Sciencemadness Discussion Board

Reductive amination - doing it without H2 and Noble Metal Catalysts!

stoichiometric_steve - 7-12-2007 at 10:31

this is one paper i had requested:

Primordial reductive amination revisited
Claudia Hubera and Günter Wächtershäuser
Tetrahedron Letters Volume 44, Issue 8, 17 February 2003, Pages 1695-1697


Abstract
Amino acids are formed efficiently by reductive amination of α-keto acids under aqueous, conditions with freshly precipitated FeS or Fe(OH)2 and with NH3, CH3NH2 or (CH3)2NH at pH values near their pKa.

<PDF>

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the authors describe a reductive amination of alpha-keto acids in low ionic strength aqueous medium with ammonia and lower aliphatic amines, their "catalyst" is freshly precipitated FeS or Fe(OH)2 from Fe(II)SO4*7H2O (in catalytic amounts!).

and the most astonishing thing is: they get pretty good yields of the corresponding amino acids!

the authors also quote that the carboxylic acid function is not involved in the mechanism of the reduction, hence this procedure might well be applicable to other water soluble substrates, maybe even to aqueous alcohol solutions.

i haven't previously seen any reductions quite like this. does this finally rid us of the use of Pd/C?

solo - 7-12-2007 at 10:52

Just to make sure we're all on the same page.......solo

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Primordial reductive amination revisited
Claudia Huber and Günter Wächtershäuser
Tetrahedron Letters Volume 44, Issue 8, 17 February 2003, Pages 1695-1697

Attachment: Primordial reductive amination revisited.pdf (64kB)
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Klute - 8-12-2007 at 04:48

This is quite a find! How could have guessed Fe2+ would be capable of reducing a imino-acid?!

I wonder what happens to the FeS2 and FeO(OH) after the reaction. FeS2 can't be that stable can it?

Though it's highly unlikely this kind of reductive amiantion could work on aliphatic imines, who knows what could happen with aromatic imines?
If anyone tries this out, I definatively want to hear about it!

not_important - 8-12-2007 at 07:06

Note the ratios
Quote:
...from 100 umol of the corresponding alpha-keto acid in the presence of 2 mmol FeS and 15 mmol NH4Cl...


1:20:150 is a lot of the reagents, even if they're cheap; so much as to get in the way of isolating products.

Wet FeS2 powder will slowly air oxidise, Fe(OH)3 will to to FeO(OH) which is pretty stable unless in acid environment where it form the Fe(III) salt.

stoichiometric_steve - 8-12-2007 at 07:15

Quote:
Originally posted by Klute
Though it's highly unlikely this kind of reductive amiantion could work on aliphatic imines


why not? thats exactly what the authors did. of course, there was a carboxylic function attached, but it didnt influence the reaction.

it's Fe(II)S, not FeS2. after the reaction, you probably end up with unchanged FeS. otherwise, it would not be employed in catalytic amounts.

the most interesting thing is that water is probably the electron donor in this system, since there are no other components that could deliver electrons.

i want to try this with pyruvic acid and methylamine to make racemic N-methylalanine.

another paper i had requested and that was supplied by solo describes Aluminum dodecatungstophosphate (AlPW12O40) as a non-hygroscopic lewis acid catalyst for Friedel-Crafts acylations.

since neat carboxylic acids can be used without solvent to acylate a variety of aromatic compounds, i hope that the N-reactivity of N-methylalanine will be low so no peptide formation occurs.

this would be the best route to cathinone analogues...

Klute - 8-12-2007 at 09:01

Damn, water is the reducer here? That's pretty unusual!
So the Fe catalyst would cause it to give off oxygen?
H2O --> 1/2 O2 + 2H+ + 2e- ??
Or could it be some kind of catalysed transfert hydrogenation? Maybe FeS would cause formate salts to decompose to H2 at a small extent, or transfert hydrogene in presence of rather strong acceptors..
So you don't think the carboxylic acid would influence the imine reactivity? Isn't the imine far more reactive with the electron redrawing properties of the COOH, compared to an simple aliphatic imine?

LSD25 - 9-12-2007 at 08:22

Yeah, what is also somewhat unusual is the references, all bar one or two were written by Wachtershauser - rings some alarm bells, what?:o

Perhaps they are telling the truth, but the fact that they are dealing with mmol quantities, massive excess of some reagents and an unusual reaction... Dunno, but I wouldn't be reaching for the champers quite yet:(

Hmmm, Wachtershauser doesn't sound Indian to me...

reply and request for pasting help

chemrox - 9-12-2007 at 17:55

Quote:
Originally posted by LSD25
Yeah, what is also somewhat unusual is the references, all bar one or two were written by Wachtershauser - rings some alarm bells, what?:o
Hmmm, Wachtershauser doesn't sound Indian to me...


What is the issue here? I'm not familiar with this gentlemen's work. Is there a problem? Why should anyone involved be Indian? This is kind of an esoteric dis. Please be more forthcoming or even better, restrained.

@steve-
can't one esterify the acid function and apply alcoholic KOH, Estweiler-Clarke, Wallach or Leukart methods? Zn and acid? Is STAB too hard on the ester or acid groups?

I'd like to paste an article here and can't recall how it's done..

[Edited on 9-12-2007 by chemrox]

not_important - 9-12-2007 at 19:38

Quote:
Originally posted by chemrox
Quote:
Originally posted by LSD25
Yeah, what is also somewhat unusual is the references, all bar one or two were written by Wachtershauser - rings some alarm bells, what?:o
Hmmm, Wachtershauser doesn't sound Indian to me...


What is the issue here? I'm not familiar with this gentlemen's work. Is there a problem? Why should anyone involved be Indian? This is kind of an esoteric dis. Please be more forthcoming or even better, restrained.


If the only refs are from the same person, with nothing related from independent researchers, you might feel a bit cautious about thee research, similar to a movie where all the reviews were from the producer.
Quote:

can't one esterify the acid function and apply alcoholic KOH, Estweiler-Clarke, Wallach or Leukart methods? Zn and acid? Is STAB too hard on the ester or acid groups?


KOH hydrolysis typical esters

esters react with amines

Is STAB able do do the reduction?

Klute - 10-12-2007 at 06:56

Quote:

another paper i had requested and that was supplied by solo describes Aluminum dodecatungstophosphate (AlPW12O40) as a non-hygroscopic lewis acid catalyst for Friedel-Crafts acylations.


I really want to hear about this when/if you do this reaction. Not been too keen on using large amounts of AlCl3, I've always restricted on performing Friedel-Crafts alkylation/acylations. Have you already aquired the two reagents to make this catalyst?
Going to see the article right away. Good luck with the reaction.

stoichiometric_steve - 10-12-2007 at 08:58

Quote:
Originally posted by chemrox@steve-
can't one esterify the acid function and apply alcoholic KOH, Estweiler-Clarke, Wallach or Leukart methods? Zn and acid? Is STAB too hard on the ester or acid groups?


most likely, this method (FeS) sucks ass, my O-Chem book says that a good way to the N-Alkylaminoacids is via the 2-bromoacids with the corresponding amines.
or you could try solo's eschweiler-clarke with oxalic acid and paraformaldehyde. personal communication with the authors of the latter method yielded no info if aminoacids could be used as substrates, though.

not_important:
you could certainly use STAB, although it's too expensive. and i think you can also use straight NaBH4 if you could manage to pre-form the imine...

Klute:
i haven't acquired neither AlNO3 nor H3PW12O40 a.k.a phosphotungstic acid (what a formula:P), but they are apparently quite affordable, and even more so when considering that the catalyst can be recycled.

stoichiometric_steve - 10-12-2007 at 15:08

Quote:
Originally posted by Klute
I realized they use quite an amount in the article, even if it's recylable... How about for a Friedel-Crafts? Have you got any related documents?
If this is getting too much off-topic, I'll use personal communications.


which article?

stoichiometric_steve - 12-12-2007 at 09:28

i'm talking about the article right below that one.