19'6 Substituents and Acid Strength

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19.6Substituents and Acid Strength
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Substituent Effects on Acidity
standard of comparison is acetic acid (X H)
pKa 4.7
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Substituent Effects on Acidity
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Substituent Effects on Acidity

• electronegative substituents withdraw electrons
  from carboxyl group increase K for loss of H

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Effect of electronegative substituent
decreasesas number of bonds between it and
carboxyl group increases.
pKa

ClCH2CH2CH2CO2H
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19.7Ionization ofSubstituted Benzoic Acids
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Hybridization Effect

• sp2-hybridized carbon is more electron-withdrawin
  g than sp3, and sp is more electron-withdrawing
  than sp2

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Table 19.3 Ionization of Substituted Benzoic
Acids

• 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 CH
3 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
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19.8Dicarboxylic Acids
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Dicarboxylic Acids
pKa
Oxalic acid
Malonic acid
Heptanedioic acid

• one carboxyl group acts as an electron-withdrawin
  g group toward the other effect decreases with
  increasing separation

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19.9Carbonic Acid
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Carbonic Acid

H2O
CO2
99.7
0.3

• CO2 is major species present in a solution of
  "carbonic acid" in acidic media

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Carbonic Acid
Ka 5.6 x 10-11
Second ionization constant

H
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19.10Sources of Carboxylic Acids
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Synthesis of Carboxylic Acids Review

• side-chain oxidation of alkylbenzenes (Section
  11.13)
• oxidation of primary alcohols (Section 15.10)
• oxidation of aldehydes (Section 17.15)

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19.11Synthesis of Carboxylic Acidsby
theCarboxylation of Grignard Reagents
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Carboxylation of Grignard Reagents
Mg
CO2
RMgX
RX
diethylether
H3O

• converts an alkyl (or aryl) halide to a
  carboxylic acid having one more carbon atom than
  the starting halide

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Carboxylation of Grignard Reagents
?
C
O


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Example Alkyl Halide
1. Mg, diethyl ether
2. CO2 3. H3O
Cl
CO2H
(76-86)
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Example Aryl Halide
1. Mg, diethyl ether
2. CO2 3. H3O
(82)
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19.12Synthesis of Carboxylic Acidsby
thePreparation and Hydrolysis of Nitriles
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Preparation and Hydrolysis of Nitriles
H3O
RX
heat
SN2
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

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Example
NaCN
DMSO
(92)
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Example Dicarboxylic Acid
BrCH2CH2CH2Br
NaCN
H2O
(77-86)
NCCH2CH2CH2CN
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via Cyanohydrin
1. NaCN
2. H