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I had noticed that the aminolysis of esters is always shown without an initial protonation step:

Mechanism for formation of amide by reaction of amine with ester

https://www.chemistrysteps.com/esters-reaction-with-amines-the-aminolysis-mechanism/

https://www.youtube.com/watch?v=1saLns0_h8M

It is also drawn the same way in Clayden's 2nd edition page 204.

I could be reading too much into this but I found it strange that this was the case because the reaction between ammonia and aldehydes/ketones to form imines can be acid catalysed, and in that instance the reaction mechanism is always drawn starting with protonation of the carbonyl oxygen, rendering the carbonyl carbon more electrophilic.

How is this reaction carried out in the lab? Is there something preventing acid catalysis? One may be inclined to say acidic conditions may cause the amine to be protonated, making it significantly less nucleophilic. But this isn't a problem for the formation of imines, as long as pH does not dip too low.

Of course, this could be overthinking. But I was just curious if there was something deeper.

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  • $\begingroup$ Adding acid renders the amine much less nucleophilic $\endgroup$
    – Andrew
    Mar 30 at 23:01
  • $\begingroup$ @Andrew thanks. But I thought that since formation of imines using ammonia and aldehyde/ketone can be acid catalysed, why not the case here? $\endgroup$
    – Heat
    Mar 30 at 23:48

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You cannot know any mechanism for certain, but in any such question, the question is how would run an experiment to support or refute a hypothesis.

If all of the textbooks say it and assuming it's correct, the acid isn't involved in the rate determining step. I suspect that the amine is more likely to deprotonate your protonated ester on average than do an addition. The acid catalysis may be helpful in getting the tetrahedral intermediate to collapse.

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