Aurelius (Hive Bee)
11-25-01 08:57
No 240265
      hydrogenation  Bookmark   

. Hydrogenation of anhydrides also occurs readily over palladium and platinum catalysts at room temperature and 1 to 5 atmospheres H2 pressure

phenylalanine anhydride?
(Chief Bee)
11-25-01 11:47
No 240286
      Re: hydrogenation  Bookmark   

I doubt you can make that anhydride without the whole thing polymerizing into some polyphenylalanine.
(Old P2P Cook)
11-25-01 19:11
No 240356
      Re: hydrogenation  Bookmark   

You could perhaps make a mixed phenylalanyl/acetyl anhydride. What are anhydrides hydrogenated to, all the way to the methyl?

On further consideration maybe even a mixed anhydride would still polymerize. My thinking had been that if you reacted phenylalanine with acetyl chloride you would not only get the mixed anhydride but also produce the acetamide of the amino group which would protect the amino group from reaction with another phenylalanyl anhydride .
(Hive Bee)
11-26-01 00:23
No 240475
      Re: hydrogenation  Bookmark   

aurelius thinks that the reduction is to the methyl but not sure. it wasn't a ref or anything, just something that sparked an idea, good or bad.  and aurelius likes the N-protection that Terbium mentioned.  the mixed anhydride reaction was actually what aurelius originally had in mind (just didn't know how to call it)

(Hive Bee)
12-04-02 17:44
No 386220
      RE: hydrogenation  Bookmark   

I've been looking at the Dakin-West reaction on Phenylalanine and other alpha-amino acids,  in which both the carboxyl and the amine group get acylated to make an oxazolone. Now since it becomes an ester on both functional groups , my thought would be to reduce both in one sweep with   triehylsilane or trichlorosilane (one refrenced by Rhodeium's post and the later by a refrence from March's 5th edition text), which would give us meth amphetamine. What do you think......
(Chief Bee)
12-04-02 18:08
No 386229
      clarification  Bookmark   

An acetyl group on an amine is called an amide, not an ester, and if reduced you would get an ethylamine, not the primary amine.
(Hive Addict)
12-05-02 00:20
No 386334
      Simple guys...  Bookmark   

This is very basic peptide chemistry.

D-Phenylalanine is boc'ed with Boc2O, neat as a melt, or reflux in CHCl3. Yield ~95%.

Now there are two ways to proceed. You can make the the unsymmetrical anhydride with Ethyl or Isobutyl Chloroformate, or the like, in DCM with Triethylamine. Or you can make the symmetrical anhydride with 0.5eq. Dicyclohexylcarbodiimide in DCM, filter off the urea bypropduct, and proceed with hydrogenation.

I would assume that Pd/C, or PtO2 would work in a situation like this. Maybe CTH can be applied here, if so, that would be wonderful.
(Hive Addict)
12-05-02 01:00
No 386358
      new novel synth  Bookmark   

perhaps all this thrown together with refs could be a novel synth?  low hydrog pressures, and RT rxn?  with the exception of the Boc2O and the chloroformates the rxn shouldn't be too hard to run (obtaining chems is the hard part)
(Hive Bee)
12-05-02 04:06
No 386405
      Would an Fmoc group be stable?  Bookmark   

Any idea if an Fmoc protectiong group on the amine would be stable to the removal of the carboxyl group? Fmoc's are easily made by treating the amine with Fmoc-OSu and NaHCO3 at r.t. for ~24 hrs.  They are much more easily removed than Boc groups, needing only mild bases.

(Hive Bee)
12-06-02 17:29
No 386875
      Re: simple guys  Bookmark   

Well if you protect the amino group with BOC as you propose then take the symmetrical route , that is treating it with DCC( dicyclohexylcarbodiimide), then you would end up with an amide at the former carboxyl  site and urea,separate from the urea and then   leave the protecting group on and maybe a catalytic hydrogenation  with PD/C?  Ok then would the hydrogenation of the product reduce the amide to an alkane?  then one would remove the protecting group and the end result would be amphetamine ................did I understand you correctly?
(Hive Bee)
12-06-02 18:18
No 386896
      Re:Clarification  Bookmark   

Thank trying to find the holy grail a person can see what's not there at times, in doing so one learns a few things.

 With that said  after reading through nearly half of the post relating to phenylalanine I feel that the person who suggested hydrogenation of phenylalanine  to amphatamine had something . With that said , he/she also forgot to tell the bee's that first he converted the phenylalanine carboxyl group to an acytl group and the NH2 became acylated via Dakin -West reaction or something similar.

 The reasoning for that is that if you hydrogenate the said product with palladium the amide group returns to and amine and the acytyl group on the former carboxyl site is made to an alcohol Now its been shown that alcohols can be reduced to CH by catalytic hydgrogenation (Wizard X) hence the reaction may go through since there is an acidic environment  with the solvent , maybe methanol , after the removal or the amide group some CO is given and combined with a rich H environment a mild acid condition may in fact exist to complete the reduction of the alcohol to the Ch3.......hence amphetamine.

Perhaps its far fetched but the chemistry seems logical enough.  No references only stuff from March, Morris and boyd, and  Mc Murry, the tools of a learning student in the fine art of chemistry.

Saludos,(Greetings) from Latin America