Dr. Wolf's CHM 201 & Chapter 18 Carboxylic Acids

Dr. Wolf's CHM 201 & Carboxylic Acid Nomenclature

Dr. Wolf's CHM 201 & Table 18.1 Systematic Name OHCOH methanoic acid O CH 3 COH ethanoic acid O CH 3 (CH 2 ) 16 COH octadecanoic acid systematic IUPAC names replace "-e" ending of alkane with "oic acid"

Dr. Wolf's CHM 201 & Table 18.1 Systematic Name Common Name OHCOH methanoic acid formic acid O CH 3 COH ethanoic acid acetic acid O CH 3 (CH 2 ) 16 COH octadecanoic acid stearic acid common names are based on natural origin rather than structure

Dr. Wolf's CHM 201 & Table 18.1 Systematic Name Common Name 2-hydroxypropanoic acid lactic acid (Z)-9-octadecenoic acid oleic acid O CH 3 CHCOH OH O (CH 2 ) 7 COH C C HH CH 3 (CH 2 ) 7

Dr. Wolf's CHM 201 & Structure and Bonding

Dr. Wolf's CHM 201 & Formic acid is planar

Dr. Wolf's CHM 201 & Formic acid is planar CO H H O 120 pm 134 pm

Dr. Wolf's CHM 201 & Electron Delocalization R C O H O R C O H O + –

Dr. Wolf's CHM 201 & Electron Delocalization stabilizes carbonyl group R C O H O R C O H O + – R C O H O + –

Dr. Wolf's CHM 201 & Physical Properties

Dr. Wolf's CHM 201 & Boiling Points Intermolecular forces, especially hydrogen bonding, are stronger in carboxylic acids than in other compounds of similar shape and molecular weight bp 31°C80°C99°COH 141°C OHO O

Dr. Wolf's CHM 201 & 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. H 3 CC OH O CCH 3 O HO

Dr. Wolf's CHM 201 & 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.

Dr. Wolf's CHM 201 & carboxylic acids are similar to alcohols in respect to their solubility in water form hydrogen bonds to water Solubility in Water H 3 CC OH O O H OHH H

Dr. Wolf's CHM 201 & Acidity of Carboxylic Acids Most carboxylic acids have a pK a close to 5.

Dr. Wolf's CHM 201 & but carboxylic acids are far more acidic than alcohols Carboxylic acids are weak acids CH 3 COH O CH 3 CH 2 OH K a = 1.8 x pK a = 4.7 K a = pK a = 16

Dr. Wolf's CHM 201 &  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

Dr. Wolf's CHM 201 & Greater acidity of carboxylic acids is attributed stabilization of carboxylate ion by inductive effect of carbonyl group resonance stabilization of carboxylate ion RCOO ++++ – RC O O – RC O O–

Dr. Wolf's CHM 201 & Figure 19.4: Electrostatic potential maps of acetic acid and acetate ion Acetic acid Acetate ion

Dr. Wolf's CHM 201 & Substituents and Acid Strength

Dr. Wolf's CHM 201 & standard of comparison is acetic acid (X = H) Substituent Effects on Acidity X CH 2 COH O K a = 1.8 x pK a = 4.7

Dr. Wolf's CHM 201 & Substituent Effects on Acidity alkyl substituents have negligible effect X CH 2 COH O X KaKaKaKa pKapKapKapKaH CH 3 CH 3 (CH 2 ) x x

Dr. Wolf's CHM 201 & Substituent Effects on Acidity electronegative substituents increase acidity X CH 2 COH O X KaKaKaKa pKapKapKapKaH F Cl 1.8 x x x

Dr. Wolf's CHM 201 & Substituent Effects on Acidity electronegative substituents withdraw electrons from carboxyl group; increase K for loss of H + X CH 2 COH O

Dr. Wolf's CHM 201 & Substituent Effects on Acidity effect of substituent decreases as number of bonds between X and carboxyl group increases X CH 2 COH OX KaKaKaKa pKapKapKapKa H 1.8 x x x ClCH 2 Cl 3.0 x ClCH 2 CH 2

Dr. Wolf's CHM 201 & Ionization of Substituted Benzoic Acids

Dr. Wolf's CHM 201 & Hybridization Effect KaKaKaKa pKapKapKapKa 6.3 x x x COH O H2CH2CH2CH2C CH COH O COH O HC C sp 2 -hybridized carbon is more electron- withdrawing than sp 3, and sp is more electron-withdrawing than sp 2

Dr. Wolf's CHM 201 & pK a Substituentorthometapara H CH F Cl CH 3 O NO Ionization of Substituted Benzoic Acids COHOX effect is small unless X is electronegative; effect is largest for ortho substituent

Dr. Wolf's CHM 201 & Salts of Carboxylic Acids

Dr. Wolf's CHM 201 & Carboxylic acids are neutralized by strong bases equilibrium lies far to the right; K is ~ as long as the molecular weight of the acid is not too high, sodium and potassium carboxylate salts are soluble in water stronger acid weaker acid RCOH + HO – RCO – + H2OH2OH2OH2OOO

Dr. Wolf's CHM 201 & unbranched carboxylic acids with carbons give carboxylate salts that form micelles in water MicellesMicellesOONa sodium stearate (sodium octadecanoate) CH 3 (CH 2 ) 16 CO O Na + –

Dr. Wolf's CHM 201 & MicellesMicellesOONa polar nonpolar sodium stearate has a polar end (the carboxylate end) and a nonpolar "tail" the polar end is "water-loving" or hydrophilic the nonpolar tail is "water-hating" or hydrophobic in water, many stearate ions cluster together to form spherical aggregates; carboxylate ions on the outside and nonpolar tails on the inside

Dr. Wolf's CHM 201 & MicellesOONa polar nonpolar

Dr. Wolf's CHM 201 & Figure 19.5 A micelle

Dr. Wolf's CHM 201 & MicellesMicelles 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.

Dr. Wolf's CHM 201 & Dicarboxylic Acids

Dr. Wolf's CHM 201 & 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 COHOHOCO pKapKapKapKa HOCCH 2 COH OO HOC(CH 2 ) 5 COH OO

Dr. Wolf's CHM 201 & Carbonic Acid

Dr. Wolf's CHM 201 & Carbonic Acid HOCOHO CO 2 + H2OH2OH2OH2O 99.7%0.3%

Dr. Wolf's CHM 201 & Carbonic Acid HOCOHO CO 2 + H2OH2OH2OH2O HOCO – O H+H+H+H+ +

Dr. Wolf's CHM 201 & Carbonic Acid HOCOHO CO 2 + H2OH2OH2OH2O HOCO – O H+H+H+H+ + overall K for these two steps = 4.3 x CO 2 is major species present in a solution of "carbonic acid" in acidic media

Dr. Wolf's CHM 201 & Carbonic Acid HOCO – O – OCO – O H+H+H+H+ + K a = 5.6 x Second ionization constant:

Dr. Wolf's CHM 201 & Sources of Carboxylic Acids

Dr. Wolf's CHM 201 & side-chain oxidation of alkylbenzenes (Chapter 11) oxidation of primary alcohols (Chapter 15) oxidation of aldehydes (Chapter 17) Synthesis of Carboxylic Acids: Review

Dr. Wolf's CHM 201 & Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents

Dr. Wolf's CHM 201 & Carboxylation of Grignard Reagents RX Mg diethyl ether RMgX CO2CO2CO2CO2 H3O+H3O+H3O+H3O+ RCOMgX O RCOH O converts an alkyl (or aryl) halide to a carboxylic acid having one more carbon atom than the starting halide

Dr. Wolf's CHM 201 & RMgX C O MgX+ –––– H3O+H3O+H3O+H3O+ diethyl ether O – R C O O R C OH O Carboxylation of Grignard Reagents

Dr. Wolf's CHM 201 & 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 Cl CO2HCO2HCO2HCO2H

Dr. Wolf's CHM 201 & Example: Aryl Halide (82%) 1. Mg, diethyl ether 2. CO 2 3. H 3 O + CH 3 CO2HCO2HCO2HCO2H Br

Dr. Wolf's CHM 201 & Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles

Dr. Wolf's CHM 201 & Preparation and Hydrolysis of Nitriles RX RCOH O 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 S N 2 mechanism, i.e. best with primary, then secondary…… tertiary gives elimination – C N RCRCRCRC N SN2SN2SN2SN2 H3O+H3O+H3O+H3O+ heat + NH 4 +

Dr. Wolf's CHM 201 & Example NaCN DMSO (77%) H2OH2OH2OH2O H 2 SO 4 heat (92%) CH 2 Cl CH 2 CN CH 2 COH O

Dr. Wolf's CHM 201 & Example: Dicarboxylic Acid BrCH 2 CH 2 CH 2 Br NaCN H2OH2OH2OH2O H 2 O, HCl heat (77-86%) NCCH 2 CH 2 CH 2 CN (83-85%) HOCCH 2 CH 2 CH 2 COH OO

Dr. Wolf's CHM 201 & via Cyanohydrin 1. NaCN 2. H + (60% from 2-pentanone) H2OH2OH2OH2O HCl, heat CH 3 CCH 2 CH 2 CH 3 O OH CNCNCNCN OH CO2HCO2HCO2HCO2H

Dr. Wolf's CHM 201 & Reactions of Carboxylic Acids: A Review and a Preview

Dr. Wolf's CHM 201 & Reactions of Carboxylic Acids Acidity (Chapter 18) Reduction with LiAlH 4 (Chapter 15) Esterification (Chapter 15) Reaction with Thionyl Chloride (Chapter 12) Reactions already discussed

Dr. Wolf's CHM 201 & Reactions of Carboxylic Acids Decarboxylation But first we revisit acid-catalyzed esterification to examine its mechanism. New reaction in this chapter

Dr. Wolf's CHM 201 & Mechanism of Acid-Catalyzed Esterification

Dr. Wolf's CHM 201 & 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)

Dr. Wolf's CHM 201 & The mechanism involves two stages: 1)formation of tetrahedral intermediate (3 steps) 2)dissociation of tetrahedral intermediate (3 steps) Mechanism of Fischer Esterification

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & Mechanism of formation of tetrahedral intermediate

Dr. Wolf's CHM 201 & Step 1 C O OH O + H CH 3 H

Dr. Wolf's CHM 201 & Step 1 C O OH O + H CH 3 H C O OH + H O CH 3 H

Dr. Wolf's CHM 201 & Step 1 C O OH + H carbonyl oxygen is protonated because cation produced is stabilized by electron delocalization (resonance) C OOH + H

Dr. Wolf's CHM 201 & Step 2 C O OH + H O CH 3 H

Dr. Wolf's CHM 201 & Step 2 C O OH + H O CH 3 H C OH OH O + CH 3 H

Dr. Wolf's CHM 201 & Step 3 O CH 3 H C OH OH O CH 3 H +

Dr. Wolf's CHM 201 & Step 3 O CH 3 H C OH OH O CH 3 H + O CH 3 H H + C OH OH O CH 3

Dr. Wolf's CHM 201 & Tetrahedral intermediate to ester stage

Dr. Wolf's CHM 201 & Step 4 C OH O OCH 3 H

Dr. Wolf's CHM 201 & Step 4 O CH 3 H H + C OH O OCH 3 H

Dr. Wolf's CHM 201 & Step 4 O CH 3 H H + C OH O OCH 3 H C OH O OCH 3 H H + O CH 3 H

Dr. Wolf's CHM 201 & Step 5 C OH O OCH 3 H H +

Dr. Wolf's CHM 201 & Step 5 C OH O OCH 3 H H + O H H+ C OH OCH 3 +

Dr. Wolf's CHM 201 & Step 5 C OH OCH 3 + C OH +

Dr. Wolf's CHM 201 & Step 6 C O OCH 3 + H O H CH 3 + O H H C O OCH 3

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & Intramolecular Ester Formation: Lactones

Dr. Wolf's CHM 201 & Lactones are cyclic esters Formed by intramolecular esterification in a compound that contains a hydroxyl group and a carboxylic acid function Lactones

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & Reactions designed to give hydroxy acids often yield the corresponding lactone, especially if the resulting ring is 5- or 6-membered. Lactones

Dr. Wolf's CHM 201 & 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 +

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & Decarboxylation of Malonic Acid and Related Compounds

Dr. Wolf's CHM 201 & Decarboxylation of Carboxylic Acids Simple carboxylic acids do not decarboxylate readily. RH + CO 2 RCOHO

Dr. Wolf's CHM 201 & Decarboxylation of Carboxylic Acids Simple carboxylic acids do not decarboxylate readily. But malonic acid does. RH + CO 2 RCOHO150°C CH 3 COH O+ CO 2 HOCCH 2 COH OO

Dr. Wolf's CHM 201 & Mechanism of Decarboxylation One carboxyl group assists the loss of the other. OOOHHO HH OHO O O HH H

Dr. Wolf's CHM 201 & Mechanism of Decarboxylation This compound is the enol form of acetic acid. OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other.

Dr. Wolf's CHM 201 & Mechanism of Decarboxylation OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other. HOCCH 3 O

Dr. Wolf's CHM 201 & Mechanism of Decarboxylation OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other. HOCCH 3 O These hydrogens play no role.

Dr. Wolf's CHM 201 & Mechanism of Decarboxylation OOOHHO RR' R R'OHHO OHO O O RR' H + COO One carboxyl group assists the loss of the other. HOCCHR' O Groups other than H may be present. R

Dr. Wolf's CHM 201 & °C Decarboxylation is a general reaction for 1,3-dicarboxylic acids 160°C CO 2 H H (74%) (96-99%) CH(CO 2 H) 2 CH 2 CO 2 H

Dr. Wolf's CHM 201 & Mechanism of Decarboxylation OOOHHO RR' R R'OHHO OHO O O RR' H + COO One carboxyl group assists the loss of the other. This OH group plays no role. HOCCHR' OR

Dr. Wolf's CHM 201 & Mechanism of Decarboxylation OOOHR" RR' R COO One carboxyl group assists the loss of the other. Groups other than OH may be present. R"CCHR' OR OO O RR' H R" R'OH+ R"

Dr. Wolf's CHM 201 & Mechanism of Decarboxylation OOOHR" RR' This kind of compound is called a  -keto acid.   R"CCHR' OR Decarboxylation of a  -keto acid gives a ketone.

Dr. Wolf's CHM 201 & Decarboxylation of a  -Keto Acid C CH 3 C O CH 3 CO 2 H 25°C CO 2 C CH 3 C O CH 3 H +

Dr. Wolf's CHM 201 & Spectroscopic Analysis of Carboxylic Acids

Dr. Wolf's CHM 201 & 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

Dr. Wolf's CHM 201 & Wave number, cm -1 Figure 19.8 Infrared Spectrum of 4-Phenylbutanoic acid C=O O—H and C—H stretch monosubstituted benzene C 6 H 5 CH 2 CH 2 CH 2 CO 2 H

Dr. Wolf's CHM 201 & proton of OH group of a carboxylic acid is normally the least shielded of all of the protons in a 1 H NMR spectrum: (  ppm; broad). 1 H NMR

Dr. Wolf's CHM 201 & Chemical shift ( , ppm) Figure 19.9 CH 2 CH 2 CH 2 COH O

Dr. Wolf's CHM 201 & C NMR Carbonyl carbon is at low field (  ppm), but not as deshielded as the carbonyl carbon of an aldehyde or ketone (  ppm).

Dr. Wolf's CHM 201 & UV-VISUV-VIS Carboxylic acids absorb near 210 nm, but UV-VIS spectroscopy has not proven to be very useful for structure determination of carboxylic acids.

Dr. Wolf's CHM 201 & Aliphatic carboxylic acids undergo a variety of fragmentations. Aromatic carboxylic acids first form acylium ions, which then lose CO. Mass Spectrometry ArCOH O ArCOH +O ArC O + Ar+

Dr. Wolf's CHM 201 & End of Chapter 18