1. WWU-Chemistry Acid Chlorides Preparation and Reactions

2. WWU-Chemistry Preparation of an Acid Chloride (“A” Method)

3. WWU-Chemistry Example

4. Example #2

5. WWU-Chemistry Preparation of Acid Chlorides (“C+” Method)

6. WWU-Chemistry 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 can’t stand HCl.

7. WWU-Chemistry Hydrolysis of an Acid Chloride Notice the direction of the equilibrium arrow. Explain why you can’t 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. WWU-Chemistry 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. WWU-Chemistry 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. WWU-Chemistry 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. WWU-Chemistry Example #2 (Primary Amine is the Nucleophile)

13. WWU-Chemistry Example #3 (Secondary Amine is the Nucleophile)

14. WWU-Chemistry 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. WWU-Chemistry Example

16. Rosenmund Reduction Recall this from Chapter 17, Section 17.17

17. WWU-Chemistry Example

18. Also...

19. By contrast, lithium aluminum hydride reduces acid chlorides all the way to alchols.

20. WWU-Chemistry 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. WWU-Chemistry Acylation of an Enamine

23. WWU-Chemistry Acylation of an Enamine -- Mechanism (Part 1)

24. WWU-Chemistry Acylation of an Enamine -- Mechanism -- Part 2

25. WWU-Chemistry Acylation of an Enamine -- Mechanism -- Part 3

26. WWU-Chemistry Overall Sequence

27. WWU-ChemistryExample

28. Example #2

29. WWU-Chemistry Also review... Conversion of acid chlorides to ketones –review material in Chapter 17, Section 17.18

30. WWU-Chemistry Using Dialkylcadmium Reagents

31. WWU-Chemistry Using Lithium Dialkylcuprates