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Topic: oxidation of pyridine derivative to N-oxide  (Read 369 times)

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Offline kriggy

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oxidation of pyridine derivative to N-oxide
« on: February 10, 2020, 03:27:00 AM »
Guys, I need a bit help:

looking for a conditions that would oxidize my pyridine derivative into the N-oxide, ideally at room temperature.
 

So far I tried excess of mCPBA in refluxing CHCl3 which si the only method that somehow worked but it took a week to fully consume the starting heterocycle. I tried peroxide with acetic acid but that didnt work at all, I tried 35% peracetic acid in acetic acid but that doesnt seem to work as well.
Im gonna try TFA+H2O2 today but are there any other conditions that could work? I dont belive I can make it at room temperature but as long as I can make the product its fine

Offline rolnor

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Re: oxidation of pyridine derivative to N-oxide
« Reply #1 on: February 10, 2020, 05:32:40 AM »
I know that you can make pertrifluoroacetic acid from trifluoroacetic acid and sodiumpercarbonate, this is a strong reagent. I dont have a reference, sorry. You should find in in Fieser&Fieser Reagents for Organic Synthesis I think.

Here is a reference:

https://www.organic-chemistry.org/chemicals/oxidations/trifluoroacetic-peracid.shtm

Offline hollytara

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Re: oxidation of pyridine derivative to N-oxide
« Reply #2 on: February 10, 2020, 09:50:18 AM »
Hopper had a review in 2009 in Progress in Heterocyclic chemistry.  The reagents discussed are MCPBA, peracetic acid, peroxy triflic acid, urea - peroxide complex, and triflic anhydride with sodium carbonate and hydrogen peroxide.  The last one is supposed to be good for resistant pyridines.

Offline rolnor

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Re: oxidation of pyridine derivative to N-oxide
« Reply #3 on: February 10, 2020, 10:41:09 AM »
Hopper had a review in 2009 in Progress in Heterocyclic chemistry.  The reagents discussed are MCPBA, peracetic acid, peroxy triflic acid, urea - peroxide complex, and triflic anhydride with sodium carbonate and hydrogen peroxide.  The last one is supposed to be good for resistant pyridines.

Do you really mean triflic anhydride? Trifluoromethanesulphonic anhydride?
A question is do you get bad conversion or byproduct formation? If the latter it does not help with stronger oxidizer maybe?

Offline kriggy

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Re: oxidation of pyridine derivative to N-oxide
« Reply #4 on: February 10, 2020, 10:42:56 AM »
Thanks guys, I think I found the review (not sure if its the exact one, Im at home atm) but they mention UHP+TFAA and it seems to work. Might have to fiddle with the equivalents a bit but it works at room temperature 

Offline hollytara

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Re: oxidation of pyridine derivative to N-oxide
« Reply #5 on: February 10, 2020, 11:10:53 AM »
Rolnor - they write it as (Tf)2O in the review, so I think that is what they meant - didn't look up the original paper

Offline hypervalent_iodine

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Re: oxidation of pyridine derivative to N-oxide
« Reply #6 on: February 10, 2020, 06:34:34 PM »
While looking for something else, I did find a paper that oxidises pyridine to the N-oxide in quantitative yield using cyclohexanone dioxirane (compound h). I don't have any experience with the cyclohexanone version, but have worked with DMDO extensively in the past with a lot of success. The only obvious concern is in terms of safety - dioxiranes tend to be vigorously unstable. DMDO you make at such low concentrations that the risk is negligible, or you generate it in situ; I wonder if you couldn't adapt their procedure to use in situ generation of the cyclohexanone dioxirane as well.

https://doi.org/10.1021/ja00030a032

Offline hollytara

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Re: oxidation of pyridine derivative to N-oxide
« Reply #7 on: February 10, 2020, 11:09:34 PM »
DMDO is a useful oxidant - have used it in the past.

Offline kriggy

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Re: oxidation of pyridine derivative to N-oxide
« Reply #8 on: February 11, 2020, 02:09:04 AM »
While looking for something else, I did find a paper that oxidises pyridine to the N-oxide in quantitative yield using cyclohexanone dioxirane (compound h). I don't have any experience with the cyclohexanone version, but have worked with DMDO extensively in the past with a lot of success. The only obvious concern is in terms of safety - dioxiranes tend to be vigorously unstable. DMDO you make at such low concentrations that the risk is negligible, or you generate it in situ; I wonder if you couldn't adapt their procedure to use in situ generation of the cyclohexanone dioxirane as well.

https://doi.org/10.1021/ja00030a032

Thanks, I tried running the raction in acetone and using oxone to  make it in situ but didnt work. However, I got full conversion using TFA+H2O2 or TFAA+UHP so Im fine now :)
THanks for help guys

Offline rolnor

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Re: oxidation of pyridine derivative to N-oxide
« Reply #9 on: February 11, 2020, 04:29:30 AM »
Great!

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