19.6 Substituents and Acid Strength

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

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

Substituent Effects on Acidity electronegative substituents increase acidity X CH 2 COH O X KaKaKaKa pKapKapKapKaH F Cl 1.8 x x x

Substituent Effects on Acidity electronegative substituents withdraw electrons from carboxyl group; increase K for loss of H + X CH 2 COH O

Substituent Effects on Acidity effect of electronegative 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

19.7 Ionization of Substituted Benzoic Acids

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

pK a Substituentorthometapara H CH F Cl CH 3 O NO Table 19.3 Ionization of Substituted Benzoic Acids COHOX effect is small unless X is electronegative; effect is largest for ortho substituent

19.8 Dicarboxylic Acids

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

19.9 Carbonic Acid

Carbonic Acid HOCOHO CO 2 + H2OH2OH2OH2O 99.7%0.3%

Carbonic Acid HOCOHO CO 2 + H2OH2OH2OH2O HOCO – O H+H+H+H+ +

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

Carbonic Acid HOCO – O – OCO – O H+H+H+H+ + K a = 5.6 x Second ionization constant:

19.10 Sources of Carboxylic Acids

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

19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents

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

RMgX C O MgX+ –––– H3O+H3O+H3O+H3O+ diethyl ether O – R C O O R C OH O Carboxylation of Grignard Reagents

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

Example: Aryl Halide (82%) 1. Mg, diethyl ether 2. CO 2 3. H 3 O + CH 3 CO2HCO2HCO2HCO2H Br

19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles

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 – C N RCRCRCRC N SN2SN2SN2SN2 H3O+H3O+H3O+H3O+ heat + NH 4 +

Example NaCN DMSO (77%) H2OH2OH2OH2O H 2 SO 4 heat (92%) CH 2 Cl CH 2 CN CH 2 COH O

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

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