19.6 Substituents and Acid Strength

1. 19.6Substituents and Acid Strength

2. O CH2COH X Substituent Effects on Acidity standard of comparison is acetic acid (X = H) Ka = 1.8 x 10-5pKa = 4.7

3. O CH2COH X X Ka pKa H 1.8 x 10-5 4.7 1.3 x 10-5 4.9 CH3 CH3(CH2)5 1.3 x 10-5 4.9 Substituent Effects on Acidity • alkyl substituents have negligible effect

4. O CH2COH X X Ka pKa H 1.8 x 10-5 4.7 2.5 x 10-3 2.6 F Cl 1.4 x 10-3 2.9 Substituent Effects on Acidity • electronegative substituents increase acidity

5. O CH2COH X Substituent Effects on Acidity • electronegative substituents withdraw electrons from carboxyl group; increase K for loss of H+

6. O CH2COH X Substituent Effects on Acidity • effect of electronegative substituent decreases as number of bonds between X and carboxyl group increases X Ka pKa H 1.8 x 10-5 4.7 Cl 1.4 x 10-3 2.9 ClCH2 1.0 x 10-4 4.0 ClCH2CH2 3.0 x 10-5 4.5

7. 19.7Ionization ofSubstituted Benzoic Acids

8. Ka pKa O 6.3 x 10-5 4.2 COH O 5.5 x 10-5 4.3 COH H2C CH O 1.4 x 10-2 1.8 COH HC C Hybridization Effect • sp2-hybridized carbon is more electron-withdrawing than sp3, and sp is more electron-withdrawing than sp2

9. O X COH 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 CH3 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

10. 19.8Dicarboxylic Acids

11. O O HOC COH O O HOCCH2COH O O HOC(CH2)5COH Dicarboxylic Acids pKa Oxalic acid 1.2 • one carboxyl group acts as an electron-withdrawing group toward the other; effect decreases with increasing separation Malonic acid 2.8 Heptanedioic acid 4.3

12. 19.9Carbonic Acid

13. O HOCOH Carbonic Acid + H2O CO2 99.7% 0.3%

14. O O HOCO– HOCOH Carbonic Acid + + H2O H+ CO2

15. O O HOCO– HOCOH Carbonic Acid • CO2 is major species present in a solution of "carbonic acid" in acidic media + + H2O H+ CO2 overall K for these two steps = 4.3 x 10-7

16. O HOCO– O –OCO– Carbonic Acid Second ionization constant: Ka = 5.6 x 10-11 + H+

17. 19.10Sources of Carboxylic Acids

18. 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)

19. 19.11Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents

20. O RCOMgX O RCOH Carboxylation of Grignard Reagents • converts an alkyl (or aryl) halide to a carboxylic acid having one more carbon atom than the starting halide Mg CO2 RMgX RX diethylether H3O+

21. •• •• O O •• •• diethylether R C R + O •• •• MgX MgX •• – •• O •• R C OH •• •• Carboxylation of Grignard Reagents d– C O •• •• H3O+

22. CH3CHCH2CH3 CH3CHCH2CH3 Example: Alkyl Halide 1. Mg, diethyl ether 2. CO2 3. H3O+ Cl CO2H (76-86%)

23. CH3 CH3 Br CO2H Example: Aryl Halide 1. Mg, diethyl ether 2. CO2 3. H3O+ (82%)

24. 19.12Synthesis of Carboxylic Acidsby thePreparation and Hydrolysis of Nitriles

25. O – N C •• •• RC N RCOH •• Preparation and Hydrolysis of Nitriles • 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 H3O+ RX heat SN2 + NH4+

26. CH2Cl CH2CN O CH2COH Example NaCN DMSO (92%) H2O H2SO4 heat (77%)

27. O O HOCCH2CH2CH2COH Example: Dicarboxylic Acid BrCH2CH2CH2Br NaCN H2O NCCH2CH2CH2CN (77-86%) H2O, HCl heat (83-85%)

28. OH O CH3CCH2CH2CH3 CH3CCH2CH2CH3 CN OH CH3CCH2CH2CH3 CO2H via Cyanohydrin 1. NaCN 2. H+ H2O HCl, heat (60% from 2-pentanone)