Chapter 18 Carboxylic Acids Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

18.1 Carboxylic Acid Nomenclature

Table 18.1 Systematic Name (Common name) O HCOH O CH 3 COH O CH 3 (CH 2 ) 16 COH Systematic IUPAC names replace "-e“ ending of alkane with "oic acid ". methanoic acid (formic acid) ethanoic acid (acetic acid) octadecanoic acid (stearic acid)

Systematic NameCommon Name 2-hydroxypropanoic acidlactic acid (Z)-9-octadecenoic acid or (Z)-octadec-9-enoic acid oleic acid O CH 3 CHCOH OH O (CH 2 ) 7 COH C C HH CH 3 (CH 2 ) 7 Table 18.1

18.2 Structure and Bonding

Formic Acid is Planar CO H HO 120 pm 134 pm

Resonance stabilizes carbonyl group. Electron Delocalization R C O H O + – R C O H O + – R C O H O Resonance is stronger in the anion.

18.3 Physical Properties

Boiling Points Intermolecular forces, especially hydrogen bonding, are stronger in carboxylic acids than in other compounds of similar shape and molecular weight. bp (1 atm):31 o C80 o C99 o C OH 141 o C OH O O alkene ketone alcohol acid

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. CH 3 C OH O CCH 3 O H O

Hydrogen-bonded Dimers A space filling model of acetic acid as a hydrogen-bonded dimer in the gas phase.

Carboxylic acids are similar to alcohols in respect to their solubility in water. They form hydrogen bonds to water. Solubility in Water CH 3 C OH O O H O H H H

18.4 Acidity of Carboxylic Acids Most carboxylic acids have a pK a close to 5.

Although they are weak acids (do not ionize completely in solution), carboxylic acids are far more acidic than alcohols. Carboxylic Acids are Weak Acids CH 3 COH O CH 3 CH 2 OH pK a = 4.7pK a = 16

 G°= 91 kJ/mol  G°= 27 kJ/mol  G°= 64 kJ/mol Free Energies of Ionization CH 3 CH 2 O – + H + CH 3 CH 2 OH CH 3 COH O CH 3 CO – + H + O

Greater Acidity of Carboxylic Acids is Attributed Stabilization of Carboxylate Ion by Inductive effect of carbonyl group Resonance stabilization of carboxylate ion RC O O ++ – O O – RC O O –

Figure 18.3(b): Electrostatic Potential Maps of Acetic Acid and Acetate Ion Acetic acid Acetate ion

18.5 Substituents and Acid Strength

standard of comparison is acetic acid (X = H) Substituent Effects on Acidity X CH 2 COH O pK a = 4.7 Electronegative substituents withdraw electrons from carboxyl group; increase K for loss of H +. X CH 2 COH O

Substituent Effects on Acidity X H Cl F pKapKa Electronegative groups increase acidity X H CH 3 CH 3 (CH 2 ) 5 pKapKa Alkyl groups have negligible effect X CH 2 COH O

Effect of electronegative substituent decreases as number of bonds between it and carboxyl group increases. pKapKa CH 3 CH 2 CHCO 2 H Cl CH 3 CHCH 2 CO 2 H Cl ClCH 2 CH 2 CH 2 CO 2 H

18.6 Ionization of Substituted Benzoic Acids

Hybridization Effect pKapKa COH O H2CH2C CH COH O O HC C sp 2 -hybridized carbon is more electron- withdrawing than sp 3, and sp is more electron-withdrawing than sp 2.

18.7 Salts of Carboxylic Acids

Carboxylic Acids are Deprotonated by Strong Bases Equilibrium lies far to the right; K is ca For low molecular weight acids, sodium and potassium carboxylate salts are soluble in water. stronger acid weaker acid RCOH + HO – RCO – + H2OH2O OO

Unbranched carboxylic acids with carbons give carboxylate salts that form micelles in water. Micelles O ONa sodium stearate (sodium octadecanoate) CH 3 (CH 2 ) 16 CO O Na + –

O ONa polar nonpolar Micelles

O ONa polarnonpolar Sodium stearate has a polar "head" (the carboxylate end) and a nonpolar "tail". The polar end is hydrophilic ("water-loving"). The nonpolar tail is hydrophobic ("water-hating"). In water, many stearate ions cluster together to form spherical aggregates; carboxylate ions are on the outside and nonpolar tails on the inside. Micelles

Figure 18.5: A micelle

The interior of the micelle is nonpolar and has the capacity to dissolve nonpolar substances. Soaps clean because they form micelles, which are dispersed in water. Grease (not ordinarily soluble in water) dissolves in the interior of the micelle and is washed away with the dispersed micelle. Micelles

18.8 Dicarboxylic Acids

Dicarboxylic Acids One carboxyl group acts as an electron- withdrawing group toward the other; effect decreases with increasing separation. Oxalic acid Malonic acid Heptanedioic acid COH O HOC O pKapKa HOCCH 2 COH OO HOC(CH 2 ) 5 COH OO

18.9 Carbonic Acid

Carbonic Acid HOCOH O CO 2 + H2OH2O HOCO – O H+H %0.3% overall K for these two steps = 4.3 x CO 2 is the major species present in the equilibria above of "carbonic acid" in acidic media.

Carbonic Acid HOCO – O – OCO – O H+H+ + K a = 5.6 x Second ionization constant:

18.10 Sources of Carboxylic Acids

1. Side-chain oxidation of alkylbenzenes (Section 11.12) 2. Oxidation of primary alcohols (Section 15.9) 3. Oxidation of aldehydes (Section 17.15) Synthesis of Carboxylic Acids: Review

18.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents

Carboxylation of Grignard Reagents RX Mg diethyl ether RMgX CO2CO2 H3O+H3O+ RCOMgX O RCOHRCOH O Converts an alkyl (or aryl) halide to a carboxylic acid having one more carbon atom than the starting halide

R MgX C O –– diethyl ether O MgX + – R C O O H3O+H3O+ R C O H O H O Carboxylation of Grignard Reagents

Example: Alkyl Halide CH 3 CHCH 2 CH 3 (76-86%) 1. Mg, diethyl ether 2. CO 2 3. H 3 O + CH 3 CHCH 2 CH 3 ClCO 2 H

Example: Aryl Halide (82%) 1. Mg, diethyl ether 2. CO 2 3. H 3 O + CH 3 CO 2 H Br CH 3

18.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles

Preparation and Hydrolysis of Nitriles RX RCOHRCOH O The reactions convert an alkyl halide to a carboxylic acid having one more carbon atom than the starting halide A limitation is that the halide must be reactive toward substitution by S N 2 mechanism. – C N RCRC N SN2SN2 H2O,H3O+H2O,H3O+ heat + NH 4 +

Example NaCN DMSO (92%) CH 2 ClCH 2 CN (77%) H2OH2O H 2 SO 4 heat CH 2 COH O

Example: Dicarboxylic Acid BrCH 2 CH 2 CH 2 Br NaCN H2OH2O (77-86%)NCCH 2 CH 2 CH 2 CN H 2 O, HCl heat (83-85%) HOCCH 2 CH 2 CH 2 COH OO

via Cyanohydrin 1. NaCN 2. H + CH 3 CCH 2 CH 2 CH 3 O OH CN (60% from 2-pentanone) H2OH2O HCl, heat CH 3 CCH 2 CH 2 CH 3 OH CO 2 H

18.13 Reactions of Carboxylic Acids: A Review and a Preview

1. Acidity (Sections ) 2. Reduction with LiAlH 4 (Section 15.3) 3. Esterification (Section 15.8) 4. Formation of acyl chlorides (Section 12.7) Reactions already discussed: Reactions of Carboxylic Acids New reactions in this chapter: 1. Decarboxylation 2. First, revisit acid-catalyzed esterification to examine the mechanism.

18.14 Mechanism of Acid-Catalyzed Esterification

Acid-catalyzed Esterification + CH 3 OH COHCOH O H+H+ + H2OH2O COCH 3 O Important fact: the oxygen of the alcohol is incorporated into the ester as shown. (also called the Fischer esterification)

The mechanism involves two stages: 1)formation of a tetrahedral intermediate from the C=O. (3 steps) 2)loss of the tetrahedral intermediate and regeneration of the C=O. (3 steps) Mechanism of Fischer Esterification C OH OCH 3 tetrahedral intermediate in esterification of benzoic acid with methanol.

First stage: formation of tetrahedral intermediate C OH OCH 3 + CH 3 OH COH O H+H+ Methanol adds to the carbonyl group of the carboxylic acid. The tetrahedral intermediate is analogous to formation of a hemiacetal structure.

Second stage: conversion of tetrahedral intermediate to ester + H2OH2O H+H+ This stage corresponds to an acid-catalyzed dehydration. COCH 3 O C OH OCH 3

Step 1 C O OH H + CH 3 O H C O OH + H H O CH 3 + Steps in the Mechanism of formation of the tetrahedral intermediate protonation

Step 1, cont. C O OH + H Protonation of the carbonyl oxygen produces a cation that is stabilized by resonance (electron delocalization). + C O OH H resonance stabilized

Step 2 CH 3 O H H C OH O + CH 3 C O OH + H Attack by methanol

Step 3 CH 3 O H H + C OH O CH 3 + tetrahedral intermediate H C OH O + CH 3 O H deprotonation

Step 4 C OH O OCH 3 H H + Steps from theTetrahedral intermediate to the Ester stage + + O CH 3 H H OCH 3 C OH O H CH 3 O H protonation of OH

Step 5 O H H + C OH OCH 3 + C OH OCH 3 + C OH + C OH O OCH 3 H H + loss of water resonance stabilized

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

Protonation of carbonyl group activates 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

18.15 Intramolecular Ester Formation: Lactones

Lactones are cyclic esters. They are formed by intramolecular esterification in a compound that contains a both a hydroxyl group and a carboxylic acid function. Lactones

Examples IUPAC nomenclature: replace the -oic acid ending of the carboxylic acid by –olide. Identify the oxygenated carbon by number. HOCH 2 CH 2 CH 2 COH O O O +H2OH2O 4-hydroxybutanoic acid4-butanolide

Examples HOCH 2 CH 2 CH 2 COH O O O +H2OH2O 4-hydroxybutanoic acid4-butanolide HOCH 2 CH 2 CH 2 CH 2 COH O O O + H2OH2O 5-hydroxypentanoic acid 5-pentanolide

Common names O O O O  -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. In the following reaction, aδ-hydroxy acid was desired but aδ-lactone formed. Lactones

Example 5-hexanolide (78%) O H3CH3C O CH 3 CCH 2 CH 2 CH 2 COH OO 1. NaBH 4 2. H 2 O, H + via: CH 3 CHCH 2 CH 2 CH 2 COH O OHOHOHOH

18.16 Decarboxylation of Malonic Acid and Related Compounds

Decarboxylation of Carboxylic Acids Simple carboxylic acids do not decarboxylate readily. RH + CO 2 RCOH O But malonic acid does (requires a β C=O). 150 o C CH 3 COH O + CO 2 HOCCH 2 COH OO

O HO O O HH H Mechanism of Decarboxylation of Malonic Acid The enol form of acetic acid. O O OHHO HH H H OH HO + C O O One carboxyl group assists the loss of the other. HOCCH 3 O

R Mechanism of Decarboxylation of Malonic Acid Substituted malonic acids do the same. HOCCHR' O R R’ OH HO + O O O RR’ H O O OHHO RR’ C O O

185°C Decarboxylation is a general reaction for 1,3-dicarboxylic acids 160°C CO 2 H H (74%) CH(CO 2 H) 2 (96-99%) CH 2 CO 2 H

Decarboxylation of Other β C=O Compounds O O OHR" RR' R β-keto acids also decarboxylate. Need not be a 1,3-diacid, just needs β-C=O. R"CCHR' O R O O O RR' H R" R' OH + R" C O O

Mechanism of Decarboxylation of  -keto acids O O OHR" RR' This kind of compound is called a  -keto acid.   R"CCHR' O R Decarboxylation of a  -keto acid gives a ketone.

Decarboxylation of a  -Keto Acid 25°C CO 2 C CH 3 C O CH 3 H + C CH 3 C O CH 3 CO 2 H

18.17 Spectroscopic Analysis of Carboxylic Acids

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. Infrared Spectroscopy

Francis A. Carey, Organic Chemistry, Fifth Edition. Copyright © 2030 The McGraw-Hill Companies, Inc. All rights reserved. Figure 18.8 Infrared Spectrum of 4-Phenylbutanoic acid

The proton on the OH group of a carboxylic acid is normally the least shielded of all of the protons in a 1 H NMR spectrum: (  ppm; broad and off-scale on a normal scan.) 1 H NMR

Chemical shift ( , ppm)

13 C NMR The carbonyl carbon is at very low field (  ppm), but is not as deshielded as the carbonyl carbon of an aldehyde or ketone (  ppm). UV-VIS Carboxylic acids absorb near 210 nm, but UV-VIS spectroscopy is not very useful for structure determination of carboxylic acids.

Aliphatic carboxylic acids undergo a variety of fragmentations. Aromatic carboxylic acids first form acylium ions, which then loses CO giving m/z = 77. Mass Spectrometry ArCOH O ArCOH + O ArC O + Ar +

End of Chapter 18 Carboxylic Acids