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Author Topic: another paper  (Read 152 times)

antibody2

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another paper
« on: April 17, 2011, 12:55:26 AM »
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Quote from: Sedit on February 05, 2011, 02:30:51 PM
79% is not bad yeilds. To return almost 80% yeilds from an amalgum reduction, esp after there lengthy workup is taken into account.
I would like someone with experience beyond reading Rhodium archives to chime in an back me up here please.

79% is nothing to sneeze at. Here is another paper where they use an activated Al to reduce an imine, in the 2nd example. But they give no details about how the Al is activated :-\

jon

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Re: another paper
« Reply #1 on: April 17, 2011, 04:51:12 AM »
activated metals refer to activation with an acid usually.
for example zinc washed in dilute hcl is considered activated zn.
hope that helps.

letters

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Re: another paper
« Reply #2 on: April 17, 2011, 11:22:53 AM »
is this about reductive amination or nitroalkene/alkane reduction?

jon

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Re: another paper
« Reply #3 on: April 17, 2011, 11:57:57 AM »
it looks like a transfer hydrogenation using a metal catalyst.

antibody2

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Re: another paper
« Reply #4 on: April 17, 2011, 04:46:22 PM »
Quote from: letters on April 17, 2011, 11:22:53 AM
is this about reductive amination or nitroalkene/alkane reduction?

In this case its actually the amine being alkylated, as opposed to the carbonyl being aminated (six of one, half a dozen of the other)

letters

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Re: another paper
« Reply #5 on: April 17, 2011, 10:28:14 PM »
antibody, the first procedure in the patent seems to be acceptable. IIRC Klute from SM has posted a procedure for methylating amines with the more benign methyl tosylate as a methylating agent. He also shows how to make the needed tosylate, all accompanied with nice pictures and writeup. look it up.
The second procedure seems a bit puzzling. as you may know, many of us have tried to monoalkylate isopropylamines. ive yet to see it work with formaldehyde/paraformaldehyde yet. not to say that it doesnt. just that its hard to get the right conditions.
See the n-methylamine is usually a more reactive species then the primary amine. it reacts quicker then the primary amine, giving you a substantial quantity of dimethylated amine. Im sure something can be done to stop it at only mono alkylation, but ive yet to test a procedure which works well.

jon

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Re: another paper
« Reply #6 on: April 18, 2011, 01:41:03 AM »
quaternization with benzaldehyde/methyliodide
methyl anything
followed by hydrolysis seems to be the tried and true.

antibody2

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Re: another paper
« Reply #7 on: April 18, 2011, 04:22:32 PM »
Letters - I've seen Klutes work over at SM, He has an impressive body of work under belt. But it was the simplicity of the this patent appealed to me, simple easy to aquire otc reagents, simple rxn, no carcinogens, no hazardous waste, doesn't get much more benign (example 2 anyways). And sometimes di-alkylation is desirable, when working with tryptamines for instance.

For mono alkylations using an XS of amine or strictly stoichiometric amounts of the carbonyl should go a long ways towards arresting the rxn at secondary amines. The secondary and any leftover primary amines can be precipitated from solution by forming a carbamate derivative by passing CO2 through the solution, leaving any overalkylated tertiary amine in solution. And then later regenerated by base hydrolysis and heat.

Jon - I think the quaternization rxns are more problematic using MeI, than when using HCHO.

« Last Edit: April 18, 2011, 04:24:50 PM by antibody2 »

letters

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Re: another paper
« Reply #8 on: April 22, 2011, 03:01:21 AM »
an xs of amine or stoichiometric amounts of carbonyl have not inhibited dialkylation in my experience.
a carbamate, if will form from plain CO2 will be way too unstable to isolate in my opinion. a carbamate from carbonic acid is very unstable! in all the mechanisms i know for carbamte group removal, the last few steps hydrolyze it to the carbonic acid carbamate which then spontaneously hydrolyzes to the amine. I dont think you can use this as you are saying, but id love to be corrected!
whenever i need to n-mono-methylate some primary amine, i usually opt for protection with a benzyl group (benzyl chloride or benzaldehyde followed by nabh4), then form the methylimine with hcho and reduce that with nabh4. then i remove the benzyl group via pd/c hydrogenation. this is well documented in the literature and in my experience works. It is tedious, but works well.

Another important thing to mention, and i think most chemists will agree with me - many patents are riddled with bunk procedure due to the authors leaving out crucial parts of the procedures in order to make stealing it that much harder (i know ive done it). some of them are fully detailed, but many many more of them arent.
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