PrimoPyro (Hive Prodigy)
03-25-02 15:16
No 287629
      New Possibility For Phenylalanine ---> Amphetamine  Bookmark   

Quoted from March's Advanced Organic Chemistry, 5th Ed., p.1156, 19-46: Reduction of Miscellaneous Nitrogen Compounds

"A cyano group can be reduced to a methyl group by treatment with a terpene such as limonene (which acts as a reducing agent) in the presence of palladium-charcoal. H2 is also effective, though higher temperatures are required. The R group may be alkyl or aryl."

Kindler, K.; Luhrs, K. Chem. Ber., 1966, 99, 227; Liebigs Ann. Chem., 1967, 707, 26

Well if this were applied to the nitrile of phenylalanine, PhCH2-CH(NH2)-CN, then the nitrile would be reduced to a methyl group, forming PhCH2-CH(NH2)-CH3, which is of course amphetamine. How to make the nitrile?



So if one were to use potassium thiocyanate with phenylalanine, forming the nitrile, one could then reduce the nitrile to a methyl with a terpene and Pd/C. smile

                                                    PrimoPyro

Vivent Longtemps La Ruche!
 
 
 
 
    Antoncho
(Official Hive Translator)
03-25-02 16:40
No 287644
      Awesome!!!  Bookmark   

This is simply W_O_W !

Afsolutely bucking awesome!!

This Letts synthesis alone is worth more than a three thumbs-up! Say, what of applying this to a subst'ed phenylacetic acid? (PolytheneSam, you're reading this?)

If only some one could give us more precise data on this synthwink - too bad, usually noone gives a fucksmile

Antoncho
 
 
 
 
    Greensnake
(Newbee)
03-25-02 17:02
No 287646
      Not sure...  Bookmark   

SWIM as professional pessimist higly doubts that this will work. Look at link:
http://themerckindex.chemfinder.com/TheMerckIndex/NameReactions/ONR233.htm

233.

Letts Nitrile Synthesis

E. A. Letts, Ber. 5, 669 (1872).

Formation of nitriles by heating aromatic carboxylic acids with metal thiocyanates

These old funny reactions almost always are fairly limited in scope.
 
 
 
 
    java
(Stranger)
03-25-02 21:24
No 287734
      re-phenylalanine to amphetamine  Bookmark   

what happens to the very active amine group , how is ist protected?  Or since its more reactive than the carboxyl end why not methylate  it first then go one to the carboxyl site with the conversion to..........what you stated.  Just a  thought  after reading Mc Murry's  text  on the chemistry of amino acids.
Note :the pK a of COOH( -)=2.6 and the pKa of NH3(+)=9.2  so the amine aide will have a greater  affinity to react .  At least that's the way I read it.
 
 
 
 
    malvaxman
(Hive Bee)
03-26-02 10:23
No 288032
      Great!  Bookmark   

Great! But I think for most bees its more easy to get 1kg amphetamine than 1g potassium thiocyanate crazy
 
 
 
 
    PrimoPyro
(Hive Prodigy)
03-26-02 10:25
No 288033
      What?  Bookmark   

Why would that be? I can go buy it from the photo supply down the street! Its $22 per 100g.

Where can I get a kilo of amphetamine for $22? tongue

                                                     PrimoPyro

Vivent Longtemps La Ruche!
 
 
 
 
    Rhodium
(Chief Bee)
03-26-02 10:31
No 288036
      nitrile & cth  Bookmark   

Just a little tidbit: The Pd/C and limonene forms a classic catalytic transfer hydrogenation (CTH) system, where the limonene gives up hydrogen atoms to the nitrile. I bet other hydrogen donors like cyclohexene, ammonium formate or hydrazine would work too.

Don't give up on the nitrile synthesis just because the hyper-simple Lett's reaction doesn't seem suitable - there are a dozen other ways to make nitriles.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
03-26-02 10:35
No 288037
      Nitrile + CTH --> Amines  Bookmark   

Rhodium: I thought that when nitriles were reduced with CTH, they formed amines?

Also, I am about to type up an additional question in my general chem question thread. Id much appreciate it if you would have a look at it in a minute.

                                                    PrimoPyro

Vivent Longtemps La Ruche!
 
 
 
 
    Rhodium
(Chief Bee)
03-26-02 11:15
No 288049
      CTH  Bookmark   

Yes, usually they do. But what would treatment with limonene/Pd-C be if not a CTH? I guess the products are simply dependent on the reaction conditions.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
03-26-02 11:21
No 288051
      I agree  Bookmark   

I agree that by definition it is a catalytic transfer hydrogenation, I just made that one distinction is all.

I wonder, could the cycloalkene be part of the same molecule as the nitrile? laugh

For instance, 1-cyclohexenyl-2-amino-propionitrile being self reduced and dehydrogenated to amphetamine. laugh

                                                    PrimoPyro

Vivent Longtemps La Ruche!
 
 
 
 
    Rhodium
(Chief Bee)
03-26-02 11:39
No 288058
      intramolecular cth  Bookmark   

In theory, yes, but one always need an excess of the hydrogen donor.
 
 
 
 
    Sunlight
(Pioneer Researcher)
03-26-02 13:45
No 288081
      More CTH  Bookmark   

CTH is super interesing reducing procedure, and I've seen in some papers that acoprding to the condicions can redice nitros selectivily without affecting for example nitriles, but it seems that there are CTH procedure to reduce nitriles to amines as well, and other to reduce oximes, I believe that the Hive should study more this kind of rxns. Could I suggest the refernce reseatcher to find and post all the CTH reductions possible ?
 
 
 
 
    Aurelius
(Hive Bee)
03-27-02 06:03
No 288408
      Primo  Bookmark   

Hey PrimoPyro, where'd you get the idea for that rxn?  aurelius posted something on this same general area a while back.  actually, aurelius still has an article from JACS or JOCS or something like that on this. 
 
 
 
 
    slappy
(Hive Bee)
03-27-02 06:48
No 288414
      Amino acid, people.  Bookmark   

It needs to be taken into accound that this is an Amino Acid. A R-COOH with and alpha-NH2 dos not react like a normal aliphatic carboxylic acid. In fact, it is a neutral species existing >95% of the time as the zwitterion. i.e., -CH(COO-)N+H3 .

The acid group is not acidic, and the amine is not basic. The way you usually get the carboxylic acid to act like an acid is to deactivate the Amine as a carbamate. Usually FMOC or BOC. And the way to get the amine to behave like an amine is to make the ester of the -COOH.
 
 
 
 
    java
(Hive Bee)
12-02-02 17:51
No 385526
      Re: Amino acid to honey  Bookmark   

Slappy: You are right about the protecting group, but one can make the alcohol without it , hence "a mixture of NaBH4 and I2  has been used to reduce amino acids to amino alcohols" see Mckennon, M.J.;Meyers, A.I.;Drauz, K.; Schwarm.M.J.Org. chem., 1993,58,3568

Primo :  page refrence on your post should be  1556 on your March's refrence.

Note:   SWIJ efforts are to make honey from   Phenylalanine so I'm always looking. So with that said (see )"Carboxylic acids can also be converted to alkanes , indirectly , by reduction of the corresponding tosylhydrazides (RCONHNH2) with LiALH4 or Borane"  quoted from Marche's 5th edition page 1552.
Note: on   this procedure one will have to use a protecting group for the amine since we want it to behave as an acid.

 Ref:

 Degani,I.;Fochi,R.J. Chem.Soc.,Perkin Trans. 1,1978,1133.

for a direct methos , (see) Le Deit, H.;Cron, S.;Le Corre, M. Terrahedron Lett.,1991, 32, 2759

Attanasi, O.;coglioti, L.; Gasparrini, F.; Misiti, D. Tetrahedron, 1975, 31,341,and cited refrences
Note :see../rhodium/chemistry /amphetamine.phenylalanine.html   I think something here will be extrapulated to use for the final step from alcohol to an alkane hence honey...........will report on the effort.

Saludos (Greetings), from Latin America