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1. 19.6
Substituents and Acid Strength

2. standard of comparison is acetic acid (X= H)
Substituent Effects on Acidity
XCH
2COH
O
K
a= 1.8 x 10
-5
pK
a= 4.7

3. Substituent Effects on Acidity
alkyl substituents have negligible effect
XCH
2COH
O
X K
a pK
a
H
CH
3
CH
3(CH
2)
5
1.8 x 10
-5
4.7
1.3 x 10
-5
4.9
1.3 x 10
-5
4.9

4. Substituent Effects on Acidity
electronegative substituents increase acidity
XCH
2COH
O
X K
a pK
a
H
F
Cl
1.8 x 10
-5
4.7
2.5 x 10
-3
2.6
1.4 x 10
-3
2.9

5. Substituent Effects on Acidity
electronegative substituents withdraw
electrons from carboxyl group; increase Kfor
loss of H
+
XCH
2COH
O

6. Substituent Effects on Acidity
effect of electronegative substituent decreases as number of
bonds between Xand carboxyl group increases
XCH
2COH
O
X K
a pK
a
H 1.8 x 10
-5
4.7
1.4 x 10
-3
2.9
1.0 x 10
-4
4.0ClCH
2
Cl
3.0 x 10
-5
4.5ClCH
2CH
2

7. 19.7
Ionization of
Substituted Benzoic Acids

8. Hybridization Effect
K
a pK
a
6.3 x 10
-5
4.2
5.5 x 10
-5
4.3
1.4 x 10
-2
1.8
COH
O
H
2CCHCOH
O
COH
O
HCC
sp
2
-hybridized carbon is more electron-
withdrawing than sp
3
, and spis more
electron-withdrawing than sp
2

9. pK
a
Substituentortho metapara
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
CH
3O 4.1 4.1 4.5
NO
2 2.2 3.5 3.4
Table 19.3 Ionization of Substituted Benzoic Acids
COH
O
X
effect is small unless X is
electronegative; effect is
largest for ortho substituent

10. 19.8
Dicarboxylic Acids

11. 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
1.2
2.8
4.3
COH
O
HOC
O
pK
a
HOCCH
2COH
OO
HOC(CH
2)
5COH
O O

12. 19.9
Carbonic Acid

13. Carbonic Acid
HOCOH
O
CO
2
+H
2O
99.7% 0.3%

14. Carbonic Acid
HOCOH
O
CO
2
+H
2O HOCO
–
O
H
++

15. Carbonic Acid
HOCOH
O
CO
2
+H
2O HOCO
–
O
H
++
overall Kfor these two steps = 4.3 x 10
-7
CO
2is major species present in a solution of
"carbonic acid" in acidic media

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

17. 19.10
Sources of Carboxylic Acids

18. 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. 19.11
Synthesis of Carboxylic Acids by the
Carboxylation of Grignard Reagents

20. Carboxylation of Grignard Reagents
RX
Mg
diethyl
ether
RMgX
CO
2
H
3O
+
RCOMgX
O
RCOH
O
converts an alkyl (or
aryl) halide to a
carboxylic acid having
one more carbon atom
than the starting halide

21. R
MgX
C
O
••
•
•
MgX
+
d–
H
3O
+
diethyl
ether
O
•
•
••
–
RC
O
••
•
•
•
•
O
•
•
••
RC
OH
••
•
•
O
•
•
••
Carboxylation of Grignard Reagents

22. Example: Alkyl Halide
CH
3CHCH
2CH
3
(76-86%)
1. Mg,
diethyl ether
2. CO
2
3. H
3O
+
CH
3CHCH
2CH
3
Cl CO
2H

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

24. 19.12
Synthesis of Carboxylic Acids
by the
Preparation and Hydrolysis of Nitriles

25. 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
–
•
•
•
•CN
RC •
•N
S
N
2
H
3O
+
heat
+ NH
4
+

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

27. Example: Dicarboxylic Acid
BrCH
2CH
2CH
2Br
NaCNH
2O
H
2O, HClheat
(77-86%)NCCH
2CH
2CH
2CN
(83-85%)HOCCH
2CH
2CH
2COH
OO

28. via Cyanohydrin
1. NaCN
2. H
+
(60% from 2-pentanone)
H
2O
HCl, heat
CH
3CCH
2CH
2CH
3
O
CH
3CCH
2CH
2CH
3
OH
CN
CH
3CCH
2CH
2CH
3
OH
CO
2H