19.13 Reactions of Carboxylic Acids: A Review and a Preview

1. 19.13Reactions of Carboxylic Acids:A Review and a Preview

2. Reactions of Carboxylic Acids Reactions already discussed • Acidity (Sections 19.4-19.9) • Reduction with LiAlH4 (Section 15.3) • Esterification (Section 15.8) • Reaction with Thionyl Chloride (Section 12.7)

3. Reactions of Carboxylic Acids New reactions in this chapter • a-Halogenation • Decarboxylation • But first we revisit acid-catalyzed esterificationto examine its mechanism.

4. 19.14Mechanism of Acid-Catalyzed Esterification

5. O H+ COH O COCH3 Acid-catalyzed Esterification (also called Fischer esterification) • Important fact: the oxygen of the alcohol isincorporated into the ester as shown. + CH3OH + H2O

6. Mechanism of Fischer Esterification • The mechanism involves two stages: • 1) formation of tetrahedral intermediate (3 steps) • 2) dissociation of tetrahedral intermediate (3 steps)

7. OH OCH3 C OH Mechanism of Fischer Esterification • The mechanism involves two stages: • 1) formation of tetrahedral intermediate (3 steps) • 2) dissociation of tetrahedral intermediate (3 steps) tetrahedral intermediate in esterification of benzoic acid with methanol

8. O COH OH OCH3 C OH First stage: formation of tetrahedral intermediate • methanol adds to the carbonyl group of the carboxylic acid • the tetrahedral intermediate is analogous to a hemiacetal + CH3OH H+

9. O COCH3 OH OCH3 C OH Second stage: conversion of tetrahedralintermediate to ester • this stage corresponds to an acid-catalyzed dehydration + H2O H+

10. Mechanism of formationoftetrahedral intermediate

11. CH3 •• O H O •• •• + H C O H •• •• Step 1

12. CH3 •• O H O •• •• + H C O H •• •• CH3 •• + H O O •• •• H C O H •• Step 1 ••

13. O H •• + H O C O H •• Step 1 •• H O •• • carbonyl oxygen is protonated because cation produced is stabilized by electron delocalization (resonance) C + •• ••

14. •• + H O CH3 C O •• •• H O H •• Step 2 ••

15. •• OH CH3 •• + C O •• H OH •• •• •• + H O CH3 C O •• •• H O H •• Step 2 ••

16. •• OH CH3 •• + CH3 C O •• O H •• •• OH •• •• H Step 3

17. •• OH CH3 •• + CH3 C O •• O H •• •• OH •• •• H •• OH CH3 •• CH3 C O •• + •• O H •• OH •• •• H Step 3

18. Tetrahedral intermediatetoester stage

19. •• OH •• •• C OCH3 •• O •• •• H Step 4

20. •• OH •• •• C OCH3 CH3 •• O O H •• •• •• H + H Step 4

21. •• OH •• •• CH3 C OCH3 •• + O •• •• O H •• H H •• OH •• •• C OCH3 CH3 •• O O H •• •• •• H + H Step 4

22. Step 5 •• OH •• •• C OCH3 •• + O H •• H

23. •• OH •• •• C OCH3 •• + O H •• H •• OH •• •• O C H •• H + •• OCH3 •• Step 5 +

24. •• •• + OH OH •• C C + •• •• OCH3 OCH3 •• •• Step 5

25. •• O •• •• CH3 H O C •• •• OCH3 •• •• + O C •• OCH3 •• Step 6 •• CH3 H O + H H

26. Key Features of Mechanism • Activation of carbonyl group by protonation of carbonyl oxygen • Nucleophilic addition of alcohol to carbonyl groupforms tetrahedral intermediate • Elimination of water from tetrahedral intermediate restores carbonyl group

27. 19.15Intramolecular Ester Formation:Lactones

28. Lactones • Lactones are cyclic esters • Formed by intramolecular esterification in acompound that contains a hydroxyl group anda carboxylic acid function

29. O O HOCH2CH2CH2COH O Examples • IUPAC nomenclature: replace the -oic acid ending of the carboxylic acid by -olide • identify the oxygenated carbon by number + H2O 4-hydroxybutanoic acid 4-butanolide

30. O O HOCH2CH2CH2COH O O O HOCH2CH2CH2CH2COH O Examples + H2O 4-hydroxybutanoic acid 4-butanolide + H2O 5-pentanolide 5-hydroxypentanoic acid

31. O O O O Common names a b a b • Ring size is designated by Greek letter corresponding to oxygenated carbon • A g lactone has a five-membered ring • A d lactone has a six-membered ring g g d g-butyrolactone d-valerolactone

32. Lactones • Reactions designed to give hydroxy acids often yield the corresponding lactone, especially if theresulting ring is 5- or 6-membered.

33. O O CH3CCH2CH2CH2COH 1. NaBH4 2. H2O, H+ O O H3C Example 5-hexanolide (78%)

34. O O CH3CCH2CH2CH2COH 1. NaBH4 OH O 2. H2O, H+ CH3CHCH2CH2CH2COH O O H3C Example via: 5-hexanolide (78%)