19.13 Reactions of Carboxylic Acids: A Review and a Preview

Acidity (Sections ) Reduction with LiAlH 4 (Section 15.3) Esterification (Section 15.8) Reaction with Thionyl Chloride (Section 12.7) Reactions already discussed Reactions of Carboxylic Acids

 Halogenation Decarboxylation But first we revisit acid-catalyzed esterification to examine its mechanism. New reactions in this chapter Reactions of Carboxylic Acids

19.14 Mechanism of Acid-Catalyzed Esterification

Acid-catalyzed Esterification + CH 3 OH COHO H+H+H+H++ H2OH2OH2OH2O COCH 3 O Important fact: the oxygen of the alcohol is incorporated into the ester as shown. (also called Fischer esterification)

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

The mechanism involves two stages: 1)formation of tetrahedral intermediate (3 steps) 2)dissociation of tetrahedral intermediate (3 steps) Mechanism of Fischer Esterification COHOH OCH 3 tetrahedral intermediate in esterification of benzoic acid with methanol

First stage: formation of tetrahedral intermediate COHOH OCH 3 + CH 3 OH COHO H+H+H+H+ methanol adds to the carbonyl group of the carboxylic acid the tetrahedral intermediate is analogous to a hemiacetal

Second stage: conversion of tetrahedral intermediate to ester COHOH OCH 3 + H2OH2OH2OH2O H+H+H+H+ this stage corresponds to an acid-catalyzed dehydration COCH 3 O

Mechanism of formation of tetrahedral intermediate

Step 1 C O OH O + H CH 3 H

Step 1 C O OH O + H CH 3 H C O OH + H O CH 3 H

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

Step 2 C O OH + H O CH 3 H

Step 2 C O OH + H O CH 3 H C OH OH O + CH 3 H

Step 3 O CH 3 H C OH OH O CH 3 H +

Step 3 O CH 3 H C OH OH O CH 3 H + O CH 3 H H + C OH OH O CH 3

Tetrahedral intermediate to ester stage

Step 4 C OH O OCH 3 H

Step 4 O CH 3 H H + C OH O OCH 3 H

Step 4 O CH 3 H H + C OH O OCH 3 H C OH O OCH 3 H H + O CH 3 H

Step 5 C OH O OCH 3 H H +

Step 5 C OH O OCH 3 H H + O H H+ C OH OCH 3 +

Step 5 C OH OCH 3 + C OH +

Step 6 C O OCH 3 + H O H CH 3 + O H H C O OCH 3

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

19.15 Intramolecular Ester Formation: Lactones

Lactones are cyclic esters Formed by intramolecular esterification in a compound that contains a hydroxyl group and a carboxylic acid function Lactones

Examples HOCH 2 CH 2 CH 2 COH O OO + H2OH2OH2OH2O 4-hydroxybutanoic acid 4-butanolide IUPAC nomenclature: replace the -oic acid ending of the carboxylic acid by -olide identify the oxygenated carbon by number

Examples HOCH 2 CH 2 CH 2 COH O HOCH 2 CH 2 CH 2 CH 2 COH O O O OO + + H2OH2OH2OH2O H2OH2OH2OH2O 4-hydroxybutanoic acid 5-hydroxypentanoic acid 4-butanolide 5-pentanolide

Common names O O OO  -butyrolactone  -valerolactone        Ring size is designated by Greek letter corresponding to oxygenated carbon A  lactone has a five-membered ring A  lactone has a six-membered ring

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

Example 5-hexanolide (78%) O H3CH3CH3CH3C O CH 3 CCH 2 CH 2 CH 2 COH OO 1. NaBH 4 2. H 2 O, H +

Example 5-hexanolide (78%) via: O H3CH3CH3CH3C O CH 3 CCH 2 CH 2 CH 2 COH OO 1. NaBH 4 2. H 2 O, H + CH 3 CHCH 2 CH 2 CH 2 COH O OHOHOHOH