CHAPTER NINETEEN Carboxylic Acids TABLE 19.2 Effect of Substituents on Acidity of Carboxylic Acids Name of acid Structure constant k* Standard of comparison Acetic acid CH3CO2H 18×10-5 Alkyl substituents have a negligible effect on acidity Propanoic acid CH3 CH2 CO2H 1.3×10-5 4.9 2-Methylpropanoic acid (CH3)2CHCO2H 4.8 2, 2-Dimethylpropanoic acid (CH3)3CCO2H 0.9×10 5.1 Heptanoic acid CH3(CH2)5CO2H 1.3×10 4.9 c-Halogen substituents increase acidity Fluoroacetic acid 2.5×10-3 2.6 Chloroacetic acid CICH2 CO 14×10-3 2.9 2.9 Dichloroacetic acid Cl2CHCO 50×10-2 1.3 Trichlo 1.3×10-1 0.9 Electron-attracting groups increase acidity Aethoxyace CH3OCH2 CO2H 2.7×10 3.6 Cyanoacetic acid 34×10-3 Nitroacetic acid O2NCH2CO2H 2.1×10-2 1.7 wIn water at25°C Inductive effects fall off rapidly as the number of o bonds betw een the group and the substituent increases. Consequently, the acid-strengthening effect of gen decreases as it becomes more remote from the carboxyl group CICH,CO,H CICH,CHCO,H CICH,CHCHCO,H Chloroacetic acid 3-Chloropropanoid Ka=1.4×1 Ka=1.0×10 Ka=3.0×10 pKa=2.9 PROBLEM 19. 4 Which is the stronger acid in each of the following pairs? (a)(CH3)3CCH2 CO H or (CH3)3NCH2 CO2H (b)CH3 CH2CO2H or CH3 CHCO2H (c) CH3 CCO2H or CH2CHCO2H d)CH3 CH2CH2 CO2H or CH3 SCH2 CO2H Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Inductive effects fall off rapidly as the number of bonds between the carboxyl group and the substituent increases. Consequently, the acid-strengthening effect of a halogen decreases as it becomes more remote from the carboxyl group: PROBLEM 19.4 Which is the stronger acid in each of the following pairs? (a) (CH3)3CCH2CO2H or (CH3)3N CH2CO2H (b) (c) (d) CH3CH2CH2CO2H CH3SCH2CO2H O X X O or CH3CCO2H O X or CH2œCHCO2H CH3CH2CO2H CH3CHCO2H OH W or ClCH2CO2H Chloroacetic acid Ka 1.4 103 pKa 2.9 ClCH2CH2CO2H 3-Chloropropanoic acid Ka 1.0 104 pKa 4.0 ClCH2CH2CH2CO2H 4-Chlorobutanoic acid Ka 3.0 105 pKa 4.5 746 CHAPTER NINETEEN Carboxylic Acids TABLE 19.2 Effect of Substituents on Acidity of Carboxylic Acids Name of acid *In water at 25°C. Acetic acid Standard of comparison. Alkyl substituents have a negligible effect on acidity. Propanoic acid 2-Methylpropanoic acid 2,2-Dimethylpropanoic acid Heptanoic acid -Halogen substituents increase acidity. Fluoroacetic acid Chloroacetic acid Bromoacetic acid Dichloroacetic acid Trichloroacetic acid Ionization constant Ka* 1.8 105 1.3 105 1.6 105 0.9 105 1.3 105 2.5 103 1.4 103 1.4 103 5.0 102 1.3 101 2.7 104 3.4 103 2.1 102 pKa 4.7 4.9 4.8 5.1 4.9 2.6 2.9 2.9 1.3 0.9 3.6 2.5 1.7 Structure CH3CO2H CH3CH2CO2H (CH3)2CHCO2H (CH3)3CCO2H CH3(CH2)5CO2H FCH2CO2H ClCH2CO2H BrCH2CO2H Cl2CHCO2H Cl3CCO2H CH3OCH2CO2H NPCCH2CO2H O2NCH2CO2H Electron-attracting groups increase acidity. Methoxyacetic acid Cyanoacetic acid Nitroacetic acid Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.7 lonization of substituted Benzoic acids SAMPLE SOLUTION (a)Think of the two compounds as substituted derivatives of acetic acid. a tert-butyl group is slightly electron-releasing and has only a mod- est effect on acidity. the compound(CH3)3 CO2H is expected to have an acid strength similar to that of acetic acid. a trimethylammonium substituent, on the other hand, is positively charged and is a powerful electron-withdrawing sub- stituent. The compound(CH3)3NCH2 CO, H is expected to be a much stronger acid han(CH3)3CCH2 CO, H. The measured ionization constants, shown as follows, con- firm this prediction (CH3)3CCH2 CO2 H ( CH3)3NCH2 CO2H Ka=5×10-6 (pKa=5.3) (pKa=1.8) Another proposal advanced to explain the acid-strengthening effect of polar sub- stituents holds that the electron-withdrawing effect is transmitted through the water mol ecules that surround the carboxylate ion rather than through successive polarization of g bonds. this is referred to as a field effect. both field and inductive contributions to the polar effect tend to operate in the same direction, and it is believed that both are Important It is a curious fact that substituents affect the entropy of ionization more than they do the enthalpy term in the expression AG°=△H°-T△S° The enthalpy term AHo is close to zero for the ionization of most carboxylic acids, regardless of their strength. The free energy of ionization AG is dominated by the C TASO term. Ionization is accompanied by an increase in solvation forces, leading to a ecrease in the entropy of the system; AS is negative, and -TASo is positive. Anions incorporate substituents capable of dispersing negative charge impose less order on 19.7 IONIZATION OF SUBSTITUTED BENZOIC ACIDS A considerable body of data is available on the acidity of substituted benzoic acids. Ben- zoic acid itself is a somewhat stronger acid than acetic acid. Its carboxyl group is attached to an sp-hybridized carbon and ionizes to a greater extent than one that is attached to an sp-hybridized carbon. Remember, carbon becomes more electron-withdrawing as its CH:CO,H CHa=CHCOH CO,H crylic acid K=1.8×10-5K K=63×10-5 (pKa4.8) (pKa4.3) PROBLEM 19.5 What is the most acidic neutral molecule characterized by the formula C3H, O2? Table 19. 3 lists the ionization constants of some substituted benzoic acids. The largest effects are observed when strongly electron-withdrawing substituents are ortho to Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
SAMPLE SOLUTION (a) Think of the two compounds as substituted derivatives of acetic acid. A tert-butyl group is slightly electron-releasing and has only a modest effect on acidity. The compound (CH3)3CCH2CO2H is expected to have an acid strength similar to that of acetic acid. A trimethylammonium substituent, on the other hand, is positively charged and is a powerful electron-withdrawing substituent. The compound (CH3)3N CH2CO2H is expected to be a much stronger acid than (CH3)3CCH2CO2H. The measured ionization constants, shown as follows, con- firm this prediction. Another proposal advanced to explain the acid-strengthening effect of polar substituents holds that the electron-withdrawing effect is transmitted through the water molecules that surround the carboxylate ion rather than through successive polarization of bonds. This is referred to as a field effect. Both field and inductive contributions to the polar effect tend to operate in the same direction, and it is believed that both are important. It is a curious fact that substituents affect the entropy of ionization more than they do the enthalpy term in the expression G° H° TS° The enthalpy term H° is close to zero for the ionization of most carboxylic acids, regardless of their strength. The free energy of ionization G° is dominated by the TS° term. Ionization is accompanied by an increase in solvation forces, leading to a decrease in the entropy of the system; S° is negative, and TS° is positive. Anions that incorporate substituents capable of dispersing negative charge impose less order on the solvent (water), and less entropy is lost in their production. 19.7 IONIZATION OF SUBSTITUTED BENZOIC ACIDS A considerable body of data is available on the acidity of substituted benzoic acids. Benzoic acid itself is a somewhat stronger acid than acetic acid. Its carboxyl group is attached to an sp2 -hybridized carbon and ionizes to a greater extent than one that is attached to an sp3 -hybridized carbon. Remember, carbon becomes more electron-withdrawing as its s character increases. PROBLEM 19.5 What is the most acidic neutral molecule characterized by the formula C3HxO2? Table 19.3 lists the ionization constants of some substituted benzoic acids. The largest effects are observed when strongly electron-withdrawing substituents are ortho to CH3CO2H Acetic acid Ka 1.8 105 (pKa 4.8) Acrylic acid Ka 5.5 105 (pKa 4.3) CH2 CHCO2H Benzoic acid Ka 6.3 105 (pKa 4.2) CO2H (CH3)3CCH2CO2H Weaker acid Ka 5 106 (pKa 5.3) (CH3)3NCH2CO2H Stronger acid Ka 1.5 102 (pKa 1.8) 19.7 Ionization of Substituted Benzoic Acids 747 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER NINETEEN Carboxylic Acids TABLE 19.3 Acidity of Some Substituted Benzoic Acids Ka (pka)* for different positions of substituent x Substituent in XC H4CO2H Ortho Para -5(4.2) .3×10-5(4.2) 63×10-5(42) 2.CH3 12×10-4(39) 53×10-5(4.3)42×10-5(44) 3.F 54×10-4(3.3) 14×10-4(39) 72×10-5(4.1) 4. CI (29) 15×10-4(3.8) 15×10-4(3.8) 14×10-3(2.9) 14×10-4(39) 92×10-5(40) 7. CH3o 81×10-5(4.1) 82×10-5(4.1) 34×10-5(4.5) 8.O2N 67×10-3(2.2)32×10-43.5) 38×10-4(34) *In water at25° group. In those cases the pk a values are clustered in the range 3.54 y of benzoic the carboxyl group. An o-nitro substituent, for example, increases the acidi acid 100-fold. Substituent effects are small at positions meta and para to the carboxyl 19.8 DICARBOXYLIC ACIDS Separate ionization constants, designated KI and K2, respectively, characterize the two successive ionization steps of a dicarboxylic acid HoC-CoH、H++HoC-Co-k1=65×10-2 Hydrogen oxalate pK1=1.2 occurs naturally in a number of plants including sorrel and eep houseplants out of the each of small children, who HOC-CO H++“OC—CO-K2=5.3×10-5 might be tempted to eat the aves or berries Hydrogen oxalate Oxalate The first ionization constant of dicarboxylic acids is larger than Ka for boxylic analogs. One reason is statistical. There are two potential sites for ionization rather than one, making the effective concentration of carboxyl groups twice as large Furthermore, one carboxyl group acts as an electron-withdrawing group to facilitate dis- sociation of the other. This is particularly noticeable when the two carboxyl groups are separated by only a few bonds. Oxalic and malonic acid, for example, are several orders of magnitude stronger than simple alkyl ervative es of acetic acid. Heptanedioic acid, in which the carboxyl groups are well separated from each other, is only slightly stronger han acetic acid HO,CCO,H HO, CCH, CO,H HO,C(CH,)5,H Oxalic acid Malonic acid Heptanedioic acid K16.5×10 K11.4×10-3 K13.1×10-5 (pk11.2) (pK12.8) (pK14.3) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
the carboxyl group. An o-nitro substituent, for example, increases the acidity of benzoic acid 100-fold. Substituent effects are small at positions meta and para to the carboxyl group. In those cases the pKa values are clustered in the range 3.5–4.5. 19.8 DICARBOXYLIC ACIDS Separate ionization constants, designated K1 and K2, respectively, characterize the two successive ionization steps of a dicarboxylic acid. The first ionization constant of dicarboxylic acids is larger than Ka for monocarboxylic analogs. One reason is statistical. There are two potential sites for ionization rather than one, making the effective concentration of carboxyl groups twice as large. Furthermore, one carboxyl group acts as an electron-withdrawing group to facilitate dissociation of the other. This is particularly noticeable when the two carboxyl groups are separated by only a few bonds. Oxalic and malonic acid, for example, are several orders of magnitude stronger than simple alkyl derivatives of acetic acid. Heptanedioic acid, in which the carboxyl groups are well separated from each other, is only slightly stronger than acetic acid. HO2CCO2H Oxalic acid K1 6.5 102 (pK1 1.2) HO2CCH2CO2H Malonic acid K1 1.4 103 (pK1 2.8) HO2C(CH2)5CO2H Heptanedioic acid K1 3.1 105 (pK1 4.3) H K1 6.5 102 Oxalic acid pK1 1.2 HOC COH O O Hydrogen oxalate (monoanion) HOC CO O O K1 H K2 5.3 105 Oxalate pK2 4.3 (Dianion) OC CO O O Hydrogen oxalate (monoanion) HOC CO O O K2 748 CHAPTER NINETEEN Carboxylic Acids TABLE 19.3 Acidity of Some Substituted Benzoic Acids Substituent in XC6H4CO2H *In water at 25°C. 1. H 2. CH3 3. F 4. Cl 5. Br 6. I 7. CH3O 8. O2N Ortho 6.3 105 (4.2) 1.2 104 (3.9) 5.4 104 (3.3) 1.2 103 (2.9) 1.4 103 (2.8) 1.4 103 (2.9) 8.1 105 (4.1) 6.7 103 (2.2) Meta 6.3 105 (4.2) 5.3 105 (4.3) 1.4 104 (3.9) 1.5 104 (3.8) 1.5 104 (3.8) 1.4 104 (3.9) 8.2 105 (4.1) 3.2 104 (3.5) Para 6.3 105 (4.2) 4.2 105 (4.4) 7.2 105 (4.1) 1.0 104 (4.0) 1.1 104 (4.0) 9.2 105 (4.0) 3.4 105 (4.5) 3.8 104 (3.4) Ka (pKa)* for different positions of substituent X Oxalic acid is poisonous and occurs naturally in a number of plants including sorrel and begonia. It is a good idea to keep houseplants out of the reach of small children, who might be tempted to eat the leaves or berries. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website