There are five major groups of carboxylic acid derivatives.
They are: acid chloride, anhydride, ester, amide and nitrile.
Carboxylic acid derivatives also differ in their reactivity towards a nucleophile. Acid Chlorides are most reactive followed by anhydride, ester, and amide.
GENERAL MECHANISM
We can think of the group next to the carbonyl (C=O) group as the leaving group (or future leaving group). For example: Cl for acid chloride, OR for ester and so on. This group will be replaced by the nucleophile that is reacting with the molecule.
This general concept will be applicable to most reactions. You will see a lot of reactions in this chapter but the good news is that they are all similar in the nucleophile replacing the leaving group.
ACID CHLORIDE REACTIONS
Acid chlorides are most reactive and can be converted into carboxylic acids, anhydrides, esters, and amides. Again, we can just think of Cl as the leaving group and the nucleophile replacing it.
1. Acid Chloride To Carboxylic Acid Conversion
Reagent: H2O
Product: Replace Cl with OH
2. Acid Chloride To Ester Conversion
Reagent: ROH
Product: Replace Cl with OR
3. Acid Chloride To Anhydride Conversion
Reagent: RCOO- ( salt of carboxylic acid)
Product: Replace Cl with OCOR
4. Reaction of Acid Chloride with Organometallic Reagents ( Grignard or Organolithium)
Reagent: 1. 2RMgX or 2RLi 2. H2O, HCl
Product: Get rid of Cl. Turn =O into OH, and add two R groups (from RMgX) to the carbon with OH
For this reaction two equivalents of grignard or organolithium reagent are needed. The first equivalent attacks C=O pushing electrons up to the oxygen. In the next step electrons from the oxygen go down to make a double bond and kicking off Cl. The reaction does not stop here! Instead, another equivalent of Grignard or organolithium attacks the c=O pushing electrons up the oxygen. Finally, we use water or acid in the second step to protonate O- to become OH.
5. Acid Chloride To Amide Conversion
Acid chloride can also be converted to an amide by reaction with NH3 (ammonia) or primary or secondary amine. This reaction is fast and irreversible.
Reagent: NH3, RNH2 (primary amine) or R2NH (secondary amine)
Product: Replace Cl with NH2, NHR or NR2.
6. Acid Chloride To Ketone Conversion
Reagent: 1.R2CuLi 2. H2O
Product: Replace Cl with R from Gilman Reagent
ANHYDRIDE REACTIONS
Anhydrides are very similar to acid chlorides in their reactions. Let's take a look:
1. Anhydride to Carboxylic Acid Conversion
This is a reaction of anhydride with water.
Reagent: H2O
Product: Replace OCOR with OH
2. Anhydride to Ester Conversion