Chapter 20: Carboxylic Acid Derivatives - NASChapter 20: Carboxylic Acid Derivatives - NAS

• All closely related and made from carboxylic acids• most are interconvertable

Acid anhydrideAcyl (or acid) chlorideCarboxylic acid

Ester Carboxamide

20.1 – Carboxylic Acid Derivative Nomenclature20.1 – Carboxylic Acid Derivative Nomenclature

Acyl Chlorides

Acid Anhydrides

20.2 – Carboxylic Acid Derivatives - Structure20.2 – Carboxylic Acid Derivatives - Structure

Extended system – like carboxylic acids

20.2 – Structure and Reactivity20.2 – Structure and Reactivity

Fig. 20.2

20.2 – Structure and Reactivity20.2 – 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 Reactivity20.2 – Structure and Reactivity

20.3 – General Mechanism for Nucleophilic Acyl Substitution20.3 – General Mechanism for Nucleophilic Acyl Substitution

Tetrahedral intermediate

20.4 – NAS Using Acid Chlorides20.4 – NAS Using Acid Chlorides

Tetrahedral intermediate

20.4 – NAS Using Acid Chlorides, e.g. Amide Synthesis20.4 – NAS Using Acid Chlorides, e.g. Amide Synthesis

20.5 – Acyl Substitution in Carboxylic Acid Anhydrides20.5 – Acyl Substitution in Carboxylic Acid Anhydrides

Maleic anhydride

Synthesis of anhydrides

Acetic anhydride

20.5 – Acyl Substitution in Carboxylic Acid Anhydrides20.5 – Acyl Substitution in Carboxylic Acid Anhydrides

Lab experiment

20.5 – Acyl Substitution in Carboxylic Acid Anhydrides20.5 – Acyl Substitution in Carboxylic Acid Anhydrides

Lab experiment

3720

20.5 – Acyl Substitution in Carboxylic Acid Anhydrides20.5 – Acyl Substitution in Carboxylic Acid Anhydrides

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

100 200 400 800

Reciprocal of Antibody Dilution

Ab

sorb

ance

at

450

nm

50 µL EtOH

1 µL MV-II-065

0.1 µL MV-II-065

0.01 µL MV-II-065

50-75% decrease in S. aureus CP

construction

Selective inhibitor of

endothelial cell proliferation

20.5 – Acyl Substitution in Carboxylic Acid Anhydrides20.5 – 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.

20.6 – Sources of Esters20.6 – Sources of Esters

20.7 – Physical Properties of Esters20.7 – Physical Properties of Esters

20.10 – Reactions of Esters20.10 – Reactions of Esters

Acid-catalyzed hydrolysis

Basic hydrolysis –

saponification

20.12 – Thioesters20.12 – Thioesters

Acetyl coenzyme A

20.13 – Amides20.13 – Amides

Hydrogen bonding

20.11-13 – Amides – Structure and Synthesis20.11-13 – Amides – Structure and Synthesis

20.14 – Intramolecular Amide Formation – Lactams20.14 – Intramolecular Amide Formation – Lactams

20.15 – Hydrolysis of Amides – not covering20.15 – Hydrolysis of Amides – not covering

20.16 – 20.17 – Preparation and Hydrolysis of Nitriles20.16 – 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 RMgX to Nitriles – Not Covering20.18 – Addition of RMgX to Nitriles – Not Covering