride  Synthesis 1987;  736-738  

Post 523004

(java: "Hydrogenolysis of Phenylalaninol.....", Serious Chemistry)which may be a solution for both this primary amino alcohol and the secondary amino alcohol, ephedrine.

SYNTHETIC COMMUNICATIONS, 26(24),4647-4654(1996) "Deoxygenation of Acylferrocenes with Sodium Borohydride and Zinc Chloride". may have some more clues. I  will try to find it or maybe someone else could find it.


Noted in the articles retrieved the one mentioned in her reference Psychokitty "A Convenient Reduction of Amino Acids and Their Derivatives" the issue of acylating the amino acid Phenylalanine prior to reduction to the alcohol is covered as to get n-methyl-Phenylalaninol. A very good article that should be a must read if you're following the issues on this thread.....java




Organikum

  • Guest
not found
« Reply #16 on: August 25, 2004, 11:03:00 AM »

Tetrahedron Letters Volume 38, Issue 6  ,  10 February 1997,  Pages 1013-1016
DOI::DOI:

10.1016/S0040-4039(96)02484-7

  




DOI not found ?




java

  • Guest
The missing Tetrahedral article....
« Reply #17 on: August 25, 2004, 01:08:00 PM »
Here it is, it was already uploaded .....but was not found easy with the search ......java

Post 514666 (missing)

(scarmani: "Et3SiH / TFA Reduction - Improvements?", Serious Chemistry)


edit: I underestand the article is not found on the bord, so heere is the copy.....java

Selectivities in Ionic Reductions of Alcohols and Ketones with
Triethylsilane / Trifluoroacetic Acid

Tetrahedron Letters, Vol. 38, No. 6, pp. 1013-1016, 1997




java

  • Guest
phenylalaninol reduction RP/I.......
« Reply #18 on: September 03, 2004, 01:58:00 PM »
After searching through the  archives here at the Hive and asking questions from knowledgeable bee's I've been able to deduce the following which can be found and read from this thread,

1. Phenylalaninol can be reduced with the RP/I method , only increasing the reactants 1.5 as much as regularly used in the reduction of ( Pseudo) Ephedrine and at least a 24 hr. reflux as  recomended by Rhodium

2.The solubility of the alcohol is slight in water, hence recomended acidic acid or Phosphoric acid.

3. There is a concern brought to my attention as to cyclozation producing cycloamines, but I wonder if by running the reaction with 1.5  in excess of the reactants will create a strong acidic environment , as recomended to avoid this.

4. there is out there a post by Assholium where he gave details of the reaction and proof of its viability.....one quoted by Labrat

Note: Trying to complete this reaction with availabe methods already know here at the hive. Yes there is the NaBh4 Al(111), the hydrogenation methods the halogenation & hydrogenation methods , the few introduced by Organikum on this thread and those by Psychokitty

Will be looking for the elusive post  to bring to light any possible complications with this procedure....java


java

  • Guest
Another primary -OH reduction method...
« Reply #19 on: September 05, 2004, 03:41:00 PM »
More recently this was posted by Kinetic and thought this to fit nicely in this thread in dealing with the reduction of Phenylalaninol to a hydrocarbon........

Post 529529

(Kinetic: "More reductions with triethylsilane/boranes", Chemistry Discourse)