Acid Chlorides Preparation and Reactions

1
Acid ChloridesPreparation and Reactions
2
Preparation of an Acid Chloride(A Method)
3
Example
4
Example 2
5
Preparation of Acid Chlorides(C Method)
6
Preparation of an Acid Chloride(C- Method)
The single advantage to this method is that it
does not produce HCl as a product. Use this
method when your molecule cant stand HCl.
7
Hydrolysis of an Acid Chloride

• Notice the direction of the equilibrium arrow.
• Explain why you cant make an acid chloride by
  reacting a carboxylic acid with hydrogen
  chloride.
• This explains why acid chlorides are very
  moisture-sensitive and why it is difficult to
  store them.

8
Preparation of an Ester(A Method)
Because the ester is so much more stable than the
acid chloride, this reaction proceeds at a rapid
rate and in high yield.
9
Example
10
Preparation of an Amide(A Method)

• Two equivalents of amine are required.
• The first equivalent acts as nucleophile to form
  the amide
• The second equivalent acts as a base and reacts
  with the HCl that is formed.

11
Example 1(Ammonia is the Nucleophile)
Because the amide is so much more stable than the
acid chloride, this reaction proceeds rapidly and
in high yield.
12
Example 2(Primary Amine is the Nucleophile)
13
Example 3(Secondary Amine is the Nucleophile)
14
Preparation of an Acid Anhydride

• This will also work with an acid chloride and a
  carboxylate anion.
• Because the acid chloride is less stable than the
  acid anhydride, this reaction proceeds rapidly
  and in good yield.

15
Example
16
Rosenmund Reduction
Recall this from Chapter 17, Section 17.17
17
Example
18
Also...
19
By contrast, lithium aluminum hydride reduces
acid chlorides all the way to alchols.
20
Example
21

• Acid chlorides react with enamines to yield
  1,3-dicarbonyl compounds
• In this reaction, the first step involves
  formation of the enamine
• see Chapter 16, Section 16.13
• The enamine, being highly nucleophilic, reacts
  with the acid chloride in a nucleophilic acyl
  substitution process.
• Hydrolysis of the resulting iminium salt yields
  the final product.

22
Acylation of an Enamine
23
Acylation of an Enamine -- Mechanism (Part 1)
24
Acylation of an Enamine -- Mechanism -- Part 2
25
Acylation of an Enamine -- Mechanism -- Part 3
26
Overall Sequence
27
Example
28
Example 2
29
Also review...

• Conversion of acid chlorides to ketones
• review material in Chapter 17, Section 17.18

30
Using Dialkylcadmium Reagents
31
Using Lithium Dialkylcuprates