Chapter 20: Carboxylic Acid Derivatives - NAS All closely related and made from carboxylic acids most are interconvertable Acid anhydrideAcyl (or acid) chlorideCarboxylic acid EsterCarboxamide

20.1 – Carboxylic Acid Derivative Nomenclature Acyl Chlorides Acid Anhydrides

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

20.2 – Structure and Reactivity Fig. 20.2

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

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

20.3 – General Mechanism for Nucleophilic Acyl Substitution Tetrahedral intermediate

20.4 – NAS Using Acid Chlorides

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

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

20.5 – Acyl Substitution in Carboxylic Acid Anhydrides Lab experiment

20.5 – Acyl Substitution in Carboxylic Acid Anhydrides Lab experiment 3720

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

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, “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,

20.6 – Sources of Esters

20.7 – Physical Properties of Esters

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

20.12 – Thioesters Acetyl coenzyme A

20.13 – Amides Hydrogen bonding

– Amides – Structure and Synthesis

20.14 – Intramolecular Amide Formation – Lactams

20.15 – Hydrolysis of Amides – not covering

20.16 – – 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

20.18 – Addition of RMgX to Nitriles – Not Covering