Chapter 19 Carboxylic Acids

19.2 Structure and Bonding 4

Formic Acid Is Planar C O H 120 pm 134 pm 5

Electron Delocalization Stabilizes carbonyl group R C O H •• • • + – R C O H •• • • R C O H •• • • + – 6

19.3 Physical Properties 7

Boiling Points O OH 141°C OH O bp (1 atm) 31°C 80°C 99°C Intermolecular forces, especially hydrogen bonding, are stronger in carboxylic acids than in other compounds of similar shape and molecular weight 8

Hydrogen-Bonded Dimers H3CC O H CCH3 Acetic acid exists as a hydrogen-bonded dimer in the gas phase. The hydroxyl group of each molecule is hydrogen-bonded to the carbonyl oxygen of the other. 8

Hydrogen-Bonded Dimers Acetic acid exists as a hydrogen-bonded dimer in the gas phase. The hydroxyl group of each molecule is hydrogen-bonded to the carbonyl oxygen of the other. 8

Form hydrogen bonds to water. Solubility in Water Carboxylic acids are similar to alcohols with respect to their solubility in water. Form hydrogen bonds to water. H3CC O H 10

19.4 Acidity of Carboxylic Acids Most carboxylic acids have a pKa close to 5. 7

Carboxylic Acids Are Weak Acids But carboxylic acids are far more acidic than alcohols. CH3COH O CH3CH2OH pKa = 4.7 pKa = 16 12

Free Energies of Ionization CH3CH2O– + H+ G° = 64 kJ/mol CH3CO– + H+ O G° = 91 kJ/mol G° = 27 kJ/mol CH3COH O CH3CH2OH 13

Inductive effect of carbonyl group: Greater Acidity of Carboxylic Acids Is Due to Stabilization of Carboxylate Ion Inductive effect of carbonyl group: RC O + – Resonance stabilization of carboxylate ion: RC O – •• • • 14

Electrostatic Potential Maps of Acetic Acid and Acetate Ion 14

19.6 Substituents and Acid Strength 21

Substituent Effects on Acidity Standard of comparison is acetic acid (X = H) X CH2COH O pKa = 4.7 22

Substituent Effects on Acidity X CH2COH O X H CH3 CH3(CH2)5 pKa 4.7 4.9 Alkyl groups have negligible effect X H F Cl pKa 4.7 2.6 2.9 Electronegative groups increase acidity 23

Substituent Effects on Acidity X CH2COH O Electronegative substituents withdraw electrons from carboxyl group; increase K for loss of H+. 23

Effect of Electronegative Substituent Decreases as Number of Bonds between It and Carboxyl Group Increases. pKa CH3CH2CHCO2H Cl 2.8 4.1 4.5 CH3CHCH2CO2H Cl ClCH2CH2CH2CO2H 23

19.7 Ionization of Substituted Benzoic Acids 26

Hybridization Effect pKa 4.2 4.3 1.8 COH O H2C CH HC C sp2-Hybridized carbon is more electron-withdrawing than sp3, and sp is more electron-withdrawing than sp2. 23

Ionization of Substituted Benzoic Acids COH O X Effect is small unless X is electronegative; effect is largest for ortho substituent. pKa Substituent Ortho Meta Para H 4.2 4.2 4.2 CH3 3.9 4.3 4.4 F 3.3 3.9 4.1 Cl 2.9 3.8 4.0 CH3O 4.1 4.1 4.5 NO2 2.2 3.5 3.4 28

19.10 Sources of Carboxylic Acids

Synthesis of Carboxylic Acids: Review Side-chain oxidation of alkylbenzenes (11.13) Oxidation of primary alcohols (15.10) Oxidation of aldehydes (17.15) 2

Synthesis of Carboxylic Acids: Review

19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents 4

Carboxylation of Grignard Reagents RCOMgX O Mg CO2 RX RMgX diethyl ether H3O+ Converts an alkyl (or aryl) halide to a carboxylic acid having one more carbon atom than the starting halide. RCOH O 5

Carboxylation of Grignard Reagents MgX + – R C O •• • • O • • •• diethyl ether – R MgX C O • • •• H3O+ R C OH •• • • O 23

Example: Alkyl Halide 1. Mg, diethyl ether CH3CHCH2CH3 CH3CHCH2CH3 2. CO2 3. H3O+ Cl CO2H (76-86%) 8

Example: Aryl Halide 1. Mg, diethyl ether 2. CO2 3. H3O+ CH3 CH3 Br (82%) 8

19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles 11

Preparation and Hydrolysis of Nitriles RCOH O – • • C N H3O+ RX RC • • N SN2 heat + NH4+ Converts an alkyl halide to a carboxylic acid having one more carbon atom than the starting halide. Limitation is that the halide must be reactive toward substitution by SN2 mechanism. 5

Example CH2Cl NaCN CH2CN DMSO (92%) (77%) H2O, H2SO4, heat CH2COH O 13

Example: Dicarboxylic Acid BrCH2CH2CH2Br NaCN H2O NCCH2CH2CH2CN (77-86%) H2O, HCl heat (83-85%) HOCCH2CH2CH2COH O 14

Example: -Hydroxy Acid from Ketone via Cyanohydrin CH3CCH2CH2CH3 O CH3CCH2CH2CH3 OH CN 1. NaCN 2. H+ H2O, CH3CCH2CH2CH3 OH CO2H HCl, heat 2-Hydroxy-2-methylpentanoic acid, an -hydroxy acid (60% from 2-pentanone) 13

19.13 Reactions of Carboxylic Acids: A Review and a Preview

Reactions of Carboxylic Acids Reactions already discussed: Acidity (19.4, 19.5-19.7) Reaction with thionyl chloride (12.7; will also see in 20.4) Reduction with LiAlH4 (15.3) Acid-catalyzed esterification (15.8) 2

Reactions of Carboxylic Acids: Review

Reactions of Carboxylic Acids: Review 1

19.14 Mechanism of Acid-Catalyzed Esterification (Fischer Esterification)

Acid-Catalyzed Esterification COH O H+ + CH3OH COCH3 O + H2O Important fact: the oxygen of the alcohol is incorporated into the ester as shown. 4

Mechanism of Fischer Esterification The mechanism involves two stages: 1) Formation of tetrahedral intermediate (3 steps) 2) Dissociation of tetrahedral intermediate (3 steps) 5

Mechanism of Fischer Esterification The mechanism involves two stages: 1) Formation of tetrahedral intermediate (3 steps) 2) Dissociation of tetrahedral intermediate (3 steps) C OH OCH3 Tetrahedral intermediate in esterification of benzoic acid with methanol 5

First Stage: Formation of Tetrahedral Intermediate COH O + CH3OH Methanol adds to the carbonyl group of the carboxylic acid. The tetrahedral intermediate is analogous to a hemiacetal. H+ C OH OCH3 5

Second Stage: Conversion of Tetrahedral Intermediate to Ester COCH3 O + H2O This stage corresponds to an acid-catalyzed dehydration. H+ C OH OCH3 5

Mechanism of Formation of Tetrahedral Intermediate 8

Step 1 O • • + H CH3 C O H •• • • •• C O H • • + CH3 8

Step 1 C O H •• • • + Carbonyl oxygen is protonated because cation produced is stabilized by electron delocalization (resonance). C O H •• • • + •• 8

Step 2 C OH •• • • O + CH3 H C O H •• • • + • • O CH3 H •• 8

Step 3 •• C OH • • O CH3 H + • • O CH3 H O • • CH3 H + •• C OH 8

Tetrahedral Intermediate to Ester Stage 8

Step 4 •• C OH O • • OCH3 H + CH3 •• C OH O • • OCH3 H O • • CH3 H + 8

Step 5 •• C OH O • • OCH3 H + + H2O C OH •• OCH3 + 8

Step 6 + O H CH3 •• C OCH3 • • O •• H CH3 C O •• OCH3 + H 8

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. 17

Review of Fischer Esterification 17

Industrial Use of Fischer Esterification: Synthesis of Dacron® Polyester http://heritage.dupont.com/touchpoints/tp_1950/overview.shtml 17

A Waste of Good Chemistry 17

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. 17

4-Hydroxybutanoic acid 4-Butanolide Example HOCH2CH2CH2COH O O + H2O 4-Hydroxybutanoic acid 4-Butanolide IUPAC nomenclature: replace the -oic acid ending of the carboxylic acid by -olide. Identify the oxygenated carbon by number. 19

4-Hydroxybutanoic acid 4-Butanolide Examples HOCH2CH2CH2COH O O + H2O 4-Hydroxybutanoic acid 4-Butanolide HOCH2CH2CH2CH2COH O + H2O 5-Hydroxypentanoic acid 5-Pentanolide 19

Ring size is designated by Greek letter. Common names    O O     -Butyrolactone -Valerolactone Ring size is designated by Greek letter. A  lactone has a five-membered ring. A  lactone has a six-membered ring. 19

Lactones Reactions designed to give hydroxy acids often yield the corresponding lactone, especially if the resulting ring is 5- or 6-membered. 17

Example CH3CCH2CH2CH2COH O via: CH3CHCH2CH2CH2COH O OH 1. NaBH4 2. H2O, H+ O H3C 5-hexanolide (78%) 20

Section 19.18 Spectroscopic Analysis of Carboxylic Acids

Infrared Spectroscopy A carboxylic acid is characterized by peaks due to OH and C=O groups in its infrared spectrum. C=O stretching gives an intense absorption near 1700 cm-1. OH peak is broad and overlaps with C—H absorptions. 6

Infrared Spectrum of 4-Phenylbutanoic Acid 8

1H NMR Proton of OH group of a carboxylic acid is normally the least shielded of all of the protons in 1H NMR spectra: ( 10-12 ppm; broad). 6

4-Phenylbutanoic Acid O CH2CH2CH2COH 1 Chemical shift (, ppm) 1.0 2.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 Chemical shift (, ppm) 1

13C NMR Carbonyl carbon is at low field ( 160-185 ppm), but not as deshielded as the carbonyl carbon of an aldehyde or ketone ( 190-215 ppm).