Chapter 20 Carboxylic Acid Derivatives NAS Carboxylic acid
Chapter 20: Carboxylic Acid Derivatives - NAS Carboxylic acid Acyl (or acid) chloride Ester Acid anhydride Carboxamide • All closely related and made from carboxylic acids • most are interconvertable
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
20. 2 – Structure and Reactivity Resonance possibilities – esters, amides, carboxylates Increasing delocalization leads to increasing stability and decreasing reactivity
20. 3 – General Mechanism for Nucleophilic Acyl Substitution Tetrahedral intermediate
20. 4 – NAS Using Acid Chlorides
20. 4 – NAS Using Acid Chlorides, e. g. Amide Synthesis Tetrahedral intermediate
20. 5 – Acyl Substitution in Carboxylic Acid Anhydrides Synthesis of anhydrides Acetic anhydride Maleic 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, 1081 -1090. • “Application of Bis(diphenylphosphino)ethane in Staudinger-type N-Glycosyl Amide Synthesis, ” D. P. Temelkoff, C. R. Smith, D. A. Kibler, S. Mc. Kee, S. Duncan, M. Zeller, M. Hunsen, and P. Norris, Carbohydr. Res. 2006, 341, 1645 -1656.
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
20. 11 -13 – Amides – Structure and Synthesis
20. 14 – Intramolecular Amide Formation – Lactams
20. 15 – Hydrolysis of Amides – not covering
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
20. 18 – Addition of RMg. X to Nitriles – Not Covering
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