fajahadita
Harmless
Posts: 4
Registered: 13-1-2007
Location: Missouri, USA
Member Is Offline
Mood: No Mood
|
|
Eschweiler-Clarke for Ethyl or Propyl groups
Does anyone think that ethyl or propyl groups could be added to a primary amine to form a tertiary without forming quarternary salts by using a
modified version of this reaction??
Assuming the imine is still formed by the formic acid do you think it's possible to replace formaldehyde with ethanal or propanal to form ethyl or
propyl groups??
\"Nothing in this world is to be feared... only understood.\" - Marie Curie
|
|
|
Furch
Hazard to Others
Posts: 130
Registered: 8-10-2006
Member Is Offline
Mood: No Mood
|
|
I don't see a difference between this reaction and other reductive aminations? It's just that the Eschweiler-Clarke uses formic acid as the reducing
agent, instead of Al, NaBH4 or the like...
The question is whether formic acid will reduce the ethyl-imine and the propyl-imine, and my guess is that it will. It's just a hunch, so go look it
up somewhere to confirm it.
- Furch
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
The Eschweiler-Clarke reaction using aldehydes/ketones other than formaldehyde becomes called the Leuckart reaction or the Leuckart-Wallach reaction. Due to the lower reactivity of non-formaldehyde carbonyl compounds, it requires temperatures
as high as 150-180°C while the Eschweiler-Clarke reaction proceeds at bellow 100°C already. The Leuckart reaction with aldehydes containing
alpha-hydrogens generally gives crap. It does however work on many ketones, very often even if they contain alpha-hydrogens. It works best with a
mixture of formamide with some formic acid or else ammonium formate for aminations equivalent to reductive aminations with NH3. With alkyl amines in
formic acid it also works but less effectively since it is preferable to use a great excess of the amine for better yield (which becomes quite
difficult with large amines).
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
solo
International Hazard
Posts: 3975
Registered: 9-12-2002
Location: Estados Unidos de La Republica Mexicana
Member Is Offline
Mood: ....getting old and drowning in a sea of knowledge
|
|
Here is a nice method ,save one needs a closed vessel to do this reaction however I wonder if the alkylation of the amine will change the
izomerization and also if it will affect OH groups ....although in the study there was an amine alcohol and it seems to have survived.......solo
--------------------------------------------------------------------------------------
A SOLVENT-FREE AND FORMALIN-FREE ESCHWEILER-CLARKE METHYLATION FOR AMINES
Thomas Rosenau,1 Antje Potthast,1 Ju¨ rgen Ro¨ hrling, Andreas Hofinger,1 Herbert Sixta,2 and Paul Kosma
SYNTHETIC COMMUNICATIONS, 32(3), 457–465 (2002)
Abstract
Primary and secondary amines are N-methylated by a mixture
of paraformaldehyde and oxalic acid dihydrate in good to
excellent yields. The reaction proceeds without involvement
of organic solvents and toxic formalin. Reaction temperatures
of 100 C are required for the decomposition of oxalic acid
into the intermediate formic acid which acts as the actual
reductant. The reaction conditions have been optimized, and
the mechanism has been elucidated by means of deuteration
experiments.
Attachment: A Solvent-Free and Formalin-Free Eschweiler-Clarke Methylation for Amines.pdf (137kB)
This file has been downloaded 6205 times
It's better to die on your feet, than live on your knees....Emiliano Zapata.
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
| Quote: | Originally posted by Nicodem
The Leuckart reaction with aldehydes containing alpha-hydrogens generally gives crap. |
I must correct myself in that this generality is not as wide as I thought. Some aldehydes with alpha-hydrogen(s) do give moderate to good yields in
the Leuckart reaction as long as the amines used are secondary (see attachment).
The Behavior of Aliphatic Aldehydes in the Leuckart-Wallach Reaction.
Peter L. de Benneville, Jane H. Macartney
J. Am. Chem. Soc., 72, (1950) 3073-3075.
Attachment: The Behavior of Aliphatic Aldehydes in the Leuckart-Wallach Reaction.pdf (346kB)
This file has been downloaded 1816 times
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
solvent free Eschweiller-Clarke
I shouldn't comment after so quick a read but I wanted to ask, is the main reason for using oxalic acid in place of formic to be "greener?" Because,
as Solo points out, higher temps are need to break up the oxalic to generate the formic you still need.
The other question was, and this may be a really dumb one, besides unsaturated rings systems as in the case of benzaldehyde, what aldehydes don't have
alpha hydrogen?
|
|
|
not_important
International Hazard
Posts: 3873
Registered: 21-7-2006
Member Is Offline
Mood: No Mood
|
|
| Quote: | Originally posted by chemrox
I shouldn't comment after so quick a read but I wanted to ask, is the main reason for using oxalic acid in place of formic to be "greener?" Because,
as Solo points out, higher temps are need to break up the oxalic to generate the formic you still need. |
The main point is no free formaldehyde, the source of CH2 to become CH3, and a somewhat unpleasant material.
Concentrated formic acid is a drag to keep around, it slowly decomposes into water and carbon monoxide. Bottles of it have been known to explode as a
result of the pressure buildup, so now they generally have a pressure release vent in the cap. Formic acid is not as pleasant to measure out as oxalic
acid is, same goes for formalin vs paraformaldehyde.
The 100 C temperature isn't that different than needed anyway.
| Quote: | | The other question was, and this may be a really dumb one, besides unsaturated rings systems as in the case of benzaldehyde, what aldehydes don't have
alpha hydrogen? |
Take acetaldehyde, look at the methyl group. Replace each hydrogen there with a methyl group, so you get (CH3)3C-CHO
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
| Quote: | | Concentrated formic acid is a drag to keep around, it slowly decomposes into water and carbon monoxide. Bottles of it have been known to explode as a
result of the pressure buildup, so now they generally have a pressure release vent in the cap. |
how should I store mine?
| Quote: |
Take acetaldehyde, look at the methyl group. Replace each hydrogen there with a methyl group, so you get (CH3)3C-CHO |
OIC yeah it was a dumb question-thanks for straightening me out
|
|
|
not_important
International Hazard
Posts: 3873
Registered: 21-7-2006
Member Is Offline
Mood: No Mood
|
|
| Quote: | Originally posted by chemrox
how should I store mine? |
How concentrated? Bought or made?
Purchased formic acid is likely to have a pressure relief cap. Acid with a strength of 90% or less doesn't appear to be a problem; the reports talk
about 98% and above. I imagine that keeping the formic acid cool will reduce the decomposition rate.
more info:
http://info.anu.edu.au/hr/OHS/Hazard_Alerts/_Formic_Acid_Exp...
| Quote: | | OIC yeah it was a dumb question-thanks for straightening me out |
"Where are my car keys", waving about the hand holding the car keys.
Sometimes you need to step back from a problem, or set it aside, to see the answer.
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
my formic is commercial and is unopened so far .. cool storage away from the lab is possible .. I like the car key analogy ;^)
|
|
|
postart
Hazard to Self
Posts: 59
Registered: 29-6-2010
Member Is Offline
Mood: No Mood
|
|
Quote: Originally posted by Furch  | I don't see a difference between this reaction and other reductive aminations? It's just that the Eschweiler-Clarke uses formic acid as the reducing
agent, instead of Al, NaBH4 or the like...
- Furch |
I thaught the Eschweiler-Clarke was for N-methylation are you saying that it can be used to reduce ketones to amines? Sherly Im misunderstanding your
statement?
|
|
|
postart
Hazard to Self
Posts: 59
Registered: 29-6-2010
Member Is Offline
Mood: No Mood
|
|
Has anyone ever heard of oxalic acid being used as a hydride donor for imine formation for reductive amination? Theoretically the oxalic acid could
dissociate giving two hydrides. One mole oxalic acid for two moles of ketone with an excess of the amine. Does this sound feasable? I couldn't find
any references of this ever being done.
|
|
|
UnintentionalChaos
International Hazard
Posts: 1454
Registered: 9-12-2006
Location: Mars
Member Is Offline
Mood: Nucleophilic
|
|
| Quote: Originally posted by postart | | Has anyone ever heard of oxalic acid being used as a hydride donor for imine formation for reductive amination? Theoretically the oxalic acid could
dissociate giving two hydrides. One mole oxalic acid for two moles of ketone with an excess of the amine. Does this sound feasable? I couldn't find
any references of this ever being done. |
This is not a long thread. If you had bothered to read to the fourth post (Which surely would have taken you all night), you would have found a
reference using oxalic acid.
Department of Redundancy Department - Now with paperwork!
'In organic synthesis, we call decomposition products "crap", however this is not a IUPAC approved nomenclature.' -Nicodem
|
|
|
postart
Hazard to Self
Posts: 59
Registered: 29-6-2010
Member Is Offline
Mood: No Mood
|
|
Its a reference of methylation for amines not reductive amination of ketones. Of course its the same mechanism.
[Edited on 10-1-2011 by postart]
[Edited on 10-1-2011 by postart]
|
|
|
postart
Hazard to Self
Posts: 59
Registered: 29-6-2010
Member Is Offline
Mood: No Mood
|
|
I was wondering while looking at this thread about making drugs.
research. don't double post.
[Edited on 29-1-2011 by Ramiel]
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
