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
This is a reaction of anhydride with alcohol
Reagent: ROH
Product: Replace OCOR with OR
3. Anhydride to Amide Conversion
This is a reaction of anhydride with ammonia or amines.
Reagent: NH2, RNH2 or R2NH
Product: replace OCOR with NH2 or NHR or NR2.
ESTER REACTIONS
1. Ester to Carboxylic Acid Conversion
Reagent: H2O, H3O+ or 1.OH-, H2O 2.H3O+
Product: Replace OR with OH
Mechanisms
2. Ester to Another Ester Conversion (Transesterification)
Reagent: R'OH with H+
Product: Replace OR with OR'
3. Ester to Alcohol Conversion: Reaction Of Ester with Grignard or Organolithium Reagents.
Reagent: 1. 2 equivalents of RMgX or RLi 2. H2O, HCl
Product: Get rid of OR on the ester, and turn =O into OH. Add two R groups from the organometallic reagent to the carbon with OH.
4. Ester To Amide Conversion
AMIDE REACTIONS
1. Amide to Carboxylic Acid Conversion
Amides are less reactive than other carboxylic acid derivatives and require more rigorous conditions for hydrolysis.
Reagent: HCl, H2O heat OR NaOH, H2O, heat
Product: replace NH2 or NHR with OH
NITRILE REACTIONS
1. Nitrile To Carboxylic Acid Conversion
Reagent: H2O, H2SO4, heat
Product: replace CN with COOH
This is a very useful reaction, for synthesis problems especially. For example, we can start with a primary alkyl halide, use CN- to do an SN2 reaction and replace halogen with CN. We can then hydrolyze CN group to become COOH.
REDUCTION
Most of the carboxylic acid deviated can be reduced using lithium aluminum hydride reagent.
Let's see how.
1. Reduction of acid chloride, carboxylic acid and ester to alcohol using LiAlH4
Mechanism Of Ester to Alcohol Hydrolysis Using LiAlH4
2. Amide To Amine Conversion Using Lithium Aluminum Hydride
3. Nitrile To Amine Conversion
Are you looking for an online organic chemistry tutor? Click HERE
We also have: General chemistry tutor online
Organic chemistry tutor online
Physical Chemistry tutor online