Nucleophilic Acyl Substitution

On to carbonyl chemistry part II! This time we will look at carboxylic acids and its derivatives, which includes acid chlorides, anhydrides, esters, and amides.

Put more succinctly, we are studying the functional groups where a carbonyl is attached to a heteroatom. These functional groups react differently than aldehydes and ketones. Why? The heteroatom changes the electronics significantly which impacts the electrophilicity of the carbonyl carbon.

Notice the title of this unit, nucleophilic acyl substitution.For this discussion, let Z represent the group attached to the carbonyl.Nucleophilic acyl substitution just means we will be substituting Z with a nucleophile.Mechanistically what needs to occur is

1)   A nucleophilic attack at the carbonyl carbon to form the tetrahedral intermediate

2)   Loss of a leaving group, which will be Z, as the carbonyl is reformed

How each of these steps occurs though changes depending on the identity of Z, reaction conditions, and reagents used. There are a lot of new reactions in this section. As we’ve said before, understanding the material will lessen the amount of memorization required for success. Listed above are a couple of questions you can ask as you try to solve each mechanism in this section. To answer these questions requires mechanistic reasoning which invokes the application of chemical concepts.

Watch the videos below to learn the details of the mechanistic pathways for substitution of carboxylic acid and its derivatives. Then test your own mechanistic reasoning skills in the practice problems.

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