1. Chapter 20: Carboxylic Acid Derivatives - NAS Carboxylic acid Acyl (or acid) chloride Acid anhydride Ester Carboxamide • All closely related and made from carboxylic acids • most are interconvertable

2. 20.1 – Carboxylic Acid Derivative Nomenclature Acyl Chlorides Acid Anhydrides

3. 20.2 – Carboxylic Acid Derivatives - Structure Extended  system – like carboxylic acids

4. 20.2 – Structure and Reactivity Fig. 20.2

5. 20.2 – Structure and Reactivity Resonance possibilities - acid chlorides and anhydrides Acid chlorides and acid anhydrides are not stabilized significantly by resonance – quite reactive towards nucleophiles

6. 20.2 – Structure and Reactivity Resonance possibilities – esters, amides, carboxylates Increasing delocalization leads to increasing stability and decreasing reactivity

7. 20.3 – General Mechanism for Nucleophilic Acyl Substitution Tetrahedral intermediate

8. 20.4 – NAS Using Acid Chlorides

9. 20.4 – NAS Using Acid Chlorides, e.g. Amide Synthesis Tetrahedral intermediate

10. 20.5 – Acyl Substitution in Carboxylic Acid Anhydrides Synthesis of anhydrides Acetic anhydride Maleic anhydride

11. 20.5 – Acyl Substitution in Carboxylic Acid Anhydrides Lab experiment

12. 20.5 – Acyl Substitution in Carboxylic Acid Anhydrides Lab experiment 3720

13. 20.5 – Acyl Substitution in Carboxylic Acid Anhydrides 50-75% decrease in S. aureus CP construction Selective inhibitor of endothelial cell proliferation

14. 20.5 – Acyl Substitution in Carboxylic Acid Anhydrides • “N-Glycoside neoglycotrimers from 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide,” D. P. Temelkoff, M. Zeller, and P. Norris, Carbohydr. Res.2006, 341, 1081-1090. • “Application of Bis(diphenylphosphino)ethane in Staudinger-type N-Glycosyl Amide Synthesis,” D. P. Temelkoff, C. R. Smith, D. A. Kibler, S. McKee, S. Duncan, M. Zeller, M. Hunsen, and P. Norris, Carbohydr. Res.2006, 341, 1645-1656.

15. 20.6 – Sources of Esters

16. 20.7 – Physical Properties of Esters

17. 20.10 – Reactions of Esters Acid-catalyzed hydrolysis Basic hydrolysis – saponification

18. 20.12 – Thioesters Acetyl coenzyme A

19. 20.13 – Amides Hydrogen bonding

20. 20.11-13 – Amides – Structure and Synthesis

21. 20.14 – Intramolecular Amide Formation – Lactams

22. 20.15 – Hydrolysis of Amides – not covering

23. 20.16 – 20.17 – Preparation and Hydrolysis of Nitriles • Protonate nitrogen, attack C with water • Proton transfer to nitrogen followed by enolization • Rest of mechanism the same as the amide hydrolysis

24. 20.18 – Addition of RMgX to Nitriles – Not Covering