Amines in Nucleophilic Acyl Substitution

[justadream]

Can amines only do nucleophilic acyl substitution only in basic conditions (in which the nitrogen from the amine attacks the carbonyl first).

Contrast this with acidic conditions in which the carbonyl's oxygen is protonated first (before the nucleophile attacks).

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[Czarcasm]

Can amines only do nucleophilic acyl substitution only in basic conditions (in which the nitrogen from the amine attacks the carbonyl first).

Contrast this with acidic conditions in which the carbonyl's oxygen is protonated first (before the nucleophile attacks).

Based on the trend in leaving group stability, acid chlorides and anhydrides (both great leaving groups), can involve a nucleophile in it's neutral state (not acid or base promoted). Everything thereafter basically needs something to push it forward. So, after anhydrides: esters and amides must be base or acid promoted to act as a leaving group (we cannot use the word catalyst here since the base or acid is being consumed). So if you wanted to form an amide from an ester, there are two ways to do this: NH3 and H+ or NH2Na (but not simply NH3). From an acid chloride however, you could simply just add NH3 because Cl- is such a great leaving group (or even add it in a base or acid promoted state - although unnecessary for this particular substrate). Ultimately, it depends on what you're starting with.

 

[justadream]

@Czarcasm

Ok so if you have an ester and want to form an amide using NH3, you're saying you can either use base or acid to help it go forth.

Let's assume we use acid. Wouldn't the acid react with the NH3 first (before the NH3 even has a chance to attack the ester's carbonyl)?

That's why I was thinking that you can't form an amide using an acid.