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Carboxylic Acids20
RETANOIC ACID
20.1 CARBOXYLIC ACIDS AND ACYL GROUPS
C O
O
carboxyl group
H R C O
O
carboxylic acids
H Ar C O
O
H
methanoic acid
H C O
O
1
H H C O
O
2
H H C O
O
H
3
C
O
H OH
134 pm
120 pm
Figure 20.1 Bonding in Carboxylic Acids
!e π bond is formed by overlap of the 2p orbitals of carbon and oxygen.
(a) Lowest energy bonding orbital in methanoic acid (formic acid)
(b) Electron distribution in methanoic acid
Regions colored red have a partial negative charge (at the carboxyl oxygens) and regions colored blue have a partial positive charge (at the hydroxyl hydrogen and carbonyl carbon).
20.1 CARBOXYLIC ACIDS AND ACYL GROUPSThe Acyl Group and Carboxylic Acid Derivatives
R C O
O
examples of esters (acyl groups shown in red)
R' R C O
O
Ar Ar C O
O
Ar'
R C NH2
O
primary amide
R C NHR
O
R C NR2
O
secondary amide tertiary amide
R C Cl
O
acid chloride
R C O
O
R C S
O
acid anhydride thioester
C R
O
R
lactone(a cyclic ester)
O
O
N O
H lactam(a cyclic amide)
N
SN
H
CO2H
CH3
CH3
C
O
O
penicillin G
H
20.2 NOMENCLATURE OF CARBOXYLIC ACIDSCommon Names of Carboxylic Acids
γ-bromo-β-ethylcaproic acid
CH3 CH2 CH CCH
Br
CH2 OH
O
αβγδε
CH2CH3
α-bromoglutaric acid
CH2 CH2 CH C
Br
αβγ
β-methyladipic acid
C CH2 CHαβγδ
HO
O
CH2
CH3
CH2 C OH
O
OH
O
CHO
O
OH
CO2H
CO2H
CO2H
CO2H
HO2C
salicylic acid phthalic acid terephthalic acid
Table 20.1Nomenclature of Carboxylic AcidsFormula Common Name IUPAC NameHCO2H formic acid methanoic acidCH3CO2H acetic acid ethanoic acidCH3CH2CO2H propionic acid propanoic acidCH3(CH2)2CO2H butyric acid butanoic acidCH3(CH2)3CO2H valeric acid pentanoic acidCH3(CH2)4CO2H caproic acid hexanoic acidCH3(CH2)6CO2H caprylic acid octanoic acidCH3(CH2)10CO2H lauric acid dodecanoic acidCH3(CH2)12CO2H myristic tetradecanoic acidCH3(CH2)14CO2H palmitic hexadecanoic acidCH3(CH2)16CO2H stearic octadecanoic acid
20.2 NOMENCLATURE OF CARBOXYLIC ACIDSIUPAC Names of Carboxylic Acids
4-bromo-3-methylpentanoic acid
CH3 CH CCH
Br
CH2 OH
O
2345
CH3
1
4--methyl-2-pentynoic acid
CCH C OH
O
2345
CH3
1CCH3
1. Name the longest continuous carbon chain containing the carboxyl carbon atom as the parent chain. Replace the !nal -e of the parent hydrocarbon by the ending -oic acid. Table 20.1 gives examples of IUPAC names of unsubstituted carboxylic acids.
Number the parent chain by assigning the number 1 to the carboxyl carbon atom. Do not add the number “1” to the name to indicate the position of the carboxyl carbon because it must be located at the end of the chain. Add the names and locations of any substituents as pre!xes to the parent name.
2.
"e carboxylic acid group has a higher priority than double or triple bonds. To name a carboxylic acid that contains a double or triple bond, replace the !nal -e of the name of the parent alkene or alkyne name with the su#x -oic acid. Indicate the position of the multiple bond with a pre!x.
3.
20.2 NOMENCLATURE OF CARBOXYLIC ACIDSIUPAC Names of Carboxylic Acids
3-hydroxy-2-methylbutanoic acid
CH3 CH CCH
OH
OH
O
234
CH3
1
2-methyl-3-oxobutanoic acid
CH3 C CCH
O
OH
O
234
CH3
1
O
CO2H
Cl
CO2H
3-oxocyclopentanecarboxylic acid cis-2-chlorocyclohexanecarboxylic acid
!e carboxylic acid functional group has a higher priority than aldehyde, ketone, halogen, hydroxyl, and alkoxy groups. Indicate the names and locations of these groups with pre"xes to the name of the parent carboxylic acid.
4.
If a carboxylic acid contains an aldehyde or ketone, the names of the carbonyl group is -oxo. !e priority order is aldehyde > ketone.
5.
Name compounds that have a —COOH group bonded to a cycloalkane ring as derivatives of the cycloalkane with the su$x carboxylic acid. !e ring atom to which the carboxyl group is attached is C-1. Do not include this number in the name.
6.
Name dicarboxylic acids by adding the su!x dioic acid to the name the parent alkane that contains both carboxylic acid groups. Number the chain starting with the carboxyl carbon closest to the "rst substituent.
7.
CH2 3 4
CH2CH3
5C OH
O
1CH2 CH2CHO
O
2-ethylpentanedioic acid
2345C OH
O
1CH2 CH2CHO
O
3-chlorohexanedioic acid
CH
Cl
CH2
6
20.2 NOMENCLATURE OF CARBOXYLIC ACIDSIUPAC Names of Carboxylic Acids
20.1 CARBOXYLIC ACIDS AND ACYL GROUPSNames of Carboxylate Anions
CH3 C O
O
sodium ethanoate (sodium acetate)
Na CH2 CH2 C O
O
K
potassium 3-phenylpropanoate(potassium β-phenylpropionate)
20.3 PHYSICAL PROPERTIES OF CARBOXYLIC ACIDSBoiling Points
CH3 C O
O
bp 118 oC
H CH3 C CH3
O
bp 56.5 oC bp -7 oC
CH3 C CH3
CH2
C
O H O
C
OHO
CH3 CH3
hydrogen-bonded dimer of acetic acid
Table 20.2Boiling Points of Carboxylic AcidsIUPAC Name Common Name Boiling Point, oCmethanoic acid formic acid 101ethanoic acid acetic acid 118propanoic acid propionic acid 141butanoic acid butyric acid 1642-methylpropanoic acid isobutyric acid 155 pentanoic acid valeric acid 1863-methylbutanoic acid isovaleric acid 1772,2-dimethylpropanoic acid pivalic acid 164hexanoic acid caproic acid 205octanoic acid caprylic acid 239decanoic acid capric 270dodecanoic acid lauric acid 299
20.3 PHYSICAL PROPERTIES OF CARBOXYLIC ACIDSMelting Points
Table 20.2Melting Points of Carboxylic AcidsNumber of Carbon Atoms
IUPAC Name Common Name Melting Point, oC
10 decanoic acid capric acid 31.312 dodecanoic acid lauric acid 43.214 tetradecanoic acid myristic acid 54.416 hexadecanoic acid myristic acid 62.818 octadecanoic acid isobutyric acid 69.9 20 eicosanoic acid arachidic acid 75.422 docosanoic acid behenic acid 79.924 tetracosanoic acid lignoceric acid 84.226 hexacosanoic acid ceratoic acid 87.7
C OH
O
CH2 CH2CHO
O
succinic acid mp 185 oC
C OH
O
CH2CHO
O
malonic acid mp 136 oC
20.3 PHYSICAL PROPERTIES OF CARBOXYLIC ACIDSSolubilities
C
O
OH3CH
H
OH
OH
HHO
H
hydrogen bonds between acetic acid and water in aqueous solution
20.4 ACIDITY OF CARBOXYLIC ACIDSResonance Stabilization of the Carboxylate Ion
CH3CH2OH + H2O CH3CH2O + H3O Ka = 1 x 10-16
CH3CO2H + H2O CH3CO2 + H3O Ka = 1.8 x 10-5
CH3 C O
O
1
CH3 C O
O
2Resonance structures of acetate ion
20.4 ACIDITY OF CARBOXYLIC ACIDSInductive Effect on Acidity
C
O
OCl H
HHδδ
δ
δ
Electron density is pulled towards the oxygen atom.
Electron density is pulled towards the carbon atom.
The chlorine atom pulls electron density to itself.
CH3CH2CHCO2H
Cl
CH3CHCH2CO2H
Cl
CH2CH2CH2CO2H
Cl
pKa 2.84 pKa 4.06 pKa 4.52
CH3CH2CH2CO2H
pKa 4.72
Table 20.4pKa Values of Carboxylic AcidsIUPAC Name Formula pKa
methanoic acid HCO2H 3.75ethanoic acid CH3CO2H 4.72propanoic acid CH3CH2CO2H 4.87butanoic acid CH3(CH2)2CO2H 4.822-methylbutanoic acid (CH3)2CHCO2H 4.84pentanoic acid CH3(CH2)3CO2H 4.812,2-dimethylmethylpropanoic acid (CH3)CCO2H 5.03
#uoroethanoic acid FCH2CO2H 2.59chloroethanoic acid ClCH2CO2H 2.86bromoethanoic acid BrCH2CO2H 2.90idoethanoic acid ICH2CO2H 3.18dichloroethanoic acid Cl2CHCO2H 1.24trichloroethanoic acid Cl3CCO2H 0.64tri#uoroethanoic acid F3CCO2H 0.23
methoxyethanoic acid CH3OCH2CO2H 3.55cyanoethanoic acid CNCH2CO2H 2.46nitroethanoic acid NO2CH2CO2H 1.72
Table 20.5pKa Values of Dicarboxylic AcidsIUPAC Name Formula pKa1 pKa2
oxalic acid HO2CCO2H 1.27 4.27malonic acid HO2CCH2CO2H 2.85 5.70succinic acid HO2C(CH2)2CO2H 4.35 5.64glutaric acid HO2C(CH2)3CO2H 4.41 5.41adipic acid HO2C(CH2)4CO2H 4.42 5.42pimelic acid HO2C(CH2)5CO2H 4.51 5.42suberic acid HO2C(CH2)6CO2H 4.52 5.41azelic acid HO2C(CH2)7CO2H 4.54 5.41sebacic acid HO2C(CH2)8CO2H 4.55 5.40
20.4 ACIDITY OF CARBOXYLIC ACIDSAcidity of Aromatic Carboxylic Acids
Table 20.6pKa Values of SubstitutedBenzoic AcidsSubstituent Ortho Meta ParaCH3O 4.06 4.10 4.47CH3 3.91 4.27 4.37H 4.20 4.20 4.20Cl 2.92 3.82 3.98NO2 2.17 3.49 3.42
C O
O
1
C O
O
2Resonance structures of benzoate ion
CO2H CO2H CO2H
NO2 OCH3
pKa = 4.20 pKa = 3.42 pKa = 4.47
20.6 SYNTHESIS OF CARBOXYLIC ACIDSOxidative Methods
KMnO4
CO2H
tetralin phthalic acidCO2H
C CH2
CH3
CH3
C CH3
OI2
OH-C CH2
CH3
CH3
C OH
O
CH3(CH2)8CH2OHCrO3
H2SO4CH3(CH2)8CO2H
1-decanol decanoic acid
CHOCrO3
H2SO4
CO2H
3-cyclohexenecarbaldehyde 3-cyclohexenecarboxylic acid
20.6 SYNTHESIS OF CARBOXYLIC ACIDSCarboxylation of Grignard Reagents
R MgBr + C
O
O
R C O
O
MgBrH3O+
R C OH
O
R X3. H3O+ R C OH
O1.Mg
etherR MgX
2. CO2
3. H3O+
1.Mg /ether2. CO2
Br
CH3
C
CH3
O
OH
20.6 SYNTHESIS OF CARBOXYLIC ACIDSHydrolysis of Nitriles
R XH3O+
R C OH
O
+ C N R C N
2. H3O+1.KCN
CH2Br CH2CO2H
20.7 REDUCTION OF CARBOXYLIC ACIDSReduction with Lithium Aluminum Hydride
C O
O
HRLiAlH4 C O
O
R Li+ + H2 + AlH3
C O
O
R Li+ + H AlH3 C O
O
R
H
AlH2
Li+
C O
O
R
H
AlH2
Li+ C H
O
R Li++ H AlH2O-
20.7 REDUCTION OF CARBOXYLIC ACIDSReduction with Diborane
BH3
THFCH2OHCCH3CH2
O
CCH3CH2
O
C OH
O
BH3
THFCH2CH2 C OH
O
O2N CH2CH2 CH2OHO2N
20.8 DECARBOXYLATION REACTIONS
R C O
O
H R H + CO2
HCH2CHO
O
HCH2CCH3
O
OHCCH2
O
CHO
O
OHCCH2
O
CCH3
O
heat
heat
malonic acid
acetoacetic acid
O C O
O C O
+
+
O
C C
OH
CH3 OHH
O
CCCH3
H
H
+CO2
H
C
O
CH3 C
H
H
Hslow fast
CO2H
CO2H
heatH
CO2H
+ CO2
1,1-cyclobutanedicarboxylic acid cyclobutanecarboxylic acid
C CH2CO2H
Oheat
C CH3
O
+ CO2
3-phenyl-3-oxopropanoic acid 1-phenyl-ethanone
O
C C
OH
HO OHH
O
CCHO
H
H
+
H
C
O
HO C
H
H
Hslow fastC
O
O
20.8 DECARBOXYLATION REACTIONSThe Hunsdiecker Reaction
CH2CH2CH2 C O
O
Ag CH2CH2CH2 BrBr2
20.8 DECARBOXYLATION REACTIONSBiochemical Decarboxylation Reactions
CO2-
C H
C
C
CO2-H
HH
CO2-
+ NAD+
CO2-
C O
C
C
HH
HH
CO2-
+ NADH + CO2
HO
isocitrate α-ketoglutarate
isocitrate dehydrogenase
Mg2+
C C
C
O2CCH2
H
O
O
O
CO2
-CO2 C CO2CCH2
H O
CO2H+
CO2-
C O
C
C
HH
HH
CO2-
α-ketoglutarate(S)-3-oxalosuccinate
C
O
CRC
O
OH H
Mg2+
C
O
CR
H
H
Mg+
+ C
O
O
20.9 REACTIONS OF CARBOXYLIC ACIDS AND THEIR DERIVATIVES: A PREVIEWNucleophilic Acyl Substitution
C
O
R'R
1. Nu
2. H3O+C
OH
NuR'
R
tetrahedral product
C
O
LRC
O
LNu
R
tetrahedral intermediate
Nu C
O
NuR
R C O
O
H Nu+
addition reaction acid-base reaction
HNu
R C O
ONuR C O
O
H
Nu
20.10 CONVERSION OF CARBOXYLIC ACIDS INTO ACYL HALIDES
COH
O
+ SOCl2
CCl
O
+ SO2 + HCl
RC
OH
O
+R
CO
O
+ HClCl
SCl
O
SCl
O
RC
O
O
SCl
O
ClR
CO
O
SCl
O
Cl
RC
O
O
SCl
O
Cl RC
O
Cl+
O
S
O
+ Cl-
20.11 CONVERSION OF CARBOXYLIC ACIDS INTO ESTERSAlkylation of Carboxylate Anions
C O
O
CH3 I C O
O
CH3 + I-+
20.11 CONVERSION OF CARBOXYLIC ACIDS INTO ESTERSEsterification With Diazomethane
R C O
O
R C O
O
CH3 + N2H C N
H
H
N+
R C O
O
H C N
H
H
N R C O
O
C N N
H
H
H+
R C O
O
C N N
H
H
H+ R C O
O
CH3 + N N
+
20.11 CONVERSION OF CARBOXYLIC ACIDS INTO ESTERSReaction of Acyl Chlorides With Alcohols
RC
O
Cl+ +R'OH
RC
O
OR'pyridine
HCl
R C O
O
R'
ClR
C
O
Cl+ +
RC
O
OR' ClO R'H
H
+
H
RC
O
OR'
H
RC
O
OR' H+
1.
C
O
Cl
+ HOCH2OH more sterically hindered 2o alcohol
less sterically hindered 1o alcohol
C
O
OCH2
OH
20.11 CONVERSION OF CARBOXYLIC ACIDS INTO ESTERSFischer Esterification
R C OH
O
CH3CH2 OH R C O
O
CH2CH3 + H2O+
Adding alcohol "pushes" the reaction to the right.
Removing water "pulls" the reaction to the right.
20.12 MECHANISM OF ESTERIFICATION
C OH
O
+CH318O H C
O
18O CH3 + H2O
R C OH
O
+ H R C OH
O H
R C OH
O H
+
-H
R C OH
O H
R C OH
O HO R'H R C O
O
R'
OH H
H
R C O
O
R'
OH H
H
R C O
O
R'
OH
H
(hydrate of an ester)
-HR C O
O
R'
O
H
(conjugate acid of an ester)
R C O
O
R'
O
HH-H2O
R C O R'
OH H H
R C O R'
O H
R C O R'
O H
-HR C O R'
O
20.13 BRIEF SYNTHETIC REVIEWFunctional Group Modifications in Organic Synthesis
O
CO2H
O
CH2OH
O
CO2H
O
CH2OHBH3
THF
O
CO2H
O
CO2CH31. CH3OH
H2SO4
2. HOCH2CH2OH
TsOH
CO2CH3
O O
3. LiAlH4
3a. H3O+
O
CH2OH
Figure 20.2 Infrared Spectrum of Acetic Acid
20.14 SPECTROSCOPY OF CARBOXYLIC ACIDSInfrared Spectroscopy
Perc
ent
Tran
smit
tanc
e
50
100
4000 3000 2000 1000Wavenumber (cm–1)
1500 500
O—H stretch 1-butanolCH3(CH2)2CH2OH
3350 cm-1
C—O stretch CH3 C OH
O
acetic acidC=O stretch
O–H stretch
Chemical shift, ppm (δ) 010 8 6 4 2
3 H triplet
TMS
2 H quartet
1 H
OCCH2
O
CH3 H
12
carboxylic acid proton
20.14 SPECTROSCOPY OF CARBOXYLIC ACIDSProton NMR Spectroscopy
Figure 20.3 Proton NMR Spectrum of Propanoic Acid
20.14 SPECTROSCOPY OF CARBOXYLIC ACIDSProton NMR Spectroscopy
Figure 20.4 C-13 NMR Spectrum of Propanoic Acid
Chemical shift, ppm (δ)
TMS
CH2
OCCH2
O
CH3 H
carbonyl carbon CH3
020406080100120140160180
181.5
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