Post on 09-Mar-2021
Carboxylic Acids: common in nature
CH3COOH
COOH
COOH COOH
odor of sour butter
odor of goats, socks palmitic acid (precursor of fat)
vinegar
COOHCH3
CH3 H
HHO OH
OH
HCholic acid
(major component of human bile)
CH3COOHCH3CHOcobalt acetate
O2 80oCCH3OH
CORh catalyst
Industrial synthesis of acetic acid:
Ch.20 Carboxylic Acids and Nitriles
Carboxylic Acids: RCO2H
CO2H CO2H1 1
Propanoic acid 4-Methylpentanoic acid
- parent chain contains the -COOH group, - carboxyl carbon is numbered as 1
20.1 Nomenclature
alkane (-e) → -oic acid
HO2CCO2H
Et
1
3-Ethyl-6-methyloctanedioic acid
-carboxylic acid
COOH
3-Bromocyclohexanecarboxylic acid
Br 1
-COOH is attached to a ring
CO2H
1-Cyclopentenecarboxylic acid1
Common Names
HCOOH
H3C COOH
COOH
COOH
COOH
COOH
COOH
Formic acid
Acetic acid
Propionic acid
Butyric acid
Oxalic acid
Acrylic acid
Benzoic acid
HOOC
HOOC COOH Malonic acid
COOHHOOC Succinic acid
HCO-
H3C CO-
CO-
CO-
CO-
CO-
CO-
Formyl
Acetyl
Propionyl
Butyryl
Oxalyl
Acryloyl
-OC
-OC CO- Malonyl
CO--OC Succinyl
Acyl groups
Benzoyl
Nitrile: RCN
CN1
4
4-Methylpentanenitrile
- nitrile- CN carbon is numbered as 1
complex nitrile -(o)ic acid → onitrile-carboxylic acid → -carbonitrile
H3C C N
Acetonitrile
CN
Benzonitrile
CN
CH3CH3
1
2
2,2-Dimethylcyclohexanecarbonitrile
R OH
Osp2
120o
planar
R OH
O
ROH
O
dimer: H-bonding (high b.p.)
20.2 Structure and Physical Properties of Carboxylic Acids
Structure
- high b.p. and m.p.- b.p. of acetic acid: 118oC
20.3 Dissociation of Carboxylic Acids
R OH
O
water-insoluble
+ NaOHH2O R O
O
water-soluble
+ H2ONa+
Acidity: weak bases (NaOH, NaHCO3) generate carboxylate, RCO2
-Na+
H3C OH
O
CH3CH2OH HCl
pKa = 16 4.75 -7
Acetic acid: only 0.1% dissociate in 0.1M solutionHCl: 100% dissociate
Alkoxide / Carboxylate ion
localized charge
H3C
H2C
OH
H3C
H2C
O
H3C O
OH
H3C O
O
H3C O
O
delocalized chargeresonance-stabilized carboxylate ion
HC
O
ONa+
Sodium formate
127 pm
HC
O
O
Formic acid
120 pm
H
134 pm
purification of acid: dissolve salts in water, extract out organic impurities with organic solvent, acidify aqueous layer to obtaincarboxylic acids
Carboxylic acids with more than six carbons are insoluble in water
20.4 Substituent Effects on Acidity
Acid pKa
CH3CH2OHCH3CH2COOHCH3COOHH2C=CHCO2HPhCO2HHOCH2COOHHCO2HICH2CO2HBrCH2CO2HClCH2CO2HFCH2CO2HF3CCO2H
164.874.754.254.193.833.753.122.682.852.590.23
strongeracid
H3C OH
O
CH2 OH
O
Cl CH OH
O
C OH
OCl
ClCl
Cl
Cl
stronger acid
Acidity of chloroacetic acids: inductive effect
CH2 O-
O
Cl
electronegative Cl stabilizes anion
- inductive effect operates through σ-bond and depends on distance
COOH
Cl COOHCl COOHCl COOH
pKa = 2.86 4.05 4.52 4.82
20.5 Substituent Effects in Substituted Benzoic Acids
OH
O
stronger acid
OH
O
O2N
OH
O
MeO
pKa = 4.46 4.19 3.41
- acidity of substituted benzoic acid correlate reactivity of thesubstituted benzene
OH
O
Y Y
pKapredict reactivity ofelectrophilic attack
"inverse relationship"
20.6 Preparation of Carboxylic Acids
Oxidation of benzylic C-H
COOHCH3 KMnO4
H2O95oC
KMnO4
H3O+O
HO+ CO2
H
HH
Oxidation of alcohol/aldehyde
R CH2OHCrO3
R COOHH2SO4, H2O
R CHOAgNO3
R COOHNH4OH
Hydrolysis of nitrile
R CN1. H2O, OH-
R COOH2. H3O+
OBr
1. KCN
3. H3O+O
COOH2. H2O, OH-
- a typical way to introduce one carbon fragment from alkyl halides
R COH-
H3O+
NN
R OH
NH
R OH
H3O+ O
R OH
Carboxylation of Grignard reagents
R CH2MgXCO2
R CH2R CH2 CO
O MgXH3O+
COOHC OO
2. H3O+
BrMg
ether
MgBr1. CO2
COOH
20.7 Reactions of Carboxylic Acids: An Overview
General reactions of carboxylic acids
CC
O
OH
CC
OH
HH
H
CC
Y
OHC
COH
OR
Deprotonation Reduction
Alpha-substitution Nucleophilic acyl substitution
CC
OH
OH
20.8 Reduction of Carboxylic Acids
LiAlH4: alkenes are not reduced
OH
O 1. LiAlH4
2. H3O+ OH
BH3: alkenes can be hydroborated, esters are not reduced
OH
O 1. BH3, THF
2. H3O+
O2N
OH
O2N
- LiAlH4 reduces both nitro and acid
20.9 Chemistry of Nitriles
RC
OH
OC NR
same oxidation level
Preparation
BrCH2R C NCH2RNaCN
SN2 substitution by -CN
C NCH2RR NH2
O SOCl2
benzene80oC
+ + 2 HClSO2
From amide: SOCl2, POCl3
R NH2
O ClS
Cl
O
R NH2
OS
Cl
O
R N
OS
Cl
O
H
R C N+SO2 + HCl
Reactions of Nitriles
R R
O
Nu-
O-
RNu
R
C NRNu-
N
NuR
products
products
alkoxide ion
imine ion
R R'
O
R NH2
H2O1. R'MgX
R OH
O
1. [H-]
R C N
2. H3O+
2. H3O+
1. [H-]
2. H3O+
R H
O
Hydrolysis: acidic or basic conditions
R CNH2O, OH-
R COOHor H3O+
C NRN
OHR
imine anion
-OH
H2O NH
OHRO
NH2R
O
OHR
Reduction: LiAlH4, DIBAL
R R NH21. LiAlH4
2. H3O+C N
to primary amine:
1. DIBAL
2. H2OC N CHO
to aldehyde:
C NRN
HR
imine anion
R H
NH2
H-H2. H3O+
LiAlH41. LiAlH4
DIBALtoluene N
HR
imine anion
H2O O
HR
Grignard addition: ketone formation
C NRN
R'R
imine anion
R R'
O
R'MgX
+MgXH3O+
+ NH3
CN 1. EtMgBr
2. H3O+
O
20.9 Spectroscopy of Carboxylic Acids and Nitriles
IR Spectroscopy
associated carboxyl (usual case)1710 cm-1
1760 cm-1
very broad2500-3300 cm-1O-H
free carboxyl (uncommon)C=O
R OH
O
R OH
O
ROH
O
1760 cm-1 1710 cm-1
2250 cm-1RCN
IR Spectrum of n-Butanoic acid
NMR Spectroscopy
165-185 ppm~ 12 ppm,
C=O13C NMRCOO-H1H NMR
CH3CH2CN
12110 11
1H NMR Spectrum
Vitamin CChemistry @ Work
Vitamin C: ascorbic acid
H
OH
OH
HO O
HO OH
Vitamin C(Ascorbic acid)
OHOHO
OHOH
OH
Glucose
Industrial synthesis of ascorbic acid from glucose
Chemistry @ Work
Chapter 20
Problem Sets
20, 26, 35, 39, 45