Sciencemadness Discussion Board

Which route to Nonivamide (Capsaicinoid)

The new One - 19-10-2018 at 10:08

Hey guy's,

since summer i love hot peppers and it's capsaicinoids.
I'm interested in the synthesis of the synthetic capsaicinoid Nonivamide, because pelargonic (nonanoic) acid and vanillin are easy to obtain.

The synthesis of capsacinoids by acylation of vanillylamine with fatty esters is a good way to perform the synthesis of nonivamide.
But i've looking for an easier way, without much effort.

Is it possible to form an schiff base of Vanillin and pelargonic acid amide with thf or ethyl acetate as solvent and molsieve 3å as water scavenger?
And the reduction of the schiff base afterwards by an addition of methanol and sodium borohydride?

Have thx and nice regards
TMO



[Edited on 19-10-2018 by The new One]

[Edited on 19-10-2018 by The new One]

Assured Fish - 19-10-2018 at 14:54

Unfortunetely no you cannot form an imine (schiff base) from an aldehyde and an amide.

The reason i think is because there is partial resonance on an amide this prevents an amide from forming a nitrogen cation (RNH3+), this is what makes it impossible for acids to form quarternary salts with amides and is also what prevents amides from reacting with ketones and aldehydes.

CuReUS - 19-10-2018 at 17:45

Quote: Originally posted by The new One  
Is it possible to form an schiff base of Vanillin and pelargonic acid amide with thf or ethyl acetate as solvent and molsieve 3å as water scavenger?
It could be done -https://www.ncbi.nlm.nih.gov/pubmed/14502613?dopt=Abstract
Quote:
And the reduction of the schiff base afterwards by an addition of methanol and sodium borohydride?
better to use cyanoborohydride or STAB

The new One - 20-10-2018 at 01:44

At first have thanks for the response.
Quote: Originally posted by Assured Fish  
Unfortunetely no you cannot form an imine (schiff base) from an aldehyde and an amide.

The reason i think is because there is partial resonance on an amide this prevents an amide from forming a nitrogen cation (RNH3+), this is what makes it impossible for acids to form quarternary salts with amides and is also what prevents amides from reacting with ketones and aldehydes.


The reaction mechanism of the leuckart reaction with formamide shows the n-formyl imine as intermediate.
So i think it's possible under the right circumstances.

STAB is another good Option for the reduction, thx CuReUs

CuReUS - 20-10-2018 at 21:50

From the paper I linked above,the initally formed imine will undergo further reactions to give crap.So I was thinking of reducing it by mixing the reagents in a specific way.
there are 2 ways to run the reaction

1.Mix both the reducing agent and pelargonic amide in a flask and slowly add vanillin to it.This would reduce the imine as soon as it is formed.On the other hand,the excess reducing agent might reduce some of the vanillin as well

2.add the reducing agent and vanillin separately to a flask containing the amide.