19.6 substituents and acid strength

19.6Substituents and Acid Strength

Substituent Effects on Aciditystandard of comparison is acetic acid (X = H)Ka = 1.8 x 10-5 pKa = 4.7

Substituent Effects on Acidityalkyl substituents have negligible effect

Substituent Effects on Acidityelectronegative substituents increase acidity

Substituent Effects on Acidityelectronegative substituents withdraw electrons from carboxyl group; increase K for loss of H+

Substituent Effects on Acidityeffect of electronegative substituent decreases as number of bonds between X and carboxyl group increases

XKapKaH1.8 x 10-54.71.4 x 10-32.91.0 x 10-44.0ClCH2Cl3.0 x 10-54.5ClCH2CH2

19.7Ionization ofSubstituted Benzoic Acids

Hybridization Effectsp2-hybridized carbon is more electron-withdrawing than sp3, and sp is more electron-withdrawing than sp2

Table 19.3 Ionization of Substituted Benzoic Acidseffect is small unless X is electronegative; effect is largest for ortho substituentpKaSubstituentorthometaparaH4.24.24.2CH33.94.34.4F3.33.94.1Cl2.93.84.0CH3O4.14.14.5NO22.23.53.4

19.8Dicarboxylic Acids

Dicarboxylic Acidsone carboxyl group acts as an electron-withdrawing group toward the other; effect decreases with increasing separationOxalic acidMalonic acidHeptanedioic acid1.22.84.3pKa

19.9Carbonic Acid

Carbonic AcidCO2+H2O99.7%0.3%

Carbonic AcidCO2+H2OH++

Carbonic AcidCO2 is major species present in a solution of "carbonic acid" in acidic mediaCO2+H2OH++overall K for these two steps = 4.3 x 10-7

Carbonic AcidH++Ka = 5.6 x 10-11Second ionization constant:

19.10Sources of Carboxylic Acids

Synthesis of Carboxylic Acids: Reviewside-chain oxidation of alkylbenzenes (Section 11.13) oxidation of primary alcohols (Section 15.10)oxidation of aldehydes (Section 17.15)

19.11Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents

Carboxylation of Grignard Reagentsconverts an alkyl (or aryl) halide to a carboxylic acid having one more carbon atom than the starting halideRXMgdiethyl etherRMgXCO2H3O+

Carboxylation of Grignard ReagentsCO dH3O+

Example: Alkyl Halide(76-86%)1. Mg, diethyl ether2. CO23. H3O+ClCO2H

Example: Aryl Halide(82%)1. Mg, diethyl ether2. CO23. H3O+

19.12Synthesis of Carboxylic Acidsby thePreparation and Hydrolysis of Nitriles

Preparation and Hydrolysis of Nitrilesconverts an alkyl halide to a carboxylic acid having one more carbon atom than the starting halidelimitation is that the halide must be reactive toward substitution by SN2 mechanismRXSN2H3O+heat+ NH4+

ExampleNaCNDMSO(77%)H2OH2SO4heat(92%)

Example: Dicarboxylic AcidBrCH2CH2CH2BrNaCNH2OH2O, HClheat(77-86%)NCCH2CH2CH2CN(83-85%)

via Cyanohydrin1. NaCN2. H+(60% from 2-pentanone)H2OHCl, heat

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