19.13 Reactions of Carboxylic Acids: A Review and a Preview 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) Reactions of Carboxylic Acids
New reactions in this chapter a-Halogenation Decarboxylation
But first we revisit acid-catalyzed esterification to examine its mechanism. 19.14 Mechanism of Acid-Catalyzed Esterification Acid-catalyzed Esterification
(also called Fischer esterification)
O H+ + COH + CH3OH
O + COCH3 + H2O
Important fact: the oxygen of the alcohol is incorporated into the ester as shown. 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
The mechanism involves two stages: 1) formation of tetrahedral intermediate (3 steps) 2) dissociation of tetrahedral intermediate (3 steps) OH
C OCH3 OH tetrahedral intermediate in esterification of benzoic acid with methanol FirstFirst stage:stage: formationformation ofof tetrahedraltetrahedral intermediateintermediate
O
COH + CH3OH methanol adds to the carbonyl group of the H+ carboxylic acid the tetrahedral
OH intermediate is analogous to a C OCH3 hemiacetal OH SecondSecond stage:stage: conversionconversion ofof tetrahedraltetrahedral intermediateintermediate toto esterester
O
COCH3 + H2O
+ H this stage corresponds to an acid-catalyzed dehydration OH
C OCH3 OH Mechanism of formation of tetrahedral intermediate StepStep 11 CH •• 3 • O• H O • + • C H
• • O H •• StepStep 11 CH •• 3 • O• H O • + • C H
• • O H ••
CH3 +•• O H • • • O • C H
• • O H •• StepStep 11
•• • •O H
C carbonyl oxygen is + O H protonated because •• cation produced is stabilized by electron •• + delocalization O H (resonance) C
• • O H •• StepStep 22
•• +
O H CH3 • • C • O • • H • O H •• StepStep 22 •• • •OH CH3 + • C O •
• H •OH ••
•• +
O H CH3 • • C • O • • H • O H •• StepStep 33 •• • •OH CH3 + • C O • CH3 • • • H •O • •OH •• H StepStep 33 •• • •OH CH3 +
• C O • CH3 • • • H •O • •OH •• H
•• • • OH CH3 • C O • CH3 •• + • • H O • •OH •• H Tetrahedral intermediate to ester stage StepStep 44
•• • • OH •• C OCH3 •• 3 • O • H •• StepStep 44
•• • • OH •• C OCH3 •• CH3 • • O • H O • H •• + H StepStep 44 •• • • OH •• CH C OCH3 CH3 •• 3 + • O • O • • H •• H H
•• • • OH •• C OCH3 •• CH3 • • O • H O • H •• + H StepStep 55 •• • • OH •• C OCH3 •• 3 + O H •• H StepStep 55 •• • • OH •• C OCH3 •• 3 + O H •• H
•• • •• • OH •• C + O + •• H •• H OCH •• 3 StepStep 55
•• •• • +OH • OH
C C + •• •• OCH OCH3 •• 3 •• StepStep 66
H •• CH3 O+
•• H • O• H •• CH O 3 C •• •• OCH3 •• •• +O H
C •• OCH •• 3 Key Features of Mechanism
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 19.15 Intramolecular Ester Formation: Lactones Lactones
Lactones are cyclic esters
Formed by intramolecular esterification in a compound that contains a hydroxyl group and a carboxylic acid function Examples
O O HOCH CH CH COH + H2O 2 2 2 O 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
O O HOCH CH CH COH + H2O 2 2 2 O 4-hydroxybutanoic acid 4-butanolide
O + H O HOCH2CH2CH2CH2COH O 2 O 5-hydroxypentanoic acid 5-pentanolide Common names
a a b O b g O O g d O g-butyrolactone d-valerolactone
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 Lactones
Reactions designed to give hydroxy acids often yield the corresponding lactone, especially if the resulting ring is 5- or 6-membered. Example
O O
CH3CCH2CH2CH2COH
1. NaBH4 + 2. H2O, H
O O
H3C 5-hexanolide (78%) Example
O O
CH3CCH2CH2CH2COH via:
1. NaBH4 OH O + 2. H2O, H
CH3CHCH2CH2CH2COH
O O
H3C 5-hexanolide (78%)