Sciencemadness Discussion Board

Catalyst for Amide hydrolysis

Triflic Acid - 29-4-2022 at 08:19

Around 7 months ago I tried to produce vanillyl amine from capsaicin. That ended badly because I had trouble finding a good source of capsaicin. Then I got a position as a chemist and stopped home chemistry altogether to focus on work. Now, I want to try that again, having found a good source of capsaicin powder. However, from the last attempt, I know that my strategy of boiling it in HCl isn't too effective. I was wondering if anyone knew of any good catalysts for amide hydrolysis. I did see some data about using metal salts to stabilize the tetrahedral intermediate, but pretty must everything was difficult to obtain triflate salts or Niobium oxide. So does anyone have any experience with mild amide hydrolysis?

Tsjerk - 29-4-2022 at 11:49

Vanillyl amine is very sensitive to heating, even in steam it decomposes. I don't know what happens, maybe it is polymerization, maybe it is oxidization. But at least it is sensitive. I can't imaging there is a way to hydrolyze the amide without destroying the amine.

Pumukli - 29-4-2022 at 11:52

Boffis did a nice hydrolysis research on DEET years ago. Check his work here in the forum (or in the prepublication section), it may give you food for thought.

[Edited on 29-4-2022 by Pumukli]

aab18011 - 29-4-2022 at 15:30

Quote: Originally posted by Triflic Acid  
Around 7 months ago I tried to produce vanillyl amine from capsaicin. That ended badly because I had trouble finding a good source of capsaicin. Then I got a position as a chemist and stopped home chemistry altogether to focus on work. Now, I want to try that again, having found a good source of capsaicin powder. However, from the last attempt, I know that my strategy of boiling it in HCl isn't too effective. I was wondering if anyone knew of any good catalysts for amide hydrolysis. I did see some data about using metal salts to stabilize the tetrahedral intermediate, but pretty must everything was difficult to obtain triflate salts or Niobium oxide. So does anyone have any experience with mild amide hydrolysis?


https://www.nature.com/articles/s41467-020-17588-5
This shows some interesting methods.

Hope it helps

AvBaeyer - 29-4-2022 at 18:01

There is a known method for the "gentle" hydrolysis of an amide in order to isolate the amine portion. This involves the reaction of the amide with ethylenediamine with a catalyst such as ammonium bromide. The reaction is driven by the formation of an imdazoline from the acid portion of the amide. The reference is

DOI: 10.1002/anie.201202354 (Angew. Chem. Int. Ed. 2012, 51, 8564 –8567)

AvB

Triflic Acid - 29-4-2022 at 21:23

AvB, thanks, that look pretty intersting. I might give that a try once I can synthesize some ethyldiamine.

Fery - 30-4-2022 at 03:38

If your goal is just preparing vanillyl amine and not to study the capsaicin hydrolysis itself, then you can try this way:
vanillin + hydroxylamine -> oxime
vanillin oxime + Zn + CH3COOH -> vanillyl amine
https://www.arcjournals.org/pdfs/ijarcs/v5-i10/1.pdf

Attachment: 1.pdf (409kB)
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Triflic Acid - 1-5-2022 at 12:06

I’m actually trying to produce vanillin from capsaicin. So that doesn’t work for me sadly.

Dr.Bob - 2-5-2022 at 11:02

Using NaOH to cleave amides can work rather than 6N HCl, which is a common method, but requires heating to 60 C or more for many hours. The time and temp mostly depend on the exact amide/protein being cleaved.