Functional Derivatives of Carboxylic Acids

1. Functional Derivatives of Carboxylic Acids

2. Nomenclature: the functional derivatives’ names are derived from the common or IUPAC names of the corresponding carboxylic acids. Acid chlorides: change –ic acid to –yl chloride Anhydrides: change acid to anhydride

3. Amides: change –ic acid (common name) to –amide -oic acid (IUPAC) to –amide Esters: change –ic acid to –ate preceded by the name of the alcohol group

4. Nucleophilic acyl substitution:

5. Mechanism: Nucleophilic Acyl Substitution 1) 2)

6. Mechanism:nucleophilic acyl substitution, acid catalyzed 1) 2) 3)

7. nucleophilic acyl substitution vs nucleophilic addition to carbonyl aldehydes & ketones – nucleophilic addition functional deriv. of carboxylic acids – nucleophilic acyl substitution

8. Acid Chlorides Syntheses: SOCl2 RCOOH + PCl3 RCOCl PCl5

9. Acid chlorides, reactions: • Conversion into acids and derivatives: • a) hydrolysis • b) ammonolysis • c) alcoholysis • Friedel-Crafts acylation • Coupling with lithium dialkylcopper • Reduction

10. acid chlorides: conversion into acids and other derivatives

11. Schotten-Baumann technique – aromatic acid chlorides are less reactive than aliphatic acid chlorides. In order to speed up the reactions of aromatic acid chlorides, bases such as NaOH or pyridine are often added to the reaction mixture.

12. acid chlorides: Friedel-Crafts acylation

13. acid chlorides: coupling with lithium dialkylcopper

14. acid chlorides: reduction to aldehydes

15. Anhydrides, syntheses: • Buy the ones you want! • Anhydrides, reactions: • Conversion into carboxylic acids and derivatives. • a) hydrolysis • b) ammonolysis • c) alcoholysis • 2) Friedel-Crafts acylation

17. 2) anhydrides, Friedel-Crafts acylation.

18. Amides, synthesis: Indirectly via acid chlorides.

19. Amides, reactions. 1) Hydrolysis.

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22. Esters, syntheses: • From acids • RCO2H + R’OH, H+ RCO2R’ + H2O • From acid chlorides and anhydrides • RCOCl + R’OH RCO2R’ + HCl • From esters (transesterification) • RCO2R’ + R”OH, H+ RCO2R” + R’OH • RCO2R’ + R”ONa RCO2R” + R’ONa

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24. “Direct” esterification is reversible and requires use of LeChatelier’s principle to shift the equilibrium towards the products. “Indirect” is non-reversible.

25. In transesterification, an ester is made from another ester by exchanging the alcohol function.

26. Esters, reactions: • Conversion into acids and derivatives • a) hydrolysis • b) ammonolysis • c) alcoholysis • Reaction with Grignard reagents • Reduction • a) catalytic • b) chemical • 4) Claisen condensation

28. Tracer studies confirm that the mechanism is nucleophilic acyl substitution:

30. Esters, reaction with Grignard reagents

32. Esters, reduction • catalytic • chemical

34. Spectroscopy: Infrared: strong absorbance ~ 1700 cm-1 for C=O RCO2R 1740 ArCO2R 1715-1730 RCO2Ar 1770 Esters also show a strong C—O stretch at 1050-1300 Amides show N—H stretch at 3050 –3550 and N—H bend in the 1600-1640 region. Nmr: NB in esters the protons on the alcohol side of the functional group resonate at lower field than the ones on the acid side. RCOO—C—H 3.7 – 4.1 ppm H—C—COOR 2 – 2.2 ppm

35. methyl propionate C=O C--O

36. butyramide C=O N—H N—H bend

37. Ethyl acetate CH3CO2CH2CH3 b c a Note which hydrogens are upfield. c b a

38. Methyl propionate CH3CH2CO2CH3 a b c Note which hydrogens are upfield. c b a